Warm Southern Breeze

"… there is no such thing as nothing."

Questions & Answers About Cannabis

Updated Monday, 28 September 2020
This page is updated 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: 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.

QUESTION: CB1 receptors are located on neurons in the CNS and PNS. Are CB1 receptors also located on cardiomyocytes?

ANSWER: Yes. CB1 receptors are located in cardiomyocytes, vascular endothelial cells as well as smooth muscle cells. Activation of these CB1 receptors may lead to oxidative stress, inflammation, fibrosis, vasodilation, and negative inotropy.

QUESTION: Smoking and vaporizing marijuana may induce an increase in heart rate. Is smoking marijuana associated with other cardiac electrical effects?

ANSWER: Yes. THC may increase catecholamine levels and therefore may theoretically increase the likelihood of arrhythmias. Various cardiac electrical effects have been described in observational studies. Atrial fibrillation was one of the more commonly reported arrhythmias. Other marijuana-associated arrhythmias reported include atrial flutter, atrioventricular block/asystole, sick sinus syndrome, ventricular tachycardia, and Brugada pattern.

QUESTION: Some cannabinoid-based medicines are used to treat chemotherapy-induced n/v. Have cannabinoid-based medicines been shown to be effective in the treatment of post-op n/v?

ANSWER: The results of studies indicate that neither nabilone or intravenous THC is effective for post-op n/v. Even premedication with nabilone was ineffective at treating post-op n/v.

QUESTION: Do cannabinoid-based medicines have a higher NNT (number needed to treat) than opioids for pain relief? Than pregabalin? Than tricyclic antidepressant (TCA) agents?

ANSWER: According to recent systematic reviews and meta-analyses (from 2016-2018), cannabinoid -based medicines have a higher NNT than opioids, pregabalin and TCAs. It was also noted that there was a higher risk of adverse events associated with cannabinoid-based medicines compared to opioids, pregabalin and TCAs.

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.

QUESTION: Does ketamine interact with the endocannabinoid system?

ANSWER: Yes. Ketamine induces the release of endocannabinoids.

QUESTION: Do CB1 and CB2 agonists facilitate endogenous opioid signaling?

ANSWER: Yes. In fact, CB1 and CB2 agonists increase the concentrations of endogenous opioids.

QUESTION: Do opioid antagonists impact the effects of cannabinoids?

ANSWER: Yes. For example, it has been shown that the administration of opioid antagonists block some of the effects of THC.

QUESTION: Is the endocannabinoid system linked to the opioid system?

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

QUESTION: True or false? Cannabinoids impact NMDA, opioid AND gamma amino butyric acid (GABA) receptors.

ANSWER: True. Not only do cannabinoids act at NMDA, opioid AND gamma amino butyric acid (GABA) receptors, but they also have activity at receptors such as adenosine, serotonergic, adrenergic, nicotinic acetylcholine, glycine, and PPAR receptors, and ion channels such as TPRV.

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.

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.

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.

 
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