"The Global Consciousness Project, also known as the EGG Project, is an international multidisciplinary collaboration of scientists, engineers, artists and others continuously collecting data from a global network of physical random number generators located in 65 host sites worldwide. The archive contains over 10 years of random data in parallel sequences of synchronized 200-bit trials every second."
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 Read the rest of this entry »
Posted by Warm Southern Breeze on Friday, December 4, 2020
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.”
“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.
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.
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.
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.
Posted by Warm Southern Breeze on Friday, November 27, 2020
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
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
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 ofSwitzerland 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.
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.
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.
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 Read the rest of this entry »
Posted by Warm Southern Breeze on Sunday, October 25, 2020
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.
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.
Over the years, in over 20 attempts, the state’s legislators quashed every effort to help the people, and not once did they ever Read the rest of this entry »
Updated Monday, 18 January 2021 This page is updated regularly, typically, at least once weekly.
While the intended audience for these Qs & As 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: 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
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
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: 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. 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.
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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.
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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: 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.
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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.
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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: 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.
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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: 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.
Posted by Warm Southern Breeze on Monday, February 18, 2019
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 Read the rest of this entry »
Posted by Warm Southern Breeze on Thursday, January 17, 2019
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 Read the rest of this entry »
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.”
![[Tokelahoma] lead image](https://static.politico.com/dims4/default/676933e/2147483647/resize/1160x%3E/quality/90/?url=https%3A%2F%2Fstatic.politico.com%2F2f%2Fd6%2F8a1ac0c5448294d73e67664f69d7%2Fsectionbreak6-new.jpg "[Tokelahoma] lead image")
