Q’s & A’s About Cannabis

Updated Sunday, 14 August 2022

Effort is made to update this page as research findings are published.

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

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

So in that sense, enjoy!

––//––

QUESTION: Does CBD alter the metabolism of methadone?

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

reference: Madden K, Tanco K, Bruera E. Clinically Significant Drug-Drug Interaction Between Methadone and Cannabidiol.Pediatrics May 2020; e20193256; https://pediatrics.aappublications.org/content/145/6/e20193256?download=true

–––

QUESTION: Is CBD addictive?

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

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

–––

QUESTION: Are the pharmacokinetics and the pharmacodynamics of Δ8 -THC and Δ9 -THC similar?

ANSWER: According to a recent review of delta-8-tetrahydrocannabinol (Δ-8-THC) pharmacology, “overall, the pharmacokinetics and pharmacodynamics of Δ-8 -THC and Δ9 -THC are very similar. Δ8 -THC is a partial agonist of the cannabinoid CB1 receptor and has cannabimimetic activity in both animals and humans. The reduced potency of Δ-8 -THC in clinical studies compared with Δ-9 -THC can be explained by weaker cannabinoid CB1 receptor affinity, although there are other plausible mechanisms that may contribute.”

reference: Michael Tagen 1, Linda E Klumpers. Review of delta-8-tetrahydrocannabinol (Δ 8 -THC): Comparative pharmacology with Δ 9 -THC. Review Br J Pharmacol. 2022 Aug;179(15):3915-3933. doi: 10.1111/bph.15865. Epub 2022 Jun 1. https://bpspubs.onlinelibrary.wiley.com/doi/epdf/10.1111/bph.15865
–––

QUESTION: How do the effects of delta-8-THC compare to those of delta-9-THC?

ANSWER: According to the results of an online survey of delta-8-THC consumers (N= 521 participants), “most delta-8-THC users experienced a lot or a great deal of relaxation (71%); euphoria (68%) and pain relief (55%); a moderate amount or a lot of cognitive distortions such as difficulty concentrating (81%), difficulties with short-term memory (80%), and alerted sense of time (74%); and did not experience anxiety (74%) or paranoia (83%). Participants generally compared delta-8-THC favorably with both delta-9-THC and pharmaceutical drugs, with most participants reporting substitution for delta-9-THC (57%) and pharmaceutical drugs (59%). Participant concerns regarding delta-8-THC were generally focused on continued legal access.”

reference: Jessica S Kruger 1 , Daniel J Kruger. Delta-9-THC’s nicer younger sibling? J Cannabis Res. 2022 Jan 4;4(1):4. doi: 10.1186/s42238-021-00115-8.

–––

QUESTION: Why did delta-8-THC products become more accessible in 2018 in the US?

ANSWER: “Delta-8’s rise started with the passing of the 2018 Farm Bill, which made hemp legal. Hemp and marijuana are both types of cannabis plants, but marijuana produces delta-9-THC and hemp doesn’t…The Farm Bill stated that hemp could be grown legally as long as it contained less than 0.3 percent THC. But,…the authors of the bill made an oversight: They defined THC specifically as delta-9-THC, which is still illegal federally. With that definition, a market for delta-8 was born.”

reference: Smith, D. G. (2022, July 1). How Delta-8 THC Works, and Why Experts Are Worried About It. New York Times. reader?url=https://www.nytimes.com/2022/07/01/well/mind/delta-8-thc-marijuana.html

–––

QUESTION: Does cannabis use lead to better sex?

ANSWER: According to an April 2022 New York Times article, “It’s hard to say with certainty that cannabis will increase desire or improve your sex life, but anecdotal evidence suggests that the right dose of cannabis can make a woman’s orgasms more satisfying and increase sex drive. This is in part because cannabis can enhance the senses and also alleviate some of the symptoms that inhibit desire, like anxiety, sleeplessness or pain. It can have positive effects for men, as well, but also several negative ones, and [individuals] should be aware of its potential downsides, too.”

reference: Caron C. “Cannabis for Better Sex? Here’s What the Science Says.” New York Times. Apr 1, 2022. https://www.nytimes.com/2022/04/01/well/live/marijuana-sex.html

–––

QUESTION: Does cannabis use help with menopausal symptoms?

ANSWER: Some studies have found that “some women use cannabis to help manage menopause symptoms like hot flashes, night sweats, insomnia and vaginal changes, such as dryness, all of which may contribute to lower libido when untreated.”

reference: Caron C. “Cannabis for Better Sex? Here’s What the Science Says.” New York Times. Apr 1, 2022. https://www.nytimes.com/2022/04/01/well/live/marijuana-sex.html

–––

QUESTION: Is cannabis use associated with better sex?

ANSWER: Over 200 people participated in an online survey that evaluated the sexual effects of cannabis, and according to the results… of 216 completed questionnaires, “112 (52.3%) said they used cannabis to alter their sexual experience. Eighty-two participants (38.7%) said sex was better, 34 (16.0%) said it was better in some ways and worse in others, 52 (24.5%) said it was sometimes better, and only 10 (4.7%) said it was worse.”

reference: Wiebe E, Just A. How Cannabis Alters Sexual Experience: A Survey of Men and Women. J Sex Med. 2019 Nov;16(11):1758-1762. doi: 10.1016/j.jsxm.2019.07.023. Epub 2019 Aug 22. PMID: 31447385. https://pubmed.ncbi.nlm.nih.gov/31447385/

–––

QUESTION: Is cannabis use associated with an increase in sexual desire?

ANSWER: Over 200 people participated in an online survey that evaluated the sexual effects of cannabis, and according to the results… 〝Of 202 participants, 119 (58.9%) said cannabis increased their desire for sex, 149 of the 202 participants (73.8%) reported increased sexual satisfaction, 144 of 199 participants (74.3%) reported an increased sensitivity to touch, and 132 of 201 participants (65.7%) reported an increased intensity of orgasms.”

–––

QUESTION: For those who have difficulty reaching orgasm, does cannabis use make it easier to reach orgasm?

ANSWER: Over 200 people participated in an online survey that evaluated the sexual effects of cannabis, and according to the results… 〝Out of 199 participants, 139 (69.8%) said they could relax more during sex, and 100 of 198 participants (50.5%) said they were better able to focus. Of the 28 participants who reported difficulty reaching orgasm, 14 said it was easier to reach orgasm while using cannabis, but only 10 said that sex was better.〞

–––

QUESTION: What percentage of oncology patients incorporate cannabinoid-based therapy into their regular self-management routine?

ANSWER: Several surveys report cannabinoid-based product use as ranging from 13% to as high as 24% of the oncology patient population.

reference: Vinette, B., Côté, J., El-Akhras, A. et al. Routes of administration, reasons for use, and approved indications of medical cannabis in oncology: a scoping review. BMC Cancer 22, 319 (2022). https://doi.org/10.1186/s12885-022-09378-7

–––

QUESTION: What are the common routes of medical marijuana administration used by people diagnosed with cancer?

ANSWER: According to a literature review, “Oils and oral solutions (e.g. homemade oils or Dronabinol oral solution), capsules (e.g. homemade capsules, Dronabinol, and Nabilone), oromucosal sprays (e.g. Nabiximols), and smoked cannabis were cited in more than 50% of the studies and reviews. Moreover, the results of a secondary data analysis indicate that oral solutions (55.2%), oromucosal sprays (27.5%), and capsules (17.3%) are the routes of administration most-frequently purchased in a New York City dispensary.”

–––

QUESTION: What is the MORE Act?

ANSWER: If passed, “The Marijuana Opportunity Reinvestment and Expungement Act, also known as the MORE Act, would remove marijuana from the controlled substances list, leaving it up to states to set their own laws. It would also release people incarcerated on cannabis-related offenses of less than 30 grams and expunge criminal penalties associated with those who manufacture, distribute and possess it.”

reference: ABC News: House set to pass legislation decriminalizing marijuana. The question remains: Will it all go up in smoke when it heads to the Senate? ByLalee Ibssa April 1, 2022 https://abcnews.go.com/Politics/house-set-pass-legislation-decriminalizing-marijuana/story?id=83763719

–––

QUESTION: What percentage of pregnant women consume cannabis products?

ANSWER: “Cannabis use among pregnant women in the United States is on the rise. Between 2002 and 2017, self-reported use more than doubled (from 3.4% to 7.0%). However, self-report may underrepresent actual use. A 2016 study in Colorado revealed that 22.4% of the pregnant women had detectable levels of the carboxylated form of Δ9-tetrahydrocannabinol (THC-COOH) in umbilical cord tissue, whereas only 2.6% self-reported use.” Note: cannabis use during pregnancy is associated with adverse neonatal outcomes.

reference: Brianna F Moore, Katherine A Sauder, Allison L B Shapiro, Tessa Crume, Gregory L Kinney, Dana Dabelea, Fetal Exposure to Cannabis and Childhood Metabolic Outcomes: The Healthy Start Study, The Journal of Clinical Endocrinology & Metabolism, 2022;, dgac101, PMID: 35357471 DOI: 10.1210/clinem/dgac101 || https://www.researchgate.net/publication/359642450_Fetal_Exposure_to_Cannabis_and_Childhood_Metabolic_Outcomes_The_Healthy_Start_Study

–––

QUESTION: Cannabis is the illicit drug most widely used by women of reproductive age in Australia. What are the effects of its use during pregnancy on neonatal outcomes?

ANSWER: “In [an] international cohort study, continued use of cannabis at 15 weeks of pregnancy was associated with significantly lower birthweight, head circumference, birth length, and gestational age at birth, as well as with more frequent severe neonatal morbidity or death.” These findings were independent of continued tobacco cigarette smoking.

reference: Luke E Grzeskowiak, Jessica A Grieger, Prabha Andraweera, Emma J Knight, Shalem Leemaqz, Lucilla Poston, Lesley McCowan, Louise Kenny, Jenny Myers, James J Walker, Gustaaf A Dekker and Claire T Roberts. The deleterious effects of cannabis during pregnancy on neonatal outcomes. Med J Aust 2020; 212 (11): 519-524. || doi: 10.5694/mja2.50624 15 Jun 2020.

–––

QUESTION: About how many people in the US work in the legal marijuana industry?

ANSWER: The state-licensed cannabis/marijuana industry added more than 100,000 new jobs in 2021. Currently, the cannabis/marijuana industry employs nearly 480,000 full-time workers. Jobs in the industry are most plentiful in California (83,607), Colorado (38,337), Michigan (31,152), and Illinois (28,992). Several other states, including Connecticut, New Jersey, and New York, are anticipated to begin licensing adult-use marijuana cultivators, manufacturers, and retailers later this year, and therefore will be hiring more people.

reference: Jobs Report 2022 Legal cannabis now supports 428,059 American jobs. https://leafly-cms-production.imgix.net/wp-content/uploads/2022/02/22132544/LeaflyJobsReport2022.pdf

–––

QUESTION: Has the National Institute of Drug Abuse (NIDA) recently provided funding for a clinical trial evaluating the efficacy of a CBD product as an opioid-sparing agent for patients with radiculopathic pain?

ANSWER: Yes. NIDA has provided funding for a double blind randomized controlled trial involving 40 participants receiving a proprietary CBD product or placebo for 4 months. The primary efficacy outcome is a change in opioid maintenance dose from baseline to the end of the treatment period. Safety and tolerability of CBD will also be assessed throughout the trial. The trial is being conducted at NYU Grossman School of Medicine.

reference: ANANDA Scientific and NYU Grossman School of Medicine Announce First Patient Enrolled in the Clinical Trial for Opioid Sparing in Participants with Radiculopathic Pain, https://www.businesswire.com/news/home/20220308005059/en/ANANDA-Scientific-and-NYU-Grossman-School-of-Medicine-Announce-First-Patient-Enrolled-in-the-Clinical-Trial-for-Opioid-Sparing-in-Participants-with-Radiculopathic-Pain

–––

QUESTION: How many medical marijuana patients are there in the US? How many licensed medical marijuana retailers are in the US?

ANSWER: According to the recently published “Americans For Safe Access’ 2021 State of the States Report,” there are more than 5.1 million medical marijuana patients in the US and there are more than 7,000 medical marijuana dispensaries serving these patients. According to this report, Idaho and Nebraska were the only 2 US states that had no medical marijuana program in place at the end of 2021.

reference: Americans For Safe Access “2021 State of the States Report”. https://american-safe-access.s3.amazonaws.com/sos2021/StateoftheStates21_Web2.22.pdf

–––

QUESTION: What are the most common reasons for medical marijuana use?

ANSWER: According to a 2020 survey involving 9,003 participants, the most common medical reasons for marijuana use were anxiety (49%), insomnia (47%), chronic pain (42%), and depression (39%). The most common forms of use were smoking and edibles, followed by vaping, concentrate, and topical.

reference: Azcarate PM, Zhang AJ, Keyhani S, Steigerwald S, Ishida JH, Cohen BE. Medical Reasons for Marijuana Use, Forms of Use, and Patient Perception of Physician Attitudes Among the US Population. J Gen Intern Med. 2020;35(7):1979-1986. doi:10.1007/s11606-020-05800-7

–––

QUESTION: Some athletes who compete at the international level are interested in consuming CBD. Is the use of CBD prohibited by the World Anti-Doping Agency?

ANSWER: No. Cannabidiol is no longer prohibited. It should be noted that while synthetic cannabidiol is not a cannabimimetic, cannabidiol extracted from cannabis plants may contain THC. THC remains a prohibited substance according to the World Anti-Doping Agency’s rules.

reference: World Anti Doping Agency. Summary of major modifications and explanatory notes. 2018. https://www.wada-ama.org/sites/default/files/prohibited_list_2018_summary_of_modifications_en.pdf. 30 March 2021.

–––

QUESTION: In the clinical trials evaluating a purified CBD product (Epidiolex) in epilepsy patients, side effects including sedation, decreased appetite, diarrhea, sleep disturbance, infections, pneumonia, viral infections and weight loss were reported. In clinical trials evaluating CBD for other disorders, were the reported adverse events similar to the reported adverse events for the epilepsy trials?

ANSWER: No. A “review and meta-analysis (N = 13) of clinical trials across multiple clinical populations (epilepsy n = 5, schizophrenia n = 2, cannabis use n = 1, Huntington’s disease n = 1, type II diabetes n = 1, non-alcoholic fatty liver disease n = 1, Crohn’s disease n = 1) or healthy controls (n = 1) found that only diarrhea remained as an adverse event when excluding studies in childhood epilepsy. Gastrointestinal adverse events are the most likely side effect of CBD use in patients without epilepsy.”

reference: Kirkland AE, Fadus MC et al.. A scoping review of the use of cannabidiol in psychiatric disorders. Psych Resear. 308 (2022). https://pubmed.ncbi.nlm.nih.gov/34952255/
PMID: 34952255 PMCID: PMC8799523 (available on 2023-02-01) DOI: 10.1016/j.psychres.2021.114347

–––

QUESTION: Does abrupt discontinuation of CBD use lead to a withdrawal syndrome?

ANSWER: No. In a 2020 study evaluating abuse liability of CBD, it was found that “abrupt withdrawal of CBD after four-weeks of use (750 mg twice daily taken orally) did not result in any symptoms of physical withdrawal.”

reference: Kirkland AE, Fadus MC et al.. A scoping review of the use of cannabidiol in psychiatric disorders. Psych Resear. 308 (2022). https://pubmed.ncbi.nlm.nih.gov/34952255/ PMID: 34952255 PMCID: PMC8799523 (available on 2023-02-01) DOI: 10.1016/j.psychres.2021.114347

–––

QUESTION: CBD is metabolized by the liver enzymes. Lithium is not. Is there any drug:drug interactions between CBD and lithium?

ANSWER: Even though lithium is not metabolized by the liver, some evidence indicates that CBD may cause an elevation in creatinine levels and alter renal function such that it negatively affects lithium metabolism, potentially leading to lithium toxicity.

reference: KKirkland AE, Fadus MC et al.. A scoping review of the use of cannabidiol in psychiatric disorders. Psych Resear. 308 (2022). https://pubmed.ncbi.nlm.nih.gov/34952255/ PMID: 34952255 PMCID: PMC8799523 (available on 2023-02-01) DOI: 10.1016/j.psychres.2021.114347

–––

QUESTION: Endocannabinoids are substances created by the body that bind to cannabinoid receptors (the same receptors to which the cannabis-derived cannabinoids bind.) What are the names of some of the endocannabinoids?

ANSWER: The endogenous cannabinoids (aka endocannabinoids) include arachidonoyl ethanolamide (also known as anandamide or AEA), 2-arachidonyl glycerol (2-AG), noladin ether (arachidonoyl glycerol ether), virodhamine, and N-arachidonoyl dopamine (NADA).

reference: Śmiarowska M, Białecka M, Machoy-Mokrzyńska A. Cannabis and cannabinoids: pharmacology and therapeutic potential Neurologia i Neurochirurgia Polska Polish Journal of Neurology and Neurosurgery 2022, DOI: 10.5603/PJNNS.a2022.0015 Copyright © 2022 Polish Neurological Society ISSN: 0028-3843, e-ISSN: 1897-4260 https://pubmed.ncbi.nlm.nih.gov/35133644/ PMID: 35133644 DOI: 10.5603/PJNNS.a2022.0015

–––

QUESTION: Do synthetic cannabinoids impact the dopaminergic system?

ANSWER: Yes, synthetic cannabinoids increase dopamine levels and also potentiate dopamine-expressing neurons. It is through this interaction with the dopaminergic system that cannabinoids (synthetic or natural) impact stress and reward regulation.

reference: Śmiarowska M, Białecka M, Machoy-Mokrzyńska A. Cannabis and cannabinoids: pharmacology and therapeutic potential. Neurologia i Neurochirurgia Polska Polish Journal of Neurology and Neurosurgery 2022, DOI: 10.5603/PJNNS.a2022.0015 Copyright © 2022 Polish Neurological Society ISSN: 0028-3843, e-ISSN: 1897-4260 https://pubmed.ncbi.nlm.nih.gov/35133644/

–––

QUESTION: Warfarin has numerous drug interactions. Does warfarin interact with marijuana?

ANSWER: The metabolic enzyme CYP2C9 is responsible for metabolizing warfarin, and THC and CBD inhibit CYP2C9. As a result, warfarin’s anticoagulant effects may be enhanced, and there may be a need to adjust the warfarin dosage to maintain therapeutic INR levels. The extent of the interaction between warfarin and THC/CBD depends upon several factors, including, the route of administration, the dose of the cannabinoids, the age of the patient, and other factors.

reference: Thomas, T.F., Metaxas, E.S., Nguyen, T. et al. Case report: Medical cannabis—warfarin drug-drug interaction. J Cannabis Res 4, 6 (2022). https://doi.org/10.1186/s42238-021-00112-x

–––

QUESTION: Numerous variables affect the likelihood of cannabinoids, such as THC and CBD, interacting with CYP450 enzymes, including the route of administration. How does smoking impact the activity of the CYP450 enzymes? Could the metabolism of some prescription medications be impacted?

ANSWER: When an individual smokes marijuana, combustion takes place and polyaromatic hydrocarbons are produced. These hydrocarbons are capable of inducing CYP1A1/2, and in turn, this could theoretically increase metabolism of some drugs, including R-warfarin. Potentially, this could lead to decreased INR levels.

reference: Thomas, T.F., Metaxas, E.S., Nguyen, T. et al. Case report: Medical cannabis—warfarin drug-drug interaction. J Cannabis Res 4, 6 (2022). https://doi.org/10.1186/s42238-021-00112-x

–––

QUESTION: Sublingual and buccal routes of administration are known to avoid first-pass metabolism by the liver. As a result, these routes of administration may have less potential for interactions with the cytochrome P450 enzymes. Why then, have there been multiple case reports describing the use of oromucosal THC products leading to supratherapeutic INRs in patients who take coumadin?

ANSWER: Two possible explanations to these findings include 1.) some of the medicine is actually swallowed instead of being absorbed via the mucosa, and the portion that is swallowed inhibits the cytochrome P450 enzymes. 2.) the oromucosal route may not completely avoid hepatic metabolic pathways.

reference: Thomas, T.F., Metaxas, E.S., Nguyen, T. et al. Case report: Medical cannabis—warfarin drug-drug interaction. J Cannabis Res 4, 6 (2022). https://doi.org/10.1186/s42238-021-00112-x

–––

QUESTION: Other than the mode of administration, what else may affect the drug:drug interaction between warfarin and marijuana?

ANSWER: Age is another factor that may impact drug:drug interactions. It has been shown that cytochrome-mediated phase I reactions decline with advancing age. (Note: phase II reactions appear to remain intact.)

reference: Thomas, T.F., Metaxas, E.S., Nguyen, T. et al. Case report: Medical cannabis—warfarin drug-drug interaction. J Cannabis Res 4, 6 (2022). https://doi.org/10.1186/s42238-021-00112-x

–––

QUESTION: The most common condition for which patients receive a medical marijuana card is chronic or severe pain. Pain is also one of the most well-researched indications for which cannabinoid-based medicines are consumed. Even though pain is one of the most well-researched qualifying conditions, most studies evaluating the use of medical cannabinoids for chronic pain are considered low or moderate quality. Why?

ANSWER: Most of the pain studies evaluating the use of medical cannabinoids for chronic pain are considered “low or moderate quality” because of multiple reasons, including small study size, inconsistencies in modes of administration, and inconsistencies in dosing (number of milligrams as well as ratio of cannabinoids) across different studies. Also, many studies are of short duration. In addition, some studies have included various types of pain (neuropathic pain, cancer pain, fibromyalgia, and rheumatoid arthritis, etc.) instead of just focusing on one type of pain.

reference: Deepika E. Slawek, Susanna A. Curtis, Julia H. Arnsten, Chinazo O. Cunningham. Clinical Approaches to Cannabis: A Narrative Review, Medical Clinics of North America, Volume 106, Issue 1, 2022, 131-152, ISSN 0025-7125, ISBN 9780323848763, https://doi.org/10.1016/j.mcna.2021.08.004.

–––

QUESTION: Has CBDV been evaluated as an anti-seizure medication in clinical trials?

ANSWER: Yes, GW Pharmaceuticals (the makers of Epidiolex) had trialed CBDV in adult epilepsy, but the study did not meet its primary endpoint of seizure reduction. That trial did not continue. However, purified CBDV is currently being evaluated for other conditions, including as a treatment for behavioral symptoms in patients with Prader Willi Syndrome (10 mg/kg/day, NCT03848481) and in autism (NCT03202303 and NCT03849456).

reference: Schlag, A.K., O’Sullivan, S.E, Zafar, R.R, Nutt, D.J, Current controversies in medical cannabis: recent developments in human clinical applications and potential therapeutics, Neuropharmacology, https://pubmed.ncbi.nlm.nih.gov/33940011/

–––

QUESTION: The psychedelic effects of all classical psychedelics, including psilocybin, are mediated by which receptors?

ANSWER: The psychedelic effects of psychedelic substances are mediated via full or partial agonism at serotonergic 5-hydroxytryptamine 2A receptors (5-HT2ARs). Psilocybin’s activity at 5-HT2ARs and the possible involvement of these receptors in mediating the hallucinogenic effects of psilocybin were first reported in 1984 by Glennon and colleagues. Of note, 5-HT2ARs are highly expressed in the visual cortex, and activation of these receptors may lead to visual hallucinations.

reference: Ling, S., Ceban, F., Lui, L.M.W. et al. Molecular Mechanisms of Psilocybin and Implications for the Treatment of Depression. CNS Drugs (2021). https://doi.org/10.1007/s40263-021-00877-y

–––

QUESTION: Other than pain sensation, is the endocannabinoid system involved in other CNS functions?

ANSWER: Yes. CB1 receptors are located in several parts of the central nervous system including brain cortex, basal ganglia, cerebellum, hippocampus, ventral posterolateral thalamus, sensory neurons, dorsal root ganglia, and dorsal horn of spinal cord. These parts of the nervous system are involved in cognitive function, memory, behavior, emotion, and pain sensation.

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

–––

QUESTION: Besides chronic pain, what are the common conditions for which patients use cannabinoid based medicines?

ANSWER: According to a 2020 study, after unspecified chronic pain, patients were most likely to report anxiety as their primary medical condition, and anxiety was the most commonly reported comorbid condition. A 2016 study found that the second and third most common medical conditions for which patients reported using medical cannabis were anxiety (58.1%) and depression (50.3%).

–––

QUESTION: Do cannabinoid receptors and opioid receptors have any similar characteristics?

ANSWER: Yes. Both have analgesic effects and both are expressed on presynaptic neurons. Also, both inhibit neurotransmitter release.

–––

QUESTION: What is the most effective combination of THC to CBD in the treatment of cancer pain? of epilepsy?

ANSWER: The most effective combinations of THC: CBD have yet to be determined. Some registered trials are currently examining the efficacy of 3:1 THC:CBD, (ClinicalTrials.gov Identifier: NCT04042545) in cancer pain and 1:20 THC:CBD (ClinicalTrials.gov Identifier:NCT03024827) in epilepsy.

–––

QUESTION: CB2 receptors are located in immune tissues (spleen, macrophages, mast cells, and brain microglia), and in peripheral tissues (keratinocytes, bone, liver, and hematopoietic cells). What happens when CB2 receptors are activated?

ANSWER: The activation of CB2 receptors results in various outcomes. One such outcome includes the inhibition of pro-inflammatory cytokine production and migration of immune cells including neutrophil and macrophages. As a result of these effects, chronic pain may be reduced.

–––

QUESTION: What do endocannabinoids do?

ANSWER: Endocannabinoids (EC) “are regulators of synaptic transmission in the brain, mediate numerous forms of plasticity, and control neuron energy metabolism. EC exert influences using a series of mechanisms and interactions with neuromediators, neurotrophic factors, and neuropeptides. The main functions of EC in the brain are retrograde synaptic signaling and neuromodulation, which maintain cellular homeostasis.”

reference: Kitchigina, V.F. Cannabinoids, the Endocannabinoid System, and Cognitive Functions: Enemies or Friends?. Neurosci Behav Physi (2021). https://doi.org/10.1007/s11055-021-01148-5.

–––

QUESTION: Does THC impact the release of glutamate or 5-hydroxytryptamine? Does THC affect dopamine secretion?

ANSWER: Yes, THC inhibits glutamate and 5-hydroxytryptamine release. Also, THC increases dopamine secretion. As a result, the transmission of pain signals is altered.

reference: Busse J W, Vankrunkelsven P, Zeng L, Heen A F, Merglen A, Campbell F et al. Medical cannabis or cannabinoids for chronic pain: a clinical practice guideline BMJ 2021; 374 :n2040 doi:10.1136/bmj.n2040. https://www.bmj.com/content/374/bmj.n2040

–––

QUESTION: Does CBD influence adenosine signaling or impact the activity of reactive oxygen species? Does CBD affect tumor necrosis factor activity or the proliferation of T cells?

ANSWER: Yes. CBD enhances adenosine receptor signaling, and decreases reactive oxygen species activity, tumor necrosis factor activity, and T cell proliferation. As a result of these effects, CBD may impart analgesic properties and anti-inflammatory properties.

–––

QUESTION: When considering adding cannabinoid-based medications to a chronic pain patient’s medical regimen, what are some of the main factors that should be considered to inform recommendations?

ANSWER: Eight patient-important outcomes that could help inform the recommendations of CBD include:(1) pain relief, (2) physical functioning, (3) emotional functioning, (4) role functioning, (5) social functioning, (6) sleep quality, (7) opioid substitution, and (8) adverse events.

–––

QUESTION: What is the most common non-serious adverse event associated with the use of medical marijuana products?

ANSWER: Dizziness is the most common non-serious adverse event. Other non-serious adverse events include nausea, sleepiness, confusion and anxiety.

–––

QUESTION: Are food and beverages containing CBD allowed to be sold in stores (other than dispensaries) and restaurants?

ANSWER: According to the Food and Drug Administration (FDA), no. However, California Governor Gavin Newsom signed into law Assembly Bill 45 (AB-45) that “prohibit[s] restrictions on the sale of dietary supplements, food, beverages, cosmetics, or pet food that include industrial hemp or cannabinoids, extracts, or derivatives from industrial hemp based solely on the inclusion of those substances.” AB-45 departs from the FDA’s guidance that CBD cannot be introduced to food products or dietary supplements sold in interstate commerce.

reference: AB-45 Industrial hemp products. Assembly Bill No. 45, CHAPTER 576; Published: 10/07/2021 02:00 PM https://leginfo.legislature.ca.gov/faces/billTextClient.xhtml?bill_id=202120220AB45

–––

QUESTION: In 2020, how many people in the US used marijuana for recreational purposes?

ANSWER: According to the Substance Abuse and Mental Health Services Administration’s (SAMHSA) 2020 National Survey of Drug Use and Health, 49.6 million people used marijuana. When stratified for age, the percentage of people who used marijuana in the past year was highest among young adults ages 18 to 25 (34.5%) followed by those ages 26 or older (16.3% ) and adolescents ages 12 to 17 (10.1%).

reference: Substance Abuse and Mental Health Services Administration’s (SAMHSA) 2020 National Survey of Drug Use and Health. https://www.samhsa.gov/data/release/2020-national-survey-drug-use-and-health-nsduh-releases

–––

QUESTION: What are the most common target symptoms for which multiple sclerosis (MS) patients use cannabinoid-based products?

ANSWER: According to a survey of 1,012 MS patients conducted through the “North American Research Committee on Multiple Sclerosis (NARCOMS) Global Multiple Sclerosis Registry: A Long-Term Study to Facilitate Research in Multiple Sclerosis,” the most common target symptoms for which patients used cannabis were: Spasticity (80%), pain (69%), and sleep (61%). The most preferred composition of cannabis-based products were: 50:50 THC:CBD (31%) and high THC/low CBD (30%).

reference: “Cannabis Use Common Among People With MS — Most don’t ask for medical guidance, survey shows” https://www.medpagetoday.com/meetingcoverage/cmsc/95315 by Judy George, Senior Staff Writer, MedPage Today; October 28, 2021

–––

QUESTION: According to a study published in the October 2021 edition of Cancer, what are the most common reasons for breast cancer patients to use cannabinoid-based products?

ANSWER: Patients most often used cannabinoid-based products for pain (78%), anxiety (57%), stress (51%) and nausea (46%). 75% of these patients considered the cannabinoids to be extremely or very helpful for relieving their symptoms and 57% of users had found no alternative for treating their symptoms.

reference: M Weiss et al. A Coala-T-Cannabis Survey Study of Breast Cancer Patients’ Use of Cannabis Before, During and After Treatment. Cancer 12 Octover 2021. https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.33906

–––

QUESTION: Do some cancer patients who use cannabis-based products believe that cannabinoids can cure cancer?

ANSWER: Yes. Some patients believe that cannabinoids can cure cancer. (IMPORTANT: To date, it has not been shown that cannabinoids cure cancer in humans.) According to a study published in Cancer, 49% of the surveyed breast cancer patients who use cannabis believed that medical cannabis could be used to treat cancer itself.

reference: M Weiss et al. A Coala-T-Cannabis Survey Study of Breast Cancer Patients’ Use of Cannabis Before, During and After Treatment. Cancer 12 October 2021. https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.33906

–––

QUESTION: On November 5, 2021, Professor Dr. Raphael Mechoulam, PhD, celebrates his 91st birthday. What are some of Dr. Mechoulam’s accomplishments that have made him an internationally respected and honored scientist?

ANSWER: Professor Dr. Raphael Mechoulam, PhD, is considered to be one of the greatest cannabinoid research scientists of all time. During his nearly 60 years of cannabinoid research, “Raphael Mechoulam has demonstrated… an amazing ability both to come up with exciting original and important ideas that have greatly helped to advance knowledge about cannabinoid preclinical and clinical pharmacology, biochemistry and medicinal chemistry, and to follow these ideas through with great effect. This is due not least to his ability (i) to set up highly talented research teams in his laboratory, to think both as a chemist and as a biologist… (ii) to recognize how his ideas/discoveries might be exploited in the clinic, and then (iii) to set up productive collaborations with clinicians, with preclinical pharmacologists/biologists, and with pharmaceutical companies.”