Is North Korea Behind U.S. Fentanyl Deaths?

Fentanyl-laced marijuana has been found in Connecticut.

This is yet ANOTHER damn good reason to:
1.) Legalize;
2.) Tax, and;
3.) Regulate
cannabis — 100%, for Adult Recreational, and Medical Use.

It should be noted, that in Connecticut, Adult Recreational Use of cannabis (aka “marijuana”) is legal, and like in every other state where it is legal, in one form, or another (as Adult Recreational and/or Medical), is subject to rigorous testing and held to the highest standards… no pun intended.
See: https://portal.ct.gov/cannabis/

The fentanyl-laced marijuana was purchased on the black market, which much like illegally-produced liquor during Prohibition, also caused death, and blindness. Now, home-based beer and wine production, along with distilling and entrepreneurship in spirituous beverage production, is legal nation-wide, and such problems are exceedingly rare.

“This is the first lab-confirmed case of marijuana with fentanyl in Connecticut and possibly the first confirmed case in the United States.”

— Dr. Manisha Juthani, MD, Connecticut Department of Public Health Commissioner

The Connecticut Overdose Response Strategy (CT ORS) and the Connecticut Department of Public Health, Office of Emergency Medical Services, have recently received reports of overdose patients who have exhibited opioid overdose symptoms and required naloxone for revival. These patients denied any opioid use and claimed to have only smoked marijuana.

Recent incidents where only marijuana use was reported but naloxone was required.

• July 2021 – 11 cases
• August 2021 – 9 cases
• September 2021 – 9 cases
• October 1 – 26, 2021 – 10 cases

The reported incidents were dispersed across Connecticut. Several jurisdictions had multiple overdoses with opioid symptoms attributed to marijuana, however, no pattern was detected. In early October 2021, Plymouth, CT, had several overdose incidents where naloxone was required for revival and patients claimed to have only smoked marijuana. At one of these overdose scenes, Plymouth Police Department was able to secure a sample of the marijuana for testing at the state laboratory, which tested positive for fentanyl.
https://portal.ct.gov/DPH/Press-Room/Press-Releases—2021/Officials-From-The-Connecticut-Overdose-Response-Strategy-And-The-DPH-Issue-Warning

A legal marijuana crop in Uruguay.

But here’s the kicker:
How long before black market fentanyl-laced marijuana makes its way down South, or to other areas of the nation?

And here’s another thought:

EVERYBODY who’s been paying attention knows how lethal fentanyl is, and the numerous deaths that are arising from its deliberate contamination in other street drugs such as heroin, methamphetamine, cocaine, and now, cannabis. And, for a person/group in such a “business” would have to be a fool to distribute a substance that they knew would kill their clientele. It’s just bad for business to destroy your customer base. So, why would any one in their proper mind do that, eh?

I submit to you that NO narcotrafficking cartel would even stoop that low, or be that stupid, to eliminate their customers.

And so, if it’s not a narcotrafficking cartel, who could it be?

It’s just my opinion, of course, but consider the possibility that it actually –might– be America’s enemies, like North Korea, Russia, China, etc. It’d be a fantastic way to eliminate your enemy little-by-little, inch-by-inch, and in that process, demoralize their resolve, and divert resources.

I continue to maintain, for example, that

Conservative Oklahoma Shows States How To Run Medical Marijuana Program

Oklahoma State Representative Scott Fetgatter (R-16)

“Anybody who wants to use marijuana is already using marijuana.
You’re not stopping that.
The goal is to eliminate the black market.”

– Oklahoma State Representative Scott Fetgatter (R-16)

Legislators there (in OK) understand at least one thing: A truly “free market” is regulated at a minimum. Of course, some regulation is necessary, and as I’ve often said, regulation makes things operate more effectively and efficiently, much like a fine-tuned automobile engine, or any sports competition. But there is a point of diminishing returns at which increased effort will not increase output.

Another benefit of minimal regulation, is reduced criminal activity.

Many have made the argument that, in a manner similar to America’s Prohibition Era, in which organized crime was born, Nixon’s 50-year failed social experiment known as the “War on Drugs” has created global narcotrafficking cartels.

And indeed, it may, or may not, surprise you know that the Drug Enforcement Administration has offices and agents worldwide. And yet, for all that effort, and money spent, drug abuse has flourished, rather than diminished, and our nation’s prisons, and jails have proliferated populations, which are much more than a mere tax burden upon society, but rob the market economy of labor, and steal husbands and fathers from families. And then, once they’ve fully “paid their debt to society,” they’re further penalized – in essence, given a life sentence – through the legally enforced social stigma of possessing an arrest record, or having served time. Just think about it: When was the last time you saw, heard, or read, of a job advertisement that specifically stated “We hire ex-cons,” or “Former felons encouraged to apply”? Probably never. So much for so-called “corrections programs,” eh?

And then, there’s this prima facie fact as well, that no one in their right mind wakes up one day and says to themselves, “Gee… I think I want to become an addict.” No one.

We human beings are complex creatures, and it is impossible to point directly to one thing, and one thing only as the cause of addiction. Suffice it to say, that there are many factors, some of which include physical (including sexual) and/or emotional abuse, or other trials and tribulations of life. Some, as well, have been victimized by poor medical care, such as over-prescribing of narcotics by reckless, lackadaisical, or greedy physicians, some of whom have operated “pill mills,” indiscriminately dispensing huge volumes of narcotics for profit.

But, even the DEA (a Federal law enforcement agency), and reputable science and medical researchers have acknowledged that “No deaths from overdose of marijuana have been reported.” The same cannot be said of beverage alcohol. It’s literally impossible to die from over-consumption of cannabis, precisely because, unlike opioids, the psychoactive ingredient – THC – does not affect the brain stem (because there are no receptors there for it to attach to), which is where the body’s respiratory drive center is located. That is a finding of science made in 2020. Now, imagine this: Science would never have advanced by learning that seemingly minor fact if “Just say NO!” was effective (and it is not).

If you’d like to know more about cannabis science, I refer you to this science and fact-based page:
Questions and Answers about Cannabis

And, without further ado, I present to you this eye-opening article which genuinely warrants further consideration, and additional discussion.

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Why Red State Oklahoma Is Home To A Booming Medical Marijuana Market

Published June 28, 2021 
By John Schroyer

People outside the cannabis industry might be surprised to learn that the most liberal medical marijuana market in the country isn’t California anymore. Nor is it Colorado, Oregon or another left-leaning blue state.

It’s politically conservative Oklahoma.

The red state has pulled a U-turn on marijuana policy since 2014, when the state’s attorney general – along with his then-counterpart in Nebraska – filed a federal lawsuit to overturn neighboring Colorado’s new recreational marijuana program.
But the U.S. Supreme Court declined to hear the case.

Fast-forward to June 2018, when Oklahoma voters soundly approved one of the loosest medical marijuana programs in the country.

Two months later, Oklahoma regulators began accepting applications for MMJ business licenses.

Sales began that December, by which point the state already had nearly 900 dispensaries, and it’s been pushing the envelope since then when it comes to MMJ policy.

Today, business is booming.

Oklahoma has more than 2,000 dispensaries – the most in the nation. And the 2021 MJBizFactbook projects

America Invented Global Narcotraffickers

Make no mistake, I openly advocate for the wholesale legalization, taxation, and regulation of cannabis similarly as is done for beverage alcohol — though I have not always. And yet, as a licensed healthcare professional, I am under no misguided notion that there are genuine scientific considerations to be had.

Like many others, this is not a simple matter, per se — it is as complex as we human beings, with myriad matters which “Just Say ‘NO!’” has never, nor will ever, satisfy. Science and understanding is not advanced by the word “NO!”

Similarly as well, there is practically no disagreement that historic American jurisprudence on the matter not only had its genesis with deep roots in racism – which remains to this day – but has almost single-handedly created the global criminal cabal of narcotrafficking enterprises that have now become international terrorist organizations. It has now become a matter of national security, and not just for the United States. Global security is predicated upon addressing these concerns.

Jesus Malverde is a mythical figure, allegedly born as Jesús Juárez Mazo on December 24, 1870, just outside Culiacán, the state capital of Sinaloa, whom is said to be the “patron saint” of “narcotraficantes” (drug traffickers), and is known by his devotees as “el ángel de los pobres” (the angel of the poor).
According to legend, he was a lifetime resident of Sinaloa, an historically poverty-stricken area which is now recognized as the de facto headquarters location for a bloodthirsty global narcotrafficking cartel bearing the state’s name, which is infamous for their nefarious misdeeds, cold-blooded murders, and other heinous acts.
The legends, which vary widely, typically assert that Malverde was a “Robinhood” type character, who stole from the wealthy and distributed to the poor. In reality, narco-money has significantly revitalized Sinaloa, and to a large extent, reinforced ancient customs, including the veneration of folk saints as Jesus Malverde.

It is, in fact, fueling the civil sociopolitical upheaval in Central American nations such as

No Smoking, No Joking: Alabama’s Medical Marijuana Law Examined

Flowering bud (female) of the Cannabis Sativa plant, aka “marijuana”

There are 49 other states to which Alabama could turn to examine what works, and what does not, and could emulate the best of the best.

But, Alabama’s gonna’ Alabama, regardless of who, or what party’s in office.

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Alabama patient advocates may have celebrated following “Guvnah Memaw’s” signature on the “Darren Wesley ‘Ato’ Hall Compassion Act” sponsored by Republican State Senator Dr. Tim Melson, MD (District 1).

But now, reality is about to set in.

The law, like so many others, is a fiasco. Citizens should rejoice the legislature cannot figure out how to connive and wheedle a gambling scheme to benefit themselves, or their “Big Mule” cronies.

Superficially, the “compassion act” sounds good.

That’s where it stops.

The law leaves patients high and dry when it comes to protecting them, and:

• Allows them to be fired without recourse, denied UC benefits, and denied Worker’s Comp benefits “regardless of the individual’s impairment or lack of impairment resulting from the use of medical cannabis.” {page 15, line 20, §20-2A-6(a)(10)} {page 16, line 13, §20-2A-6(a)(11)(c)}

But then, patient abandonment & neglect is Alabama’s forte.

• Allows DHR to remove children from a patient’s household, and states that the agency shall not be prohibited from “considering a parent or caretaker’s use of medical cannabis as a factor for determining the welfare of a child.” {page 16, line 19, §20-2A-6(a)(11)(d)}

• Penalizes diversion much more harshly than trafficking <500lbs of marijuana – 2 to 20 years vs 5 years + $50,000 fine, respectively. {Section 13A-12-231(1)(a)&(b)}

• Automatically suspends the driver’s license of “any person who is recommended a daily dosage of medical cannabis that exceeds 75 mg… regardless of whether he or she holds a valid medical cannabis card.” {page 99, line 9, Section 6}

• Taxes collected, over and above the board’s operating expenses, less 10%, will go to… The General Fund. {page 22, line 18, §20-2A-10(3)(c)}

No surprise there. It’s Alabama’s slush fund.

• Has an even number of voting board members (12), assuring deadlock on

Research: Most Religious Americans Support Broad Cannabis Legalization

A Pew Research Center survey conducted April 5-11, 2021 among 5109 randomly sampled U.S. adults who were all members of Pew Research Center’s American Trends Panel – a group of over 10,000 adults randomly selected from throughout all 50 states who regularly participate in Pew’s surveys – found that most religiously affiliated Americans favor broad cannabis legalization.

Compared with other religiously affiliated groups, at 44%, White Evangelicals were

Birmingham, Alabama Mayor Randall Woodfin Pardons 15,000 Cannabis Offenders On 420

Birmingham, Alabama Mayor Randall Woodfin has used the executive authority of the mayor’s office to issue blanket pardons for all misdemeanor marijuana-related offenses issued by the city from 1990-2020.

His actions were on April 20th, a day adopted by cannabis advocates as their celebratory day, and he Tweeted that,

“Today, I issued a pardon of 15,000 people convicted of marijuana possession in Birmingham between 1990-2020. These pardons are

Feel Like Overturning A Few Elections? Here’s Where It’s Now Happening.

Imagine for a minute, if you can, what it would be like for your elected Representatives and Senators, at either the State, or Federal level to literally “undo,” or attempt to “undo,” an election that was in every way conducted properly (meaning ethically, honestly, and openly, in accordance with all applicable laws), simply because they didn’t “like” the way The People voted – the results or outcome of the election wasn’t to their suiting, or liking.

There was such an attempt at the State level by the former President – the most notably infamous one being an hour-long phone call to the Georgia Secretary of State Brad Raffensperger, of which there is a publicly available audio recording of the entire call (transcript of entire call here), in which the former President said numerous times “I just want to find 11,780 votes” (Joe Biden won Georgia by a margin of 11,779 votes) – trying to enlist Secretary Raffensberger’s assistance in his effort to “find” votes which would dishonestly, unjustly, inequitably, and illegally “throw” the election to himself.

The Fulton County, Georgia District Attorney and the Georgia State Attorney General’s Office are both investigating that matter in order to determine what, if any, election-related laws were broken in the course of that phone call, which may include “the solicitation of election fraud, the making of false statements to state and local governmental bodies, conspiracy, racketeering, violation of oath of office and any involvement in violence or threats related to the election’s administration.”

The audio taped recording of the Trump-Raffensperger phone call is quite likely much worse than any of the numerous covert so-called “smoking gun” audio tapes of Richard Nixon’s presidency. Nixon’s numerous recorded conversations with staff, and others, including of his phone calls, which detailed his involvement in the numerous crimes of the Watergate burglary/break-in, also revealed him to be paranoid.

And cockamamie conspiracy theories aside – especially and particularly the one of “The BIG Lie,” as told by the former President – NO ONE made any overt, or clandestine effort or attempt to “steal” any election from anyone. PERIOD.

But the point of the matter is this:
There are
GENUINELY
now-ongoing efforts
to literally “undo”
the results of honest elections
in the United States.

No, this is NOT a joke… and, NO this is NOT a conspiracy theory.

It is a documented fact.

What does it say for democracy and the democratic process if the expressed will of the people is somehow, overridden, undone, or cancelled?

Yeah… it’s that “cancel culture” thing.

And it is Republicans who are doing it.

Remember the thing about “psychological projection” – a morbid behavior in which people deny or defend in themselves the very characteristic or behavior they abjure and detest in others? It’s a type of “blame shifting,” and a refusal to accept either reality or responsibility.

Read for yourself the following 2 news items to learn what GOP-Banana Republican types are doing in some states.

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Marijuana Foes Deploy New ‘Playbook’ To Thwart State Legalization, Upend Election Results

By Jeff Smith
Published February 18, 2021
https://mjbizdaily.com/marijuana-legalization-foes-aim-to-overturn-election-results/

Efforts to thwart voter-approved marijuana legalization in Mississippi, Montana and South Dakota are evidence of a “playbook” that reflects new legal strategies and greater willingness among local government officials to nullify election results, experts say.

Those efforts – led by anti-marijuana politicians and other opponents – threaten to stop or delay the implementation of new medical and recreational cannabis markets that would generate hundreds of millions of dollars in sales a year.

In Idaho, some state lawmakers are

New International Guidelines For Cannabis In Treating Chronic Pain

New Guidelines Issued on Medical Cannabis for Chronic Pain

International task force shares recommendations for dosing, administering.

by Ryan Basen, Enterprise & Investigative Writer, MedPage
September 13, 2020

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Chronic pain patients can be treated with medical cannabis following one of three protocols based on patient characteristics, according to an international task force at the virtual PAINWeek meeting.

Note the words “NO OPIATES” PROMINENTLY displayed on the label.

Citing limited clinician knowledge about medical cannabis treatment and the opioid crisis, one task force member said the recommendations are timely.

“We as a task force believe it’s extremely important to bring [medical cannabis] to patients,” Alan Bell, MD, of the University of Toronto, told MedPage Today. “Our main focus was to provide directions to clinicians.”

Medical cannabis has been suggested to treat chronic pain, the task force noted, but too many providers still do not utilize it because there has not been accepted guidelines about dosing and administration. Others prescribe medical cannabis without knowing how patients can properly dose.

“There’s a huge knowledge gap and no way clinicians can fall back on a specified dosing regimen,” Bell said.

Led by Arun Bhaskar, MD, of Imperial College Healthcare NHS Trust Pain Management Centre in London, the 20-clinician Global Task Force on Dosing and Administration of Medical Cannabis in Chronic Pain used a modified Delphi process. Among their recommendations:

• Treat the majority of patients along the “routine” scale. This means

Arizona Voters Approve Adult Recreational Use of Cannabis

In November, Arizonans voted overwhelmingly to legalize recreational sales of cannabis to adults.

By a margin of 653,982 votes, or 50.2113%, Arizona voters in that state’s General Election approved Arizona Proposition 207, known as the “Smart and Safe Arizona Act.”

The state’s fiscal analysis stated that “Annual state and local sales tax collections on these purchases may reach $88 million in the next several years. The initiative also requires a one-time transfer from the Medical Marijuana Fund of $45 million for the Department of Health Services, a university tuition program, and an impaired driving program.”

Among other provisions, as stated in its purpose, the “Act permits limited possession, transfer, cultivation, and use of marijuana (as defined) by adults 21 years old or older; protects employer and property owner rights; bans smoking in public places; imposes a 16% excise tax on marijuana to fund public safety, community colleges, infrastructure, and public health and community programs; authorizes state and local regulations for the sale and production of marijuana by a limited number of licensees; requires impairment to the slightest degree for marijuana DUls; transfers monies from the Medical Marijuana Fund; permits expungement of some marijuana violations; and prescribes penalties for violations.”

Distribution of taxes collected upon its sale would be as follows:
• 33.0% to community colleges
• 31.4% to local law enforcement and fire departments
• 25.4% to the state and local transportation programs
• 10.0% to public health and criminal justice programs
• 0.2% to the Attorney General for enforcement

The state estimates that “based on a projected tax base of $1 billion, total state and local tax collections would be $254 million, including $166 million to the Smart and Safe Arizona Fund.”

“In its Medium-Series Population Projections, the Arizona Office of Economic Opportunity (OEO) estimates that Arizona’s population will have reached 7.59 million by 2023. Given the $137 estimate for per capita sales, the OEO population estimate implies Arizona would have $1.04 billion of recreational marijuana sales in 2023.”

$254,391,600

Their revenue and sales estimates are based upon western states experiences, and they wrote that, “Arizona marijuana sales may increase further after the third year. States with more than 3 years of sales data have experienced continued growth in years 4 and 5. In Colorado, Oregon, and Washington recreational marijuana sales grew by a weighted average of 20.5% in year 4. In Colorado, the only state with 5 full years of data, sales grew by another 11.2% in year 5. We do not attempt, however, to project past the third year due to the speculative nature of long-run forecasting.”

The Arizona analysis also examines the cost associated with expungement, meaning the legal elimination of any criminal record associated with whatever record is being expunged. They cited a Pew Charitable Trusts analysis in November 2017, which stated in part that, “California only had 1,506 applications for expungement its first year of legalization and Oregon saw only 1,206 petitions combined between 2015-2017. Furthermore, the 192,000 estimate includes all convictions for marijuana possession, whereas the initiative provides the expungement option only to those who were convicted of marijuana possession of 2.5 ounces or less.”

They also note as well, that “the initiative does provide a revenue source for DPS administrative costs. The initiative authorizes DPS to collect a “reasonable fee determined by the Director” for costs to “correct the petitioner’s criminal history record” unless the individual is indigent.”

Control, or rather, elimination of the illicit black market is also a strong motivator for government in the legalization, taxation, and regulation of cannabis, especially and particularly for Adult Recreational Use. To that end, Arizona’s fiscal analysts wrote that, “If the limited number of retail locations authorized under the initiative is insufficient to meet demand, then current marijuana users may be more likely to continue to purchase illegally or from medical dispensaries, potentially decreasing the size of the legal market.”

Elimination of the illicit black market was also a very strong motivating factor in Oklahoma’s recent liberalization of cannabis laws, particularly and especially for medical use. See “Oklahoma Has Become A Free Market Utopia For Weed,” published 11/2/2020 for more details. Of course as well, an “unintended consequence” for ALL states which have liberalized their cannabis laws, is an INCREASE in private enterprise, and entrepreneurship – the veritable “holy grail” of most Republicans… and Democrats, if folks would be honest about the matter.

Arizona’s fiscal analysts also acknowledge a very important, yet almost-overlooked matter: It is of local regulation. They write that, “the proposition grants

House Banana Republicans Cower From Weed, Senate Slave Driver “Moscow” Mitch McConnell Goes Up In Smoke

Despite numerous polls from various polling organizations showing an increasing desire of a majority of Americans to legalize cannabis, House Banana Republicans have run away from The People’s will and desire to continue to exact increasingly costly tolls upon taxpayers burdened by incarcerating its consumers.

Pew Research Centers latest findings on Americans’ attitudes toward cannabis show that “an overwhelming majority of U.S. adults (91%) say marijuana should be legal either for medical and recreational use (59%) or that it should be legal just for medical use (32%),” and that “fewer than one-in-ten (8%) prefer to keep marijuana illegal in all circumstances.”

Gallup Polling most recently found similar figures.

“The 68% of U.S. adults who currently back the measure is not statistically different from last year’s 66%; however, it is nominally Gallup’s highest reading, exceeding the 64% to 66% range seen from 2017 to 2019,” they wrote on November 9, 2020.

Fifteen states and the District of Columbia have legalized the plant for recreational purposes, while 36 states – plus the District of Columbia, Guam, Puerto Rico, and the U.S. Virgin Islands – have legalized the drug for medical purposes.

Cannabis, also commonly known as “marijuana,” remains illegal under U.S. federal law.
H.R.3884 Marijuana Opportunity Reinvestment and Expungement Act of 2019 or the MORE Act of 2019 (“To decriminalize and deschedule cannabis, to provide for reinvestment in certain persons adversely impacted by the War on Drugs, to provide for expungement of certain cannabis offenses, and for other purposes.”) was introduced by Jerrold Nadler (D, NY-10), had 120 cosponsors, passed through 8 committees: House – Judiciary; Energy and Commerce; Agriculture; Education and Labor; Ways and Means; Small Business; Natural Resources; Oversight and Reform.

Roll Call Number 235 on Roll Call 235, Bill Number: H. R. 3884, was held Friday, December 04, 2020, 01:08 PM EST, in the 116th Congress, 2nd Session.
The votes were:

Yea: 228

Nay: 164

Present: 0

Not Voting: 38

Status: Passed

Roll Call 235, Bill Number: H. R. 3884

Party	Yeas	Nays	Present	Not Voting
Democratic	222	6	0	4
Republican	5	158	0	34
Independent	1	0	0	0
Total	228	164	0	38

This bill decriminalizes marijuana.

Specifically, it removes marijuana from the list of scheduled substances under the Controlled Substances Act and eliminates criminal penalties for an individual who manufactures, distributes, or possesses marijuana.

The bill also makes other changes, including the following:

• • replaces statutory references to marijuana and marihuana with cannabis,
  • requires the Bureau of Labor Statistics to regularly publish demographic data on cannabis business owners and employees,
  • establishes a trust fund to support various programs and services for individuals and businesses in communities impacted by the war on drugs,
  • imposes a 5% tax on cannabis products and requires revenues to be deposited into the trust fund,
  • makes Small Business Administration loans and services available to entities that are cannabis-related legitimate businesses or service providers,
  • prohibits the denial of federal public benefits to a person on the basis of certain cannabis-related conduct or convictions,
  • prohibits the denial of benefits and protections under immigration laws on the basis of a cannabis-related event (e.g., conduct or a conviction),
  • establishes a process to expunge convictions and conduct sentencing review hearings related to federal cannabis offenses, and
  • directs the Government Accountability Office to study the societal impact of cannabis legalization.

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WashingtonPost.com

House Votes To Decriminalize Marijuana As GOP Resists National Shift On Pot

by Mike DeBonis
December 4, 2020 at 2:34 p.m. EST

The measure is not expected to pass into law, and, due to political skittishness, it was only voted on after the November election and more than a year after it emerged from committee. But the House took a stand at a moment of increasing momentum, with voters last month opting to liberalize marijuana laws in five states — including three that President Trump won handily.

Friday’s vote, however, was largely along party lines, with

Oklahoma Has Become A Free Market Utopia For Weed

Nothing short of amazing!

Other states should take notice.

Oklahoma State Representative Scott Fetgatter (R-16)

Witness the Free Market and Free Enterprise at work collaborating with government with practically nominal regulation.

The primary difference being, is that the heavy hammer of law hangs over the heads of individuals whom violate the law, and licensing/permitting is required throughout the process – from producer to consumer – and, it is taxed.

“Anybody who wants to use marijuana is already using marijuana.
You’re not stopping that.
The goal is to eliminate the black market.”
– Oklahoma State Representative Scott Fetgatter (R-16)

“They’ve literally done what no other state has done: free-enterprise system, open market, wild wild west. It’s survival of the fittest.”
– Tom Spanier, owner of Tegridy Market (a dispensary that takes its name from South Park) with his wife in Oklahoma City last year

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How One of the Reddest States Became the Nation’s Hottest Weed Market

Oklahoma entered the world of legal cannabis late, but its hands-off approach launched a boom and a new nickname: ‘Toke-lahoma.’

Photographs for Politico Magazine by Misty Keasler/Redux

By PAUL DEMKO

11/27/2020 07:09 AM EST

Paul Demko is the cannabis editor at POLITICO Pro.
https://www.politico.com/news/magazine/2020/11/27/toke-lahoma-cannabis-market-oklahoma-red-state-weed-legalization-437782

WELLSTON, Oklahoma—One day in the early fall of 2018, while scrutinizing the finances of his thriving Colorado garden supply business, Chip Baker noticed a curious development: transportation costs had spiked fivefold. The surge, he quickly determined, was due to huge shipments of cultivation supplies—potting soil, grow lights, dehumidifiers, fertilizer, water filters—to Oklahoma.

Baker, who has been growing weed since he was 13 in Georgia, has cultivated crops in some of the world’s most notorious marijuana hotspots, from the forests of Northern California’s Emerald Triangle to the lake region of Switzerland to the mountains of Colorado. Oklahoma was not exactly on his radar. So one weekend in October, Baker and his wife Jessica decided to take a drive to see where all their products were ending up.

Voters in the staunchly conservative state had just four months earlier authorized a medical marijuana program and sales were just beginning. The Bakers immediately saw the potential for the fledgling market. With no limits on marijuana business licenses, scant restrictions on who can obtain a medical card, and cheap land, energy and building materials, they believed Oklahoma could become a free-market weed utopia and they wanted in.

Chip Baker smokes a joint in his house at the farm where he grows marijuana in Wellston, Oklahoma.

Within two weeks, they found a house to rent in Broken Bow and by February had secured a lease on an empty Oklahoma City strip mall. Eventually they purchased a 110-acre plot of land down a red dirt road about 40 miles northeast of Oklahoma City that had previously been a breeding ground for fighting cocks and started growing high-grade strains of cannabis with names like Purple Punch, Cookies and Cream and Miracle Alien.

“This is exactly like Humboldt County was in the late 90s,” Baker says, as a trio of workers chop down marijuana plants that survived a recent ice storm. “The effect this is going to have on the cannabis nation is going to be incredible.”

Oklahoma is now the biggest medical marijuana market in the country on a per capita basis. More than 360,000 Oklahomans—nearly 10 percent of the state’s population—have acquired medical marijuana cards over the last two years. By comparison, New Mexico has the country’s second most popular program, with about 5 percent of state residents obtaining medical cards. Last month, sales since 2018 surpassed $1 billion.

To meet that demand, Oklahoma has more than 9,000 licensed marijuana businesses, including nearly 2,000 dispensaries and almost 6,000 grow operations. In comparison, Colorado—the country’s oldest recreational marijuana market, with a population almost 50 percent larger than Oklahoma—has barely half as many licensed dispensaries and less than 20 percent as many grow operations. In Ardmore, a town of 25,000 in the oil patch near the Texas border, there are 36 licensed dispensaries—roughly one for every 700 residents. In neighboring Wilson (pop. 1,695), state officials have issued 32 cultivation licenses, meaning about one out of 50 residents can legally grow weed.

“Turns out rednecks love to smoke weed. That’s the thing about cannabis: It really bridges socio-economic gaps.”

– Chip Baker

What is happening in Oklahoma is almost unprecedented among the 35 states that have legalized marijuana in some form since California voters backed medical marijuana in 1996. Not only has the growth of its market outstripped other more established state programs but it is happening in a state that has long stood out for its opposition to drug use. Oklahoma imprisons more people on a per-capita basis than just about any other state in the country, many of them non-violent drug offenders sentenced to lengthy terms behind bars. But that state-sanctioned punitive streak has been overwhelmed by two other strands of American culture—a live-and-let-live attitude about drug use and an equally powerful preference for laissez-faire capitalism.

“Turns out rednecks love to smoke weed,” Baker laughs. “That’s the thing about cannabis: It really bridges socio-economic gaps. The only other thing that does it is handguns. All types of people are into firearms. All types of people are into cannabis.”

Indeed, Oklahoma has established arguably the only free-market marijuana industry in the country. Unlike almost every other state, there are no limits on how many business licenses can be issued and cities can’t ban marijuana businesses from operating within their borders. In addition, the cost of entry is far lower than in most states: a license costs just $2,500. In other words, anyone with a credit card and a dream can take a crack at becoming a marijuana millionaire.

“They’ve literally done what no other state has done: free-enterprise system, open market, wild wild west,” says Tom Spanier, who opened Tegridy Market (a dispensary that takes its name from South Park) with his wife in Oklahoma City last year. “It’s survival of the fittest.”

The hands-off model extends to patients, as well. There’s no set of qualifying conditions in order to obtain a medical card. If a patient can persuade a doctor that he needs to smoke weed in order to soothe a stubbed toe, that’s just as legitimate as a dying cancer patient seeking to mitigate pain. The cards are so easy to obtain—$60 and a five-minute consultation—that many consider Oklahoma to have a de facto recreational use program.

But lax as it might seem, Oklahoma’s program has generated a hefty amount of tax revenue while avoiding some of the pitfalls of more intensely regulated programs. Through the first 10 months of this year, the industry generated more than $105 million in state and local taxes. That’s more than the $73 million expected to be produced by the state lottery this fiscal year, though still a pittance in comparison to the overall state budget of nearly $8 billion. In addition, Oklahoma has largely escaped the biggest problems that have plagued many other state markets: Illegal sales are relatively rare and the low cost to entry has made corruption all but unnecessary.

Chip Baker’s farm in Wellston, Oklahoma. Top left: Plastic coverings are raised to allow air circulation and easier access to the plants. Top right: Alex Knight harvests cannabis plants. Middle image: Chip Baker identifies the cannabis plant that he believes is the best of the entire crop. Baker shares his cannabis cultivation knowledge on a podcast called The Real Dirt. Bottom left: Chris Hayes snips a tie connecting bamboo supports to a plant before harvesting it. Bottom right: The farm uses soil bags Baker designed to efficiently grow and harvest plants.

All of which has made Oklahoma an unlikely case study for the rest of the country, which continues its incremental march toward universal legalization. Oklahoma is

Mississippi Voters To Decide On Medical Marijuana

If you have family and friends whom reside in Mississippi, the following will be of particular interest to you.

If not, it will still be of significant interest. We’ll explain why momentarily.

First, some background.

This year, Mississippians will have the opportunity to vote on whether, or not, they want to avail themselves, their loved ones, and friends, of the opportunity to use cannabis to treat the symptoms of their diseases.

The bill which would bring Medical Marijuana to Mississippi is called Initiative 65. The bill is fully written, and is not a mere hollow proposal. Establishing a complete infrastructure, Initiative 65 thoroughly lays out the plans by and through which cannabis would become available to medically qualifying Mississippians, including the regulatory agency and mechanism, the taxation structure, prescriptive authority, distributive network, farming and production facilities, product safety testing mandates, and more.

Mississippi, like some other states, has a public initiative process by and through which citizens have the ability to facilitate legislative action outside of their legislature. It is a direct type of democratic involvement, which for them is ensconced in their State Constitution. The Mississippi Secretary of State’s website writes explicitly that, “The Mississippi initiative law affords voters an avenue for addressing important constitutional issues which the State Legislature does not.”

The site further references the qualifying conditions that must be met in order for any prospective measure to be placed on the ballot – and win – by stating that,

“for an initiative measure to be placed on the ballot, a minimum of 106,190 certified signatures must be gathered with at least 21,238 certified signatures from each of the five congressional districts as they existed in the year 2000. Signatures must be certified by county circuit clerks. A completed petition is filed with the Secretary of State’s Office, along with a $500 filing fee. Not only must an initiative receive a majority of the total votes cast for that particular initiative, it must also receive more than 40% of the total votes cast in that election.”

Suffice it to say, the state law establishes a very high standard which prospective initiative measures must meet in order for them to be placed on the ballot, and then to pass. Whereas in most other states, a simple majority is often all that’s required for any candidate or measure to win, or to pass, in Mississippi, that state’s Initiative Law requires that IN ADDITION TO meeting all other qualifying conditions, it must be voted upon by AT LEAST 40.1% of all voters/ballots cast.

For purposes of illustration – if there are 100 TOTAL voters/ballots cast in an election, and only 30 out of the 100 voters voted on the measure (called an “undervote,” a condition in which all voters do not bother to vote on a particular race or measure), and voted for it to pass, and the nay votes were -0- (zero), despite the 30-0 victory margin, it will NOT pass, because it did NOT “receive more than 40% of the total votes cast in that election.”

Again, despite the fact that more voters voted FOR the measure to pass, than voted against it (which in this example would be zero -0-), or did NOT vote upon it, the measure still would not be considered to have passed.

Enter Mississippians for Compassionate Care.

Comprised of 76 diverse individuals from a variety of backgrounds including Physicians, Nurse Practitioners and Professors, Registered Nurses, Republican and Democratic politicians, Party Executive Committee members, State Legislators, and Local Officials from both major parties, Ministers, retired Military Service members, Business Owners and Executives, District Attorneys, retired Law Enforcement Officers, and more, they are the members of the steering committee which are guiding the measure called Initiative 65 which, if approved by voters, would establish a Medical Marijuana Law in Mississippi.

Initiative 65 is a well-though-out bill, one which is thoroughly considered, and the bill for the prospective measure contains practically every aspect of consideration which would be involved in establishing an entire infrastructure for Medical Marijuana.

The bill MS Initiative 65 Proposed Measure may be read/downloaded here.

Enter the Mississippi State Legislature.

Over the years, in over 20 attempts, the state’s legislators quashed every effort to help the people, and not once did they ever

Questions & Answers About Cannabis

NOTE: The more frequently, regularly updated version of this entry is found on the front page of this blog, which is linked here:
https://warmsouthernbreeze.wordpress.com/questions-answers-about-cannabis/

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Updated Tuesday, 26 October 2021

Effort is made to update this page regularly.

While the intended audience for these Q’s & A’s is meant primarily for medical, and healthcare science professionals, they may still be of some interest, or use, by others –– particularly for those who do not know that there is legitimate science behind the use, and recommendation of cannabis in various therapies.

From Franz Eugen Köhler’s Medizinal-Pflantzen. Published and copyrighted by Gera-Untermhaus, FE Köhler in 1887 (1883–1914). Hemp plant. A–flowering male and B–seed-bearing female plant, actual size; 1-male flower, enlarged detail; 2&3-pollen sac of same from various angles; 4-pollen grain of same; 5-female flower with cover petal; 6-female flower, cover petal removed; 7-female fruit cluster, longitudinal section; 8-fruit with cover petal; 9-same without cover petal; 10-same; 11-same in cross-section; 12-same in longitudinal section; 13-seed without hull.

So in that sense, enjoy!

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QUESTION: How should a clinician monitor the outcome of cannabinoid-based therapy?

ANSWER: As suggested by the Australian Centre for Cannabinoid Clinical and Research Excellence, monitoring should initially involve reviewing the patient weekly in person, and via phone if required in the interim between clinical reviews.
“There are three areas of outcomes that should be considered:
1.) Symptom control
“A pre-defined measure of success should be negotiated with the patient prior to commencement of therapy. This can be measured by using a validated tool, for example by the Palliative Care Symptom Assessment Scale.”
2.) Drug adverse events
“Careful monitoring of patients for adverse events and the need for a change in dosage is important. Adverse events may become apparent after commencement or after change in dose… Adverse events may be related to other concurrent medications. Doses of these medicines should be adjusted as appropriate.”
3.) Pathology monitoring
“Drug concentrations of drugs where there is a potential or actual drug-drug interaction may be important. Cannabidiol may cause hepatocellular injury. Patient’s liver function biochemistry should be monitored prior to initiation and periodically as clinically indicated.“

reference: Prescribing Cannabis Medicines for Chronic Non-cancer Pain v2 September 2019 c10. – by the Australian Centre for Cannabinoid Clinical and research Excellence https://www.ces.edu.co/wp-content/uploads/2020/09/acre-prescribing-guidance-chronic-non-cancer-pain.pdf

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QUESTION: Some patients use cannabinoid-based medicines to treat nausea and vomiting. Is one of the side effects of cannabinoid-based medicines nausea/ vomiting?

ANSWER: Yes. The adverse event profile of cannabinoid-based formulations is dependent upon the ratio of CBD:THC, the presence of other cannabinoids and terpenes, and the dose consumed. The known common adverse effects of cannabinoid-based medicines include sedation/somnolence, dizziness, anxiety, cognitive dysfunction, nausea, vomiting, diarrhea, vertigo, increased or decreased appetite and dry mouth.

reference: “Brenneisen R, Egli A, ElSohly MA, Henn V, Spiess Y. The effect of orally and rectally administered delta9-tetrahydrocannabinol on spasticity: a pilot study with 2 patients. Int. J. Clin. Pharmacol. Ther. 1996 Oct;34(10)446-52. https://pubmed.ncbi.nlm.nih.gov/8897084/

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QUESTION: Even if an individual employs the same mode of administration over time, the effects of cannabinoids may change for that individual. Provide some reasons why this may be so.

ANSWER: The effects of cannabinoids may change over time due to multiple factors, including:
• Tolerance to the cannabinoids may develop
• A change in the patient’s health status/ medical condition may change over time and lead to physiological changes in the endocannabinoid system (For example, inflammation impacts the ECS. Also, impaired G.I./liver function affects the absorption and metabolism of cannabinoids.)
• The patient may start or stop taking a medication that interacts with cannabinoids or affects the metabolism of the cannabinoid-based product.
• Physiologic changes in the endocannabinoid system take place as patients age.

reference: Grotenhermen F. Clinical pharmacokinetics of cannabinoids. J Cannabis Ther, 2003; 3(1): 3-51. https://www.tandfonline.com/doi/abs/10.1300/J175v03n01_02 Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers. 2007;4(8):1770-804. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689518/

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QUESTION: The effects of cannabinoids are dependent upon the route of administration, the health of the consumer and other factors. There is also interindividual variation. Provide some reasons why the effects of cannabinoids vary among individuals.

ANSWER: There are many reasons why the effects of cannabinoids vary among individuals. SOME of the reasons are: diet, age, health of the patient, and co-administered medications may impact metabolism and efficacy of cannabinoid-based products. Also, some patients have a genetic profile such that they are predisposed to experience side effects (for ex., exacerbation of a psychotic disorder/schizophrenia) after exposure to THC. In addition, patients that have been consuming cannabinoid-based products long-term react differently than patients who have never consumed cannabinoid-based products.

reference: Grotenhermen F. Clinical pharmacokinetics of cannabinoids. J Cannabis Ther, 2003; 3(1): 3-51. https://www.tandfonline.com/doi/abs/10.1300/J175v03n01_02 Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers. 2007;4(8):1770-804. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689518/

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QUESTION: How should the cannabinoid-based therapy be withdrawn?

ANSWER: According to the Health Canada document entitled “Information for Health Care Professionals – Cannabis (marihuana, marijuana) and the Cannabinoids,” “If intolerable adverse effects appear without significant benefit, dosing should be tapered and stopped. Tapering guidelines have not been published, but the existence of a withdrawal syndrome suggests that tapering should be done slowly (i.e. over several days or weeks).” Note: When discontinuing cannabidiol therapies used for the treatment of seizure disorders, the dose should be decreased gradually. As with all antiepileptic drugs, abrupt discontinuation should be avoided when possible, to minimize the potential risk of increased seizure frequency and status epilepticus.

reference: Grotenhermen F. Clinical pharmacokinetics of cannabinoids. J Cannabis Ther, 2003; 3(1): 3-51. https://www.tandfonline.com/doi/abs/10.1300/J175v03n01_02. Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers. 2007;4(8):1770-804. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689518/

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QUESTION: What is the half life of CBD? How does it compare to the half life of THC?

ANSWER: The half life of CBD is 18-32 hours, which is similar to the half life of THC of 20-30 hours. Both CBD and THC are distributed to fatty tissues and highly perfused organs such as brain, heart, lung, and liver.

reference: Medical Marijuana, Recreational Cannabis, and Cardiovascular Health: A Scientific Statement From the American Heart Association. Robert L. Page II , Larry A. Allen , Robert A. Kloner , Colin R. Carriker, Catherine Martel , Alanna A. Morris , Mariann R. Piano , Jamal S. Rana , Jorge F. Saucedo , … See all authors. Originally published 5 Aug 2020. https://www.ahajournals.org/doi/full/10.1161/CIR.0000000000000883

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QUESTION: What are some of the more common reasons dermatologists recommend cannabinoid-based medicines?

ANSWER: According to the results of a survey of 145 dermatologists, 91 % of dermatologists were in support of medical cannabis use and 13.8 % have recommended it for a dermatologic condition. Atopic dermatitis (45 %) and psoriasis (40 %) were the most common. The most common form of administration was topical (75 %). The main reasons for not recommending medical cannabis were limited knowledge (56 %) and lack of experience (48 %).

reference: Perceptions and recommendation behaviors of dermatologists for medical cannabis: A pilot survey. Samuel Yeroushalmi, Kamaria Nelson, AndrewSparks, AdamFriedman. https://pubmed.ncbi.nlm.nih.gov/33220620/

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QUESTION: Has the use of a transdermal gel for regional and systemic delivery of CBD been evaluated for the treatment of epilepsy?

ANSWER: Yes. A transdermal gel for regional and systemic delivery of CBD (Zynerba Pharmaceuticals) is in clinical development for treatment of epilepsy, developmental and epileptic encephalopathy, fragile-X syndrome, and osteoarthritis. NOTE: As of September 2021, the company’s website indicates that the product is not yet approved by government regulatory bodies, including the United States Food and Drug Administration (FDA) and other agencies, and must be tested to see if it is an effective and safe treatment.

reference: A Review of the Safety and Effectiveness of Select Ingredients in Compounded Topical Pain Creams.” National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. https://www.nap.edu/catalog/25689/compounded-topical-pain-creams-review-of-select-ingredients-for-safety

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QUESTION: Have human studies evaluated the effects of cannabinoid consumption on cortisol levels?

ANSWER: Yes – Human studies have demonstrated that the consumption of cannabinoids modulate cortisol release. Acutely, the consumption of cannabis (or THC) by naive or infrequent cannabis users may increase the secretion of cortisol. In chronic cannabis users, the stimulatory effect of THC on cortisol levels is blunted. This blunted response suggests that a tolerance develops. Some studies have reported that chronic cannabis users exhibit elevated basal cortisol levels, but that stress- induced activation of the axis is blunted in chronic adult and adolescent cannabis users.

reference: Meah, F., Lundholm, M., Emanuele, N. et al. The effects of cannabis and cannabinoids on the endocrine system. Rev Endocr Metab Disord (2021). Aug 30, 2021. https://doi.org/10.1007/s11154-021-09682-w

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QUESTION: Do endocannabinoids impact insulin release?

ANSWER: Yes. Endocannabinoids act in an autocrine and paracrine fashion to mediate the activity of the pancreas and mediate insulin secretion. – It has been shown that endocannabinoids influence basal as well as glucose-induced insulin release. Also, endocannabinoids have been shown to have an effect on β cell proliferation and survival. (Pancreatic β cells are the cells that synthesize and secrete insulin.)

reference: Meah, F., Lundholm, M., Emanuele, N. et al. The effects of cannabis and cannabinoids on the endocrine system. Rev Endocr Metab Disord (2021). Aug 30, 2021. https://doi.org/10.1007/s11154-021-09682-w

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QUESTION: Can children with developmental and epileptic encephalopathies tolerate adjunctive cannabidiol (CBD) transdermal gel, and is CBD gel associated with reduced seizure frequency?

ANSWER: Yes, CBD is well tolerated, and is associated with a reduction in seizure activity – frequency and intensity – in children, including improvements in alertness, energy, improved sleep, and in cognition or concentration. According to a JAMA Open Network article published in September 2021, in a “nonrandomized controlled trial, CBD transdermal gel was well tolerated over 6.5 months of treatment, with 60% of patients experiencing a treatment-related adverse event, 96% of which were mild or moderate. A 43.5% reduction in seizure frequency was observed in focal impaired awareness seizures and tonic-clonic seizures.” Also, the researchers stated that “Parents and caregivers noted improvements in social or interpersonal engagement and irritability (33 of 43 [77%] participants); alertness, energy, and sleep (23 of 43 [53%]); and cognition or concentration (20 of 43 [47%]).”

reference: Scheffer IE, Hulihan J, Messenheimer J, et al. Safety and Tolerability of Transdermal Cannabidiol Gel in Children With Developmental and Epileptic Encephalopathies: A Nonrandomized Controlled Trial. JAMA Netw Open. 2021;4(9):e2123930. doi:10.1001/jamanetworkopen.2021.23930 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2783716

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QUESTION: What influences chronic pain patients’ use of medical cannabinoids?

ANSWER: The British Medical Journal recently published results of a systematic review that explored values and preferences towards medical cannabis (MC) among people living with chronic pain. The results were as follows: “High to moderate certainty evidence showed that patient’s use of MC for chronic pain was influenced by both positive (eg, support from friends and family) and negative social factors (eg, stigma surrounding cannabis use). Most patients using MC favoured products with balanced ratios of THC and CBD, or high levels of CBD, but not high THC preparations. Many valued the effectiveness of MC for symptom management even when experiencing adverse events related to concentration, memory or fatigue. Reducing use of prescription medication was a motivating factor for use of MC, and concerns regarding addiction, losing control or acting strangely were disincentives. Out-of-pocket costs were a barrier, whereas legalisation of MC improved access and incentivised use.”

reference: Zeng L, Lytvyn L, Wang X, et al Values and preferences towards medical cannabis among people living with chronic pain: a mixed-methods systematic review BMJ Open 2021;11:e050831. doi: 10.1136/bmjopen-2021-050831. https://bmjopen.bmj.com/content/11/9/e050831#ref-10

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QUESTION: Do cannabinoids affect the male reproduction system?

ANSWER: Yes. Cannabinoid receptors are located in multiple parts of the male reproductive system, including the hypothalamus, pituitary, Leydig cells, and sperm. The binding of cannabinoids to cannabinoid 1 receptors may lead to a reduction in plasma testosterone, LH and FSH.

reference: Meah, F., Lundholm, M., Emanuele, N. et al. The effects of cannabis and cannabinoids on the endocrine system. Rev Endocr Metab Disord (2021). Aug 30, 2021 https://doi.org/10.1007/s11154-021-09682-w

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QUESTION: How does anandamide’s activation of CB1 receptors on sperm cells impact sperm cells?

ANSWER: Activation of CB1 receptors on sperm by anandamide – a fatty acid neurotransmiter endocannabinoid, or THC, leads to reduction of sperm survival and motility, and inhibition of fertilization capacity by hindering the capacitation-induced acrosome reaction needed to penetrate the zona pellucida.

reference: Meah, F., Lundholm, M., Emanuele, N. et al. The effects of cannabis and cannabinoids on the endocrine system. Rev Endocr Metab Disord (2021). Aug 30, 2021 https://doi.org/10.1007/s11154-021-09682-w

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QUESTION: Marijuana use has been associated with an impairment of spermatogenesis and testicular function. How long will those effects last?

ANSWER: It has been reported that recovery of spermatogenesis and testicular cell function status post exposure to marijuana is approximately about 45 days.

reference: Meah, F., Lundholm, M., Emanuele, N. et al. The effects of cannabis and cannabinoids on the endocrine system. Rev Endocr Metab Disord (2021). Aug 30, 2021 https://doi.org/10.1007/s11154-021-09682-w

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QUESTION: How do endocannabinoids differ from many other neurotransmitters?

ANSWER: Endocannabinoids are very lipophilic and therefore cannot be stored in vesicles like many other neurotransmitters. The precursors of endocannabinoids are present in lipid membranes and, upon activation of some G-protein coupled receptors, these precursors are released into the extracellular space. Endocannabinoids are synthesized on demand in post-synaptic structures and travel retrograde through the synaptic cleft to cannabinoid type 1 receptors located presynaptically. Activation of cannabinoid type 1 receptors leads to inhibition of neurotransmitter release.

reference: Meah, F., Lundholm, M., Emanuele, N. et al. The effects of cannabis and cannabinoids on the endocrine system. Rev Endocr Metab Disord (2021). Aug 30, 2021 https://doi.org/10.1007/s11154-021-09682-w

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QUESTION: Polycystic ovarian syndrome (PCOS) is a syndrome associated with hyperandrogenism, menstrual irregularities, and polycystic ovaries. Is there any evidence that the endocannabinoid system is involved in the development of PCOS?

ANSWER: Yes. In a human study that evaluated the possibility of a link between the endocannabinoid system and PCOS, the researchers found that the endometrium of PCOS patients exhibited reduced levels of fatty acid amide hydrolase, (the catabolic enzyme for anandamide), compared to women without PCOS. This finding correlated with increased levels of anandamide in patients with PCOS. Also the activation of the ECS and overexpression of CB1 receptors may be associated with insulin resistance in women in PCOS.

reference: Meah, F., Lundholm, M., Emanuele, N. et al. The effects of cannabis and cannabinoids on the endocrine system. Rev Endocr Metab Disord (2021). Aug 30, 2021. https://doi.org/10.1007/s11154-021-09682-w

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QUESTION: Does marijuana impact platelet function?

ANSWER: Yes. Some cannabinoids have antiplatelet and antithrombogenic effects. However, in some instances marijuana use has been reported to have the opposite effect and promote platelet aggregation.

reference: Meah, F., Lundholm, M., Emanuele, N. et al. The effects of cannabis and cannabinoids on the endocrine system. Rev Endocr Metab Disord (2021). Aug 30, 2021. https://doi.org/10.1007/s11154-021-09682-w

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QUESTION: Are endocannabinoids hydrophilic or lipophilic?

ANSWER: Endocannabinoids are lipophilic neurotransmitters. They mediate agonist as well as antagonist effects via cannabinoid receptors found in the brain and peripheral nervous system.

reference: Meah, F., Lundholm, M., Emanuele, N. et al. The effects of cannabis and cannabinoids on the endocrine system. Rev Endocr Metab Disord (2021). Aug 30, 2021 https://doi.org/10.1007/s11154-021-09682-w

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QUESTION: When the endocannabinoid system was originally discovered in the 1990’s, it was described as a neural communication system. Does the endocannabinoid system have functions other than neural communication?

ANSWER: Yes. The endocannabinoid system can be found in almost every cell/ tissue and this system plays an important role in the normal functioning of many organ systems.

reference: Meah, F., Lundholm, M., Emanuele, N. et al. The effects of cannabis and cannabinoids on the endocrine system. Rev Endocr Metab Disord (2021). Aug 30, 2021 https://doi.org/10.1007/s11154-021-09682-w

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QUESTION: How do exogenous cannabinoids (phytocannabinoids or synthetic cannabinoids) affect physiologic systems like the endocrine system?

ANSWER: Exogenous cannabinoids bind to endogenous cannabinoid receptors in various organs, and may also modulate cannabinoid receptor expression. As a result, exogenous cannabinoids may alter endocannabinoid target effects and organ function.

reference: Meah, F., Lundholm, M., Emanuele, N. et al. The effects of cannabis and cannabinoids on the endocrine system. Rev Endocr Metab Disord (2021). Aug 30, 2021 https://doi.org/10.1007/s11154-021-09682-w

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QUESTION: True or false? Cannabinoid type 1 receptors are G-protein coupled receptors found in multiple organ systems, including the nervous system, skeletal system, lungs, cardiovascular system, musculoskeletal system, gi tract, and the lymph system, as well as in many endocrine organs, including the hypothalamus, pituitary, thyroid, adrenals, uterus, ovaries, testes, and placenta.

ANSWER: The statement is true, but the density and level of expression of cannabinoid receptors varies in the different organ systems.

reference: Meah, F., Lundholm, M., Emanuele, N. et al. The effects of cannabis and cannabinoids on the endocrine system. Rev Endocr Metab Disord (2021). Aug 30, 2021 https://doi.org/10.1007/s11154-021-09682-w

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QUESTION: On what cell surfaces are cannabinoid type 2 receptors typically found?

ANSWER: Cannabinoid type 2 receptors, like type 1 receptors, are G-protein coupled receptors; the type 2 receptors are primarily on the surface of the immune system cells, tonsils, the gi tract, bone, and peripheral nerve endings. Expression is highly inducible and is most often expressed when there is active inflammation or injury.

reference: Meah, F., Lundholm, M., Emanuele, N. et al. The effects of cannabis and cannabinoids on the endocrine system. Rev Endocr Metab Disord (2021). Aug 30, 2021 https://doi.org/10.1007/s11154-021-09682-w

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QUESTION: In some legal states, edibles, such as candies, baked goods, beverages and condiments (butter and oils) containing THC may be sold. Is 2.5mg of THC in an edible a low dose or high dose of THC to be consumed orally?

ANSWER: The dosing of THC always needs to be adjusted on an individual basis. For reference, 2.5 mg is the lowest dose of dronabinol, a synthetic THC that is FDA-approved.

reference: Meehan-Atrash, J., Luo, W., & Strongin, R. M. (2017). Toxicant Formation in Dabbing: The Terpene Story. ACS Omega, 2(9), 6112–6117. https://doi.org/10.1021/acsomega.7b01130

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QUESTION: Does short term treatment with THC rich cannabis induce clinical remission and improve quality of life in patients with mild to moderately active ulcerative colitis?

ANSWER: Yes, according to a recent study. However, these beneficial clinical effects were NOT associated with significant anti-inflammatory improvement in the Mayo endoscopic score or laboratory markers for inflammation. These results were derived from a double-blind, randomized, placebo-controlled trial, – 32 patients received either cigarettes containing 0.5 g of dried cannabis flowers with 80mg THC or placebo cigarettes for 8 weeks. Parameters of disease including Lichtiger disease activity index, C reactive protein (CRP), calprotectin, Mayo endoscopic score and quality of life (QOL) were assessed before, during and after treatment.

reference: Cannabis is associated with clinical but not endoscopic remission in ulcerative colitis: A randomized controlled trial Timna Naftali , Lihi Bar-Lev Schleider, Fabiana Scklerovsky Benjaminov, Fred Meir Konikoff, Shelly Tartakover Matalon, Yehuda Ringel Published: February 11, 2021 https://doi.org/10.1371/journal.pone.0246871

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QUESTION: What are the effects of cannabis-based therapies on oxaliplatin-induced peripheral neuropathy among oncology patients?

ANSWER: The results of a retrospective study indicated that the rate of neuropathy was reduced among patients treated with cannabis-based therapies and oxaliplatin. This reduction was more significant in patients who received cannabis-based products prior to treatment with oxaliplatin, suggesting a protective effect. (A large prospective trial examining the effects of cannabis-based products on oxaliplatin-induced neuropathy is planned.)

reference: Waissengrin B, Mirelman D, Pelles S, et al. Effect of cannabis on oxaliplatin-induced peripheral neuropathy among oncology patients: a retrospective analysis. Theranpeutic Advances in Medical Oncology. January 2021. doi: 10.1177/1758835921990203. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876573/

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QUESTION: The Veterans Health Administration (VHA) abides by the classification of cannabis as a Schedule I substance. Does the VHA prohibit their clinicians from speaking with their patients about cannabis?

ANSWER: No, the VHA recently recommended that clinicians discuss cannabis with their patients. However, according to a study published in February 2021, VHA clinicians identified several factors that inhibit conversations about cannabis use with their patients including the unfamiliarity with pharmacology, formulations, and dosing of cannabis; and uncertainty regarding VHA policy.

reference: Vivian A Christensen, Shannon M Nugent, Chelsea K Ayers, Benjamin J Morasco, Devan Kansagara; A qualitative study of VHA clinicians’ knowledge and perspectives on cannabis for medical purposes; Family Practice, 2021; cmaa151, https://doi.org/10.1093/fampra/cmaa151

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QUESTION: True or false? CBD interacts with transient receptor potential cation channel subfamily V member 1 (TRPV1) receptors.

ANSWER: True. It has been found in rat models of acute inflammation that the vanilloid TRPV1 receptor mediates the antihyperalgesic effect of cannabidiol.

reference: Maguire R.F, Wilkinson D.J., England T.J., O’Sullivan S.E.; The Pharmacological Effects of Plant-Derived versus Synthetic Cannabidiol in Human Cell Lines. Medical Cannabis and Cannabinoids. July 29 2021. https://www.karger.com/Article/Pdf/517120

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QUESTION: True or false? CBD interacts with serotonin 1 A receptors (5HT1A) and impacts cellular activity of some cell lines.

ANSWER: True. In in vitro models, COX-2 and PPAR-γ confer cannabidiol-induced apoptosis of human lung cancer cells.

reference: Ramer R, Heinemann K, Merkord J, Rohde H, Salamon A, Linnebacher M, et al.; COX-2 and PPAR-γ confer cannabidiol-induced apoptosis of human lung cancer cells. Mol Cancer Ther. 2013 Jan 1;12(1):69–82. https://mct.aacrjournals.org/content/12/1/69

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QUESTION: Did the “Stay at Home” orders during COVID lead to a significant decrease in sales of cannabinoid-based products in Alaska, Colorado, Oregon and Washington?

ANSWER: No. Actually, cannabis sales increased in all four states coinciding with state stay-at-home orders, and sales reached a three-year peak in all four states between May and July 2020.

reference: Schauer GL et al. Cannabis sales increases during COVID-19: Findings from Alaska, Colorado, Oregon, and Washington, International J of Drug Pol Vol 98, 2021. https://www.sciencedirect.com/science/article/abs/pii/S0955395921002899

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QUESTION: Are cannabinoid receptors present on skin cells?

ANSWER: Yes. Cannabinoid receptors are present on many types of skin cells, including keratinocytes and fibroblasts. The results of preliminary studies evaluating the effects of cannabis extracts on skin cells indicate that hemp extracts may reduce oxidative stress, inhibit skin aging processes and positively affect the viability of skin cells. Analyses also showed that hydrogels based on cannabis extracts have a positive effect on skin hydration.

reference: Zagórska-Dziok,M.; Bujak, T.; Ziemlewska, A.; Nizioł-Łukaszewska, Z. Positive Effect of Cannabis sativa L. Herb Extracts on Skin Cells and Assessment of Cannabinoid-Based Hydrogels Properties. Molecules 2021, 26, 802. https://www.mdpi.com/1420-3049/26/4/802

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QUESTION: The labels of some probiotic supplements indicate that probiotics support a healthy immune system, strengthen digestive balance, help maintain a balance of healthy intestinal bacteria, help breakdown undigested carbohydrates and sugars, and facilitate the absorption of nutrients. Do cannabis-based edibles exhibit pre-biotic/probiotic properties?

ANSWER: In addition to cannabinoids, flavonoids, terpenoids, and polysaccharides may be present in cannabis-based edibles, and these cannabis constituents may exhibit prebiotic/probiotic properties and improve the composition of the gut microbiome.

reference: Cannabis and Cannabis Edibles: A Review; Han Peng and Fereidoon Shahidi* J. Agric. Food Chem. 2021, XXXX, XXX, XXX-XXX. © 2021 American Chemical Society Publication Date: February 8, 2021 https://doi.org/10.1021/acs.jafc.0c07472

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QUESTION: What is the most common mode of administration of CBD?

ANSWER: According to an online survey conducted in 2017-2018, the most common method of CBD administration was sublingual, followed by vaping, oral ingestion of capsules and liquids, smoking, edibles, and topical administration.

reference: Corroon J, Phillips JA. A cross-sectional study of cannabidiol users. Cannabis Cannabinoid Res 2018; 3(1):152–61. https://pubmed.ncbi.nlm.nih.gov/30014038/

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QUESTION: Does THC have a dose-dependent effect on sleep?

ANSWER: Yes – Human experimental data suggests “THC has a dose-dependent effect on sleep—low doses appear to decrease sleep onset latency and increase slow-wave sleep and total sleep time, while high doses appear to cause sleep disturbances.” Also, “limited evidence from clinical studies also suggest that certain cannabinoids (cannabis, nabilone, dronabinol, nabiximols) may improve sleep in patients with disturbances in sleep associated with certain chronic disease states.”

reference: https://www.canada.ca/content/dam/hc-sc/documents/services/drugs-medication/cannabis/information-medical-practitioners/information-health-care-professionals-cannabis-cannabinoids-eng.pdf

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QUESTION: Is there ANY evidence that CBD attenuates the THC-induced psychosis?

ANSWER: Yes – “Emerging evidence from pre-clinical, clinical and epidemiological studies suggests CBD may attenuate THC-induced psychosis.”

reference: https://www.canada.ca/content/dam/hc-sc/documents/services/drugs-medication/cannabis/information-medical-practitioners/information-health-care-professionals-cannabis-cannabinoids-eng.pdf

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QUESTION: Efficacy and safety of add-on cannabidiol (CBD) to treat seizures associated with Lennox Gastaut Syndrome (LGS) was demonstrated in two randomized controlled trials (RCTs). Have the long-term effects of CBD use to treat the drug resistant seizures of LGS been evaluated?

ANSWER: Yes. 366 patients enrolled in a long-term open-label extension trial. The results are as follows: “Adverse events (AEs) occurred in 96% of patients, serious AEs in 42%, and AE-related discontinuations in 12%. Common AEs were convulsion (39%), diarrhea (38%), pyrexia (34%), and somnolence (29%). Fifty-five (15%) patients experienced liver transaminase elevations more than three times the upper limit of normal; 40 (73%) were taking concomitant valproic acid. Median percent reductions from baseline ranged 48%–71% for drop seizures and 48%–68% for total seizures through 156 weeks. Across all 12-week visit windows, 87% or more of patients/caregivers reported improvement in the patient’s overall condition on the Subject/Caregiver Global Impression of Change scale.”

reference: Patel, AD, Mazurkiewicz-Bełdzińska, M, Chin, RF, Gil-Nagel, A, Gunning, B, Halford, JJ, et al. Long-term safety and efficacy of add-on cannabidiol in patients with Lennox–Gastaut syndrome: Results of a long-term open-label extension trial. Epilepsia. 2021; 00: 1– 12. https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.17000

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QUESTION: CBD interacts with warfarin. Does this drug:drug interaction lead to an increased risk of bleeding or a decrease in warfarin’s anticoagulation effect?

ANSWER: The inhibition of CYP2C19 by CBD can increase levels of warfarin, and multiple reports have indicated that the interaction between warfarin and CBD results in an increased risk of bleeding.

reference: 1.) Treese NM, Flowers M. Pharmacist’s guide to CBD oil. US Pharm. 2020; 45(3):20-23. https://www.uspharmacist.com/article/pharmacists-guide-to-cbd-oil 2.) Welty TE, Chapman KE, Faught RE, Kotloski RJ. American Epilepsy Society (AES): Written Comments to Norman E. “Ned” Sharpless, MD, Acting Commissioner of Food and Drugs, U.S. Food and Drug Administration (FDA), Department of Health and Human Services (HHS): on Docket ID# FDA-2019-N-1482, Scientific Data and Information about Products Containing Cannabis or Cannabis-Derived Compounds; Public Hearing; Request for Comments: Submitted on: July 16, 2019. Epilepsy Currents 2019; 19(6):361-368. doi:10.1177/1535759719878716. https://journals.sagepub.com/doi/10.1177/1535759719878716

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QUESTION: Have CBD’s effects in monkeys been evaluated?

ANSWER: Yes, according to a World Health Organization Cannabidiol (CBD) report in November 2017, in studies involving the use of CBD in monkeys, no effect on a wide range of physiological and biochemical parameters or significant effects on animal behavior were noted unless extremely high doses of CBD (e.g., in excess of 150 mg/kg iv as an acute dose or in excess of 30 mg/kg orally daily for 90 days) were administered.

reference: World Health Organization (WHO) – Expert Committee on Drug Dependence Thirty-ninth Meeting Cannabidiol (CBD) Pre-Review Report Agenda Item 5.2 Geneva, 6-10 November 2017 See: https://www.who.int/medicines/access/controlled-substances/5.2_CBD.pdf

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QUESTION: PRE-CLINICAL studies show that certain cannabinoids (THC, CBD, THCV, CBDV) and cannabinoid acids (THCA and CBDA) suppress acute nausea and vomiting. Do PRE-CLINICAL studies also show that those same cannabinoids and cannabinoid acids suppress anticipatory nausea?

ANSWER: Yes. In addition, there is limited evidence from CLINICAL studies that suggests that the use of certain cannabinoids and cannabis may provide relief from chemotherapy-induced nausea and vomiting (CINV).

reference: https://www.canada.ca/content/dam/hc-sc/documents/services/drugs-medication/cannabis/information-medical-practitioners/information-health-care-professionals-cannabis-cannabinoids-eng.pdf

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QUESTION: Evidence from observational studies and clinical studies suggests that marijuana (limited evidence) and prescription cannabinoids (e.g. dronabinol, nabilone, or nabiximols) may be useful in alleviating one or several co-occurring symptoms often experienced by patients in the palliative care setting. What are some of these palliative care setting symptoms?

ANSWER: These symptoms may include, but are not limited to, intractable nausea and vomiting associated with chemotherapy or radiotherapy, anorexia/cachexia, severe intractable pain, severe depressed mood and anxiety, and insomnia. Also, a limited number of observational studies suggest that the use of cannabinoids in the palliative care setting may be associated with a decrease in the number of some medications used by palliative care patients.

reference: https://www.canada.ca/content/dam/hc-sc/documents/services/drugs-medication/cannabis/information-medical-practitioners/information-health-care-professionals-cannabis-cannabinoids-eng.pdf

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QUESTION: Available evidence from human clinical studies suggests that marijuana (limited evidence) and prescription cannabinoid-based medicines (dronabinol) may increase appetite and caloric intake, and promote weight gain in patients with HIV/AIDS. Has the use of cannabinoid-based medicines in cancer or anorexia nervosa been evaluated, too?

ANSWER: Yes. The evidence for dronabinol is mixed and effects modest for patients with cancer and weak for patients with anorexia nervosa.

reference: https://www.canada.ca/content/dam/hc-sc/documents/services/drugs-medication/cannabis/information-medical-practitioners/information-health-care-professionals-cannabis-cannabinoids-eng.pdf

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QUESTION: Evidence from PRE-CLINICAL studies suggests THC, CBD and nabiximols improve multiple sclerosis (MS) associated symptoms of tremor, spasticity and inflammation. Has the utility of cannabinoids for MS symptoms been evaluated in CLINICAL STUDIES?

ANSWER: Yes. -the available evidence from CLINICAL studies suggest marijuana (limited evidence) and certain cannabinoids (dronabinol, nabiximols (Sativex), THC/CBD) are associated with some measure of improvement in some MS symptoms and spinal cord injury (SCI), including spasticity, spasms, pain, sleep and symptoms of bladder dysfunction.

reference: https://www.canada.ca/content/dam/hc-sc/documents/services/drugs-medication/cannabis/information-medical-practitioners/information-health-care-professionals-cannabis-cannabinoids-eng.pdf

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QUESTION: An oral CBD product (Epidiolex®) has been approved by the FDA for the treatment of certain drug-resistant seizures, including Dravet syndrome and Lennox-Gastaut syndrome. Does THC also have anti-seizure properites?

ANSWER: The available evidence from pre-clinical studies suggests that some CB1 receptor agonists (including THC) may have either pro- or anti-epileptic properties.

reference: https://www.canada.ca/content/dam/hc-sc/documents/services/drugs-medication/cannabis/information-medical-practitioners/information-health-care-professionals-cannabis-cannabinoids-eng.pdf

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QUESTION: What is the half life of CBD?

ANSWER: The half life of CBD is dependent upon the mode of administration. When administered intravenously, the half life of CBD is 18-30 hours, when administered via inhalation, the half life is 27-35 hours, and when administered orally, the half life is 2-5 days.

reference: SOUZA, A.A.F. de; SILVA, A.F.M. da .; ABREU, L.R. de; SILVA, T.F. da; GRECO, G.; SANTOS, S. da S.; GONZAGA, R.V.; Medicinal uses of Cannabis sp. Research, Society and Development, [S.l.], v.10, n.7, p.e58010716930, 2021. DOI: 10.3344

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QUESTION: N-arachidonoyl ethanolamine (AEA) aka anandamide, and 2- arachidonoyl glycerol (2-AG) are the two most well-studied endocannabinoids. Are there other endocannabinoids?

ANSWER: Other than Anandamide and 2-AG, there are other endocannabinoids: “virodhamine… acts as a full and selective CB1 agonist; N-arachidonyl- dopamine (NADA) is a CB1 agonist and potent activator of TrpV1; and palmitoylethanolamide (PEA) is involved with anti- inflammatory, analgesic and neuroprotective processes.”

reference: SOUZA, A. A. F. de; SILVA , A. F. M. da .; ABREU , L. R. de .; SILVA, T. F. da .; GRECO, G. .; SANTOS, S. da S. .; GONZAGA, R. V. Medicinal uses of Cannabis sp. . Research, Society and Development, [S. l.], v. 10, n. 7, p. e58010716930, 2021. DOI: 10.33448/rsd-v10i7.16930. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/16930. Acesso em: 2 jul. 2021. https://rsdjournal.org/index.php/rsd/article/view/16930

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QUESTION: What are THCA-A and CBDA?

ANSWER: THCA-A (tetrahydrocannabinolic acid-A) and CBDA (cannabidiolic acid ) are the acid forms (the carboxylated forms) of THC and CBD, and these acid forms are found in the cannabis plant. Decarboxylation of THCA-A and CBDA takes place when the plant products are heated, and results in the bioactive compounds THC and CBD, respectively.

reference: SOUZA, A. A. F. de; SILVA , A. F. M. da .; ABREU , L. R. de .; SILVA, T. F. da .; GRECO, G. .; SANTOS, S. da S. .; GONZAGA, R. V. Medicinal uses of Cannabis sp. . Research, Society and Development, [S. l.], v. 10, n. 7, p. e58010716930, 2021. DOI: 10.33448/rsd-v10i7.16930. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/16930. Acesso em: 2 jul. 2021. https://rsdjournal.org/index.php/rsd/article/view/16930

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QUESTION: Are cannabinoids lipophilic or hydrophylic?

ANSWER: Cannabinoids are actually highly lipophilic. In fact, oral and topical cannabinoid products are often administered with a carrier to facilitate their absorption. The high lipophilicity of cannabinoid-based products is associated with a THC and CBD oral absorption range of only 10 to 20%.

reference: SOUZA, A. A. F. de; SILVA , A. F. M. da .; ABREU , L. R. de .; SILVA, T. F. da .; GRECO, G. .; SANTOS, S. da S. .; GONZAGA, R. V. Medicinal uses of Cannabis sp. . Research, Society and Development, [S. l.], v. 10, n. 7, p. e58010716930, 2021. DOI: 10.33448/rsd-v10i7.16930. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/16930. Acesso em: 2 jul. 2021. https://rsdjournal.org/index.php/rsd/article/view/16930

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QUESTION: N-arachidonoyl ethanolamine (AEA) aka anandamide, and 2- arachidonoyl glycerol (2-AG) are the two most well-studied endocannabinoids. Are there other endocannabinoids?

ANSWER: Other than Anandamide and 2-AG, there are other endocannabinoids: “virodhamine… acts as a full and selective CB1 agonist; N-arachidonyl- dopamine (NADA) is a CB1 agonist and potent activator of TrpV1; and palmitoylethanolamide (PEA) is involved with anti- inflammatory, analgesic and neuroprotective processes.”

reference: SOUZA, A. A. F. de; SILVA , A. F. M. da .; ABREU , L. R. de .; SILVA, T. F. da .; GRECO, G. .; SANTOS, S. da S. .; GONZAGA, R. V. Medicinal uses of Cannabis sp. . Research, Society and Development, [S. l.], v. 10, n. 7, p. e58010716930, 2021. DOI: 10.33448/rsd-v10i7.16930. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/16930. Acesso em: 2 jul. 2021. https://rsdjournal.org/index.php/rsd/article/view/16930

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QUESTION: Cannabinoids may impact gastro-intestinal motility and gastro-intestinal secretory activity. Have these effects been noted in IBD patients who consume marijuana to treat their conditions?

ANSWER: Yes. In fact, according to population studies, diarrhea was one of the most common symptoms that improved with cannabis use.

reference: Storr M, Devlin S, Kaplan GG, Panaccione R, Andrews CN. Cannabis use provides symptom relief in patients with inflammatory bowel disease but is associated with worse disease prognosis in patients with Crohn’s disease. Inflamm Bowel Dis. 2014;20(3):472–80. https://doi.org/10.1097/01.MIB.0000440982.79036.d6.

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QUESTION: Are blunts and joints the same thing?

ANSWER: No. Blunts and joints are not the same. Blunts consist of marijuana wrapped in tobacco leaves, whereas joints consist of marijuana wrapped in cigarette paper.

reference: Cooper ZD, Haney M. Comparison of subjective, pharmacokinetic, and physiological effects of marijuana smoked as joints and blunts. Drug and Alcohol Dependence. Vol 103 Iss 3, 1 August 2009, Pages 107-113. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776770/ https://rdcu.be/cnacn

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QUESTION: How does THC impact the gastro-intestinal system of a patient with IBD?

ANSWER: Cannabis might be a mediator within the gastrointestinal system, affecting inflammation, motility and the secretory response. Also, some cannabinoids increase appetite. A thorough 2021 review article summarized the current research evaluating the relationship between cannabinoid-based medicines and the treatment of IBD. A summary of their highlights include the following: “Patients with IBD often experience pain, nausea, and decreased appetite. As described here, in multiple studies, patients with IBD reported a significant improvement in symptoms and quality of life metrics with the use of cannabis. While initially promising, additional double-blind, placebo-controlled studies have found that even though CBD may improve perceived symptoms, it does not reduce inflammation or address underlying disease activity. These studies failed to demonstrate that when given cannabis, patients with IBD had an improvement in inflammatory markers [including CRP and calprotectin] or mucosal healing on endoscopy compared to patients with IBD in placebo conditions.”

reference: Buckley, M.C., Kumar, A. & Swaminath, A. Inflammatory Bowel Disease and Cannabis: A Practical Approach for Clinicians. Adv Ther (2021). https://doi.org/10.1007/s12325-021-01805-8. https://rdcu.be/cnacn

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QUESTION: Cannabis-based products may be some of the world’s oldest medicines. Documents dating back thousands of years BC describe the use of cannabis-based medicines in many Eastern cultures. What is the Chinese character for cannabis? Is that character used to represent other things?

ANSWER: The Chinese character for cannabis is 大麻 and the Chinese character for anesthesia is 麻木. The character 麻 means to “have pins and needles”

reference: Schlag, A.K., O’Sullivan, S.E, Zafar, R.R, Nutt, D.J, Current controversies in medical cannabis: recent developments in human clinical applications and potential therapeutics, Neuropharmacology; https://doi.org/10.1016/j.neuropharm.2021.108586 . And Google translation.

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QUESTION: Has the terpenoid caryophyllene, which is found in the cannabis plant, been found to significantly reduce craving to cigarettes?

ANSWER: Yes, according to one study with significant findings (P <0.01). Forty-eight cigarette smokers participated in a 3-h session conducted after deprivation from smoking overnight. The subjects were randomly assigned to one of three conditions: one group of smokers puffed on a device that delivered a vapor from essential oil of black pepper (black pepper contains caryophyllene); a second group puffed on the device with a mint/menthol cartridge, and a third group used a device containing an empty cartridge. Subjects puffed and inhaled ad libitum from the device throughout the session during which no smoking was allowed. Reported craving for cigarettes was significantly reduced in the pepper-containing device group relative to each of the two control conditions. Also, it was noted that negative affect and some somatic symptoms of anxiety were alleviated in the pepper-containing device group relative to the unflavored placebo. The authors suggested that one possible mechanism is via CB2 receptor agonism, with caryophyllene being a CB2R agonist.

reference: Rose JE, Behm FM. Inhalation of vapor from black pepper extract reduces smoking withdrawal symptoms. Drug Alcohol Depend. 1994 Feb;34(3):225-9. doi: 10.1016/0376-8716(94)90160-0. PMID: 8033760.

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QUESTION: The most common conditions for which cannabinoid-based medicines are used include chronic pain, anxiety, and depression. Of these 3 conditions, which , if any, is there a high strength of evidence for the efficacy of cannabinoid-based medicines.

ANSWER: Of the three conditions (chronic pain, anxiety and depression) there is only a high strength of evidence for chronic pain.

reference: Schlag, A.K., O’Sullivan, S.E, Zafar, R.R, Nutt, D.J, Current controversies in medical cannabis: recent developments in human clinical applications and potential therapeutics, Neuropharmacology; https://doi.org/10.1016/j.neuropharm.2021.108586.

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QUESTION: How does the endocannabinoid system impart analgesic effects?

ANSWER: The endocannabinoid system inhibits release of presynaptic neurotransmitters, modifies postsynaptic neuronal excitability, activates descending inhibitory pathways, and reduces neuroinflammation.

reference: Chung M, Kim H, Abdi S. Update on cannabis and cannabinoids for cancer pain. Current Opinion in Anesthesiology. 2020, 33:825 – 831. https://pubmed.ncbi.nlm.nih.gov/33110020/ DOI:10.1097/ACO.0000000000000934

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QUESTION: There is a high strength of evidence for the efficacy of cannabinoid-based medicines for the treatment of intractable epilepsy, multiple sclerosis and cancer-related nausea. Which of these 3 conditions has the greatest relative number of patients using cannabinoid -based medicines to treat the condition?

ANSWER: Among epilepsy, multiple sclerosis and cancer-related nausea, the least number of patients use cannabinoid-based medicines for intractable epilepsy and the greatest number of people use cannabinoid-based medicines for cancer-related nausea.

reference: Schlag, A.K., O’Sullivan, S.E, Zafar, R.R, Nutt, D.J, Current controversies in medical cannabis: recent developments in human clinical applications and potential therapeutics, Neuropharmacology; https://doi.org/10.1016/j.neuropharm.2021.108586.

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QUESTION: CB1 receptors are abundant in the CNS, including areas involved in pain transmission. CB2 receptors are mostly located on peripheral tissues and immune cells. Are CB2 receptors involved with pain transmission?

ANSWER: Yes. When activated, CB2 receptors may modulate peripheral afferent pain fiber activity and immune-mediated neuro-inflammatory processes. For example, CB2 activation may lead to the inhibition of prostaglandin synthesis and/or mast cell degranulation; both of these cellular activities can precipitate and maintain chronic pain states.

reference: Current Psychiatry. 2021 May;20(5):21-23, 28-33 | doi:10.12788/cp.0121, and MD Raphael J. Leo Raymond M. St. Marie. “Cannabinoid-Based Medications for Pain.” MDedge Psychiatry, 3 May 2021, https://www.mdedge.com/psychiatry/article/239193/pain/cannabinoid-based-medications-pain.

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QUESTION: Haloperidol is an antipsychotic medication and used to treat schizoaffective disorders and schizophrenia. Is the metabolism of haloperidol impacted by THC?

ANSWER: Yes, THC inhibits CYP3A4, the enzyme that metabolizes haloperidol, and therefore the co-administration of THC and haloperidol may result in an increased availability of haloperidol.

reference: Current Psychiatry. 2021 May;20(5):21-23, 28-33 | doi:10.12788/cp.0121, and MD Raphael J. Leo Raymond M. St. Marie. “Cannabinoid-Based Medications for Pain.” MDedge Psychiatry, 3 May 2021, https://www.mdedge.com/psychiatry/article/239193/pain/cannabinoid-based-medications-pain.

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QUESTION: What has been the most common mode of administration of cannabinoid-based medicines (CBMs) in RCTs examining the efficacy of CBMs to treat pain?

ANSWER: Most RCTs evaluated inhaled herbal CBMs and oromucosal spray (nabiximols (Sativex) – an oral spray with 50:50 mix of THC:CBD); there is a paucity of data derived from studies evaluating the effectiveness of other CBM formulations.

reference: Current Psychiatry. 2021 May;20(5):21-23, 28-33 | doi:10.12788/cp.0121, and MD Raphael J. Leo Raymond M. St. Marie. “Cannabinoid-Based Medications for Pain.” MDedge Psychiatry, 3 May 2021, https://www.mdedge.com/psychiatry/article/239193/pain/cannabinoid-based-medications-pain.

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QUESTION: Do oral mucosal spray cannabinoid-based medicines (CBMs) have the same bioavailability as ingested CBMs?

ANSWER: No. The administration of CBMs via oromucosal sprays (sublingual) avoids first-pass metabolism (although some of the product is swallowed) and therefore sublingual administration has a higher bioavailability than ingested formulations.

reference: Current Psychiatry. 2021 May;20(5):21-23, 28-33 | doi:10.12788/cp.0121, and MD Raphael J. Leo Raymond M. St. Marie. “Cannabinoid-Based Medications for Pain.” MDedge Psychiatry, 3 May 2021, https://www.mdedge.com/psychiatry/article/239193/pain/cannabinoid-based-medications-pain.

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QUESTION: Is the bioavailability of THC greater with inhaled cannabinoid-based medicines (CBMs) or ingested CBMs?

ANSWER: The bioavailability of inhaled CBMs is nearly 30% while the bioavailability of ingested CBMs is approximately 4%-20%. (It should be noted that the bioavailability is higher with vaporized cannabis as compared with combusted (smoked) cannabis products.

reference: Current Psychiatry. 2021 May;20(5):21-23, 28-33 | doi:10.12788/cp.0121, and MD Raphael J. Leo Raymond M. St. Marie. “Cannabinoid-Based Medications for Pain.” MDedge Psychiatry, 3 May 2021, https://www.mdedge.com/psychiatry/article/239193/pain/cannabinoid-based-medications-pain.

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QUESTION: The most well studied endocannabinoids are N-arachidonoyl- ethanolamine (AEA; anandamide) and 2-arachidonoylglycerol (2-AG). Are these two neurotransmitters stored in the presynaptic neurons?

ANSWER: No. Unlike most neurotransmitters, neither AEA or 2-AG is stored within vesicles in presynaptic neuron axons. They are actually produced on demand; they are synthesized from arachidonic acid of the membranes of post-synaptic neurons, and then they are released directly into the synapse and bind to receptors on the pre-synaptic neuron. In other words, they act in a retrograde fashion.

reference: Current Psychiatry. 2021 May;20(5):21-23, 28-33 | doi:10.12788/cp.0121, and MD Raphael J. Leo Raymond M. St. Marie. “Cannabinoid-Based Medications for Pain.” MDedge Psychiatry, 3 May 2021, https://www.mdedge.com/psychiatry/article/239193/pain/cannabinoid-based-medications-pain.

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QUESTION: Some NFL players strongly believe that it’s safer for them to use marijuana to treat pain than to take prescription medication. What has the NFL done in response to this claim?

ANSWER: For years, the NFL suspended a player if the player tested positive for marijuana multiple times. That changed due to an agreement approved in 2020. Now, the pain management committee of the NFL and the NFL Players Association will provide $1 million in funding for research into pain management and cannabinoids. Specifically, the research is evaluating marijuana as a potential alternative to opioids. Also, the NFL is investigating how using cannabis-based products and CBD to treat pain affects performance in elite athletes.

reference: https://www.nfl.com/news/nfl-nflpa-will-provide-funding-for-research-into-pain-treatment-including-medica

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QUESTION: The results of recent clinical trials indicate that Cannabidiol (CBD) reduces seizures among patients with refractory epilepsies of various etiologies. Most of these clinical studies report efficacy over short time periods (<1 year). Is CBD effective long term?

ANSWER: Yes. A May 2021 study demonstrated that CBD does not lose its efficacy in controlling seizures over a treatment period of up to 60 months. In addition, other results on the efficacy and tolerability of CBD in the treatment of refractory epilepsies, suggest that CBD is an effective, safe, and well-tolerated anti-epileptic drug for long-term use.

reference: The long-term efficacy of cannabidiol in the treatment of refractory epilepsy. Sandip Patel, Reid Grinspoon, Bradley Fleming, Lauren A. Skirvin, Christina Wade. 29 May 2021 https://doi.org/10.1111/epi.16936

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QUESTION: Some patients in the US may wish to travel with CBD to Canada, or vice versa. CBD is legally sold in the US and in Canada. So, is it legal to transport CBD across the US/Canadian border?

ANSWER: The transporting of cannabis (in any form, including oils containing THC or cannabidiol) into or out of Canada without special authorization from Health Canada is a serious criminal offense.

reference: Cannabis in Canada – What you need to know; https://www.canada.ca/content/dam/hc-sc/documents/services/drugs-medication/cannabis/resources/cannabis-act-what-you-need-to-know.pdf

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QUESTION: For what health conditions is the therapeutic applicability of CBD being evaluated?

ANSWER: The range of conditions for which CBD has been (or is being) assessed is quite diverse. Currently, clinical trials are evaluating CBD’s analgesic, neuroprotective, antiepileptic, anxiolytic, antipsychotic, anti-inflammatory, antitumor and anti-hypoxia/ischemia properties. According to a March 2021 search of the National Library of Medicine’s database, clinicaltrials.gov, there were more than 300 registered clinical trials that involve the use of CBD as a therapeutic intervention.

reference: Clinicaltrials.gov

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QUESTION: Does pretreatment with CBD prevent the transient psychotic symptoms induced by THC?

ANSWER: According to a study in humans, pretreatment with CBD does diminish THC’s psychotic effects. This particular study involved 6 healthy volunteers who were given THC intravenously on two separate occasions – once with a placebo pretreatment and once with a CBD pretreatment.

reference: Atakan Z. Cannabis, a complex plant: Different compounds and different effects on individuals. Ther Adv Psychopharmacol 2012 Dec; 2(6):241-254. doi:10.1177/2045125312457586. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736954/

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QUESTION: Has any national drug administration approved a CBD-containing product for therapeutic use in conditions other than epilepsy?

ANSWER: Yes. The oromucosal spray Sativex (nabiximols) is a cannabis extract that contains the principal cannabinoids delta-9-tetrahydrocannibinol (THC) and cannabidiol (CBD) in a 50:50 ratio, as well as specific minor cannabinoids and other non-cannabinoid components. Regulatory approval has been obtained in numerous countries outside the United States for the treatment of multiple sclerosis symptoms (nerve pain, spasticity, overactive bladder, and other symptoms).

reference: GW Pharmaceuticals website. Sativex. https://www.gwpharm.com/healthcare-professionals/sativex

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QUESTION: Some patients consume CBD hoping that it will cure their cancer. Do the findings of clinical research studies indicate that CBD cures cancer?

ANSWER: No. There is no substantial clinical evidence to support that cannabinoids (natural or synthetic), including CBD, can effectively and safely treat cancer in humans.

reference: NO CLINICAL RESEARCH CITATION

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QUESTION: Epidiolex is an FDA-approved oral CBD solution indicated for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC) in one year of age and older. Can it be prescribed for indications other than these three seizure disorders (i.e. off label)?

ANSWER: Yes, Epidiolex may be prescribed off-label, but insurance coverage may be subject to pre-authorization.

reference: GW Pharmaceuticals press release: “GW Pharmaceuticals plc and Its U.S. Subsidiary Greenwich Biosciences, Inc. Announce That EPIDIOLEX® (cannabidiol) Oral Solution Has Been Descheduled And Is No Longer A Controlled Substance” April 6, 2020. https://ir.gwpharm.com/news-releases/news-release-details/gw-pharmaceuticals-plc-and-its-us-subsidiary-greenwich-1 Accessed April 30, 2020. GW Pharmaceuticals website. Sativex. https://www.gwpharm.com/healthcare-professionals/sativex accessed Mar 31, 2021.

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QUESTION: St. John’s wort is an over the counter medication used as a remedy for mild depression. Does St. John’s wort interact with CBD?

ANSWER: Yes. St. Johns wort inhibits some of the liver enzymes that metabolize CBD. As a result, there is an increase in bioavailability of CBD, and a possible increase of adverse effects associated with CBD consumption.

reference: Brown JD, Winterstein AG. Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. J Clin Med. 2019;8(7):989. Published 2019 Jul 8. doi:10.3390/jcm8070989. https://pubmed.ncbi.nlm.nih.gov/31288397/

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QUESTION: A seizure disorder is a qualifying condition in many medical marijuana state programs. Does CBD interact with commonly prescribed anti-epileptic medications?

ANSWER: Yes. According to a presentation at the 2014 annual meeting of the American Epilepsy Society, an increasing dose of CBD was associated with significant increases in serum levels of topiramate, rufinamide, and N-desmethylclobazam. Also, there is a significant association between increasing CBD doses and increased zonisamide and eslicarbazepine serum levels.

reference: Friedman D, Cilio MR, Tilton N, et al. The effect of Epidiolex (cannabidiol) on serum levels of concomitant anti-epileptic drugs in children and young adults with treatment-resistant epilepsy in an expanded access program. Presented at the annual meeting of the American Epilepsy Society, Seattle, December 5–9, 2014; abstract.

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QUESTION: Is CBD addictive?

ANSWER: According to the drug package insert of an FDA-approved CBD product, CBD is not addictive.

reference: GW Pharmaceuticals website. Sativex. https://www.gwpharm.com/healthcare-professionals/sativex accessed Mar 31, 2021.

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QUESTION: Proton pump inhibitors (PPIs) are commonly used to relieve the symptoms of gastro-esophageal reflux disease (GERD). Do PPIs interact with CBD?

ANSWER: Yes. PPIs inhibit some of the liver enzymes that metabolize CBD. As a result, there is an increase in bioavailability of CBD, and a possible increase of adverse effects associated with CBD consumption.

reference: Brown JD, Winterstein AG. Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. J Clin Med. 2019;8(7):989. Published 2019 Jul 8. doi:10.3390/jcm8070989. https://pubmed.ncbi.nlm.nih.gov/31288397/

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QUESTION: Other than pill form, in what forms is CBD sold?

ANSWER: There are multiple CBD product types, including CBD oils (for oral/sublingual administration or vaporization), gummy candies, joint balms, creams, lotions, and capsules. CBD is also being sold in food products, beverages and healthcare goods, including hair products and skincare products. CBD has even been marketed as an ingredient in sleeping masks and dog treats.

reference: “Ads Pitching CBD as a Cure-all Are Everywhere. Oversight Hasn’t Kept Up.” The New York Times, Aug 13, 2019 – https://www.nytimes.com/2019/08/13/business/media/cbd-marijuana-fda.html – accessed Aug 2019.

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QUESTION: Does CBD alter the metabolism of methadone?

ANSWER: Yes. Cannabidiol inhibits CYP3A4 and CYP2C19, both of which are involved in the metabolism of methadone. As a result, the co-administration of CBD and methadone may lead to increased sedation.

reference: Madden K, Tanco K, Bruera E. Clinically Significant Drug-Drug Interaction Between Methadone and Cannabidiol. Pediatrics May 2020; e20193256; DOI: https://doi.org/10.1542/peds.2019-3256.
https://pediatrics.aappublications.org/content/145/6/e20193256

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QUESTION: The FDA has approved a CBD product (Epidiolex) for the treatment of 3 rare forms of epilepsy. What is the mechanism of action of CBD in this anti-epileptic medication? How does CBD exert its anti-convulsant effects?

ANSWER: According to the prescribing information of this FDA-approved product, “The precise mechanisms by which Epidiolex exerts its anticonvulsant effect in humans are unknown. Cannabidiol does not appear to exert its anticonvulsant effects through interaction with cannabinoid receptors.”

reference: Highlights for prescribing information for Epidiolex https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210365lbl.pdf

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QUESTION: Fluoxetine (sold under the name Prozac) is a commonly prescribed antidepressant of the SSRI – Selective Serotonin Reuptake Inhibitor – class. Does Fluoxetine impact the metabolism of CBD?

ANSWER: Yes. Fluoxetine inhibits some of the liver enzymes that metabolize CBD. As a result, there is an increase in bioavailability of CBD, and a possible increase of adverse effects associated with CBD consumption.

reference: Brown JD, Winterstein AG. Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. J Clin Med. 2019;8(7):989. Published 2019 Jul 8. doi:10.3390/jcm8070989. https://pubmed.ncbi.nlm.nih.gov/31288397/

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QUESTION: Some patients apply CBD topically. Does CBD easily penetrate the skin?

ANSWER: Due to CBD’s large size and hydrophobic properties, CBD does not penetrate the skin efficiently, however, permeation-enhancing gels have been developed. Currently, CBD-containing gels are being evaluated for the treatment of several pediatric disorders, and a heterogeneous group of rare and ultra-rare epilepsies known as developmental and epileptic encephalopathies.

reference: https://zynerba.com/in-development/zygel/

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QUESTION: Have CBD’s effects on human embryonic development been fully evaluated?

ANSWER: No, but according to a World Health Organization Cannabidiol (CBD) report in November 2017, in studies involving the use of CBD in monkeys, no effect on a wide range of physiological and biochemical parameters or significant effects on animal behavior were noted unless extremely high doses of CBD (e.g., in excess of 150 mg/kg iv as an acute dose or in excess of 30 mg/kg orally daily for 90 days) were administered.

reference: World Health Organization (WHO) – Expert Committee on Drug Dependence Thirty-ninth Meeting Cannabidiol (CBD) Pre-Review Report Agenda Item 5.2 Geneva, 6-10 November 2017

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QUESTION: CBD interacts with warfarin. Does this drug:drug interaction lead to an increased risk of bleeding or a decrease in warfarin’s anticoagulation effect?

ANSWER: The inhibition of CYP2C19 by CBD can increase levels of warfarin, and multiple reports have indicated that the interaction between warfarin and CBD results in an increased risk of bleeding.

reference: Treese NM, Flowers M. Pharmacist’s guide to CBD oil. US Pharm. 2020; 45(3):20-23. https://www.uspharmacist.com/article/pharmacists-guide-to-cbd-oil

Welty TE, Chapman KE, Faught RE, Kotloski RJ. American Epilepsy Society (AES): Written Comments to Norman E. “Ned” Sharpless, MD, Acting Commissioner of Food and Drugs, U.S. Food and Drug Administration (FDA), Department of Health and Human Services (HHS): on Docket ID# FDA-2019-N-1482, Scientific Data and Information about Products Containing Cannabis or Cannabis-Derived Compounds; Public Hearing; Request for Comments: Submitted on: July 16, 2019. Epilepsy Currents 2019; 19(6):361-368. doi:10.1177/1535759719878716

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QUESTION: What is the most common mode of CBD administration?

ANSWER: According to a 2017–2018 online survey evaluating modes of CBD administration, the most common method of CBD administration was sublingual, followed by vaping, oral ingestion of capsules and liquids, smoking, edibles, and topical administration

reference: Corroon J, Phillips JA. A cross-sectional study of cannabidiol users. Cannabis Cannabinoid Res. 2018;3(1):152–61. https://pubmed.ncbi.nlm.nih.gov/30014038/

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QUESTION: A common adverse effect of chronic recreational marijuana use is cannabinoid hyperemesis syndrome. In fact, cannabinoid hyperemesis syndrome is a near daily diagnosis in many Canadian emergency departments. Anecdotal evidence supports the use of haloperidol to treat cannabinoid hyperemesis syndrome. Is haloperidol more effective than odansetron for the treatment of the nausea and vomiting associated with cannabinoid hyperemesis syndrome?

ANSWER: According to the results of a randomized controlled trial involving 33 patients with cannabinoid hyperemesis syndrome, haloperidol (0.05 mg/kg or 0.1 mg/kg) was superior to odansetron 8mg for average reduction from baseline in abdominal pain and nausea at 2 hours, and was associated with the need for fewer rescue antiemetics and shorter time to ED departure. In this study, there were 2 haloperidol and 6 ondansetron return ED visits for ongoing nausea/vomiting, as well as 2 return visits for acute dystonia, both in the higher dose haloperidol group.

reference: Ruberto, A., Sivilotti, M., Forrester, S., Hall, A., Crawford, F., & Day, A. (2020). LO69: Haloperidol versus ondansetron for hyperemesis due to cannabis (HaVOC): A randomized, controlled clinical trial. CJEM, 22(S1), S32-S33. doi:10.1017/cem.2020.124. https://www.researchgate.net/publication/341353323_LO69_Haloperidol_versus_ondansetron_for_hyperemesis_due_to_cannabis_HaVOC_a_randomized_controlled_clinical_trial

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QUESTION: Cannabinoid receptors have been located in the central nervous system and the peripheral nervous system, as well as on immune cells. Have cannabinoid receptors been isolated in reproductive tissues/cells?

ANSWER: In addition to cannabinoid receptors being identified in the hypothalamus and the pituitary gland, cannabinoid receptors have also been identified on ovary, endometrial tissue, testes, and spermatozoa. In fact, research suggests that marijuana may alter the release of FSH and LH, ovulation, sperm motility, fertilization, as well as placentation.

reference: Caitlin Dunne, MD, FRCSC. THE EFFECTS OF CANNABIS ON FEMALE AND MALE REPRODUCTION. BCMJ, vol. 61 , No. 7 , September 2019 , Pages 282-285. https://bcmj.org/articles/effects-cannabis-female-and-male-reproduction

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QUESTION: What is the most common route of administration for the synthetic cannabinoids K2 or Spice?

ANSWER: K2 and Spice are used for recreational purposes, and smoking is the most common route of administration. Spraying or mixing the synthetic cannabinoids on dried plant material allows one to smoke it (using a pipe, a water pipe, or rolling the drug-laced plant material in cigarette papers). Also, liquid synthetic cannabinoids have been designed to be vaporized via e-cigarettes.

reference: Drugs of Abuse – A DEA Resource Guide /2020 Edition. https://www.dea.gov/sites/default/files/2020-04/Drugs%20of%20Abuse%202020-Web%20Version-508%20compliant-4-24-20_0.pdf

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QUESTION: What are K2 and Spice?

ANSWER: K2 and Spice are synthetic cannabinoid “designer drugs” that are intended to mimic the effects of THC. These synthetic cannabinoids are sold as “herbal incense” at convenience stores/gas stations, smoke shops and via the internet. They are produced in powder form, and then often dissolved in solvents, so they can be applied to dry plant material to make the “herbal incense” products.

rreference: Drugs of Abuse – A DEA Resource Guide /2020 Edition. https://www.dea.gov/sites/default/files/2020-04/Drugs%20of%20Abuse%202020-Web%20Version-508%20compliant-4-24-20_0.pdf

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QUESTION: Respiratory depression is associated with the overdose of opioids or benzodiazepines. Is respiratory depression associated with an overdose of cannabinoids? Why or why not?

ANSWER: Respiratory depression is not associated with cannabinoid use because CB1 receptors are not located in the midbrain, the part of the brain responsible for respiratory drive.

reference: Levinsohn EA, Hill KP. Clinical uses of cannabis and cannabinoids in the United States. J Neurol Sci. 2020 Apr 15;411:116717. doi: 10.1016/j.jns.2020.116717. Epub 2020 Jan 30. PMID: 32044684. https://pubmed.ncbi.nlm.nih.gov/32044684/

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QUESTION: As of January 2020, how many Americans were using marijuana-based products for medicinal purposes?

ANSWER: It has been estimated that more than 2 million Americans use marijuana for medical reasons. Some of the many ailments being treated with marijuana include: chronic pain, PTSD, depression, sleep disorders, multiple sclerosis (MS), cancer-related ailments, and GI disorders. Some indications are supported by good scientific evidence, but some are not.

reference: Levinsohn EA, Hill KP. Clinical uses of cannabis and cannabinoids in the United States. J Neurol Sci. 2020 Apr 15;411:116717. doi: 10.1016/j.jns.2020.116717. Epub 2020 Jan 30. PMID: 32044684. https://pubmed.ncbi.nlm.nih.gov/32044684/

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QUESTION: Cannabinoids are metabolized by many of the same cytochrome P450 enzymes as warfarin. In fact, THC, CBD and CBN can inhibit the hydroxylation of warfarin, and thus lead to an increase in INR. Do cannabinoids also affect the metabolism of heparin? Is the metabolism of direct oral anticoagulants (DOACs), including rivaroxaban, edoxaban, and apixaban, impacted by cannabinoids?

ANSWER: While cannabinoids do not alter the metabolism of heparin, cannabinoids may impact the metabolism of DOACs. DOAC levels may increase, leading to an increased risk of bleeding.

reference: Jessica Greger, PharmD, Vernice Bates, MD, Laszlo Mechtler, MD, and Fran Gengo, PharmD. A Review of Cannabis and Interactions With Anticoagulant and Antiplatelet Agents. The Journal of Clinical Pharmacology 2019, 0(0) 1–7. https://accp1.onlinelibrary.wiley.com/doi/abs/10.1002/jcph.1557?af=R

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QUESTION: Does CBD interact with receptors other than CB1 or CB2?

ANSWER: Yes. CBD has cannabinoid receptor-independent properties. For example, CBD is an agonist at the TRPV1 receptor and has agonist properties at the 5-HT1A/2A/3A serotonergic receptors. CBD is also a capsaicin analog. CBD has antagonist activity on alpha-1 adrenergic and μ-opioid receptors, too. In addition, CBD has been found to inhibit synaptosomal uptake of noradrenaline, dopamine, serotonin, and gamma-amino butyric acid. CBD also inhibits anandamide uptake.

reference: Levinsohn EA, Hill KP. Clinical uses of cannabis and cannabinoids in the United States. J Neurol Sci. 2020 Apr 15;411:116717. doi: 10.1016/j.jns.2020.116717. Epub 2020 Jan 30. PMID: 32044684. https://pubmed.ncbi.nlm.nih.gov/32044684/

reference: Brown JD, Winterstein AG. Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. J Clin Med. 2019 Jul 8;8(7):989. doi: 10.3390/jcm8070989. PMID: 31288397; PMCID: PMC6678684. https://pubmed.ncbi.nlm.nih.gov/31288397/

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QUESTION: Cannabinoid receptors are located throughout various parts of the CNS, including the basal ganglia, hippocampus, cerebellum and cerebral cortex, and in the peripheral nervous system. Do these receptors have effects on neurotransmitters such as serotonin?

ANSWER: Yes. CB receptor activity not only impacts serotonin, but it also affects acetylcholine, dopamine, glutamate, and GABA, as well as NMDA and opioid receptor systems.

reference: Levinsohn EA, Hill KP. Clinical uses of cannabis and cannabinoids in the United States. J Neurol Sci. 2020 Apr 15;411:116717. doi: 10.1016/j.jns.2020.116717. Epub 2020 Jan 30. PMID: 32044684. https://pubmed.ncbi.nlm.nih.gov/32044684/

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QUESTION: Epidemiological studies indicate that as many as 15% of inflammatory bowel disease (IBD) patients may use cannabinoids to ameliorate some of their symptoms, including improvement in diarrhea, abdominal pain and appetite. Do the studies show that cannabinoids are effective in Crohn’s disease?

ANSWER: Although the findings of studies examining the efficacy of cannabinoids in Crohn’s disease indicate that cannabinoids do not improve inflammatory markers or endoscopic score, the results indicate that THC reduces the Crohn’s disease activity index by >100 points (on a scale of 0–450).

reference: Naftali T, Dor M. Cannabis for the Treatment of Inflammatory Bowel Disease: A True Medicine or a False Promise?. Rambam Maimonides Med J 2020;11 (1):e0008. Review. doi:10.5041/RMMJ.10390. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000156/

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QUESTION: Some cancer patients use medical marijuana to treat various cancer-associated ailments. What are some of the ailments ameliorated by medical marijuana?

ANSWER: According to one study involving 96 cancer patients receiving supportive cancer care, the data support the safety and effectiveness of medical marijuana as a complementary option for improving pain control, appetite and quality of life for cancer patients. The top three adverse events of this study included drowsiness, low energy and nausea. (Note: other studies indicate that chemotherapy-induced nausea and vomiting is ameliorated by medical marijuana.)

reference: Safety and effectiveness of medical cannabis as a complementary option for supportive cancer care: Results from the Cannabis Pilot Project. Antonio Vigano, Saro Aprikian, Popi Kasvis, Virginie Bacis, Amna Al Harrasi, Nathalie M Aubin, MariaLuisa Vigano, and Manuel Borod. Journal of Clinical Oncology 2020 38:15_suppl, 12106-12106.
https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.12106

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QUESTION: What is Sativex®?

ANSWER: Sativex® is a buccal (oral) spray containing Δ-9-THC and CBD (2.7 mg Δ-9-THC and 2.5 mg CBD per spray) and it is indicated for spasticity and neuropathic pain in multiple sclerosis, and as adjunctive analgesia for moderate to severe cancer pain. While Sativex® is approved in several European countries, Canada, and other countries, it has not been approved for medical use in the U.S.

reference: Brown JD, Winterstein AG. Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. J Clin Med. 2019;8(7):989. Published 2019 Jul 8. doi:10.3390/jcm8070989.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678684/

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QUESTION: According to the results of a survey of breast cancer patients’ use of cannabinoid products, 42% of survey participants had used medical cannabinoid products to relieve symptoms. What symptoms were treated with cannabinoid products?

ANSWER: Members of the Breastcancer.org and Healthline communities were asked to participate in a survey during the period of 12/16/2019 – 1/19/2020. According to the results of the survey, cannabinoids were used to relieve insomnia (70%), pain (59%), anxiety (57%), stress (51%), and nausea/vomiting (46%).

reference: A survey of breast cancer patients’ use of cannabis before, during, and after treatment. Marisa C. Weiss, Julianne Hibbs, Terri W. McHugh, Meghan Buckley, Sharon Larson, Nancye Green, Virginia G. Kaklamani, Rowan T. Chlebowski, and Diana Martinez. Journal of Clinical Oncology 2020 38:15_suppl, e19210-e19210. https://ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.e19210

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QUESTION: Are cannabinoids an effective analgesic agent in the acute pain setting? Are cannabinoids an effective analgesic agent in the chronic pain setting?

ANSWER: According to the results of multiple randomized controlled trials examining the efficacy of cannabinoids to treat acute pain, THC, nabilone and other cannabinoid-based products were not associated with a reduction in pain, but were associated with adverse side effects, including sedation. In contrast to the lack of efficacy in the acute pain setting, cannabinoids are effective analgesic agents in the chronic pain setting. According to 2 systematic reviews involving a total of 29 randomized controlled trials (RCTs), 22 of the 29 RCTs demonstrated that cannabinoids do have a modest analgesic effect in the management of chronic pain.

reference: Vulfsons S, Minerbi A, Sahar T. Cannabis and Pain Treatment-A Review of the Clinical Utility and a Practical Approach in Light of Uncertainty. Rambam Maimonides Med J. 2020;11(1):e0002. Published 2020 Jan 30. doi:10.5041/RMMJ.10385. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000155/

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QUESTION: What are the common modes of administration of medical marijuana used by cancer patients?

ANSWER: According to a survey completed by 183 cancer patients of an oncology clinic at Sutter Medical Center in Sacramento, California, over 50% reported use of oils and tinctures and 44% used edibles. A smaller percentage consumed cannabis-based products via vaping (26%) or smoking (30%). Topical use was preferred by fewer patients (17%). Over 58% of patients stated they used more than one method.

reference: Patterns of use of medical cannabis in a community oncology clinic. Deepti Behl, Stacy D. D’Andre, and Carol Parise, Journal of Clinical Oncology 2020. 38:15_suppl, e24111-e24111. https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.e24111

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QUESTION: What CBD products, if any, have been evaluated and approved by the FDA?

ANSWER: CBD is marketed in various forms, including oils, capsules, food products, cosmetics/topical lotions and creams, and CBD products are marketed for pets, too. These products are sold in grocery stores, specialty stores, and convenience stores across the US and on the internet. However, only one prescription CBD product has been approved by the FDA. It is called Epidiolex. It is approved to treat rare, severe pediatric epilepsy disorders.

reference: FDA Advances Work Related to Cannabidiol Products with Focus on Protecting Public Health, Providing Market Clarity – March 5 2020. https://www.fda.gov/news-events/press-announcements/fda-advances-work-related-cannabidiol-products-focus-protecting-public-health-providing-market

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QUESTION: On the current (last revised May 2020) US Department of Justice Firearms Transaction Record form, is there a question related to the unlawful use of, or addiction to marijuana, depressants, stimulants, narcotics and other controlled substances?

ANSWER: Yes. There is a question related to drug use. In fact, there is a warning note that reads as follows: “Warning: The use or possession of marijuana remains unlawful under Federal law regardless of whether it has been legalized or decriminalized for medicinal or recreational purposes in the state where you reside.”

reference: U.S. Department of Justice Bureau of Alcohol, Tobacco, Firearms and Explosives OMB No. 1140-0020, Firearms Transaction Record. https://www.atf.gov/firearms/docs/4473-part-1-firearms-transaction-record-over-counter-atf-form-53009/download

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QUESTION: Does consuming a high fat/high calorie meal at the same time as you take liquid CBD orally impact the amount of CBD absorbed into the bloodstream?

ANSWER: Yes. According to studies performed by a pharmaceutical company that manufactures the FDA-approved CBD product called Epidiolex, a high fat/high calorie meal can increase CBD absorption by up to 5 fold.

reference: Epidiolex insert. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210365lbl.pdf

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QUESTION: It has been estimated that a significant proportion of cancer patients (18.3-40.0%) in the United States use marijuana or cannabinoid-based products. Does the evidence indicate that cannabinoid-based products are effective in treating cancer-related pain? chemotherapy-induced nausea and vomiting? Cancer-related cachexia (wasting)?

ANSWER: According to a study published in the Journal of Clinical Oncology, there is substantial evidence for the effectiveness of marijuana and cannabinoids in treating cancer-related pain; specifically, an oral THC/CBD spray. Also, there is conclusive evidence that marijuana and cannabinoids effectively relieve chemotherapy-induced nausea and vomiting; (specifically, oral THC). However, there is inconclusive evidence about the effectiveness of cannabinoid-based products in treating cancer-related cachexia (wasting).

reference: A systematic review of evidence for cannabis and cannabinoids as adjuvant therapy in palliative and supportive oncology care.
Sebastian Jugl, Shailina Keshwani, Lauren Adkins, Coy D. Heldermon, Almut Winterstein, and Amie Goodin. Journal of Clinical Oncology 2020. 38:15_suppl, 12091-12091 https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.12091

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QUESTION: Do cannabinoids affect the function of the gastrointestinal system?

ANSWER: It appears that cannabinoids affect many functions of the digestive system, including the regulation of the production of digestive enzymes, gastrointestinal motility, and visceral inflammation as well as visceral sensation.

reference: Izzo AA, Sharkey KA. Cannabinoids and the gut: New developments and emerging concepts. Pharmacol Ther 2010 04;126(1879-016; 0163-7258; 1):21-38. https://pubmed.ncbi.nlm.nih.gov/20117132/

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QUESTION: Marijuana use is not associated with a decrease in respiratory drive. Why not?

ANSWER: In the lower brainstem areas that control respiratory function/respiratory drive, cannabinoid receptor expression is low, and this accounts for the lack of decreased respiratory drive and the absence of a risk of fatal respiratory arrest with the use of medical marijuana and pharmaceutical grade cannabinoid drugs.

reference: Herkenham M, Lynn AB, Little MD, et al. Cannabinoid receptor localization in brain. Proc Natl Acad Sci USA. 1990; 87:1932–1936.38. https://pubmed.ncbi.nlm.nih.gov/2308954/

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QUESTION: What is the pharmacokinetic profile of marijuana when it is administered orally?

ANSWER: The psychoactive and physiological effects of orally consumed marijuana typically appear approximately 90 minutes after ingestion, reach their maximum after 2-3 hours and last for about 4-12 hours. However, there is a heterogeneous response to oral marijuana consumption and some individuals may not appreciate the peak effect until 6 hours after consumption.

reference: Grotenhermen F. Clinical pharmacokinetics of cannabinoids. J Cannabis Ther, 2003; 3(1): 3-51. https://www.tandfonline.com/doi/abs/10.1300/J175v03n01_02

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QUESTION: Does marijuana affect appetite and metabolism?

ANSWER: Marijuana has been reported to stimulate appetite. There is a high concentration of CB1 receptors in the areas of the brain that control food intake and satiety, and these findings suggest that there is an association between marijuana consumption and appetite regulation. Additionally, studies suggest that the endocannabinoid system modulates taste sensation as well as the metabolism of lipids and glucose.

references: Di Marzo V, Matias I. Endocannabinoid control of food intake and energy balance. Nat.Neurosci. 2005; 8: 585-589. https://pubmed.ncbi.nlm.nih.gov/15856067/
• Farrimond JA, Mercier MS, Whalley BJ, Williams CM. Cannabis sativa and the endogenous cannabinoid system: therapeutic potential for appetite regulation. Phytother.Res. 2011; 25: 170-188. https://pubmed.ncbi.nlm.nih.gov/21213357/
• Matias I, Bisogno T, Di Marzo V. Endogenous cannabinoids in the brain and peripheral tissues: regulation of their levels and control of food intake. Int.J.Obes.(Lond). 2006; 30 Suppl 1: S7-S12. https://pubmed.ncbi.nlm.nih.gov/16570107/

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QUESTION: Does the dosing of cannabinoid-based drugs need to be adjusted for patients with hepatic disease?

ANSWER: Cannabinoids are metabolized by the liver and excreted through the GI tract and kidney. When considering cannabinoid therapy for patients with severe liver impairment, the dosage may need to be adjusted. For example, according to the prescribing information for an FDA-approved cannabidiol product, “dose adjustment is recommended in patients with moderate (Child-Pugh B) hepatic impairment or severe (Child-Pugh C) hepatic impairment. It may be necessary to have slower dose titration in patients with moderate or severe hepatic impairment than in patients without hepatic impairment. [This drug] does not require dose adjustment in patients with mild (Child-Pugh A) hepatic impairment.”

Epidiolex prescribing information highlights:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210365lbl.pdf

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QUESTION: Does the endocannabinoid system modulate pain without the being triggered by THC or other phytocannabinoids?

ANSWER: Yes. Neural and non-neural cells of injured tissues produce endocannabinoids, including anandamide and 2-AG, and when these endocannabinoids activate the CB receptors, pain signals are modulated. Note: CB1 receptors are abundant in nociceptive and non-nociceptive sensory neurons of the dorsal root ganglion (DRG), the spinal cord, the brain, mast cells, macrophage defense cells, the trigeminal ganglion (TG), and epidermal keratinocytes. Few CB2 receptors are expressed in these regions, but the density of CB2 receptors increases when peripheral nerve damage occurs.

reference: Breijyeh Z,Jubeh B, Bufo SA, Karaman R, Scrano L. Cannabis: A Toxin-Producing Plant with Potential Therapeutic Uses. Toxins (Basel). 2021 Feb 5;13(2):117. doi.10.3390/toxins13020117. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915118/

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QUESTION: Other than via pills, capsules and liquid preparations, are there any other vehicles by which medical marijuana can be consumed orally?

ANSWER: In addition to pills, capsules and liquid preparations, medical marijuana can be consumed orally by ingesting marijuana-infused edibles, such as baked goods, candies, gummies, chocolates, lozenges, and beverages. It must be noted that the amounts of the various cannabinoids in edibles may not be consistent throughout a single baked product (a cookie, for example) or across a batch of baked products. As a result, it is difficult to estimate the amount of marijuana contained in each portion of edible product.

reference: Barrus DG, Capogrossi KL, Cates SC, et al. Tasty THC: Promises and Challenges of Cannabis Edibles. Methods Rep RTI press. 2016; 2016:10.3768/rtipress.2016.op.0035.1611. http://europepmc.org/article/MED/28127591

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QUESTION: Do some cannabinoids reduce spasticity?

ANSWER: Studies have suggested that some cannabinoids effectively reduce the spasticity associated with multiple sclerosis, and, in fact, the federal drug agencies of several countries (but not the US) have approved a cannabinoid-based formula (50:50 THC:CBD) called Sativex (nabiximols) for the treatment of severe spasticity in multiple sclerosis. The cannabinoids act on the presynaptic CB1 receptors, and the receptor activation reduces massive glutamate release and regulates glutamatergic excitability during spasticity. The American Academy of Neurology proposes that the use of oral cannabinoid extracts or an oromucosal cannabinoid spray (1:1 THC:CBD) by MS patients may reduce symptoms of spasticity.

reference: Yadav V. Bever C. Jr et al. Summary of evidence –based guideline: complimentary and alternative medicine in multiple sclerosis: Report of the guideline development subcommittee of the American Academy of neurology. Neurology 2014. 82(12): 1083-1092. https://pubmed.ncbi.nlm.nih.gov/24663230/

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QUESTION: Is marijuana a sedative or stimulant?

ANSWER: Marijuana is a CNS depressant and may cause drowsiness or somnolence. Its CNS depressant effects are additive with other CNS depressants, including opioids. There is moderate evidence that marijuana or cannabinoids are effective for improving short-term sleep outcomes in individuals with sleep disturbance associated with obstructive sleep apnea syndrome, fibromyalgia, chronic pain, and multiple sclerosis.

reference: Kumar RN, Chambers WA, Pertwee RG. Pharmacological actions and therapeutic uses of cannabis and cannabinoids. Anaesthesia. 2001; 56: 1059-1068. https://pubmed.ncbi.nlm.nih.gov/11703238/

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QUESTION: What is the pharmacokinetic profile of marijuana when it is smoked?

ANSWER: When herbal marijuana is smoked via a cigarette or a pipe, THC, CBD and other phytocannabinoids, as well as terpenoids, are vaporized by the heat of combustion and inhaled. Inhaled constituents quickly pass from alveoli into the bloodstream and readily cross the blood-brain barrier. CNS effects appear within seconds to a few minutes of inhalation, reach a maximum after 15-30 minutes, and taper off within 2-3 hours. It must be noted that the amounts of cannabinoids consumed are, in part, dependent upon the patient’s inhalation techniques, including the quality and efficiency of inhalation, duration of inhalation, and spacing of inhalations.

references: Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers. 2007;4(8):1770-804. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689518/.
• Grotenhermen F. Clinical pharmacokinetics of cannabinoids. J Cannabis Ther, 2003; 3(1): 3-51. https://www.tandfonline.com/doi/abs/10.1300/J175v03n01_02

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QUESTION: What is the pharmacokinetic profile of marijuana when it is smoked?

ANSWER: When herbal marijuana is smoked via a cigarette or a pipe, THC, CBD and other phytocannabinoids, as well as terpenoids, are vaporized by the heat of combustion and inhaled. Inhaled constituents quickly pass from alveoli into the bloodstream and readily cross the blood-brain barrier. CNS effects appear within seconds to a few minutes of inhalation, reach a maximum after 15-30 minutes, and taper off within 2-3 hours. It must be noted that the amounts of cannabinoids consumed are, in part, dependent upon the patient’s inhalation techniques, including the quality and efficiency of inhalation, duration of inhalation, and spacing of inhalations.

references: Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers. 2007;4(8):1770-804. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689518/.
• Grotenhermen F. Clinical pharmacokinetics of cannabinoids. J Cannabis Ther, 2003; 3(1): 3-51. https://www.tandfonline.com/doi/abs/10.1300/J175v03n01_02

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QUESTION: What are endocannabinoids?

ANSWER: Endocannabinoids (also called endogenous cannabinoids) are endogenous agonists of the receptors to which delta-9- tetrahydrocannabinol (THC) also binds. Two of the most well studied endocannabinoids are derivatives of arachidonic acid: N-arachidonoylethanolamine (also called anandamide or AEA) and 2-arachidonoylglycerol (2-AG).

reference: Atakan, Z. “Cannabis, a complex plant: different compounds and different effects on individuals.” Therapeutic advances in psychopharmacology 2012; 2(6): 241-54. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736954/

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QUESTION: What are terpenes?

ANSWER: Terpenes are aromatic hydrocarbons and just like the phytocannabinoids, terpenes are manufactured in the glands of the cannabis flower. Terpenes may influence the uptake and effects of phytocannabinoids. The terpenes found in cannabis include limonene, pinene, myrcene, delta-3-carene, eucalyptol and humulene.

reference: Russo EB. Taming THC:potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J of Pharmacolo. 2011;163(7):1344-1364. doi:10.1111/j.1476-5381.2011.01238. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165946/

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QUESTION: THC and CBD have significantly different receptor binding capacities, and thus different pharmacological effects. Are the differences in binding capacity due to different chemical compositions?

ANSWER: THC and CBD actually have the same chemical formula, C21H30O2. They are structural isomers. The key structural difference between the two molecules is that there is an oxygen-containing closed ring in THC that is open in CBD. This one structural difference leads to significantly different receptor binding capacities and thus different pharmacological effects of the two substances.

reference: de Meijer EP, Bagatta M, Carboni A, et al. The inheritance of chemical phenotype in Cannabis sativa L. Genetics. 2003;163(1):335-346. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1462421/

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QUESTION: True or False? CB1 receptors are only found on nerve cells.

ANSWER: False. In addition to the brain, nociceptive and non-nociceptive sensory neurons of the dorsal root ganglion (DRG), and the spinal cord, CB1 receptors are abundant in mast cells, macrophage defense cells, epidermal keratinocytes, adipose, liver, pancreas and skeletal muscle cells.

reference: Breijyeh Z, Jubeh B, Bufo SA, Karaman R, Scrano L. Cannabis: A Toxin-Producing Plant with Potential Therapeutic Uses. Toxins (Basel). 2021 Feb 5;13(2):117. doi.10.3390/toxins13020117 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915118/

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QUESTION: What is the most common qualifying condition reported by medical marijuana patients?

ANSWER: Currently and historically, the most common qualifying condition reported by medical marijuana patients is chronic pain. In fact, according to Boehnke et al’s analysis of 2016 data, chronic pain was the qualifying condition reported by medical marijuana patients nearly 65 percent of the time.

reference: Boehnke et al. Qualifying Conditions of medical cannabis license holders in the United States. Health Affairs Vol 38, No2: Hospitals, Health IT and more. https://doi.org/10.1377/hlthaff.2018.05266. https://www.healthaffairs.org/doi/abs/10.1377/hlthaff.2018.05266

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QUESTION: Epidiolex is an FDA-approved seizure medication derived from plant material (it is not a synthetic CBD product). Is it possible that a patient taking Epidiolex will test positive for THC?

ANSWER: Epidiolex is cannabidiol (CBD) derived from marijuana, not hemp, and therefore there may be traces of cannabinoids other than CBD. Patients using Epidiolex may test positive for marijuana/THC on drug screening.

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QUESTION: Is it a good idea to store THC products in glass jars?

ANSWER: THC has the ability to bind to glass and plastic. Therefore, THC products are often stored in basic or organic solvents in amber silicate glassware to avoid loss.

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QUESTION: Do CBD products that contain less than 0.3 percent THC violate the Controlled Substances Act?

ANSWER: Industrial hemp (which contains less than 0.3 percent THC) is no longer considered to be a controlled substance, but CBD products that contain less than 0.3 percent THC are not legal. The CBD products no longer violate the Controlled Substances Act, but they do violate the Food, Drug, and Cosmetic (FD&C) Act, according to the FDA. Any CBD food or purported dietary supplement products in interstate commerce is in violation of the FD&C Act, according to the principal deputy FDA commissioner.

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QUESTION: What is industrial hemp?

ANSWER: Industrial hemp and marijuana are cultivated from the same species, but industrial hemp has concentrations of THC less than 0.3 percent. Industrial hemp, a high-fiber plant, is used to make various products, including textiles as well as biodegradable plastics. The 2018 Farm Bill, signed into law by President Donald Trump, removed industrial hemp, from the definition of marijuana in the Controlled Substances Act.

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QUESTION: Of all state-approved health conditions, what are the 7 most frequent health conditions for which patients seek to obtain a medical marijuana card?

ANSWER: Chronic noncancer pain, multiple sclerosis and other motor neuron disorders, epilepsy, cancer-related symptoms, mental health disorders (primarily anxiety disorders such as PTSD), glaucoma, and symptoms related to irritable bowel diseases top the list of reasons to apply for a medical marijuana card.

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QUESTION: CBD is legally sold in US supermarkets, pharmacies and convenience stores. CBD is also legally sold in Canada. So, is it legal to transport CBD across the US/Canadian border?

ANSWER: According to Canada’s national laws, “the transporting of cannabis (in any form, including oils containing THC or cannabidiol) into or out of Canada without special authorization from Health Canada is a serious criminal offense. “

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QUESTION: Does the dosing of CBD need to be adjusted in patients with liver disease?

ANSWER: According to the prescribing information packet of Epidiolex (an FDA-approved CBD product),, dose adjustment is recommended in patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment. Dose adjustment in patients with mild (Child-Pugh A) hepatic impairment is not needed.

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QUESTION: Are physicians required to notify the DEA when prescribing Epidiolex (a CBD product derived from the cannabis plant)?

ANSWER: Prior to April 2020, Epidiolex was classified as a schedule V drug under the Controlled Substances Act. On April 6, 2020, the manufacturers of Epidiolex “received notification from the United States Drug Enforcement Administration (DEA) confirming that Epidiolex ® (cannabidiol) is no longer subject to the Controlled Substances Act (CSA).” Since Epidiolex is no longer a controlled substance, physicians are not required to notify the DEA when prescribing the medication. The descheduling of Epidiolex also enables physicians to prescribe this medicine free of the requirements of state prescription drug monitoring programs.

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QUESTION: Is the use of marijuana for medicinal reasons an acceptable explanation for a positive drug test result in ANY Federal agency drug testing program?

ANSWER: As of March 2021, the answer to this question is still ‘NO.’ ALL Federal drug testing programs – regardless whether the programs under the regulatory and legal auspices of the Department of Health and Human Services, the Department of Defense, the Department of Transportation, or the Nuclear Regulatory Commission, or any other Federal agency – have taken the identical stance: Use of Schedule I drugs by individuals in Federally regulated workplaces is unacceptable, and any individual who tests positive for a Schedule I drug will have a positive drug test on his or her record.

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QUESTION: If a patient uses a CBD product, will a THC drug screen be positive?

ANSWER: The answer to this question depends on 2 things: 1.) Is the patient consuming pure CBD or full spectrum CBD. (Full spectrum CBD contains multiple cannabinoids, including THC.) and 2.) The sensitivity of the drug screening test.

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QUESTION: How should cannabis products be stored?

ANSWER: Products should be stored in opaque containers, in a cool dry location, and in a place that is not accessible to children or pets, or individuals who should not be handling the cannabis-based products.

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QUESTION: What are some of the microbial and fungal contaminants that can be present in cannabis products?

ANSWER: Aspergillus and Salmonella and Aflatoxin may be present in cannabis products. It is important to review the certificate of analysis to determine if the cannabis product contains any of these contaminants.

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QUESTION: What should be listed on a Certificate of Analysis (CoA)?

ANSWER: First, a Certificate of Analysis (CoA) should be from an independent and properly certified testing laboratory, and not from the retailer. CoA should show the amount and concentration of major cannabinoids and terpenes present in the tested sample, as well as testing data regarding the lack of (or presence of) microbial organisms, fungal contaminants, the levels of heavy metals, and amount of pesticide and residual solvents.

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QUESTION: Does raw cannabis flower contain CBD or CBDA?

ANSWER: The raw flower contains CBDA (the acid form of cannabidiol). When the raw cannabis material is heated via vaporization, smoking or baking, the CBDA is converted to CBD.

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QUESTION: CBD products are marketed as full spectrum, broad spectrum and CBD isolate products. What are the differences between these products?

ANSWER: While full CBD spectrum products contain a full array of cannabinoids, (including THC) and terpenes, broad spectrum products are manufactured in a way that the product does not contain THC. CBD isolate products are often sold as 99%+ pure CBD and they do not contain other cannabinoids or any terpenes, unless specified on the label.

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QUESTION: How many people in the US die each day from overdoses involving PRESCRIPTION opioids?

ANSWER: According to recent data published by the Center for Disease Control (CDC), approximately 41 people/day are dying from an overdose involving prescription opioids. This CDC website – https://www.cdc.gov/rxawareness/index.html – provides resources for individuals struggling with opioid drug abuse.

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QUESTION: What is Rick Simpson oil (aka RSO)?

ANSWER: Solvent-based concentrates are made by extraction of the plant matter with chemical solvents. In this method, cannabis is soaked in the solvent and then the cannabis is removed by straining. Then, the solvent is boiled off, and a sticky cannabis resin remains. These extracts are often a very dark color (green to black) and contain residuals from the solvents used. These products are sometimes referred to as Rick Simpson Oil (RSO), named after the individual that made this type of extraction popular.

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QUESTION: Some people consume cannabinoids via “dabbing.” Describe this method of consumption.

ANSWER: Basically, with dabbing, a cannabis concentrate is applied to a hot platform and the cannabinoids are volatilized. The vapor then passes through a water-pipe device and is inhaled by the consumer. The hot platform (commonly called “the nail”) is usually constructed from quartz, ceramic or titanium. This nail is heated, often with a blow torch, and after the nail is hot, a small amount of cannabis concentrate is applied. Vaporization of the cannabinoids is immediate. Inhalation by the consumer during application of the cannabis concentrate draws the vapors from around the nail into the water pipe.

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QUESTION: Other than butane, what are some of the chemical solvents used to create cannabis concentrates? Other than using solvents to create cannabis concentrates, what other methods to produce cannabis concentrates can be used?

ANSWER: Hexane, isopentane, isopropyl alcohol, acetone, and propane are used to make cannabis concentrates. In addition to using solvents, concentrates can also be manufactured via a dry method, a water-based method or a CO2 based method.

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QUESTION: Do all medical marijuana legal states allow the sale of products manufactured through butane extraction and supercritical CO2 extraction?

ANSWER: Supercritical CO2 extraction does not leave residual hydrocarbons, while butane extraction does. As a result, some states will allow the sale of supercritical CO2 extraction products, but not allow the sale of butane extracts.

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QUESTION: In addition to butane extraction, supercritical CO2 extraction is another process used to manufacture cannabis extracts. What is the major difference in the end products of the two processes?

ANSWER: Supercritical CO2 extraction does not leave any trace of hydrocarbon solvents in the end product, while butane extraction does. The viscosity of the supercritical CO2 products is less than the viscosity of the butane extraction products. As a result of a lower viscosity, supercritical CO2 extraction process products can be used in vaporizer pens on its own without cutting agents. While products derived from a butane extraction are used in dabbing, products derived from supercritical CO2 extraction are not.

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QUESTION: Some patients may use shatter, budder, crumble, pull-and-snap, and/or wax. Are all of these products exactly the same?

ANSWER: All of these products are cannabis extracts, but it is the specific manufacturing/ processing of the hash oil cannabis products that will determine the consistency of the product. Depending upon the consistency and other physical characteristics, the product will be called shatter, budder, crumble, pull-and-snap or wax.

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QUESTION: Does short term treatment with THC rich cannabis induce clinical remission and improve quality of life in patients with mild to moderately active ulcerative colitis?

ANSWER: Yes, according to a recent study. However, these beneficial clinical effects were not associated with significant anti-inflammatory improvement in the Mayo endoscopic score or laboratory markers for inflammation. These results were derived from a double-blind, randomized, placebo-controlled trial, – 32 patients received either cigarettes containing 0.5 g of dried cannabis flowers with 80mg THC or placebo cigarettes for 8 weeks. Parameters of disease including Lichtiger disease activity index, C reactive protein (CRP), calprotectin, Mayo endoscopic score and quality of life (QOL) were assessed before, during and after treatment.

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QUESTION: In some legal states, edibles, such as candies, baked goods, beverages and condiments (butter and oils) containing THC may be sold. Is 2.5mg of THC in an edible a low dose or high dose of THC to be consumed orally?

ANSWER: The dosing of THC always needs to be adjusted on an individual basis. For reference, 2.5 mg is the lowest dose of dronabinol, a synthetic THC that is FDA-approved.

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QUESTION: When speaking with their clinicians, patients may use the terms “dabs”, “wax”, or “butane honey oil” – what do these terms mean?

ANSWER: Dabs, wax and butane honey oil are all highly concentrated cannabis extracts of THC. These THC products are often smoked or vaporized. Because these THC products are quite highly concentrated, the consumption of only a very small amount may produce a significant effect.

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QUESTION: What is “hashish”?

ANSWER: Hashish is a crude product made up of compacted sticky resin glands of the cannabis plant. The popularity of hashish has been diminished by the availability of cannabis concentrates.

reference: Special Report | February 2018
Contemporary Routes of Cannabis Consumption: A Primer for Clinicians
Jeramy Peters, DO; Joseph Chien, DO
The Journal of the American Osteopathic Association, February 2018, Vol. 118, 67-70. doi: https://doi.org/10.7556/jaoa.2018.020

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QUESTION: Are smoking marijuana and vaporizing marijuana equally efficient? (In other words, are the cannabinoids absorbed to the same extent with smoking vs. vaporizing? )

ANSWER: When ingesting marijuana via a vaporizer, the user absorbs up to 33% of the total cannabinoids present in herbal mixture. When smoking, an individual typically absorbs about 25% of the cannabinoids present in herbal mixture.

reference: Special Report | February 2018
Contemporary Routes of Cannabis Consumption: A Primer for Clinicians
Jeramy Peters, DO; Joseph Chien, DO
The Journal of the American Osteopathic Association, February 2018, Vol. 118, 67-70. doi: https://doi.org/10.7556/jaoa.2018.020

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QUESTION: The amounts of marijuana in a joint, blunt, spliff or bowl are not standardized. How does a clinician estimate the amount of marijuana being used by the patient?

ANSWER: When trying to assess the quantity of marijuana consumed by a patient, multiple questions should be addressed, including: how often and how much the patient typically purchases, how many bowls (or joints, or blunts or spliffs) the patient smokes each time he consumes marijuana, and how many times he uses marijuana before he needs to purchase again. It must be noted that the total amount of cannabinoids present in marijuana is not equal to the amount that is ingested. (when smoking, an individual typically absorbs about 25% of the cannabinoids present in herbal marijuana mixture.) Also, the concentration of the cannabis-based product must be considered, as well.

reference: Special Report | February 2018
Contemporary Routes of Cannabis Consumption: A Primer for Clinicians
Jeramy Peters, DO; Joseph Chien, DO
The Journal of the American Osteopathic Association, February 2018, Vol. 118, 67-70. doi: https://doi.org/10.7556/jaoa.2018.020

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QUESTION: Are smoking marijuana and vaporizing marijuana equally efficient? (In other words, are the cannabinoids absorbed to the same extent with smoking vs. vaporizing? )

ANSWER: When ingesting marijuana via a vaporizer, the user absorbs up to 33% of the total cannabinoids present in herbal mixture. When smoking, an individual typically absorbs about 25% of the cannabinoids present in herbal mixture.

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QUESTION: A patient may be speaking to you about his marijuana consumption, and he may use the terms joints, blunts and spliffs, and bowl. What do these terms mean?

ANSWER: A joint is a cigarette of marijuana, a blunt is a marijuana cigar, and a spliff can refer to marijuana mixed with tobacco, though some people use this term when referring to a cone-shaped joint with a filter. A bowl refers to the chamber of a pipe.

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QUESTION: In patients 60 years old or older, does long term (3 months) marijuana use impact blood pressure?

ANSWER: According to a recent study that was published in the European Journal of Internal Medicine, amongst adults 60 years or older with hypertension, marijuana treatment for 3 months was associated with a reduction in 24-hours systolic and diastolic blood pressure. At 3 months follow-up, the mean 24-hours systolic and diastolic blood pressures were reduced by 5.0 mmHg and 4.5 mmHg, respectively (p<0.001 for both). The nadir for the blood pressure and heart rate was achieved at 3 hours post-administration. The proportion of normal dippers changed from 27.3% before treatment to 45.5% afterward. No significant changes were seen in the different metabolic parameters assessed by blood tests, anthropometric measurements, or ECG exam.

reference: Cannabis is associated with blood pressure reduction in older adults – A 24-hours ambulatory blood pressure monitoring study Ran Abuhasira, Yosef S. Haviv, Merav Leiba, Adi Leiba, Larisa Ryvo, Victor Novack Published:January 20, 2021 DOI: European J of Int. Medicine https://doi.org/10.1016/j.ejim.2021.01.005

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QUESTION: What are the effects of cannabis-based therapies on oxaliplatin-induced peripheral neuropathy among oncology patients?

ANSWER: The results of a retrospective study indicated that the rate of neuropathy was reduced among patients treated with cannabis-based therapies and oxaliplatin. This reduction was more significant in patients who received cannabis-based products prior to treatment with oxaliplatin, suggesting a protective effect. (A large prospective trial examining the effects of cannabis-based products on oxaliplatin-induced neuropathy is planned.)

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QUESTION: In older adults, is there a significant positive association between THC dose and incidence rate ratio for dizziness or lightheadedness and thinking or perception disorder when the THC is combined with CBD?

ANSWER: A systematic review and metaregression analysis published In JAMA (February 2021) evaluated the THC neuropsychiatric symptoms among adults 50 years and older. The authors examined 30 RCTs [Randomized Controlled Trials] using THC-only cannabis-based medicines (CBM) (total THC exposure, 1252.83 person-years) and 24 RCTs using CBMs with different combinations of cannabidiol (CBD) and THC (total THC and CBD exposure, 388.56 person-years). They did find a significant positive association between THC dose and incidence rate ratio for dizziness or lightheadedness (estimate, 0.05; 95% CI, 0.02-0.08; P = .001) and thinking or perception disorder (estimate, 0.07; 95% CI, 0.03-0.11; P < .001) for the THC-ONLY studies, but there were no associations with any other neuropsychiatric adverse effects for the THC and CBD combination studies.

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QUESTION: Can prison inmates use medical cannabis?

ANSWER: In New Mexico, the prison inmates can use cannabis. In 2021, a New Mexico landmark case concluded that inmates CAN use medical cannabis. As stated by the victorious lawyer, ‟the law is clear: You must, under existing law, provide incarcerated persons with the ability to access medical cannabis free from penalty. That’s the law.” Importantly, the ruling specifies that this applies to those on probation, house arrest or in prison.

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QUESTION: In 2020, the 20 member ‘Global Task Force on Dosing and Administration of Medical Cannabis in Chronic Pain’ developed recommendations for the dosing of cannabinoids for patients suffering with severe pain. What were those recommendations?

ANSWER: According to the recommendations of the ‘Global Task Force on Dosing and Administration of Medical Cannabis in Chronic Pain,’ patients suffering from severe pain and those patients who have a history of significant prior cannabis consumption can use a 50:50 CBD-THC product and start with a dose of 2.5-5 mg of each compound 1 or 2 times/day.

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QUESTION: In 2020, recommendations for the dosing of THC in the elderly population were developed by the 20 member ‘Global Task Force on Dosing and Administration of Medical Cannabis in Chronic Pain.’ What were their recommendations for the dosing of THC in the elderly population?

ANSWER: According to the recommendations of the ‘Global Task Force on Dosing and Administration of Medical Cannabis in Chronic Pain,’ elderly patients, patients with severe co-morbidity or patients who take multiple medications should be managed through a conservative route; start with THC doses at 1 mg/day and the dose should be titrated up slowly.

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QUESTION: What are some of the more common reasons dermatologists recommend cannabinoid-based medicines?

ANSWER: According to the results of a survey of 145 dermatologists, 91 % of dermatologists were in support of medical cannabis use and 13.8 % have recommended it for a dermatologic condition. Atopic dermatitis (45 %) and psoriasis (40 %) were the most common. The most common form of administration was topical (75 %). The main reasons for not recommending medical cannabis were limited knowledge (56 %) and lack of experience (48 %).

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QUESTION: In 2020, the 20 member ‘Global Task Force on Dosing and Administration of Medical Cannabis in Chronic Pain’ developed recommendations for the dosing of cannabinoids. For what pain conditions are medical cannabinoids a viable option?

ANSWER: According to the global task force, cannabinoids may be effective for neuropathic, inflammatory, nociplastic* and mixed pain conditions. *Nociplastic pain is defined as: “Pain that arises from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain.”

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QUESTION: Have any PRECLINICAL studies shown that cannabinoids have anti-neoplastic (anti-cancer) effects?

ANSWER: Yes – PRECLINICAL studies have shown that cannabinoids exhibit anti -tumor properties in different ADULT cancers, including breast, melanoma, pancreatic, lymphoma, glioblastoma, lung, hepatocellular, colorectal, prostate, and other cancers. This data has been obtained from EXPERIMENTAL models of cancer, including genetically engineered mouse models.

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QUESTION: The use of cannabinoid-based products for medicinal purposes is legal in Canada at the federal level. Is the medicinal use of cannabinoid-based products legal at the federal level in Mexico, too?

ANSWER: Yes, as of January 13, 2021, the use of cannabinoid-based products for medicinal purposes is legal in Mexico. Mexican President López Obrador published regulations for the production, research and use of medicinal marijuana. The federal government’s official gazette published the new regulations that authorize the government to oversee the production of marijuana for research and medicinal purposes. Pharmacies will be allowed to supply cannabis-based medicines to authorized patients. In addition, the regulatory framework permits the importation of seeds, cannabis derivatives to be used in medicinal products, and processed marijuana-based medications to Mexico.

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QUESTION: Does the National Basketball Association (NBA) test their players for cannabis use?

ANSWER: Prior to the 2020-2021 season, the NBA had randomly conducted cannabis testing on players, but the NBA and National Basketball Players Association announced they will stop testing players for cannabis use during the 2020–2021 season in response to the stress and quarantining brought on by the COVID-19 global pandemic, and also based on COVID safety to limit unnecessary contacts,. Although cannabis testing is paused for now, random testing for performance-enhancing drugs will continue.

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QUESTION: As of 2018, what percentage of the population uses marijuana?

ANSWER: The 2018 World Health Organization (WHO) data suggest that approximately 2.5% of the global population (147 million) use marijuana.

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QUESTION: Researchers have evaluated the anti-neoplastic (anti-cancer) effects of cannabinoids. What have the results indicated?

ANSWER: Over the past two decades, PRECLINICAL data indicate that THC, CBD, as well as some synthetic cannabinoids induce apoptosis of cancer cells and inhibit tumor proliferation, metastasis, and angiogenesis. Note: The results of preclinical trials are NOT equivalent to clinical trials.

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QUESTION: What are the two most well-studied endocannabinoids?

ANSWER: The best-characterized endocannabinoids are 2-arachidonoylglycerol (also called 2-AG) and N- arachidonoylethanolamide (also called AEA or anandamide). These endocannabinoids are lipid-based molecules that are synthesized from arachidonic acid from the cellular membrane. These two endocannabinoids are signaling molecules that bind to and stimulate cannabinoid receptors CB1R and CB2R.

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QUESTION: Which US states had the greatest sales of cannabis products in 2020?

ANSWER: Florida, a medical marijuana only state, had more than $1.2 billion in sales, and was the nation’s fourth largest cannabis market. Only California, Colorado and Washington (all medical and recreational use states) out sold Florida.

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QUESTION: CB1 receptors are expressed by neurons in the brain, especially in the cerebral cortex, basal ganglia, cerebellum, and hippocampus. Are CB1 receptors expressed in other parts of the nervous system? Are CB1 receptors present on cells outside of the nervous system?

ANSWER: In addition to being expressed by neurons in the brain, CB1 receptors are also expressed in parts of the peripheral and autonomic nervous system. CB1 receptors are also expressed on several other tissues, including heart, lung, reproductive organs, thymus and spleen.

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QUESTION: Does the consumption of THC and CBD via vaporization impair driving ability?

ANSWER: A recent study published in JAMA examined the magnitude and duration of driving impairment following vaporization of cannabis containing various concentrations of THC and CBD. The results of the study indicated that the impairment of driving after consuming vaporized THC-dominant and 50:50 THC/CBD cannabis compared with placebo was significantly greater at 40-100 minutes but not at 240-300 minutes after vaporization. There were no significant differences between CBD-dominant cannabis and placebo found, but the doses tested may not represent common usage.

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QUESTION: To which receptor do cannabinoids bind that impact pain sensation?

ANSWER: In addition to acting on cannabinoid receptors (CB1 and CB2), cannabinoids may modulate pain by interacting with the G protein-coupled receptor 55 (GPR55) and GPR18 and other G protein-coupled receptors such as serotonin and opioids receptors. Cannabinoids also interact with TRPV-1 receptors. CBD and THC (along with the endocannabinoid, Anadamide) activate glycine receptors, and as a result, lead to analgesia in inflammatory and neuropathic pain.

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QUESTION: Does the anti-fungal agent ketoconazole interact with cannabinoids?

ANSWER: Yes. Ketoconazole Inhibits the metabolism of THC and CBD and can significantly increase concentrations of THC and CBD. In contrast, drugs such as rifampicin, carbamazepine and St John’s Wort induce cytochrome enzyme activity and lower THC and CBD concentrations.

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QUESTION: If a patient is allergic to tomatoes or tobacco, is the patient a good candidate for medical marijuana therapy?

ANSWER: Patients who have previously experienced an allergic reaction to tobacco or tomato are at increased risk for developing an allergy to the products from the cannabis plant.

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QUESTION: Is a “full spectrum” product the same as a “whole plant” product?

ANSWER: No. “Whole plant” products contain fats, waxes and fibrous materials not found in “full spectrum” products.

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QUESTION: What does “full spectrum” marijuana mean? What does “broad spectrum” mean?

ANSWER: Full spectrum means that the product contains all of the original compounds found in the flower of the cannabis plant (cannabinoids, terpenes and flavonoids). In contrast, broad spectrum products are processed in such a manner as to ensure that the final product does NOT contain THC.

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QUESTION: Describe the exact mechanism of action of Epidiolex.

ANSWER: According to the Epidiolex FDA Approved Package Insert, (Greenwich Biosciences, Inc.), the precise mechanism(s) by which Epidiolex exerts its anticonvulsant effects in humans are unknown. It does not appear to be through cannabidiol receptors.

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QUESTION: Have the results of studies examining the impact of maternal marijuana use identified a unique phenotypic congenital anomaly?

ANSWER: Studies evaluating maternal use of marijuana have not found a unique phenotypic signature of prenatal exposure of marijuana. There does appear to be an increased risk of congenital anomalies, particularly gastroschisis, though.

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QUESTION: In 2018, Epidiolex was approved for the treatment of seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS). Has the FDA approved Epidiolex for any other conditions since 2018?

ANSWER: Yes. On July 31, 2020, the U.S. Food and Drug Administration approved Epidiolex (cannabidiol or CBD) oral solution for the treatment of seizures associated with tuberous sclerosis complex (TSC) in patients one year of age and older.

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QUESTION: Does the use of cannabinoid-based products impact female sexual function, including desire, arousal, lubrication, orgasm, satisfaction, and pain?

ANSWER: According to a study published in the journal Sexual Medicine, an increased frequency of marijuana use is associated with improved sexual function among females. (i.e. – sexual desire increased, arousal increased, orgasm domain increased, and sexual satisfaction increased.) Interestingly, it was noted that chemovar type and method of consumption did not impact outcomes, though.

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QUESTION: Does consuming a high fat/high calorie meal at the same time as you take liquid CBD orally impact the amount of CBD absorbed into the bloodstream?

ANSWER: Yes. According to studies performed by a pharmaceutical company that manufactures an FDA- approved CBD product, a high fat/high calorie meal can increase CBD absorption by up to 5 fold.

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QUESTION: Did the United Nations Commission for Narcotic Drugs vote in December 2020 to accept the World Health Organization’s (WHO) recommendation to remove cannabis and cannabis resin for medicinal purposes from Schedule IV of the 1961 Single Convention on Narcotic Drugs?

ANSWER: Yes, and it was a close one (27 to 25), with the United States and many European nations in favor. The US published a statement about its rationale for the vote – “The vote of the United States to remove cannabis and cannabis resin from Schedule IV of the Single Convention while retaining them in Schedule I is consistent with the science demonstrating that while a safe and effective cannabis-derived therapeutic has been developed, cannabis itself continues to pose significant risks to public health and should continue to be controlled under the international drug control conventions. Further, this action has the potential to stimulate global research into the therapeutic potential and public health effects of cannabis, and to attract additional investigators to the field, including those who may have been deterred by the Schedule IV status of cannabis.”

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QUESTION: The House of Representatives approved the MORE Act. Is marijuana legal now?

ANSWER: The House of Representatives approved the bill called the MORE Act on December 4, 2020, but marijuana is not legal at the federal level. The bill must go to the Senate, and then the White House for the President to sign. Until the President signs it, it’s not a law – it’s just a bill.

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QUESTION: What is the MORE act?

ANSWER: The Marijuana Opportunity, Reinvestment, and Expungement (MORE) Act (HR 3884 / S. 2227) is bipartisan legislation that removes marijuana from the Controlled Substances Act, thus decriminalizing the substance at the federal level and enabling states to set their own policies.

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QUESTION: Do cannabinoids affect cardiac function?

ANSWER: Low doses of cannabinoids have been associated with tachycardia, hypertension and increased contractility (an increased sympathetic response). In contrast, high doses of cannabinoids enhance parasympathetic tone leading to dose-dependent bradycardia and hypotension.

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QUESTION: What percentage of US medical marijuana legal states list cancer as a qualifying condition?

ANSWER: Cancer is listed as a qualifying condition in 100% of the US medical marijuana states, but the patterns of cannabinoid use among patients with breast cancer (one of the most common cancers in the US) is unknown. NOTE: Cannabinoids have been shown to ameliorate some of the symptoms associated with cancer and the side effects associated with some cancer treatments, however, cannabinoids have not been shown to be an effective anti-cancer agent.

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QUESTION: Epidemiological studies indicate that as many as 15% of inflammatory bowel disease (IBD) patients may use cannabinoids to ameliorate some of their symptoms, including improvement in diarrhea, abdominal pain and appetite. Do the studies show that cannabinoids are effective?

ANSWER: There are few studies evaluating cannabinoid use in IBD, and those studies are small. In Crohn’s disease, it has been demonstrated that THC reduces the Crohn’s disease activity index by >100 points (on a scale of 0–450). Also, two small studies involving ulcerative colitis patients showed a marginal benefit. However, no improvement in inflammatory markers or in endoscopic score in either disease was detected.

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QUESTION: The findings of multiple randomized controlled trials (RCTs) indicate that cannabinoids effectively treat chronic pain. Do cannabinoids effectively treat the chronic pain associated with fibromyalgia?

ANSWER: No. According to a Cochrane systematic review published in 2016 on the use of cannabinoids to treat fibromyalgia, there is no convincing, unbiased, high-quality evidence suggesting that a cannabinoid-based medicine (nabilone) is of value in treating people with fibromyalgia. Furthermore, the tolerability of nabilone was low in people with fibromyalgia. Also, the results of a 2019 study where 4 varieties of pharmaceutical grade marijuana were administered by single shot vapor to fibromyalgia patients indicated that none of the 4 marijuana varieties had an effect greater than placebo. (Note: The data from the 2019 study could not be used to extrapolate the long-term effects of cannabinoids on fibromyalgia-associated pain.)

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QUESTION: Some cancer patients use medical marijuana to treat various cancer-associated ailments. What are some of the ailments ameliorated by medical marijuana?

ANSWER: According to one study involving 96 cancer patients receiving supportive cancer care, the data support the safety and effectiveness of medical marijuana as a complementary option for improving pain control, appetite and quality of life for cancer patients. The top three adverse events of this study included drowsiness, low energy and nausea, and were reported in 28% of patients, with 9% having to stop using the medical marijuana. (Note: other studies indicate that chemotherapy-induced nausea and vomiting is ameliorated by medical marijuana.)

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QUESTION: Side effects of short-term cannabinoid-based therapy may differ from person to person, and the same person may experience different side effects at different times. What factors influence the probability and the severity of adverse events?

ANSWER: Many factors influence the likelihood and the severity of adverse events, including the type of cannabinoid preparation; the mode of administration; the dose administered; the patient’s expectations, the patient’s prior experience with cannabinoid-based therapies, and the age of the patient. Drug–drug interactions may also lead to adverse events.

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QUESTION: Side effects of short-term cannabinoid-based therapy may differ from person to person, and the same person may experience different side effects at different times. What factors influence the probability and the severity of adverse events?

ANSWER: Many factors influence the likelihood and the severity of adverse events, including the type of cannabinoid preparation; the mode of administration; the dose administered; the patient’s expectations, the patient’s prior experience with cannabinoid-based therapies, and the age of the patient. Drug–drug interactions may also lead to adverse events.

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QUESTION: What is Sativex®?

ANSWER: Sativex® is a buccal (oral) spray containing Δ-9-THC and CBD (2.7 mg Δ-9-THC and 2.5 mg CBD per spray) and it is indicated for spasticity and neuropathic pain in multiple sclerosis, and as adjunctive analgesia for moderate to severe cancer pain. While Sativex® is approved in several European countries, Canada, and other countries, it has not been approved for medical use in the U.S.

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QUESTION: Other than feeling “high” what are some of the reported psychological CNS-related side effects associated with cannabinoid use?

ANSWER: Psychological side effects associated with cannabinoid use include: restless/anxiety/nervousness, depressed mood, dysphoria, confusion, dissociation, hallucinations, hyperactivity, weird dreams, paranoia and psychosis.

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QUESTION: Are cannabinoids an effective analgesic agent in the acute pain setting?

ANSWER: No. According to the results of multiple randomized controlled trials examining the efficacy of cannabinoids to treat acute pain, THC, nabilone and other cannabinoid-based products were not associated with a reduction in pain, but were associated with adverse side effects, including sedation.

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QUESTION: What are the common modes of administration of medical marijuana used by cancer patients?

ANSWER: According to a survey completed by 183 cancer patients of an oncology clinic at Sutter Medical Center in Sacramento, California, over 50% reported use of oils and tinctures and 44% used edibles. A smaller percentage consumed cannabis-based products via vaping (26%) or smoking (30%). Topical use was preferred by fewer patients (17%). Over 58% of patients stated they used more than one method.

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QUESTION: What CBD products, if any, have been evaluated and approved by the FDA?

ANSWER: CBD is marketed in various forms, including oils, capsules, food products, cosmetics/topical lotions and creams, and CBD products are marketed for pets, too. These products are sold in grocery stores, specialty stores, and convenience stores across the US and on the internet. However, only one prescription CBD product has been approved by the FDA. It is called Epidiolex. It is approved to treat rare, severe pediatric epilepsy disorders.

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QUESTION: On the current (last revised May 2020) US Department of Justice Firearms Transaction Record form, is there a question related to the unlawful use of, or addiction to marijuana, depressants, stimulants, narcotics and other controlled substances?

ANSWER: Yes. There is a question related to drug use. In fact, there is a warning note that reads as follows: “Warning: The use or possession of marijuana remains unlawful under Federal law regardless of whether it has been legalized or decriminalized for medicinal or recreational purposes in the state where you reside.”

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QUESTION: Does consuming a high fat/high calorie meal at the same time as you take liquid CBD orally impact the amount of CBD absorbed into the bloodstream?

ANSWER: Yes. According to studies performed by a pharmaceutical company that manufactures the FDA-approved CBD product called Epidiolex, a high fat/high calorie meal can increase CBD absorption by up to 5 fold.

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QUESTION: What psychiatric condition is most often listed as a qualifying condition for medical marijuana?

ANSWER: The psychiatric diagnosis most often listed as a qualifying condition by the medical marijuana legal US states is PTSD, but other psychiatric diagnoses include Tourette syndrome, Alzheimer’s disease, and autism.

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QUESTION: Is marijuana use linked to higher hospital mortality in COPD patients?

ANSWER: Actually, no. According to a nationwide population-based study, patients diagnosed with COPD who reported using marijuana had less risk of in-hospital mortality and pneumonia than non-users. The results from this study, which was performed by Yale physicians, indicated that marijuana use was associated with a 37.6% reduction in the odds of dying in the hospital (OR 0.624, 95% CI 0.407-0.958, P=0.0309) among COPD patients. This same study also found that COPD patients who admitted to using marijuana had an 11.8% lower risk of pneumonia (OR 0.882, 95% CI 0.806-0.964, P=0.0059). Note: these findings may be a correlation rather than a causation, according to some clinicians not associated with the study. Also, the authors performed a retrospective analysis of COPD-associated hospitalizations over the years 2005-2014. (Pre-COVID)

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QUESTION: Is there a governmental office to which patients can report any adverse effects from CBD products?

ANSWER: Yes, even though CBD (with the exception of Epidiolex) is not approved by the FDA, patients can report any adverse effects from CBD products to the FDA’s MedWatch program.

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QUESTION: To date, has the FDA approved cannabis for the treatment of any psychiatric condition?

ANSWER: No. However, the FDA has approved 1 cannabis-derived medication (CBD) called Epidiolex and 2 cannabis-related medications (dronabinol and nabilone) for specific indications. Dronabinol is a synthetic THC product that is used as an antiemetic agent. It is approved for treating or preventing nausea and vomiting caused by chemotherapeutic agents, and as an appetite stimulant for individuals with AIDS. Nabilone is a synthetic that is structurally similar to THC. It is approved for treating chemotherapy induced nausea and vomiting.

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QUESTION: What percentage of Americans support marijuana legalization?

ANSWER: In a 2019 Pew Research Center survey, 67% of Americans supported marijuana legalization. Since that 2019 survey, more US states have legalized recreational marijuana.

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QUESTION: Does ketamine interact with cannabinoids?

ANSWER: Yes. Ketamine is a CYP3A4 substrate, and thus may inhibit the metabolism of cannabinoids, including THC. This, in turn, can increase blood levels of cannabinoids and possibly lead to fatal dysrhythmias, heart attack, or stroke, according to the American Heart Association. Also, ketamine levels may increase which can lead to negative effects, including agitated delirium, respiratory depression (ketamine is primarily an NMDA antagonist, but it may also bind to mu and the sigma receptors.)

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QUESTION: What is the most common reason for cannabinoid use among cancer survivors?

ANSWER: The most common reason for cannabinoid use among cancer survivors was pain. Other common reasons why cancer survivors used cannabinoids include sleeping problems and anxiety.

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QUESTION: What are the most common reasons older adults use cannabis-based products?

ANSWER: According to an anonymous survey of 568 adults age 65 or older, the majority (78%) used cannabinoids for medical purposes only, with the most common targeted conditions/symptoms being pain/arthritis (73%), sleep disturbance (29%), anxiety (24%), and depression (17%). Of note, only 41% reported that their healthcare provider knew that they use cannabinoids for medicinal purposes.

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QUESTION: Are symptoms of OCD significantly reduced after smoking or vaporizing marijuana?

ANSWER: Data from an app that tracks the changes of medical marijuana patients’ symptoms as a function of different doses and strains of cannabis across time was analyzed. The results indicate that inhaled cannabinoids appear to have short-term beneficial effects on symptoms of OCD. However, tolerance to the effects on intrusions may develop over time.

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QUESTION: Which US states have legalized adult-use marijuana possession and have also legalized adult-use marijuana sales?

ANSWER: As of October 10, 2020, the following 11 US states had legalized adult use marijuana possession and adult use marijuana sales: Alaska, California, Colorado, Illinois, Maine, Massachusetts, Michigan, Nevada, Oregon, Vermont, and Washington. Washington DC and Guam have also legalized adult use marijuana sales. In November 2020, Arizona, Montana, New Jersey and South Dakota legalized recreational marijuana, too.

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QUESTION: Are there any US states that do NOT deny solid organ transplants for patients that use marijuana for medicinal purposes?

ANSWER: Legislation has passed in at least 7 US states (California, Washington, Illinois, Arizona, Delaware, New Hampshire, and Maine) that explicitly forbids denial of transplantation listing on the basis of an individual’s use of medical marijuana. *Of note, transplant recipients take immunosuppressive drugs, and inhaled smoked or vaporized marijuana can expose the consumer to life-threatening pulmonary infections (Aspergillosis, for example). Typically, most US state solid organ transplant programs have recommended that individuals with active drug or alcohol abuse not undergo transplantation.

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QUESTION: Does THC stimulate the sympathetic or parasympathetic system?

ANSWER: Tetrahydrocannabinol stimulates the sympathetic nervous system while inhibiting the parasympathetic nervous system. After THC consumption, there may be increases heart rate, myocardial oxygen demand, supine blood pressure, and platelet activation. (Of note, THC is associated with endothelial dysfunction and oxidative stress.)

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QUESTION: What is the half life of CBD? How does it compare to the half life of THC?

ANSWER: The half life of CBD is 18-32 hours, which is similar to the half life of THC of 20-30 hours. Both CBD and THC are distributed to fatty tissues and highly perfused organs such as brain, heart, lung, and liver.

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QUESTION: At what point during gestation are endocannabinoid receptors expressed in the fetus?

ANSWER: Endocannabinoid receptors are first expressed in the fetus at 5 to 6 weeks’ gestation.

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QUESTION: Did past-month cannabis use among pregnant US women increase or decrease during the 15 year span of 2002 to 2017?

ANSWER: Past-month cannabis use among pregnant US women more than doubled from 2002 (3.4%) to 2017 (7.0%).

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QUESTION: Is prenatal exposure to cannabis associated with child outcomes?

ANSWER: The results of a cross-sectional analysis published in a September 2020 JAMA Psychiatry journal, indicate that prenatal exposure does impact child outcome. This particular cross-sectional analysis involved 11,489 children (655 exposed to cannabis prenatally) and the findings indicate that prenatal cannabis exposure after maternal knowledge of pregnancy was associated with greater psychopathology (i.e., internalizing, externalizing, attention, thought, and social problems, as well as psychotic-like experiences) during middle childhood, even after accounting for potentially confounding variables.

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QUESTION: Does marijuana use during pregnancy affect the birth weight of the baby?

ANSWER: Yes. According to a 2018 study by Campbell et al., marijuana use during pregnancy triples the likelihood of having a low birth weight baby, even after adjusting for factors such as socioeconomic status, medical history, and other substance use such as tobacco smoking

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QUESTION: What percentage of 12th graders in the US have used marijuana at least once in their life?

ANSWER: According to the National Institute on Drug Abuse’s Monitoring the future, nearly one half of all 12th-graders in the United States have used marijuana in their lifetime, with more than one third during the past year, and almost one quarter in the past month.

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QUESTION: What percentage of individuals who misuse prescription opioids seek treatment?

ANSWER: Only 8% of individuals who misuse prescription opioids seek treatment. Of note, approximately 80% of heroin users first misused prescription opioids.

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QUESTION: How does CBD impact the cardiovascular system?

ANSWER: CBD reduces heart rate and blood pressure, and improves vasodilation in models of endothelial dysfunction. Also, CBD reduces inflammation and vascular hyperpermeability in diabetic models.

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QUESTION: Compared to previous years, has the number of opioid deaths since the COVID pandemic increased or decreased?

ANSWER: Since the beginning of the COVID-19 pandemic, a dramatic increase in the number of opioid overdose deaths has been reported. According to a recent report put out by the American Medical Association, opioid overdose deaths have increased in more than 35 states since the pandemic began. This surge is believed to be multifactorial, and due to isolation, economic issues, disruptions to the drug trade and other factors.

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QUESTION: How many adolescents in the US misused opioids in 2018?

ANSWER: In 2018, 699,000 adolescents between the ages of 12 and 17 misused opioids, with the vast majority misusing prescription opioids. Of these 699,000 adolescents, 108,000 had opioid use disorder.

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QUESTION: Does substance use disorder increase the risk for COVID-19?

ANSWER: Yes, according to an analysis of electronic health records (EHR). As reported by Nora D. Volkow, MD, director of the National Institute on Drug Abuse, and colleagues, the evaluation of over 73 million electronic health records, the risk of COVID-19 was far greater among patients diagnosed with a substance use disorder in the past year compared with the general population after adjusting for age, gender, race, and insurance type.

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QUESTION: Does the oral administration of CBD alter plasma concentrations of diazepam?

ANSWER: CBD can alter the toxicity or efficacy of other drugs through inhibition of certain enzymes. For example, increases in the plasma concentration of diazepam have been reported when the diazepam is coadministered with Epidiolex (a CBD product).

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QUESTION: Has the use of a transdermal gel for regional and systemic delivery of CBD been evaluated for the treatment of epilepsy?

ANSWER: Yes. A transdermal gel for regional and systemic delivery of CBD (Zynerba Pharmaceuticals) is in clinical development for treatment of epilepsy, developmental and epileptic encephalopathy, fragile-X syndrome, and osteoarthritis. NOTE: As of September 2020, the company’s website indicates that the product is not yet approved by government regulatory bodies, including the United States Food and Drug Administration (FDA) and other agencies, and must be tested to see if it is an effective and safe treatment.

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QUESTION: Is cannabidiol in compounded topical pain creams safe to use?

ANSWER: According to the National Academies of Science, Engineering and Medicine’s 2020 publication A Review of the Safety and Effectiveness of Select Ingredients in Compounded Topical Pain Creams, “there is insufficient evidence on the safety of topical application of cannabidiol. However, if systemic absorption to therapeutic levels is achieved through topical application, there is potential for side effects similar to other routes of administration (e.g., oral).”

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QUESTION: Does cannabidiol in compounded topical pain creams penetrate the skin of animals?

ANSWER: According to the National Academies of Science, Engineering and Medicine’s 2020 publication, A Review of the Safety and Effectiveness of Select Ingredients in Compounded Topical Pain Creams, “there is limited preclinical evidence to suggest that cannabidiol penetrates animal skin. Modifications to the ingredient or excipient may increase aqueous solubility and increase absorption.”

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QUESTION: In PRECLINICAL studies, it has been shown that cannabinoids induce apoptosis of cancer cells. Do cannabinoids induce apoptosis of normal non-malignant cells?

ANSWER: According to the results of PRECLINICAL studies, including in vitro studies and and studies in mice, cannabinoids induce apoptosis of cancer cells without causing negative effect on the viability of normal non-malignant cells. In some mouse models, it has been noted that cannabinoids act synergistically with standard anti-cancer drugs or radiation therapy to reduce tumor growth. These studies have not detected overt signs of toxicity in the treated animals. NOTE: The observations noted in culture or animal models do NOT always readily translate into clinical benefit.

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QUESTION: Most of the currently available scientific evidence for anti-neoplastic activity of cannabinoids is derived from PRECLINICAL models, including in vitro studies and studies involving mouse models. What have the results of these PRECLINICAL studies indicated?

ANSWER: These PRECLINICAL studies have reported that THC and some other cannabinoids can activate the CB1 and CB2 receptors on the surface of cancer cells and impact the intracellular signaling pathways of the cancer cells. Some effects include (1) apoptosis of the cancer cells (2) the blockade of cancer cell proliferation (3) inhibition of tumor angiogenesis and (4) inhibition of metastasis. NOTE: the results of PRECLINICAL studies do NOT always correlate with CLINICAL outcome/benefit.

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QUESTION: Clinical trials evaluating the use of human monoclonal antibodies against interleukin 1 and interleukin 6 to treat cytokine storm syndrome in COVID-19 patients are underway or in the planning stage. Are there any possible significant pharmacodynamic interactions between monoclonal antibodies and CBD?

ANSWER: Yes. The combination of monoclonal antibody agents, including eculizumab and sarilumab, or other immuno/myelosuppressive agents with CBD may potentiate the risk of infection.

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QUESTION: Nelfinavir is an HIV-1 protease inhibitor. Patients who have HIV may be taking this drug and may also be using cannabinoids to treat some of the symptoms associated with the HIV infection. Does Nelfinavir interact with CBD? (Of note, Nelfinavir may also inhibit SARS-Cov-2 replication.)

ANSWER: The combination of Nelfinavir and CBD may lead to an increase risk of diarrhea and/or headache.

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QUESTION: Dexamethasone, a commonly used corticosteroid to treat various inflammatory conditions, has been recommended for use in COVID-19 patients with severe respiratory symptoms (according to data from Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial). Does THC interact with dexamethasone? Does CBD interact with dexamethasone?

ANSWER: Both THC and CBD have possible pharmacodynamic interactions with dexamethasone. While the combination of THC and dexamethasone may lead to an increase in euphoria, the combination of CBD and dexamethasone may lead to a potentiation of immunosuppression and an increase in risk of infection, and could increase the risk of headache.

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QUESTION: Darunavir with cobicistat has been used to treat HIV and it has also been trialed for the treatment of COVID-19 infection. Are there any possible pharmacodynamic interactions between CBD and Darunavir/ Cobicistat?

ANSWER: Yes, this drug combination may increase headache and/or diarrhea.

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QUESTION: What is the most common qualifying condition reported by medical marijuana patients?

ANSWER: Currently and historically the most common qualifying condition reported by medical marijuana patients is chronic pain. In fact, according to an analysis by Boehnke et al, chronic pain was the qualifying condition reported by medical marijuana patients nearly 65 percent of the time (according to 2016 data).

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QUESTION: Hydrochloroquine has been trailed as a therapy for COVID-19 infections. Does this drug interact with CBD? If so, what are the potential consequences?

ANSWER: The combination of CBD and hydrochloroquine may lead to an increase of headache and/or diarrhea risk.

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QUESTION: Baricitnib, a drug approved for the treatment of rheumatoid arthritis, may reduce COVID-19 viral entry and mitigate inflammation. (A clinical trial evaluating this drug has begun in Italy .) Does CBD interact with Baricitnib?

ANSWER: Yes. A possible pharmacodynamic interaction between Baricitnib and CBD may develop, and there may be an increased effect on tumor necrosis factor. There may also be an increased risk of serious infection, malignancy or thrombosis.

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QUESTION: There may be pharmacokinetic and pharmacodynamic drug–drug interactions between cannabinoids and medications used to treat COVID infections. Azithromycin may have anti-viral activity and has been co-administered with hydroxychloroquine in a RCT of COVID treatment. Does Azithromycin interact with CBD?

ANSWER: Yes, a possible pharmacodynamic interaction may occur and lead to an increase risk for diarrhea.

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QUESTION: Did the number of naloxone prescriptions increase, decrease or stay the same during the time span of 2010 to 2018?
ANSWER: According to research conducted by the Urban Institute, prescriptions for naloxone increased by more than 70-fold from 2010 to 2018. (3,300 to 236,000 prescriptions). The most significant increase in naloxone prescriptions occurred after 2016.

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QUESTION: What have been the most frequently filled prescriptions at US pharmacies in 2020? Are most of them prescriptions for pain relief?

ANSWER: According to research conducted by GoodRx, an online platform that provides users with coupons for discounts on prescription drugs, the 10 most frequently filled prescriptions are: Atorvastatin, Lisinopril, Albuterol, Levothyroxine, Amlodipine, Gabapentin (for the treatment of nerve pain or seizures in adults), Omeprazole, Glucophage, Losartan, and Hydrocodone/acetaminophen (for the treatment of moderate to severe pain.)

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QUESTION: Greater social acceptance of marijuana may result in some prospective parents to reason that it could be used to treat morning sickness. Does marijuana use have any implications for fetal neurodevelopment?

ANSWER: A study evaluating the association between maternal marijuana use during pregnancy and child neurodevelopmental outcomes posed the following question: “Was there an association between cannabis exposure in pregnancy and child neurodevelopmental outcomes in a Canadian cohort?” The results of this retrospective study in Canada found that children exposed to marijuana in utero had a moderately elevated risk of developing autism spectrum disorder. Autism incidence was 4.0 per 1,000 person-years among children exposed to cannabis in pregnancy versus 2.42 among unexposed children (adjusted hazard ratio [HR] 1.51, 95% CI 1.17-1.96)

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QUESTION: In 2020, the 20 member ‘Global Task Force on Dosing and Administration of Medical Cannabis in Chronic Pain’ developed recommendations for the dosing of cannabinoids. These recommendations were presented at a virtual meeting. One of their recommendations addressed the use of medicinal cannabinoids in patients with severe pain. What were the recommendations for the dosing of cannabinoids for patients suffering with severe pain?

ANSWER: According to the recommendations of the ‘Global Task Force on Dosing and Administration of Medical Cannabis in Chronic Pain,’ patients suffering from severe pain and those patients who have a history of significant prior cannabis consumption can use a 50:50 CBD-THC product and start with a dose of 2.5-5 mg of each compound 1 or 2 times/day.

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QUESTION: In 2020, the 20 member ‘Global Task Force on Dosing and Administration of Medical Cannabis in Chronic Pain’ developed recommendations for the dosing of cannabinoids. These recommendations were presented at a virtual meeting. One of their recommendations addressed the use of medicinal cannabinoids in elderly patients. What were the recommendations for the dosing of THC in the elderly population?

ANSWER: According to the recommendations of the ‘Global Task Force on Dosing and Administration of Medical Cannabis in Chronic Pain,’ elderly patients, patients with severe co-morbidity or patients who take multiple medications should be managed through a conservative route; start with THC doses at 1 mg/day and the dose should be titrated up slowly.

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QUESTION: In 2020, the 20 member ‘Global Task Force on Dosing and Administration of Medical Cannabis in Chronic Pain’ developed recommendations for the dosing of cannabinoids. These recommendations were presented at a virtual PAINWeek meeting. One of their recommendations included “Treat the majority of patients along the “routine” scale.” What does this mean?

ANSWER: Treating the majority of patients along the “routine” scale means to start with a dose of 5 mg of cannabidiol (CBD) twice daily, and tetrahydrocannabinol (THC) should only be added if the patient does not respond to at least 40 mg of CBD daily. If THC is added, the starting dose should be 2.5-mg daily. THC doses should be capped at 40 mg daily.

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QUESTION: In 2017, the National Academies of Sciences, Engineering and Medicine (NASEM) published The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. According to this report, are cannabinoids an effective treatment for chronic pain?

ANSWER: According to this report, “There is conclusive or substantial evidence that cannabis or cannabinoids are effective for the treatment of chronic pain in adults (cannabis).”

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QUESTION: Do cannabinoids decrease or increase g.i. motility?

ANSWER: The pharmacological actions of cannabinoids include decreased gastrointestinal motility, secretion, and emptying.

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QUESTION: Does dronabinol increase appetite in HIV/AIDS patients?

ANSWER: There is limited to moderate evidence to suggest that dronabinol, a synthetic pharmaceutical preparation of delta-9-tetrahydrocannabinol, may be effective in stimulating appetite and weight gain among patients suffering from HIV wasting syndrome. In 1992, the US Food and Drug Administration approved dronabinol for the treatment of AIDS-related anorexia.

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QUESTION: What is the most prevalent side effect of opioids in cancer patients?

ANSWER: Constipation is reported as the most prevalent and most disabling side effect of opioids in both cancer and non-cancer pain patients, with a prevalence as high as 90%.

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QUESTION: What are conduction-based vaporizers?

ANSWER: Conduction-based vaporizers heat herbal cannabis on a surface that is warmed, such as a metal plate, which then allows compounds to passively volatilize. Meanwhile, the consumer generates a steady inhalation, similar to the technique used by asthma patients with metered-dose inhalers or nebulizers to achieve pulmonary administration.

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QUESTION: What physiological systems are affected by the endocannabinoid system?

ANSWER: In addition to regulating neuronal excitability and inflammation in pain circuits, the endocannabinoid system has been shown to play a regulatory role in movement, appetite, hypothalamic-pituitary-adrenal axis modulation, immunomodulation, mood, blood pressure, bone density, tumor surveillance, neuroprotection and reproduction. The endocannabinoid system has also been shown to affect sensory perception, cardiac output, cerebral blood flow and intraocular pressure.

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QUESTION: What does cannabinergic mean?

ANSWER: Any drug that modifies or interacts with the endocannabinoid system is ‘cannabinergic’.

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QUESTION: What is the pharmacological profile of buccally administered cannabinoids?

ANSWER: With buccal administration, a mix of cannabinoids can be sprayed on to the oral mucosa and the medicine is absorbed through the mucous membranes. Peak plasma concentrations usually occur within 2-4 hrs after administration. When compared to inhalation of cannabinoids, buccal administration of cannabinoids is associated with lower blood levels of cannabinoids because absorption is slower, redistribution into fatty acids occurs rapidly and some of the cannabinoids undergo first pass metabolism.

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QUESTION: Nabiximols (a cannabinoid medicine containing THC and CBD) is approved in many European countries for the treatment of neuropathic pain, spasticity and bladder dysfunction in patients suffering from multiple sclerosis. What are the potential drug interactions between nabiximols and analgesic medications?

ANSWER: The nabiximols product monograph cautions prescribers against combining nabiximols with amitriptyline or fentanyl because these drugs are metabolized by the same enzymes as nabiximols. Potential drug interactions with other opioids (oxycodone, tramadol and methadone) also exist.

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QUESTION: What is the purpose of urine drug testing?

ANSWER: Urine drug tests typically screen for the patient’s prescribed opioids and the commonly abused drugs: cocaine, amphetamines, alcohol, barbiturates, opiates and benzodiazepines. Although a urine drug test can confirm if the patient is taking the prescribed opioid, it cannot determine if the patient is taking the prescribed dose.

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QUESTION: What are the drugs that are inhibitors to cytochrome P450 and therefore decrease the metabolism of cannabinoids?

ANSWER: THC is oxidized by the cytochrome P450 (CYP) mixed-function oxidases 2C9, 2C19 and 3A4 1. Therefore, substances that inhibit these CYP isoenzymes (e.g. fluoxetine, cimetidine, clarithromycin, ketoconazole, verapamil, indinavir, among others) can potentially increase the bioavailability of THC, and thus increase the chance of experiencing THC-related side effects.

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QUESTION: Why do NSAIDS relieve pain?

ANSWER: NSAIDs reduce the production of prostaglandin E2 (PGE2) and prostacyclin (PGI2), which mediate pain and inflammation.

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QUESTION: Describe the process of vaporization of cannabis.

ANSWER: Vaporization is a smokeless delivery system in which warm air or heat of 180°C to 200°C, rather than a flame, is used to convert cannabinoids and other compounds into a fine mist that can be inhaled. Due to their volatility, cannabinoids will vaporize at temperatures of 180°C to 200°C, but will not combust and therefore few combustion by-products such as soot or polycyclic aromatic hydrocarbons are produced. As temperatures increase, the amount of cannabinoids released increases, and the amount of combustion by-products increases, too.

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QUESTION: The pharmacological properties of cannabigerol have been investigated. What have the studies shown?

ANSWER: Cannabigerol (CBG) is the phytocannabinoid precursor molecule, and demonstrates weak partial agonism at CB1 and CB2. In in vitro studies, CBG displays analgesic and anti-erythemic effects. CBG also displays anti-hypertensive activity.

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QUESTION: The pharmacological properties of tetrahydrocannabivarin have been investigated. What have the studies shown?

ANSWER: Tetrahydrocannabivarin (THCV) is a CB1 antagonist at low doses, but displays weak agonistic effects at high doses. In obese mice models, THCV reduced appetite, produced weight loss and decreased body fat and leptin concentration.

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QUESTION: What is the pharmacologic profile of cannabis when it is vaporized?

ANSWER: The pharmacologic profile of cannabis when it is vaporized is similar to the profile when it is smoked. Psychoactive effects appear within 90 seconds, reach a maximum after 15-30 minutes, and taper off within 2-3 hours.

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QUESTION: What is the pharmacologic profile of cannabis when it is smoked?

ANSWER: When herbal cannabis is smoked, the active ingredients in cannabis are vaporized by the heat of combustion and inhaled. Inhaled constituents quickly pass from alveoli into the bloodstream and readily cross the blood-brain barrier. Psychoactive effects appear within 90 seconds, reach a maximum after 15-30 minutes, and taper off within 2-3 hours. This short onset of action makes dose titration possible, by spacing inhalations at 90-second intervals.

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QUESTION: The pharmacological properties of cannabichromene have been investigated. What have the studies shown?

ANSWER: Cannabichromene (CBC) is a potent anadamide uptake inhibitor and thus may modulate the endocannabinoid system similarly to CBD. In mice studies, it has been shown that CBC has anti-inflammatory properties and analgesic activity. CBC has other pharmacological properties, as well.

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QUESTION: The pharmacological properties of cannabinol have been investigated. What have the studies shown?

ANSWER: Cannabinol (CBN) is the oxidative by-product of THC and appears after long storage. It is a weaker partial agonist at CB1 and CB2 as compared to THC. In in vitro studies, it has been found that cannabinol is anticonvulsant and anti-inflammatory, and stimulates bone formation.

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QUESTION: It is the mixture of phytocannabinoids, terpenes and other active components present in a cannabis product that ultimately determines the therapeutic effects and side effects. Does CBD affect THC absorption and tolerance?

ANSWER: CBD has long been thought to influence the effects of THC. This thinking was extended to consider that CBD potentiates some of the beneficial effects of THC, as it reduces the psychoactive effects of THC and thus could improve tolerability. CBD may counteract some of the functional consequences of CB1 receptor activation in the brain. This effect has been used to explain why high CBD:THC cannabis use is less associated with the development of psychotic symptoms compared to low CBD:THC cannabis. Also, CBD is thought to interact with the cytochrome p450 enzymes that metabolize THC and thus may alter the metabolism and influence the effects of the THC consumed. It has been proposed that THC and CBD act synergistically in therapeutic use.

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QUESTION: Does methadone alter cardiac conduction?

ANSWER: Yes. Methadone is known to prolong QTc intervals in up to 16% of patients. Studies have shown a linear dose response curve, with higher doses leading to a higher propensity for QTc prolongation. This has led to an FDA “black box” warning for methadone and the recommendation for routine ECG monitoring.

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QUESTION: How have medical advances altered opioid use in cancer patients?

ANSWER: Cancer is no longer considered a “terminal disease.” Because of significant advances in surgical, radiation, and chemotherapeutic treatments, more than 50% of cancer patients are living greater than 2 years after the diagnosis of cancer. This allows for more cancer patients to develop chronic pain. All of these factors have led to more cancer patients taking opioids long-term.

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QUESTION: What are terpenes (or terpenoids)?

ANSWER: Terpenes are aromatic components produced in the glandular part of the cannabis plant’s flower bud. Terpenes are manufactured by many plants (not just the cannabis plant) and can be found in many food products, including coffee beans, ginger and cinnamon. Often, it is the terpenes that are responsible for a plant’s odor.

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QUESTION: Does smoking marijuana impact the metabolism of theophylline?

ANSWER: It may. Reports have indicated that smoking marijuana may increase the clearance of theophylline. Note: this effect appears to be a direct result of the hydrocarbons found in marijuana smoke rather than the cannabis-based products, as there is a lack of evidence for enzyme induction when cannabis-based drugs are consumed via oral ingestion.

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QUESTION: Do the hydrocarbons in marijuana smoke impact drug metabolism?

ANSWER: Possibly. Similar to cigarette smoke, the hydrocarbons in marijuana smoke appear to induce the activity of some cytochromes, including CYP1A2.

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QUESTION: What criteria should be used when selecting a CBD hemp product?

ANSWER: According to a 2019 Mayo Clinic publication, the following 4 questions should be asked, and the answers to each of the questions should be “yes” :
1. Does the hemp product meet the quality standards of the Current Good Manufacturing Practices Certification from the FDA, or the European Union, Australian or Canadian organic certification, or the National Science Foundation International Certification?
2. Does the manufacturer have an independent review adverse event reporting system?
3. Is the product certified organic or ecofarmed?
4. Have the company’s products been lab tested to confirm THC levels to be < 0.3% and to confirm that no pesticides or heavy metals are present?

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QUESTION: Is full spectrum CBD the same as whole plant CBD?

ANSWER: No. Whole plant CBD contains fats, waxes and fibrous materials not found in full spectrum CBD.

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QUESTION: Is the plasma concentration of Epidiolex (CBD) affected by co-administration of high fat/high calorie food?

ANSWER: Yes. It has been that if CBD is co-administered with a high fat/high calorie meal, the plasma concentration of CBD may increase by as much as 5-fold.

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QUESTION: Describe the exact mechanism of action of Epidiolex.

ANSWER: According to the Epidiolex FDA Approved Package Insert, (Greenwich Biosciences, Inc.), the precise mechanism(s) by which Epidiolex exerts its anticonvulsant effects in humans are unknown. It does not appear to be through cannabidiol receptors.

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QUESTION: Epidiolex has been approved for the treatment of seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS). Has the FDA approved Epidiolex for any other conditions?

ANSWER: Yes. On July 31, 2020, the U.S. Food and Drug Administration approved Epidiolex (cannabidiol or CBD) oral solution for the treatment of seizures associated with tuberous sclerosis complex (TSC) in patients one year of age and older.

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QUESTION: The International Association for the Study of Pain (IASP) has updated the definition of pain. What is their new definition of pain?

ANSWER: After 40+ years, the IASP has revised their definition of pain to reflect advances in our understanding of pain. The revised definition emphasizes that tissue damage is not required. The updated definition of pain is: “An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage.” The revised definition also includes 6 notes:
1.) Pain is always a personal experience that is influenced to varying degrees by biological, psychological, and social factors
2.) Pain and nociception are different phenomena, and pain cannot be inferred solely from activity in sensory neurons
3.) Through life experiences, people learn the concept of pain
4.) A person’s report of an experience as pain should be respected
5.) Although pain usually serves an adaptive role, it may have adverse effects on function and social and psychological well-being
6.) Verbal description is only one of several behaviors to express pain, and an inability to communicate does not negate the possibility that a human or a nonhuman animal experiences pain

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QUESTION: What is oliceridine (Olinvyk)? Is it a new FDA-approved opioid?

ANSWER: According to an August 7, 2020 FDA news release, “the FDA approved Olinvyk (oliceridine), an opioid agonist for the management of moderate to severe acute pain in adults, where the pain is severe enough to require an intravenous opioid and for whom alternative treatments are inadequate. Olinvyk is indicated for short-term intravenous use in hospitals or other controlled clinical settings, such as during inpatient and outpatient procedures. It is not indicated for at-home use.” https://www.fda.gov/news-events/press-announcements/fda-approves-new-opioid-intravenous-use-hospitals-other-controlled-clinical-settings

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QUESTION: What is the safety profile of Olinvyk?

ANSWER: According to an August 7, 2020 FDA news release, “The safety profile of Olinvyk is similar to other opioids. As with other opioids, the most common side effects of Olinvyk are nausea, vomiting, dizziness, headache and constipation. Olinvyk should not be given to patients with significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment; known or suspected gastrointestinal obstruction; or known hypersensitivity to the drug. Prolonged use of opioid analgesics during pregnancy can result in neonatal opioid withdrawal syndrome.” “Olinvyk carries a boxed warning about addiction, abuse and misuse; life-threatening respiratory depression; neonatal opioid withdrawal syndrome; and risks from concomitant use with benzodiazepines or other central nervous system depressants. Unlike other opioids for intravenous administration, Olinvyk has a maximum recommended daily dose limit of 27 milligrams.” https://www.fda.gov/news-events/press-announcements/fda-approves-new-opioid-intravenous-use-hospitals-other-controlled-clinical-settings

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QUESTION: Changes in fetal growth have been described in some epidemiological studies examining the impact of maternal use of marijuana. Do the long‐term patterns of physical growth appear to be affected?

ANSWER: No, long-term physical growth does not appear to be affected. In contrast, long‐term impacts on psychological health have been noted and include increased rates of depressive symptoms and anxiety as well as delinquency.

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QUESTION: Does the use of cannabinoid-based products impact female sexual function?

ANSWER: According to a study published in the journal Sexual Medicine, an increased frequency of marijuana use is associated with improved sexual function among females. Interestingly, it was noted that chemovar type and method of consumption did not impact outcomes, though.

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QUESTION: CBD and medical marijuana are legal in Florida and California. Do the major amusement parks in these states and other legal marijuana states allow medical marijuana patients to carry CBD and medical marijuana into the amusement parks?

ANSWER: With a few exceptions, the answer is no. Medical marijuana and CBD products are not allowed in Disney parks and resorts (including hotels, shopping and restaurants). Six Flags, Universal, and Cedar Fair also prohibit all forms of legal cannabinoid products, including CBD. In contrast, Sea World properties (which include all Busch Gardens and Sea World parks) allow visitors to carry CBD—but no forms of medical marijuana with significant amounts of THC.

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QUESTION: According to an estimate by the United Nations, what percentage of the world’s population used cannabis products in 2016?

ANSWER: The UN estimated that in 2016, 3.9% of the world’s population used cannabis products. (3.9% of the world population is equivalent to ~ 192.2million people)—The UN’s data suggest that there was an increase of 16% compared with estimates of the previous decade.

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QUESTION: Does the Food and Drug Administration (FDA) currently certify the levels of THC contained within CBD products?

ANSWER: Actually, no. The FDA does not regulate the CBD products sold in convenience stores, grocery stores and on line. Although they are labeled as containing no THC, some may actually contain a small amount of THC. (Note: The FDA does monitor the CBD product called Epidiolex.)

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QUESTION: Has the FDA approved any drugs that contain a purified drug substance derived from cannabis?
ANSWER: Yes. Epidiolex oral solution contains purified cannabidiol that has been extracted from the cannabis plant, and this drug has been approved by the FDA. The FDA has also approved medications, such as marinol, that contain synthetic THC.

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QUESTION: Do cannabinoids induce clinical remission or affect inflammation in inflammatory bowel disease patients?

ANSWER: According to a systematic review with meta-analysis of the efficacy of cannabis and cannabinoids for inflammatory bowel disease, cannabis/cannabinoids do not induce clinical remission or affect inflammation in IBD patients. (No effect on inflammatory biomarkers was observed.) However, in this systematic review it was found that cannabis/cannabinoids significantly improved patient-reported symptoms and quality of life. (Clinical symptoms (abdominal pain, general well-being, nausea, diarrhea, and poor appetite) all improved with cannabis/cannabinoids on Likert-scales.) This systematic review involved 15 nonrandomized studies and 5 randomized controlled trials.

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QUESTION: In July of 2020, the FDA announced that labeling for opioid analgesics and medicine to treat opioid use disorder (OUD) must be updated. What do the updates entail?

ANSWER: The updates include that naloxone availability be routinely discussed as part of prescribing opioid analgesics and OUD medicines. The labelling changes also recommend that health care professionals consider prescribing naloxone when they prescribe medicines to treat OUD. Additionally, the labeling changes recommend “that health care professionals consider prescribing naloxone to patients being prescribed opioid pain medicines who are at increased risk of opioid overdose… A naloxone prescription should also be considered for patients prescribed opioids who have household members, including children, or other close contacts at risk for accidental ingestion or opioid overdose.”

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QUESTION: Do cannabinoid-based medicines impact the deposition of Amyloid β peptide in Alzheimer’s disease?

ANSWER: According to the results of a systematic review, the findings of 9 animal studies indicated that cannabis-based medicines might modulate Amyloid β modifications and inhibit the progression of Alzheimer’s disease. (The maximum and minimum cannabinoid dosages, mostly CBD and THC in animal studies, were 0.75 and 50 mg/kg, respectively. The cannabinoids (CBD and THC) were injected for 10 to 21 days.)

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QUESTION: What is the most common mode of CBD administration?

ANSWER: According to a 2017–2018 online survey evaluating modes of CBD administration, the most common method of CBD administration was sublingual, followed by vaping, oral ingestion of capsules and liquids, smoking, edibles, and topical administration.

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QUESTION: In what dosage forms are pharmaceutical fentanyl products supplied?

ANSWER: Pharmaceutical fentanyl products are currently available in the following dosage forms: oral transmucosal lozenges (AKA fentanyl “lollipops”), buccal tablets and sublingual tablets, sublingual sprays, nasal sprays, transdermal patches, and injectable formulations.

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QUESTION: Chronic pelvic pain affects up to 15% of women in the United States. Cannabinoid receptors are expressed on reproductive tissues (including the uterus) and non-reproductive pelvic tissues. Do patients with chronic pelvic pain use cannabinoid-based products to ameliorate their symptoms?

ANSWER: The conclusions of a survey of 122 chronic pelvic pain female patients indicated that up to 23% report using cannabinoid-based products as an adjunct to their prescribed therapies. The patients use a variety of formulations and doses of cannabinoid-based products, and most report daily or weekly use. Most users report improvement in symptoms, but did acknowledge that side effects are common.

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QUESTION: Describe the chemical makeup of endocannabinoids.

ANSWER: Endocannabinoids are ester, ether, and amide derivatives of long chain polyunsaturated fatty acids. Arachidonic acid is an example of a polyunsaturated fatty acid in endocannabinoids.

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QUESTION: How is the endocannabinoid system linked to the opioid system?

ANSWER: Opioid receptors and CB receptors are located within the same neurons within the CNS. In addition, cannabinoids activate kappa and delta receptors to initiate a release of endogenous opioids.

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QUESTION: Does the co-administration of THC and alcohol impact serum THC levels?

ANSWER: Yes. According to a study by Hartman in 2015, alcohol may increase serum THC levels.

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QUESTION: Some producers of cannabinoid products will provide a certificate of analysis (CoA) from an independent and certified testing laboratory. What information is typically displayed on a CoA?

ANSWER: CoAs typically indicate the amount and concentration of major cannabinoids and terpenes present, and data regarding the presence of microbial/ fungal contaminants, levels of heavy metals, and presence and concentration of pesticide and solvent residues.

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QUESTION: Drug screens are sometimes done in the pre-operative. Is it clinically useful to do a drug screen for the presence of cannabinoids or cannabinoid metabolites?

ANSWER: Drug screens for the presence of cannabinoids and metabolites of cannabinoids will not inform the healthcare provider of the recency of marijuana use, as cannabinoids can remain in the body for several weeks.

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QUESTION: Does CBD isolate contain any other cannabinoids or terpenes?

ANSWER: CBD isolate is CBD in its molecular form, and is typically sold as 99+% pure. Unless indicated on the label, products made with CBD isolate do not contain any other cannabinoids or terpenes.

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QUESTION: What does “broad spectrum” mean?
ANSWER: Broad spectrum and full spectrum are not synonymous. Broad-spectrum products are processed in such a manner as to ensure that the final product does NOT contain THC.

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QUESTION: What does “full spectrum” marijuana product mean?

ANSWER: Full spectrum means that the product contains all of the original compounds found in the flower of the cannabis plant (cannabinoids, terpenes and flavonoids).

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QUESTION: Have the results of studies conducted between 2003-2017 indicated that cannabinoids are effective at treating chronic non-cancer pain?

ANSWER: Yes. Lynch and Ware published 2 systematic reviews (SR). One SR evaluated trials from 2003 to 2010 and the other SR evaluated trials from 2010 to 2014. Of the 29 RCTs evaluated in the 2 SRs, 22 of them demonstrated that cannabinoids have a modest analgesic effect and are safe in the management of chronic pain. The modes of administration explored in these 29 SRs included: smoking, oromucosal and oral. All 6 smoked cannabis trials showed a positive analgesic response.

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QUESTION: Epidemiological studies indicate that as many as 15% of inflammatory bowel disease (IBD) patients may use cannabinoids to ameliorate some of their symptoms, including improvement in diarrhea, abdominal pain and appetite. Do the studies show that cannabinoids are effective?

ANSWER: There are few studies evaluating cannabinoid use in IBD, and those studies are small. In Crohn’s disease, it has been demonstrated that THC reduces the Crohn’s disease activity index by >100 points (on a scale of 0–450). Also, two small studies involving ulcerative colitis patients showed a marginal benefit. However, no improvement in inflammatory markers or in endoscopic score in either disease was detected.

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QUESTION: The findings of multiple RCTs indicate that cannabinoids effectively treat chronic pain. Do cannabinoids effectively treat the chronic pain associated with fibromyalgia?

ANSWER: No. According to a Cochrane systematic review published in 2016 on the use of cannabinoids to treat fibromyalgia, there is no convincing, unbiased, high-quality evidence suggesting that a cannabinoid-based medicine (nabilone) is of value in treating people with fibromyalgia. Furthermore, the tolerability of nabilone was low in people with fibromyalgia. Also, the results of a 2019 study where 4 varieties of pharmaceutical grade marijuana were administered by single shot vapor to fibromyalgia patients indicated that none of the 4 marijuana varieties had an effect greater than placebo. (Note: The data from the 2019 study could not be used to extrapolate the long-term effects of cannabinoids on fibromyalgia-associated pain.)

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QUESTION: Some cancer patients use medical marijuana to treat various cancer-associated ailments. What are some of the ailments ameliorated by medical marijuana?

ANSWER: According to one study involving 96 cancer patients receiving supportive cancer care, the data support the safety and effectiveness of medical marijuana as a complementary option for improving pain control, appetite and quality of life for cancer patients. The top three adverse events of this study included drowsiness, low energy and nausea, and were reported in 28% of patients, with 9% having to stop using the medical marijuana. (Note: other studies indicate that chemotherapy-induced N/V and anxiety are ameliorated by medical marijuana.)

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QUESTION: Side effects of short-term cannabinoid-based therapy may differ from person to person, and the same person may experience different side effects at different times. What factors influence the probability and the severity of adverse events?

ANSWER: Many factors influence the likelihood and the severity of adverse events, including the type of cannabinoid preparation; the mode of administration; the patient’s expectations, the patient’s prior experience with cannabinoid-based therapies, and the age of the patient. Drug–drug interactions may also lead to adverse events.

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QUESTION: According to the results of a survey of breast cancer patients’ use of cannabinoid products before, during, and after treatment, 42% of survey participants had used medical cannabinoid products to relieve symptoms. What symptoms were treated with the cannabinoid products?

ANSWER: Members of the Breastcancer.org and Healthline communities were asked to participate in a survey during the period of 12/16/2019 – 1/19/2020. Among the 832 respondents who completed screening, 725 met the eligibility criteria, and 612 (84%) completed the survey. According to the results, the symptoms for which cannabinoids were used included insomnia (70%), pain (59%), anxiety (57%), stress (51%), and nausea/vomiting (46%). The results also indicated that cannabinoids were used prior to treatment in 24%, during treatment in 79%, and after treatment in 54%. Of subjects reporting cannabis use during treatment: 86% used it during chemotherapy, 71% during HER2 therapy, 65% during hormonal therapy, 49% during breast radiation, and 47% during radiation for metastatic sites. Post-surgical use was reported in 51% after mastectomy alone, 40% after lumpectomy, and 38% after mastectomy/reconstruction.

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QUESTION: Other than feeling “high” what are some of the reported psychological CNS-related side effects associated with cannabinoid use?

ANSWER: Psychological side effects associated with cannabinoid use include: restless/anxiety/nervousness, depressed mood, dysphoria, confusion, dissociation, hallucinations, hyperactivity, weird dreams, paranoia and psychosis.

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QUESTION: Are cannabinoids an effective analgesic agent in the chronic pain setting?

ANSWER: In contrast to the lack of efficacy in the acute pain setting, cannabinoids are effective analgesic agents in the chronic pain setting. According to 2 systematic reviews involving a total of 29 RCTs, 22 of the 29 RCTs demonstrated that cannabinoids have a modest analgesic effect in the management of chronic pain. The following modes of administration were examined in the RCTs: smoked cannabis (6 trials), oromucosal and oral cannabis extract (11 trials), nabilone (8 trials), dronabinol (2 trials), THC-11 acid analogue (2 trials), and fatty acid amide hydrolase inhibitor (1 trial).

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ANSWER: Are cannabinoids an effective analgesic agent in the acute pain setting?

ANSWER: No. According to the results of multiple RCT examining the efficacy of cannabinoids to treat acute pain, THC, nabilone and other cannabinoid-based products were not associated with a reduction in pain, but were associated with adverse side effects, including sedation.

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QUESTION: What are the common modes of administration of medical marijuana used by cancer patients?

ANSWER: According to a survey completed by 183 cancer patients of an oncology clinic at Sutter Medical Center in Sacramento, California, over 50% reported use of oils and tinctures and 44% used edibles. A smaller percentage consumed cannabis-based products via vaping (26%) or smoking (30%). Topical use was preferred by fewer patients (17%). Over 58% of patients stated they used more than one method.

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QUESTION: It has been estimated that a significant proportion of cancer patients (18.3-40.0%) in the United States use cannabis or cannabinoid-based products. Does the evidence indicate that cannabinoid-based products are effective in treating cancer-related pain? chemotherapy-induced n/v? cancer-related cachexia?

ANSWER: According to a study published in the Journal of Clinical Oncology, there is substantial evidence for the effectiveness of cannabis and cannabinoids in treating cancer-related pain; specifically, oromucosal THC/CBD spray. Also, there is conclusive evidence that cannabis and cannabinoids effectively relieve chemotherapy-induced nausea and vomiting; (specifically, oral THC). However, there is inconclusive evidence about the effectiveness of cannabinoid-based products in treating cancer-related cachexia.

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QUESTION: Does the administration of marijuana affect insulin levels in humans?

ANSWER: In a DBRCT involving 20 participants, it was found that marijuana consumed via oral, smoked, or vaporized routes affected blood concentrations of some metabolic hormones, including insulin. In fact, the results of this study indicate that acute marijuana use blunted the insulin spike associated with the consumption of a brownie.

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QUESTION: Are there any special considerations for patients who consume cannabinoid-based products and are undergoing plastic surgery?

ANSWER: Yes. On occasion, plastic surgeons administer atropine and/or epinephrine during a procedure. Both of these medications can increase heart rate, and cannabinoids may potentiate the increase in heart rate.

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QUESTION: Cannabinoid receptors have been located in the central nervous system and the peripheral nervous system, as well as on immune cells. Have cannabinoid receptors been isolated in reproductive tissues/cells?

ANSWER: In addition to cannabinoid receptors being identified in the hypothalamus and the pituitary gland, cannabinoid receptors have also been identified on ovary, endometrial tissue, testes, and spermatozoa. In fact, research suggests that marijuana may alter the release of FSH and LH, ovulation, sperm motility, fertilization, as well as placentation.

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QUESTION: What are K2 and Spice?

ANSWER: K2 and Spice are synthetic cannabinoid “designer drugs” that are intended to mimic the effects of THC. These synthetic cannabinoids are sold as “herbal incense” at convenience stores/gas stations, smoke shops and via the internet. They are produced in powder form, and then often dissolved in solvents, so they can be applied to dry plant material to make the “herbal incense” products.

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QUESTION: Heroin is processed from morphine, an extract from the poppy plant. Heroin is often depicted as a white powder. Is heroin sold in forms other than white powder?

ANSWER: In addition to white powder, heroin is sold as a brownish powder, or as a black sticky/tar-like substance (AKA black tar heroin). Heroin is either sold in pure form or is “cut” with other drugs (quinine, for example) or with other white powdery substances, including sugar, starch or powdered milk.

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QUESTION: Respiratory depression is associated with the overdose of opioids or benzodiazepines. Is respiratory depression associated with an overdose of cannabinoids? Why or why not?

ANSWER: Respiratory depression is not associated with cannabinoid use because CB1 receptors are not located in the midbrain, the part of the brain responsible for respiratory drive.

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QUESTION: As of January 2020, how many Americans were using marijuana-based products for medicinal purposes?
ANSWER: It has been estimated that more than 2 million Americans use marijuana for medical reasons. Some of the many ailments being treated with marijuana include: chronic pain, PTSD, depression, sleep disorders, multiple sclerosis (MS), cancer-related ailments, and GI disorders. Some indications are supported by good scientific evidence, but many are not.

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QUESTION: Rohypnol® is the trade name for the benzodiazepine called unitrazepam. Has this drug ever been approved by the Food and Drug Administration for medical use in the United States?

ANSWER: No, but outside the US, Rohypnol® is prescribed to treat insomnia. Rohypnol® has been referred to as a date rape drug or roofies. Before 1997, Rohypnol® was manufactured as a white tablet, and when mixed in liquids, it was colorless, tasteless, and odorless. In 1997, the manufacturer responded to concerns about the drug’s role in sexual assaults, and reformulated the drug. Now, Rohypnol® is produced as an olive green tablet with a speckled blue core that when dissolved in light-colored drinks will change the color of the liquid to blue. Of note, generic versions of the drug may not contain the blue dye.

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QUESTION: What is the Chemical Diversion and Trafficking Act (CDTA) of 1988?

ANSWER: The CDTA is an Act that regulated 12 (drug manufacturing) precursor chemicals, eight essential chemicals, tableting machines, and encapsulating machines. The Act imposed recordkeeping and import/export reporting requirements on transactions involving these regulated products. One of the goals of this Act was to reduce the supply of methamphetamine. As of 2020, the DEA regulates more than 40 chemicals that are often used in the production of illicit drugs.

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QUESTION: Cannabinoids are metabolized by many of the same cytochrome P450 enzymes as warfarin, including CYP3A4, CYP2C9, and CYP2C19. THC, CBD and CBN can inhibit the CYP2C9-mediated hydroxylation of warfarin, and thus lead to an increase in INR. Do cannabinoids also affect the metabolism of heparin? Is the metabolism of direct oral anticoagulants (DOACs), including rivaroxaban, edoxaban, and apixaban, impacted by cannabinoids?

ANSWER: While cannabinoids do not alter the metabolism of heparin, cannabinoids may impact the metabolism of DOACs. DOACs are substrates of P-gp and are absorbed by the gut through the P-gp efflux transporter. Cannabinoids may bind to P-gp membrane transporters and alter DOAC metabolism. DOAC levels may increase, leading to an increased risk of bleeding.

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QUESTION: CBD is a CB1 antagonist and a negative allosteric modulator at CB2. Does CBD interact with receptors other than CB1 or CB2?

ANSWER: Yes. CBD has cannabinoid receptor-independent properties. For example, CBD is an agonist at the TRPV1 receptor and has agonist properties at the 5-HT1A/2A/3A serotonergic receptors. CBD is also a capsaicin analog. CBD has antagonist activity on alpha-1 adrenergic and μ-opioid receptors, too. In addition, CBD has been found to inhibit synaptosomal uptake of noradrenaline, dopamine, serotonin, and gamma-amino butyric acid. CBD also inhibits anandamide uptake.

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QUESTION: Cannabinoid receptors are located throughout various parts of the CNS, including the basal ganglia, hippocampus, cerebellum and cerebral cortex, and in the peripheral nervous system. Do these receptors have effects on neurotransmitters such as serotonin?

ANSWER: Yes. CB receptor activity not only impacts serotonin, but it also affects acetylcholine, dopamine, glutamate, and GABA, as well as NMDA and opioid receptor systems.

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QUESTION: The Controlled Substances Act (CSA) regulates five classes of drugs. What are they?

ANSWER: The Controlled Substances Act (CSA) regulates five classes of drugs, including narcotics, depressants, stimulants, hallucinogens and anabolic steroids. All controlled substances have abuse potential or they are immediate precursors to substances that have abuse potential. Note: Alcohol and tobacco are specifically exempt from
control by the CSA.

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QUESTION: Methamphetamine is a Schedule II highly addictive stimulant. What is methamphetamine’s mechanism of action that leads to the “rush” and “high”?

ANSWER: It is believed that the “rush” and the “high” associated with amphetamine use result from the release of very high levels of dopamine into areas of the brain that regulate feelings of pleasure.

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QUESTION: Methadone, morphine and heroin are all narcotics. Do they all have a similar chemical structure?
ANSWER: No. Morphine and heroin (which is derived from morphine) have a similar structure. Methadone, which is a synthetic narcotic, does not have a similar structure to morphine.

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QUESTION: Methamphetamine is a controlled substance and is classified as a Schedule II drug. Schedule II drugs have a high potential for abuse and have an accepted medical use. What medical use(s) does methamphetamine have?

ANSWER: As of April 2020, there is only one legal “meth” product, and it is sold under the name Desoxyn®. It has very limited use in the treatment of obesity and ADHD.

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QUESTION: Is the analgesic potency of hydromorphone more or less than the potency of morphine?

ANSWER: Hydromorphone is (2 to 8 times) more potent than morphine but not as potent as fentanyl.

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QUESTION: Chronic pelvic pain affects up to 15% of women in the United States. Cannabinoid receptors are expressed on reproductive tissues (including the uterus) and non-reproductive pelvic tissues. Do patients with chronic pelvic pain use cannabinoid-based products to ameliorate their symptoms?

ANSWER: The conclusions of a survey of 122 chronic pelvic pain female patients indicated that up to 23% report using cannabinoid-based products as an adjunct to their prescribed therapies. The patients use a variety of formulations and doses of cannabinoid-based products, and most report daily or weekly use. Most users report improvement in symptoms, but did acknowledge that side effects are common.

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QUESTION: In what dosage forms are pharmaceutical fentanyl products supplied?

ANSWER: Fentanyl pharmaceutical products are currently available in the following dosage forms: oral transmucosal lozenges (AKA fentanyl “lollipops”), buccal tablets and sublingual tablets, sublingual sprays, nasal sprays, transdermal patches, and injectable formulations.

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QUESTION: Fentanyl, morphine and heroin are all analgesics. Which one of the three is the most potent analgesic?

ANSWER: Fentanyl is the most potent analgesic of the three. It is about 100 times more potent than morphine and 50 times more potent than heroin, as an analgesic agent.

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QUESTION: What are common street names for marijuana?

ANSWER: Often, marijuana concentrates look similar to honey with either a brown or gold color, and many of the street names refer to the golden brown color. The terms wax, ear wax, honey oil, budder, butane hash oil, butane honey oil (BHO), shatter, dabs (dabbing), black glass, and errl have all been used to refer to marijuana concentrates.

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QUESTION: What is hashish?

ANSWER: Hashish (AKA hash) is a THC-rich resin from the cannabis plant. This resin is collected and processed into various forms, including balls, cakes or cookies. Pieces of hashish can be broken off, and placed in pipes or cigarettes for smoking. Some individuals mix hashish with tobacco. Hashish products are considered to be Schedule I substances.

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QUESTION: What is the most common route of administration for the synthetic cannabinoids K2 or Spice?

ANSWER: K2 and Spice are used for recreational purposes, and smoking is the most common route of administration. Spraying or mixing the synthetic cannabinoids on dried plant material allows one to smoke it (using a pipe, a water pipe, or rolling the drug-laced plant material in cigarette papers). Also, liquid synthetic cannabinoids have been designed to be vaporized via e-cigarettes.

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QUESTION: Does marijuana use alter the sexual intercourse experience?

ANSWER: An online survey posed questions regarding various aspects of sexual experience and how those aspects were impacted by marijuana use. The results indicated that marijuana helped individuals relax, heightened their sensitivity to touch, and increased intensity of feelings, thus enhancing their sexual experience, while others found that marijuana interfered by making them sleepy and less focused or had no effect on their sexual experience.

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QUESTION: CB1 receptors are located on neurons in the CNS and PNS. Are CB1 receptors also located on cardiomyocytes?

ANSWER: Yes. CB1 receptors are located in cardiomyocytes, vascular endothelial cells as well as smooth muscle cells. Activation of these CB1 receptors may lead to oxidative stress, inflammation, fibrosis, vasodilation, and negative inotropy.

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QUESTION: Some cannabinoid-based medicines are used to treat chemotherapy-induced n/v. Have cannabinoid-based medicines been shown to be effective in the treatment of post-op n/v?

ANSWER: The results of studies indicate that neither nabilone or intravenous THC is effective for post-op n/v. Even premedication with nabilone was ineffective at treating post-op n/v.

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QUESTION: Does ketamine interact with the endocannabinoid system?

ANSWER: Yes. Ketamine induces the release of endocannabinoids.

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QUESTION: Do CB1 and CB2 agonists facilitate endogenous opioid signaling?

ANSWER: Yes. In fact, CB1 and CB2 agonists increase the concentrations of endogenous opioids.

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QUESTION: Is the endocannabinoid system linked to the opioid system?

ANSWER: Yes. Opioid receptors and CB receptors are located within the same neurons within the CNS. In addition, cannabinoids activate kappa and delta receptors to initiate a release of endogenous opioids.

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QUESTION: How do cannabinoids modulate pain sensation? In other words, describe the mechanism of action of cannabinoids.

ANSWER: Endocannabinoids are synthesized in the postsynaptic neuron in response to stimuli such as pain, stress and inflammation. Endocannabinoids travel in a retrograde fashion and activate the presynaptic CB receptors. Antinociceptive effects occur when either endocannabinoids or phytocannabinoids activate presynaptic inhibitory CB1 receptors. Stimulation of CB1 receptors (G protein coupled receptors (Gi,Go)) leads to a reduction of cAMP production via the inhibition of adenylyl cyclase. This results in an action on voltage gated calcium and potassium channels – there is a depression of neuronal excitability and a reduction of neurotransmitter release.

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QUESTION: A study by Jamal et al. published in the European Journal of Anaesthesiology reported that marijuana users required a higher dose of morphine s/p abdominal surgery. They estimated that there was a 23% increased opioid dose requirement. Have the results of studies examining the opioid requirements s/p orthopedic surgery also shown that marijuana users require more opioids than patients who do not use marijuana?

ANSWER: In a retrospective study including 3793 patients, patient-reported postoperative outcomes of 155 marijuana users were compared with those of 155 non-users. The results indicate that pre-operative marijuana users had higher pain scores at rest and on movement but did not consume more post-operative opioid analgesics. The cannabinoid users also reported a greater incidence of post-operative sleep impairment.

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QUESTION: CBD is a negative allosteric modulator. What does that mean?

ANSWER: A negative allosteric modulator changes the shape of the receptor and, as a result, reduces the binding ability of components that typically bind to the receptor. In the case of cannabinoids, CBD alters the shape of CB1 receptors, and THC along with endogenous cannabinoids do not bind to the CB1 receptor to the same degree as they do when CBD is not present.

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QUESTION: Some producers of cannabinoid products will provide a Certificate Of Analysis (CoA) from an independent certified testing laboratory. What information is typically displayed on a CoA?

ANSWER: CoAs typically indicate the amount and concentration of major cannabinoids and terpenes present, and data regarding the presence of microbial/ fungal contaminants, levels of heavy metals, and presence and concentration of pesticide and solvent residues.

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QUESTION: What medications alleviate the symptoms of marijuana withdrawal?

ANSWER: There are no general guidelines to treat the symptoms of marijuana withdrawal, but it has been reported that benzodiazepines and synthetic THC products used for the treatment of chemotherapy induced N/V may help alleviate some of the symptoms.

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QUESTION: What does “broad spectrum” mean?

ANSWER: Broad-spectrum products are processed in such a manner as to ensure that the final product does NOT contain THC.

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QUESTION: What does “full spectrum” marijuana product mean?

ANSWER: Full spectrum means that the product contains all of the original compounds found in the flower of the cannabis plant (cannabinoids, terpenes and flavonoids).

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QUESTION: Over 2 million Americans with cardiovascular disease use marijuana. Warfarin interacts with marijuana. Do statins interact with cannabinoids?

ANSWER: Yes. Statins and cannabinoids are metabolized by the same liver enzymes. The co-administration of cannabinoids and statins can lead to a decrease in statin metabolism. As a result, the potency of the statins may increase, and lead to hypotension.

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QUESTION: Although Illinois and Nevada have both legalized the use of medical and recreational marijuana, it is illegal to take marijuana on a flight from Chicago to Las Vegas. The reason – airspace is regulated by the federal government and marijuana is illegal under federal law. Do any US airports have “marijuana amnesty boxes” for the disposal of marijuana?

ANSWER: Yes. In addition to 2 airports in Chicago, Mc Carran International Airport in Las Vegas and the Colorado Springs Airport have installed amnesty boxes for passengers who need to surrender their marijuana before boarding a flight.

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QUESTION: What are the precursors for the most commonly naturally occurring phytocannabinoids?

ANSWER: The precursors for THC, CBD and CBC are olivetolic acid and geranyl pyrophosphate. These precursors undergo a condensation reaction which results in the formation of cannabigerolic acid (CBGA). A cyclase enzyme converts CBGA into either tetrahydrocannabinolic acid (THCA) or cannabidiolic acid (CBDA) or cannabichromenic acid (CBCA). Then, heat decarboxylates these cannabinoids into THC, CBD or CBC, respectively.

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QUESTION: True or false? Cannabinoids impact NMDA, opioid AND gamma amino butyric acid (GABA) receptors.

ANSWER: True. Not only do cannabinoids act at NMDA, opioid AND gamma amino butyric acid (GABA) receptors, but they also have activity at receptors such as adenosine, serotonergic, adrenergic, nicotinic acetylcholine, glycine, and PPAR receptors, and ion channels such as TRPV.

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QUESTION: Are pupillary responses to light affected by marijuana?

ANSWER: Yes – marijuana may impair pupillary responses.

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QUESTION: Is the legalization of medical marijuana associated with an increase in sexual activity?

ANSWER: Yes, according to researchers from the University of Connecticut and Georgia State University, the legalization of medical marijuana is associated with an increase in sexual activity. Of note, the study also determined that there’s a decrease in the use of contraceptives and an increase in the number of births following the enactment of medical marijuana policies. This study was published in the Journal of Health Economics.

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QUESTION: What is the definition of drug diversion?

ANSWER: In the National Academies of Sciences, Engineering & Medicine’s Framing Opioid Prescribing Guidelines for Acute Pain: Developing the Evidence (2020), drug diversion is defined as the transfer of regulated prescription drugs from the legal market to illegal markets. The sharing of drugs with other individuals for medical or nonmedical purposes is NOT considered to be drug diversion. (The sharing of drugs is drug misuse.)

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QUESTION: Is it legal to carry marijuana on a Greyhound bus?

ANSWER: No. Greyhound Lines bans alcohol and drugs (including marijuana) “anywhere on the bus (including in your checked baggage).”

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QUESTION: Animal research studies on CBD’s potential therapeutic effects often employ rodents. Is CBD administered to rodents the same way CBD is administered to humans?

ANSWER: No. CBD is commonly administered to rodents either via intraperitoneal injection or via the oral route. In contrast, CBD has been studied in humans using oral administration or inhalation, but not via intraperitoneal. The pharmacokinetics of these various routes of administration differ and therefore the blood concentrations of CBD may differ.

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QUESTION: Has the use of CBD been evaluated for the treatment of heroin addiction?

ANSWER: Yes. Dr. Yasmin Hurd, director of the Addiction Institute of Mount Sinai in NYC led a double-blind study of 42 recovering heroin addicts and found that CBD reduced both cravings and cue-based anxiety, both of which can cycle people back into using heroin.

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QUESTION: Does CBD modulate 5-HT1A receptor activity?

ANSWER: Yes, and this modulation may directly improve hyperarousal/insomnia symptoms in PTSD patients.

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QUESTION: Is the US VA Office of research and Development conducting any clinical trials that evaluate the use of CBD for the treatment of PTSD?

ANSWER: Yes. A RCT evaluating the efficacy of using CBD as an adjunctive to prolonged exposure therapy (PE therapy)) was started in March 2019 and will conclude on September 30,2023. The trial will compare PE + CBD to PE + placebo in a sample of 136 military Veterans with PTSD at the VA San Diego Medical Center.

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QUESTION: Is it legal to transport marijuana on Amtrak’s railway?

ANSWER: Amtrak has a strict policy: “The use or transportation of marijuana in any form for any purpose is prohibited, even in states or countries where recreational use is legal or permitted medically.”

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QUESTION: Do any medical marijuana legal states accept out-of-state medical marijuana authorizations?

ANSWER: Yes. About twenty states accept out-of-state medical marijuana authorizations, BUT reciprocity laws vary from state to state. In some states, visitors are required to sign up for the medical marijuana program 30 days in advance and pay a $50 nonrefundable fee. The state’s purchasing limit may differ for permanent vs. temporary residents. In Oregon, for example, residents can possess up to 24 ounces, while visitors are allowed only one ounce.

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QUESTION: Does the CBD molecule contain an aromatic ring?

ANSWER: Yes, it does. The CBD molecule contains a cyclohexene ring and an aromatic ring (a phenolic ring). Of interest, the rings are located in planes that are almost perpendicular to each other.

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QUESTION: Describe the chemical makeup of endocannabinoids.

ANSWER: Endocannabinoids are ester, ether, and amide derivatives of long chain polyunsaturated fatty acids. Arachidonic acid is an example of a polyunsaturated fatty acid in endocannabinoids.

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QUESTION: Does chronic use of THC and/or CBD by individuals with multiple sclerosis impact cerebral glucose metabolism?

ANSWER: The results of “The Effects of Chronic Δ-9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) use on Cerebral Glucose Metabolism in Multiple Sclerosis: A Pilot Study” published in 2019 in ‘Applied Physiology, Nutrition and Metabolism‘ indicate that “Compared to non-users, THC-users had hypermetabolism of three regions (p < 0.039, d >1.17) in left temporal areas, while CBD-users had hypometabolism of five regions (p < 0.032, d > 1.31) in left temporal areas.”

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QUESTION: True or False? According to the results of a survey conducted by the FDA, about 90% of US adults understand that FDA-approved prescription drugs may cause harm.

ANSWER: False. The results of the survey indicate that 42.9% of consumers were not able to accurately report that FDA‐approved prescription drugs may cause harm.

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QUESTION: The FDA approves the language used on package inserts of prescription drugs. Does the FDA also approve the language of “direct-to -consumer” ads?

ANSWER: Actually, no. The language, including the risk or benefit statements, used in “direct to consumer” ads is not FDA-approved.

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QUESTION: Based on data from the 2016 to 2017 National Survey on Drug Use and Health and the U.S. Department of Health and Human Services, do more people in the US smoke marijuana or tobacco cigarettes”

ANSWER: According to the 2016 to 2017 National Survey on Drug Use and Health, more than 39 million people smoke marijuana, and according to data from the U.S. Department of Health and Human Services, 34.3 million people smoke tobacco cigarettes. Recent trends show that the number of marijuana smokers is rising while the number of cigarette smokers is declining.

—

QUESTION: CB1 receptors are located on neurons in the CNS and PNS. Are CB1 receptors also located on cardiomyocytes?

ANSWER: Yes. CB1 receptors are located in cardiomyocytes, vascular endothelial cells as well as smooth muscle cells. Activation of these CB1 receptors may lead to oxidative stress, inflammation, fibrosis, vasodilation, and negative inotropy.

—

QUESTION: Smoking and vaporizing marijuana may induce an increase in heart rate. Is smoking marijuana associated with other cardiac electrical effects?

ANSWER: Yes. THC may increase catecholamine levels and therefore may theoretically increase the likelihood of arrhythmias. Various cardiac electrical effects have been described in observational studies. Atrial fibrillation was one of the more commonly reported arrhythmias. Other marijuana-associated arrhythmias reported include atrial flutter, atrioventricular block/asystole, sick sinus syndrome, ventricular tachycardia, and Brugada pattern.

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QUESTION: Some cannabinoid-based medicines are used to treat chemotherapy-induced n/v. Have cannabinoid-based medicines been shown to be effective in the treatment of post-op n/v?

ANSWER: The results of studies indicate that neither nabilone or intravenous THC is effective for post-op n/v. Even premedication with nabilone was ineffective at treating post-op n/v.

—

QUESTION: Do cannabinoid-based medicines have a higher NNT (number needed to treat) than opioids for pain relief? Than pregabalin? Than tricyclic antidepressant (TCA) agents?

ANSWER: According to recent systematic reviews and meta-analyses (from 2016-2018), cannabinoid -based medicines have a higher NNT than opioids, pregabalin and TCAs. It was also noted that there was a higher risk of adverse events associated with cannabinoid-based medicines compared to opioids, pregabalin and TCAs.

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QUESTION: The 2017 National Academies of Sciences, Engineering and Medicine’s (NASEM)review on the health effects of cannabinoid-based medicines concluded that there was conclusive or substantial evidence for the use cannabis or cannabinoids for the treatment of pain in adults. Do other national regulatory bodies have similar conclusions to the NASEM’s conclusion?

ANSWER: Actually, no. The Health Products Regulatory Authority of Ireland does not support the use of cannabinoid-based medicines for the treatment of chronic pain. Also, the European Pain Federation’s recent position paper recommended cannabinoid-based medicines be considered for chronic neuropathic pain only as a third line agent. Furthermore, the European Pain Federation found that the results of the studies examining chronic non-cancer pain indicated that there was insufficient evidence for the use of cannabinoid-based medicines for the treatment of non-neuropathic chronic non-cancer pain.

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QUESTION: Does ketamine interact with the endocannabinoid system?

ANSWER: Yes. Ketamine induces the release of endocannabinoids.

—

QUESTION: Do CB1 and CB2 agonists facilitate endogenous opioid signaling?

ANSWER: Yes. In fact, CB1 and CB2 agonists increase the concentrations of endogenous opioids.

—

QUESTION: Do opioid antagonists impact the effects of cannabinoids?

ANSWER: Yes. For example, it has been shown that the administration of opioid antagonists block some of the effects of THC.

—

QUESTION: Is the endocannabinoid system linked to the opioid system?

ANSWER: Yes. Opioid receptors and CB receptors are located within the same neurons within the CNS. In addition, cannabinoids activate kappa and delta receptors to initiate a release of endogenous opioids.

—

QUESTION: True or false? Cannabinoids impact NMDA, opioid AND gamma amino butyric acid (GABA) receptors.

ANSWER: True. Not only do cannabinoids act at NMDA, opioid AND gamma amino butyric acid (GABA) receptors, but they also have activity at receptors such as adenosine, serotonergic, adrenergic, nicotinic acetylcholine, glycine, and PPAR receptors, and ion channels such as TPRV.

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QUESTION: How do cannabinoids modulate pain sensation? In other words, describe the mode of action of cannabinoids.

ANSWER: The endocannabinoid system, consisting of the cannabinoid₁ receptor (CB₁R) and cannabinoid₂ receptor (CB₂R), endogenous cannabinoid ligands (endocannabinoids), and metabolizing enzymes, is present throughout the pain pathways. Endocannabinoids, phytocannabinoids, and synthetic cannabinoid receptor agonists have antinociceptive effects in animal models of acute, inflammatory, and neuropathic pain. CB₁R and CB₂R located at peripheral, spinal, or supraspinal sites are important targets mediating these antinociceptive effects. The mechanisms underlying the analgesic effects of cannabinoids likely include inhibition of presynaptic neurotransmitter and neuropeptide release, modulation of postsynaptic neuronal excitability, activation of the descending inhibitory pain pathway, and reductions in neuroinflammatory signaling. The large body of preclinical evidence in support of cannabinoids as potential analgesic agents is supported by clinical studies demonstrating their efficacy across a variety of pain disorders.

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QUESTION: EXPERIMENTAL pain studies indicate that cannabinoids may be an effective therapy for acute and chronic pain. Have the results of CLINICAL studies also shown that cannabinoids are effective at alleviating acute and chronic pain?

ANSWER: In contrast to experimental studies, the results of clinical trials with cannabinoids provide only moderate-quality evidence for the relief of chronic pain. Also, the analgesic effects of cannabinoids have not been found to be superior to placebo in acute pain. In addition, pre-operative and peri-operative marijuana use may increase post-operative perceived pain.

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QUESTION: A study published in the European Journal of Anaesthesiology, by Jamal et al. reported that marijuana users required a higher dose of morphine s/p abdominal surgery. They estimated that there was a 23% increased opioid dose requirement. Have the results of studies examining the opioid requirements s/p orthopedic surgery also shown that marijuana users require more opioids than patients who do not use marijuana?

ANSWER: In a retrospective study including 3793 patients, patient-reported postoperative outcomes of 155 marijuana users were compared with those of 155 non-users. The results indicate that pre-operative marijuana users had higher pain scores at rest and on movement but did NOT consume more post-operative opioid analgesics. The cannabinoid users also reported a greater incidence of post-operative sleep impairment.

16-Year Study: Medical Marijuana Laws Decrease Underage Use

Results of a large-scale, 16-year anonymized research project found that states with Medical Marijuana Laws (MMLs) and decriminalization statutes, underage cannabis consumption declines, especially among minority youth.

One concern some have regarding legalization of cannabis – whether for Medical (MMJ), or Adult Recreational Use (ARU) – is whether or not it will adversely affect youth. Specifically, a question often asked is, “will legalizing cannabis increase underage consumption?”

Lead Researcher Dr Rebekah Levine Coley said that, “Some people have argued that decriminalizing or legalizing medical marijuana could increase cannabis use amongst young people, either by making it easier for them to access, or by making it seem less harmful.”

“However, we saw the opposite effect,” said Dr Coley, and noted that results of the 16-year-long study show that in states where MMJ is legal, rates of underage consumption of cannabis have declined.

Those findings occurred even after accounting for other variables, including policies on

Teen Grey Matter and Cannabis Use

In a recently published article entitled “Grey Matter Volume Differences Associated with Extremely Low Levels of Cannabis Use in Adolescence,” in the Journal of Neuroscience, 14 January 2019 edition, pp3375-17, researchers wrote in part that “We identified extensive regions in the bilateral medial temporal lobes as well as the bilateral posterior cingulate, lingual gyri, and cerebellum that showed greater GMV in the cannabis users.”

News items related to that newly published research are focusing upon that singular line as if it’s something negative. Since when did INCREASED grey matter become something dangerous, or cause for concern? Colloquially, the term “grey matter” is used to describe the brain, and by extension, brain power. So let’s examine this matter (no pun intended) in more detail.

But before proceeding further, it bears mentioning that adolescents should NOT be consuming cannabis, neither alcohol, nor tobacco. And try as much as we want, we will not ever stop underage consumption of any adults-only substance. The BEST we can do is to educate them, and others, of potential risks involved in its use – especially and particularly underage use – and deny them opportunities to consume alcohol, tobacco, and cannabis. THAT is a strategy which has PROVEN to work, because the trite “Just say ‘no'” has never worked, nor will it ever.

Dr David Robert Grimes is a physicist, cancer researcher and science writer, who was the joint recipient of the 2014 Nature / Sense About Science Maddox Prize and wrote in a brief anti-marijuana article dated 15th May 2017 entitled “The rise of the cannabis cult: don’t believe the hype about medical marijuana” that