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Fitzcharles and colleagues raise a number of important concerns stemming from the need for more rigorous research into therapeutic applications of cannabinoids. Unfortunately, their arguments are undermined by their unsubstantiated claims about the relative risks of cannabis compared to opioids.
The authors acknowledge there are several symptoms and conditions for which cannabis has shown to be effective (e.g., severe childhood epilepsy, chemotherapy-induced nausea, palliation at end-of-life) and suggest that the evidence is not sufficient to support other conditions that are commonly thought to improve with cannabis, including chronic non-cancer pain. This conclusion is debatable, especially in light of the recent consensus reached by the United States’ National Academies of Science, Engineering, and Medicine that there is substantial evidence to support cannabinoids for the treatment of chronic pain.[1] We take particular issue with the authors’ assertions that the relative lower harms of cannabinoids as compared to opioids are merely public “perception” and, that without more cannabis research, we may see “a potential disaster similar to the opioid epidemic in North America.”
We agree that more high-quality research is needed on the possible health benefits and acute and chronic harms of cannabis use. We are one of many research groups in Canada planning or conducting experimental trials into cannabinoid-based therapies. However, suggesting cannabis might spark a public health problem on the level of the current opioid overdose crisis is not supported by scientific evidence. Although cannabis use is neither risk-free nor a panacea, the risks it poses of physical dependence and accidental overdose compared to opioid use are substantially lower—indeed, fatal overdose with cannabis has never been documented and is thought to be impossible.[2] Especially in the era of the opioid overdose crisis, the common sequelae of opioid use disorder (e.g., fatal overdose, bloodborne diseases acquisition or transmission) are hardly comparable to those of cannabis use disorder at either individual or population levels. The lower relative risks associated with cannabis are reflected in substantially lower rates of cannabis-associated morbidity, mortality and societal costs compared to opioids in Canada, despite much higher levels of exposure.[3] Simply put: it is not perception that cannabis has lower relative harms than cannabis; it is evidence.
The authors’ viewpoint also overlooks an emerging body of preliminary research (including some from controlled trials) describing beneficial relationships between cannabis use or access and rates of opioid use and related harms including overdose. For example, population-level research from the United States has reported lower rates of opioid-related mortality,[4] opioid analgesic dispensations,[5,6] and opioid-related hospitalizations[7] in jurisdictions with licit access to medical cannabis. Multiple studies of people who use medical cannabis have documented both ad-hoc and intentional reductions in opioid use, often in the context of chronic pain.[8,9] Recent experimental trials in humans have demonstrated that lower doses of opioids co-administered with cannabinoids achieved equivalent analgesia to higher doses of opioids[10] and administration of cannabidiol reduced cue-induced opioid craving among people with opioid use disorder.[11] In our three prospective cohorts of people at high risk of opioid overdose in Vancouver, we have found a number of beneficial longitudinal associations with consistent cannabis use, such as superior engagement in opioid agonist therapies for opioid use disorder,[12] reduced frequency of illicit opioid use in the context of chronic pain,[13] and lower rates of exposure to fentanyl.[14]
We strongly agree with the authors’ views that governments, regulators and other stakeholders must support high-quality independent research into cannabis in order to mitigate its harms and maximize its potential benefits. However, these clinical, public health and regulatory research priorities are likely to miss the mark without a clear-eyed and accurate appraisal of the existing scientific evidence on cannabinoids and human health—however limited it may be.
References
1. National Academies of Sciences, Engineering, Medicine. The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research. Washington, D.C.: The National Academies Press, 2017. Available: http://nationalacademies.org/hmd/reports/2017/health-effects-of-cannabis... (accessed 2017 January 31).
2. Iversen L. Is Cannabis Safe? The Science of Marijuana. New York: Oxford University Press; 2018.
3. Canadian Substance Use Costs and Harms Scientific Working Group. Canadian Substance Use Costs and Harms. Ottawa: Canadian Institute for Substance Use Research and Canadian Centre on Substance Use and Addiction, 2018. Available: https://www.ccsa.ca/sites/default/files/2019-04/CSUCH-Canadian-Substance... (accessed 2019 October 17).
4. Gladden RM, Martinez P, Seth P. Fentanyl Law Enforcement Submissions and Increases in Synthetic Opioid-Involved Overdose Deaths - 27 States, 2013-2014. MMWR Morb Mortal Wkly Rep 2016;65(33):837-43.
5. Bachhuber MA, Saloner B, Cunningham CO, Barry CL. Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010. JAMA Intern Med 2014;174(10):1668-73.
6. Powell D, Pacula RL, Jacobson M. Do medical marijuana laws reduce addictions and deaths related to pain killers? J Health Econ 2018;58:29-42.
7. Shi Y. Medical marijuana policies and hospitalizations related to marijuana and opioid pain reliever. Drug Alcohol Depend 2017;173:144-50.
8. Boehnke KF, Litinas E, Clauw DJ. Medical cannabis use is associated with decreased opiate medication use in a retrospective cross-sectional survey of patients with chronic pain. J Pain 2016;17(6):739-44.
9. Reiman A, Welty M, Solomon P. Cannabis as a Substitute for Opioid-Based Pain Medication: Patient Self-Report. Cannabis Cannabinoid Res 2017;2(1):160-6.
10. Bradford AC, Bradford WD, Abraham A, Bagwell Adams G. Association between US state medical cannabis laws and opioid prescribing in the Medicare Part D population. JAMA Intern Med 2018;178(5):667-72.
11. Cooper ZD, Bedi G, Ramesh D, Balter R, Comer SD, Haney M. Impact of co-administration of oxycodone and smoked cannabis on analgesia and abuse liability. Neuropsychopharmacology 2018;43(10):2046-55.
12. Hurd YL, Spriggs S, Alishayev J, Winkel G, Gurgov K, Kudrich C, et al. Cannabidiol for the reduction of cue-induced craving and anxiety in drug-abstinent individuals with heroin use disorder: a double-blind randomized placebo-controlled trial. Am J Psychiatry 2019;Epub ahead of print.
13. Socias ME, Wood E, Lake S, Nolan S, Fairbairn N, Hayashi K, et al. High-intensity cannabis use is associated with retention in opioid agonist treatment: a longitudinal analysis. Addiction 2018;113(12):2250-58.
14. Lake S, Walsh Z, Kerr T, Cooper ZD, Buxton J, Wood E, et al. Frequency of cannabis and illicit opioid use among people who use drugs and report chronic pain: a longitudinal analysis. PLoS Med 2019;In Press.