Monday, November 22, 2021

Do the benefits of medical cannabinoids outweigh the harms?

 - Jennifer Middleton, MD, MPH

A recent systematic review and accompanying BMJ Clinical Practice Guideline have been creating media buzz regarding medical marijuana and cannabinoids. The systematic review authors comprehensively searched a broad range of databases for randomized controlled trials of at least 20 participants with chronic pain who were followed for a minimum of 1 month. They identified 32 trials with a total of nearly 5200 participants to include in the systematic review. Study durations ranged from 1.0-5.5 months, and most (28) studied non-cancer-related chronic pain. Most studies (29) compared medical cannabis and/or cannabinoids with placebo. After analyzing the data, the authors concluded that:

Compared with placebo, non-inhaled medical cannabis probably results in a small increase in the proportion of patients experiencing at least the minimally important difference (MID) of 1 cm (on a 10 cm visual analogue scale (VAS)) in pain relief (modelled risk difference (RD) of 10% (95% confidence interval 5% to 15%), based on a weighted mean difference (WMD) of −0.50 cm (95% CI −0.75 to −0.25 cm, moderate certainty)). Medical cannabis taken orally results in a very small improvement in physical functioning (4% modelled RD (0.1% to 8%) for achieving at least the MID of 10 points on the 100-point SF-36 physical functioning scale, WMD of 1.67 points (0.03 to 3.31, high certainty)), and a small improvement in sleep quality (6% modelled RD (2% to 9%) for achieving at least the MID of 1 cm on a 10 cm VAS, WMD of −0.35 cm (−0.55 to −0.14 cm, high certainty)). 

The authors interpreted these findings as "moderate to high certainty evidence" that the use of medical cannabis and cannabinoids was associated with a "small to very small" improvement in pain, functioning, and sleep. They also reported on adverse events that occurred more frequently in the medical cannabis and cannabinoids patients, including cognitive impairment and nausea/vomiting. 

This systematic review's findings informed an accompanying Clinical Practice Guideline in the same issue of BMJ, in which the guideline authors issued "a weak recommendation to offer a trial of non-inhaled medical cannabis or cannabinoids, in addition to standard care and management (if not sufficient), for people living with chronic cancer or non-cancer pain." The guideline development panel included three of the authors of the above systematic review, patients, and "clinicians with content expertise," who acknowledge that their recommendation "reflects a high value placed on small to very small improvements in self reported pain intensity, physical functioning, and sleep quality, and willingness to accept a small to modest risk of mostly self limited and transient harms." They acknowledge that their guideline contradicts previous guidelines issued by NICE, the American Society of Clinical Oncology, and Canadian Family Physician, arguing that those guidelines were limited by an overly "selective review of the evidence" and a "failure to consider patient values and preferences."

These conflicting guidelines attest to the continued controversy regarding the use of marijuana and/or cannabinoids in medicine. Currently, 36 US states and 4 US territories permit their use. As this recent JAMA editorial attests, "[t]his heterogeneous approach to policy making can directly affect patients and clinicians because they are left to interpret mixed messages from lawmakers about the safety and efficacy of medical cannabis use." The AAFP's position paper on "Marijuana and Cannabinoids: Health, Research, and Regulatory Considerations" acknowledges the burgeoning evidence base regarding these substances' potential medical benefit while also cautioning against their established harms. A 2015 AFP editorial, "Effectiveness, Adverse Events, and Safety of Medical Marijuana," affirms both benefits and harms while calling for reclassification of cannabis as a schedule II drug by the US Food and Drug Administration (FDA) to permit more rigorous outcomes-based research. 

Patients will doubtless continue to inquire about medical cannabis and cannabinoids while we await more definitive evidence; for those clinicians practicing in states where they are an option, discussing the balance of known benefits and harms can help patients make an informed decision. This AFP By Topic on Chronic Pain provides overviews of additional therapeutic options to consider, and stay tuned for "Cannabis Essentials: Tools for Clinical Practice," coming in next month's issue of AFP.