Reference: BMJ. 2021 Sep 8
Chronic pain remains a common and challenging condition. Use of cannabis or isolated cannabinoid compounds for the treatment of chronic pain is growing but data regarding its efficacy are conflicting. A systematic review and meta-analysis of randomized controlled trials (RCTs) was recently published evaluating the efficacy and risks of cannabis and cannabinoids for this hard-to-treat entity.
RCTs were included if they enrolled at least 20 participants with pain lasting >3 months who were randomized to cannabis or cannabinoids versus placebo or active comparator and were followed for at least 1 month. Outcomes collected included pain (at rest), physical functioning, sleep quality, emotional functioning, role functioning, social functioning, and adverse events. Pain intensity and sleep quality were converted to a 10 cm visual analogue scale (VAS). Physical functioning, emotional functioning, and role functioning were converted to distinct 100-point 36-Item Short Form scales.
In total, 32 RCTs with 5,174 participants were included in this systematic review. Twenty-eight trials enrolled adults with chronic non-cancer pain, including but not limited to neuropathic pain, spasticity related pain, nociplastic pain, and nociceptive pain. Four trials enrolled adults with chronic cancer-related pain. Most of the studies used oral forms of cannabinoids, including tetrahydrocannabinol (THC) (9 trials), a combination of THC and cannabidiol (CBD) (14 trials), palmitoylethanolamide (PEA) (5 trials), or cannabidivarin (1 trial). Topical CBD was used in two trials. The most common control was placebo (29 trials). Follow-up ranged from 1 to 5.5 months. Adults with a history of substance use disorder and mental illness were excluded from most trials. Random-effects-model meta-analyses found that non-inhaled cannabinoids likely result in more participants experiencing improved pain by 1 cm on a 10 cm VAS, the minimally important difference. Oral cannabinoids also slightly improve physical functioning (modelled risk difference [RD] 4%) and sleep quality (RD 6%), but not emotional, role, or social functioning. Oral cannabinoids were associated with small increases in transient cognitive impairment (RD 2%), vomiting (RD 3%), drowsiness (RD 5%), impaired attention (RD 3%), nausea (RD 5%, and dizziness (RD 9-28%) compared to placebo.
Based on these results, non-inhaled forms of cannabinoids may provide some (albeit small) benefit for chronic pain. It’s difficult however, to draw any definitive conclusions given the heterogeneity of the interventions studied and spectrum of chronic pain treated. The unexplained inclusion of studies of PEA is a major confounder and stands in contrast to many other meta-analyses of cannabinoids for chronic pain. These results are also not generalizable to adults with a history of substance use disorder or mental illness and don’t speak to any concerns about the potential for misuse. That being said, use of cannabis for medical reasons is here to stay and likely represents a reasonable alternative to other medications (like opioids) to treat chronic pain.This review provides some evidence for the use of non-inhaled cannabinoids for chronic pain while simultaneously highlighting the need for separate analyses for the different preparations and modalities. To put it bluntly, rather than lumping everything together in one meta-analysis, independent evaluation of cannabis or isolated cannabinoids may bolster the evidence and aid in standardization of its use.
For more information, see the topic Medical Uses of Cannabinoids-Chronic pain in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Nicole Jensen, MD, family physician at WholeHealth Medical. Edited by, Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Dan Randall, MD, Deputy Editor at DynaMed; Carina Brown, MD, Assistant Professor at Cone Health Family Medicine Residency; Katharine DeGeorge, MD, MS, Deputy Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia; Vincent Lemaitre, PhD, Medical Writer at DynaMed and Christine Fessenden, Editorial Operations Assistant at DynaMed.