Warm Southern Breeze

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Questions & Answers About Cannabis

Updated Thursday, 22 July 2021

Effort is made to update this page regularly, and often, at least once weekly.

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

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

So in that sense, enjoy!

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QUESTION: What is the half life of CBD?

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

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

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

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

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

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QUESTION: What are THCA-A and CBDA?

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

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

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QUESTION: Are cannabinoids lipophilic or hydrophylic?

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

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

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

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

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

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

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

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

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QUESTION: Are blunts and joints the same thing?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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QUESTION: How does the endocannabinoid system impart analgesic effects?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

reference: Clinicaltrials.gov

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

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

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

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

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

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

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

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

reference: NO CLINICAL RESEARCH CITATION

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

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

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

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

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

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

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

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

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

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

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QUESTION: Is CBD addictive?

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

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

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

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

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

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

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

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

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

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

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

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QUESTION: Does CBD alter the metabolism of methadone?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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QUESTION: What are K2 and Spice?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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QUESTION: What is Sativex®?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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QUESTION: Does marijuana affect appetite and metabolism?

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

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

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

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

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

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

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

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

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

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

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

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QUESTION: Do some cannabinoids reduce spasticity?

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

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

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QUESTION: Is marijuana a sedative or stimulant?

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

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

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

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

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

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

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

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

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QUESTION: What are endocannabinoids?

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

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

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QUESTION: What are terpenes?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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QUESTION: What is industrial hemp?

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

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

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

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

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

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

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

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

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

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

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

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

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

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QUESTION: How should cannabis products be stored?

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

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

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

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

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

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QUESTION: Does raw cannabis flower contain CBD or CBDA?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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QUESTION: What is “hashish”?

ANSWER: Hashish is a crude product made up of compacted sticky resin glands of the cannabis plant. The popularity of hashish has been diminished by the availability of cannabis concentrates.
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QUESTION: Are smoking marijuana and vaporizing marijuana equally efficient? (In other words, are the cannabinoids absorbed to the same extent with smoking vs. vaporizing? )
ANSWER: When ingesting marijuana via a vaporizer, the user absorbs up to 33% of the total cannabinoids present in herbal mixture. When smoking, an individual typically absorbs about 25% of the cannabinoids present in herbal mixture.
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QUESTION: The amounts of marijuana in a joint, blunt, spliff or bowl are not standardized. How does a clinician estimate the amount of marijuana being used by the patient?
ANSWER: When trying to assess the quantity of marijuana consumed by a patient, multiple questions should be addressed, including: how often and how much the patient typically purchases, how many bowls (or joints, or blunts or spliffs) the patient smokes each time he consumes marijuana, and how many times he uses marijuana before he needs to purchase again. It must be noted that the total amount of cannabinoids present in marijuana is not equal to the amount that is ingested. (when smoking, an individual typically absorbs about 25% of the cannabinoids present in herbal marijuana mixture.) Also, the concentration of the cannabis-based product must be considered, as well.

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

ANSWER: When ingesting marijuana via a vaporizer, the user absorbs up to 33% of the total cannabinoids present in herbal mixture. When smoking, an individual typically absorbs about 25% of the cannabinoids present in herbal mixture.
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QUESTION: A patient may be speaking to you about his marijuana consumption, and he may use the terms joints, blunts and spliffs, and bowl. What do these terms mean?
ANSWER: A joint is a cigarette of marijuana, a blunt is a marijuana cigar, and a spliff can refer to marijuana mixed with tobacco, though some people use this term when referring to a cone-shaped joint with a filter. A bowl refers to the chamber of a pipe.

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

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

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

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

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

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

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QUESTION: Can prison inmates use medical cannabis?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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QUESTION: Describe the exact mechanism of action of Epidiolex.

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

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

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

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

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

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

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

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

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

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

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

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

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

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QUESTION: What is the MORE act?

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

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QUESTION: Do cannabinoids affect cardiac function?

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

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

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

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

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

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

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

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

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

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

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

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

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

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QUESTION: What is Sativex®?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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QUESTION: What percentage of Americans support marijuana legalization?

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

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QUESTION: Does ketamine interact with cannabinoids?

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

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

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

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

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

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

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

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

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

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

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

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QUESTION: Does THC stimulate the sympathetic or parasympathetic system?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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QUESTION: How does CBD impact the cardiovascular system?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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QUESTION: What are conduction-based vaporizers?

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

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

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

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QUESTION: What does cannabinergic mean?

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

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

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

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

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

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QUESTION: What is the purpose of urine drug testing?

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

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

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

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QUESTION: Why do NSAIDS relieve pain?

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

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QUESTION: Describe the process of vaporization of cannabis.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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QUESTION: Does methadone alter cardiac conduction?

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

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

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

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QUESTION: What are terpenes (or terpenoids)?

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

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QUESTION: Does smoking marijuana impact the metabolism of theophylline?

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

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

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

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

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

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

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

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

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

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QUESTION: Describe the exact mechanism of action of Epidiolex.

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

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

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

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

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

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

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

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QUESTION: What is the safety profile of Olinvyk?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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QUESTION: Describe the chemical makeup of endocannabinoids.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

ANSWER: Members of the Breastcancer.org and Healthline communities were asked to participate in a survey during the period of 12/16/2019 – 1/19/2020. Among the 832 respondents who completed screening, 725 met the eligibility criteria, and 612 (84%) completed the survey. According to the results, the symptoms for which cannabinoids were used included insomnia (70%), pain (59%), anxiety (57%), stress (51%), and nausea/vomiting (46%). The results also indicated that cannabinoids were used prior to treatment in 24%, during treatment in 79%, and after treatment in 54%. Of subjects reporting cannabis use during treatment: 86% used it during chemotherapy, 71% during HER2 therapy, 65% during hormonal therapy, 49% during breast radiation, and 47% during radiation for metastatic sites. Post-surgical use was reported in 51% after mastectomy alone, 40% after lumpectomy, and 38% after mastectomy/reconstruction.

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

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

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

ANSWER: In contrast to the lack of efficacy in the acute pain setting, cannabinoids are effective analgesic agents in the chronic pain setting. According to 2 systematic reviews involving a total of 29 RCTs, 22 of the 29 RCTs demonstrated that cannabinoids have a modest analgesic effect in the management of chronic pain. The following modes of administration were examined in the RCTs: smoked cannabis (6 trials), oromucosal and oral cannabis extract (11 trials), nabilone (8 trials), dronabinol (2 trials), THC-11 acid analogue (2 trials), and fatty acid amide hydrolase inhibitor (1 trial).

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

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

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

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

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

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

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QUESTION: Does the administration of marijuana affect insulin levels in humans?

ANSWER: In a DBRCT involving 20 participants, it was found that marijuana consumed via oral, smoked, or vaporized routes affected blood concentrations of some metabolic hormones, including insulin. In fact, the results of this study indicate that acute marijuana use blunted the insulin spike associated with the consumption of a brownie.

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QUESTION: Are there any special considerations for patients who consume cannabinoid-based products and are undergoing plastic surgery?

ANSWER: Yes. On occasion, plastic surgeons administer atropine and/or epinephrine during a procedure. Both of these medications can increase heart rate, and cannabinoids may potentiate the increase in heart rate.

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

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

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QUESTION: What are K2 and Spice?

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

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QUESTION: Heroin is processed from morphine, an extract from the poppy plant. Heroin is often depicted as a white powder. Is heroin sold in forms other than white powder?

ANSWER: In addition to white powder, heroin is sold as a brownish powder, or as a black sticky/tar-like substance (AKA black tar heroin). Heroin is either sold in pure form or is “cut” with other drugs (quinine, for example) or with other white powdery substances, including sugar, starch or powdered milk.

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

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

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QUESTION: As of January 2020, how many Americans were using marijuana-based products for medicinal purposes?
ANSWER: It has been estimated that more than 2 million Americans use marijuana for medical reasons. Some of the many ailments being treated with marijuana include: chronic pain, PTSD, depression, sleep disorders, multiple sclerosis (MS), cancer-related ailments, and GI disorders. Some indications are supported by good scientific evidence, but many are not.

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QUESTION: Rohypnol® is the trade name for the benzodiazepine called unitrazepam. Has this drug ever been approved by the Food and Drug Administration for medical use in the United States?

ANSWER: No, but outside the US, Rohypnol® is prescribed to treat insomnia. Rohypnol® has been referred to as a date rape drug or roofies. Before 1997, Rohypnol® was manufactured as a white tablet, and when mixed in liquids, it was colorless, tasteless, and odorless. In 1997, the manufacturer responded to concerns about the drug’s role in sexual assaults, and reformulated the drug. Now, Rohypnol® is produced as an olive green tablet with a speckled blue core that when dissolved in light-colored drinks will change the color of the liquid to blue. Of note, generic versions of the drug may not contain the blue dye.

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QUESTION: What is the Chemical Diversion and Trafficking Act (CDTA) of 1988?

ANSWER: The CDTA is an Act that regulated 12 (drug manufacturing) precursor chemicals, eight essential chemicals, tableting machines, and encapsulating machines. The Act imposed recordkeeping and import/export reporting requirements on transactions involving these regulated products. One of the goals of this Act was to reduce the supply of methamphetamine. As of 2020, the DEA regulates more than 40 chemicals that are often used in the production of illicit drugs.

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QUESTION: Cannabinoids are metabolized by many of the same cytochrome P450 enzymes as warfarin, including CYP3A4, CYP2C9, and CYP2C19. THC, CBD and CBN can inhibit the CYP2C9-mediated hydroxylation of warfarin, and thus lead to an increase in INR. Do cannabinoids also affect the metabolism of heparin? Is the metabolism of direct oral anticoagulants (DOACs), including rivaroxaban, edoxaban, and apixaban, impacted by cannabinoids?

ANSWER: While cannabinoids do not alter the metabolism of heparin, cannabinoids may impact the metabolism of DOACs. DOACs are substrates of P-gp and are absorbed by the gut through the P-gp efflux transporter. Cannabinoids may bind to P-gp membrane transporters and alter DOAC metabolism. DOAC levels may increase, leading to an increased risk of bleeding.

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QUESTION: CBD is a CB1 antagonist and a negative allosteric modulator at CB2. Does CBD interact with receptors other than CB1 or CB2?

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

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

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

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QUESTION: The Controlled Substances Act (CSA) regulates five classes of drugs. What are they?

ANSWER: The Controlled Substances Act (CSA) regulates five classes of drugs, including narcotics, depressants, stimulants, hallucinogens and anabolic steroids. All controlled substances have abuse potential or they are immediate precursors to substances that have abuse potential. Note: Alcohol and tobacco are specifically exempt from
control by the CSA.

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QUESTION: Methamphetamine is a Schedule II highly addictive stimulant. What is methamphetamine’s mechanism of action that leads to the “rush” and “high”?

ANSWER: It is believed that the “rush” and the “high” associated with amphetamine use result from the release of very high levels of dopamine into areas of the brain that regulate feelings of pleasure.

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QUESTION: Methadone, morphine and heroin are all narcotics. Do they all have a similar chemical structure?
ANSWER: No. Morphine and heroin (which is derived from morphine) have a similar structure. Methadone, which is a synthetic narcotic, does not have a similar structure to morphine.

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QUESTION: Methamphetamine is a controlled substance and is classified as a Schedule II drug. Schedule II drugs have a high potential for abuse and have an accepted medical use. What medical use(s) does methamphetamine have?

ANSWER: As of April 2020, there is only one legal “meth” product, and it is sold under the name Desoxyn®. It has very limited use in the treatment of obesity and ADHD.

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QUESTION: Is the analgesic potency of hydromorphone more or less than the potency of morphine?

ANSWER: Hydromorphone is (2 to 8 times) more potent than morphine but not as potent as fentanyl.

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

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

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

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

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QUESTION: Fentanyl, morphine and heroin are all analgesics. Which one of the three is the most potent analgesic?

ANSWER: Fentanyl is the most potent analgesic of the three. It is about 100 times more potent than morphine and 50 times more potent than heroin, as an analgesic agent.

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QUESTION: What are common street names for marijuana?

ANSWER: Often, marijuana concentrates look similar to honey with either a brown or gold color, and many of the street names refer to the golden brown color. The terms wax, ear wax, honey oil, budder, butane hash oil, butane honey oil (BHO), shatter, dabs (dabbing), black glass, and errl have all been used to refer to marijuana concentrates.

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QUESTION: What is hashish?

ANSWER: Hashish (AKA hash) is a THC-rich resin from the cannabis plant. This resin is collected and processed into various forms, including balls, cakes or cookies. Pieces of hashish can be broken off, and placed in pipes or cigarettes for smoking. Some individuals mix hashish with tobacco. Hashish products are considered to be Schedule I substances.

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

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

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QUESTION: Does marijuana use alter the sexual intercourse experience?

ANSWER: An online survey posed questions regarding various aspects of sexual experience and how those aspects were impacted by marijuana use. The results indicated that marijuana helped individuals relax, heightened their sensitivity to touch, and increased intensity of feelings, thus enhancing their sexual experience, while others found that marijuana interfered by making them sleepy and less focused or had no effect on their sexual experience.

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

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

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

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

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QUESTION: Does ketamine interact with the endocannabinoid system?

ANSWER: Yes. Ketamine induces the release of endocannabinoids.

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

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

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

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

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QUESTION: How do cannabinoids modulate pain sensation? In other words, describe the mechanism of action of cannabinoids.

ANSWER: Endocannabinoids are synthesized in the postsynaptic neuron in response to stimuli such as pain, stress and inflammation. Endocannabinoids travel in a retrograde fashion and activate the presynaptic CB receptors. Antinociceptive effects occur when either endocannabinoids or phytocannabinoids activate presynaptic inhibitory CB1 receptors. Stimulation of CB1 receptors (G protein coupled receptors (Gi,Go)) leads to a reduction of cAMP production via the inhibition of adenylyl cyclase. This results in an action on voltage gated calcium and potassium channels – there is a depression of neuronal excitability and a reduction of neurotransmitter release.

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QUESTION: A study by Jamal et al. published in the European Journal of Anaesthesiology reported that marijuana users required a higher dose of morphine s/p abdominal surgery. They estimated that there was a 23% increased opioid dose requirement. Have the results of studies examining the opioid requirements s/p orthopedic surgery also shown that marijuana users require more opioids than patients who do not use marijuana?

ANSWER: In a retrospective study including 3793 patients, patient-reported postoperative outcomes of 155 marijuana users were compared with those of 155 non-users. The results indicate that pre-operative marijuana users had higher pain scores at rest and on movement but did not consume more post-operative opioid analgesics. The cannabinoid users also reported a greater incidence of post-operative sleep impairment.

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QUESTION: CBD is a negative allosteric modulator. What does that mean?

ANSWER: A negative allosteric modulator changes the shape of the receptor and, as a result, reduces the binding ability of components that typically bind to the receptor. In the case of cannabinoids, CBD alters the shape of CB1 receptors, and THC along with endogenous cannabinoids do not bind to the CB1 receptor to the same degree as they do when CBD is not present.

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

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

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QUESTION: What medications alleviate the symptoms of marijuana withdrawal?

ANSWER: There are no general guidelines to treat the symptoms of marijuana withdrawal, but it has been reported that benzodiazepines and synthetic THC products used for the treatment of chemotherapy induced N/V may help alleviate some of the symptoms.

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QUESTION: What does “broad spectrum” mean?

ANSWER: Broad-spectrum products are processed in such a manner as to ensure that the final product does NOT contain THC.

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

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

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QUESTION: Over 2 million Americans with cardiovascular disease use marijuana. Warfarin interacts with marijuana. Do statins interact with cannabinoids?

ANSWER: Yes. Statins and cannabinoids are metabolized by the same liver enzymes. The co-administration of cannabinoids and statins can lead to a decrease in statin metabolism. As a result, the potency of the statins may increase, and lead to hypotension.

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QUESTION: Although Illinois and Nevada have both legalized the use of medical and recreational marijuana, it is illegal to take marijuana on a flight from Chicago to Las Vegas. The reason – airspace is regulated by the federal government and marijuana is illegal under federal law. Do any US airports have “marijuana amnesty boxes” for the disposal of marijuana?

ANSWER: Yes. In addition to 2 airports in Chicago, Mc Carran International Airport in Las Vegas and the Colorado Springs Airport have installed amnesty boxes for passengers who need to surrender their marijuana before boarding a flight.

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QUESTION: What are the precursors for the most commonly naturally occurring phytocannabinoids?

ANSWER: The precursors for THC, CBD and CBC are olivetolic acid and geranyl pyrophosphate. These precursors undergo a condensation reaction which results in the formation of cannabigerolic acid (CBGA). A cyclase enzyme converts CBGA into either tetrahydrocannabinolic acid (THCA) or cannabidiolic acid (CBDA) or cannabichromenic acid (CBCA). Then, heat decarboxylates these cannabinoids into THC, CBD or CBC, respectively.

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

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

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QUESTION: Are pupillary responses to light affected by marijuana?

ANSWER: Yes – marijuana may impair pupillary responses.

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QUESTION: Is the legalization of medical marijuana associated with an increase in sexual activity?

ANSWER: Yes, according to researchers from the University of Connecticut and Georgia State University, the legalization of medical marijuana is associated with an increase in sexual activity. Of note, the study also determined that there’s a decrease in the use of contraceptives and an increase in the number of births following the enactment of medical marijuana policies. This study was published in the Journal of Health Economics.

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QUESTION: What is the definition of drug diversion?

ANSWER: In the National Academies of Sciences, Engineering & Medicine’s Framing Opioid Prescribing Guidelines for Acute Pain: Developing the Evidence (2020), drug diversion is defined as the transfer of regulated prescription drugs from the legal market to illegal markets. The sharing of drugs with other individuals for medical or nonmedical purposes is NOT considered to be drug diversion. (The sharing of drugs is drug misuse.)

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QUESTION: Is it legal to carry marijuana on a Greyhound bus?

ANSWER: No. Greyhound Lines bans alcohol and drugs (including marijuana) “anywhere on the bus (including in your checked baggage).”

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QUESTION: Animal research studies on CBD’s potential therapeutic effects often employ rodents. Is CBD administered to rodents the same way CBD is administered to humans?

ANSWER: No. CBD is commonly administered to rodents either via intraperitoneal injection or via the oral route. In contrast, CBD has been studied in humans using oral administration or inhalation, but not via intraperitoneal. The pharmacokinetics of these various routes of administration differ and therefore the blood concentrations of CBD may differ.

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QUESTION: Has the use of CBD been evaluated for the treatment of heroin addiction?

ANSWER: Yes. Dr. Yasmin Hurd, director of the Addiction Institute of Mount Sinai in NYC led a double-blind study of 42 recovering heroin addicts and found that CBD reduced both cravings and cue-based anxiety, both of which can cycle people back into using heroin.

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QUESTION: Does CBD modulate 5-HT1A receptor activity?

ANSWER: Yes, and this modulation may directly improve hyperarousal/insomnia symptoms in PTSD patients.

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QUESTION: Is the US VA Office of research and Development conducting any clinical trials that evaluate the use of CBD for the treatment of PTSD?

ANSWER: Yes. A RCT evaluating the efficacy of using CBD as an adjunctive to prolonged exposure therapy (PE therapy)) was started in March 2019 and will conclude on September 30,2023. The trial will compare PE + CBD to PE + placebo in a sample of 136 military Veterans with PTSD at the VA San Diego Medical Center.

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QUESTION: Is it legal to transport marijuana on Amtrak’s railway?

ANSWER: Amtrak has a strict policy: “The use or transportation of marijuana in any form for any purpose is prohibited, even in states or countries where recreational use is legal or permitted medically.”

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QUESTION: Do any medical marijuana legal states accept out-of-state medical marijuana authorizations?

ANSWER: Yes. About twenty states accept out-of-state medical marijuana authorizations, BUT reciprocity laws vary from state to state. In some states, visitors are required to sign up for the medical marijuana program 30 days in advance and pay a $50 nonrefundable fee. The state’s purchasing limit may differ for permanent vs. temporary residents. In Oregon, for example, residents can possess up to 24 ounces, while visitors are allowed only one ounce.

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QUESTION: Does the CBD molecule contain an aromatic ring?

ANSWER: Yes, it does. The CBD molecule contains a cyclohexene ring and an aromatic ring (a phenolic ring). Of interest, the rings are located in planes that are almost perpendicular to each other.

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QUESTION: Describe the chemical makeup of endocannabinoids.

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

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QUESTION: Does chronic use of THC and/or CBD by individuals with multiple sclerosis impact cerebral glucose metabolism?

ANSWER: The results of “The Effects of Chronic Δ-9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) use on Cerebral Glucose Metabolism in Multiple Sclerosis: A Pilot Study” published in 2019 in ‘Applied Physiology, Nutrition and Metabolism‘ indicate that “Compared to non-users, THC-users had hypermetabolism of three regions (p < 0.039, d >1.17) in left temporal areas, while CBD-users had hypometabolism of five regions (p < 0.032, d > 1.31) in left temporal areas.”

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QUESTION: True or False? According to the results of a survey conducted by the FDA, about 90% of US adults understand that FDA-approved prescription drugs may cause harm.

ANSWER: False. The results of the survey indicate that 42.9% of consumers were not able to accurately report that FDA‐approved prescription drugs may cause harm.

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QUESTION: The FDA approves the language used on package inserts of prescription drugs. Does the FDA also approve the language of “direct-to -consumer” ads?

ANSWER: Actually, no. The language, including the risk or benefit statements, used in “direct to consumer” ads is not FDA-approved.

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QUESTION: Based on data from the 2016 to 2017 National Survey on Drug Use and Health and the U.S. Department of Health and Human Services, do more people in the US smoke marijuana or tobacco cigarettes”

ANSWER: According to the 2016 to 2017 National Survey on Drug Use and Health, more than 39 million people smoke marijuana, and according to data from the U.S. Department of Health and Human Services, 34.3 million people smoke tobacco cigarettes. Recent trends show that the number of marijuana smokers is rising while the number of cigarette smokers is declining.

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

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

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

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

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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