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Cannabinoid Research Update: TREATMENT OF PAIN

cannabinoids for the treatment of painThree interesting articles crossed my desk on this topic in the past couple of weeks. In one, my former colleague Alex Capano et al published “Evaluation of the effects of CBD hemp extract on opioid use and quality of life indicators in chronic pain patients: A prospective cohort study,” in Postgraduate Medicine.1 They recruited 131 patients, between ages 30 and 65, from a private pain management clinic. All had been using prescribed opioids for at least a year, and had a history of moderate to severe chronic pain for at least 3 years. They excluded patients with substance abuse disorder, a psychotic disorder, or a history of an overdose or a positive (for other than opioids) urine drug screen in the preceding year.1

Patients were offered the opportunity to take commercially-available full-spectrum gelcaps each containing 15.7mg hemp-derived CBD, 0.5mg THC, 0.3mg CBDV, 0.9mg CBDA, 0.8mg CBC, and a hemp terpene blend. Patients who chose to participate (128/131) self-titrated their dose, and no other changes were made to their pain management regimen. In all, 97 patients completed the 8-week study. More than half (53.4%) of those were able while taking the CBD extract to reduce their use of opioid medications by the end of week 8. A handful of others also noted being able to reduce of stop their anti-anxiety or insomnia meds. In addition, 94% of the hemp CBD users reported improved quality of life on up to four validated scales. There were no adverse events of any consequence. The 3 who chose to take CBD had showed no change in their opioid use.1

There are of course substantial limitations to an open-label, non-controlled, optional enrollment and use, self-titrated study. Nonetheless, the potential for a nonintoxicating, nonaddictive, natural substance to reduce reliance on opioids in the setting of chronic pain deserves our attention, and points like so many similar studies in the cannabinoid-pain field to the need for broad, rigorous, and (of course) well-funded studies to explore this potential further.

A similar idea was explored in a retrospective cohort study published in Cannabis and Cannabinoid Research by Takakua et al, “The impact of medical cannabis on intermittent and chronic opioid users with back pain: How cannabis diminished prescription opioid usage.”2 In a single-center study from a cannabis medical practice site in California, 180 patients with low back pain were identified; 61 of those were using prescription opioids and formed the cohort for this study. Patients were followed for an extended period of time, during which 32 (51%) reported being able to stop all opioid usage (median time 6.4 years). Of the remaining 29, 31% reported reduced opioid use, 10% held to baseline use, and 59% increased their usage of opioids.2

There were no standard cannabis protocols for dosing, and the only variable in this study to predict reduction in opioid usage was higher dosing of cannabis. Unlike the Capano study above, THC dosing in excess of 0.3% (the maximum allowed from hemp) was provided. The authors postulate that “the combined effects of opioids plus cannabis—and possibly reducing muscle spasms, anxiety, depression, and improved sleep that are often associated with chronic lower back pain—may have provided the relief necessary to allow for a reduction in the prescribed doses of opioids. We therefore believe this supports a synergistic relationship between opioids and cannabis.”2 My opinion? If only it were that straightforward. This study did not define chronicity of the back pain, did not standardize an approach to cannabis therapy, did not account for other concomitant medications, and had results almost at equipoise after years of follow-up. Look, I want cannabinoids to help us solve the opioid crisis, too, but let’s approach the problem a bit more rigorously than this.

Finally, Wong and colleagues just published “Analgesic effects of cannabinoids for chronic non-cancer pain: A systematic review and meta-analysis with meta-regression” in Journal of Neuroimmune Pharmacology.3 Now, full transparency: most everything that follows the colon in that last sentence (including the name of the journal!) sounds pretty intimidating to me. Anyway, these authors performed a systematic review and meta-analysis of RCTs in the non-cancer pain space to see what could be learned from many studies of the analgesic efficacy and adverse effects of cannabinoids. They performed a meta-analysis of analgesic efficacy and then a meta-regression to compare the analgesic efficacy for neuropathic versus non-neuropathic pain conditions.

They objectively evaluated the 43 RCTs they identified after screening for risk of bias (by The Cochrane Risk of Bias tool) and measuring strength of the evidence was assessed using the Grade of Recommendations Assessment, Development, and Evaluation (GRADE) scale. From the 33 studies that compared cannabinoids to placebo, the mean pain score (on a scale 0-10) reduction was -0.70, which was statistically significant, but from a clinical perspective is more consistent with a random effect. Meta-regression showed that whatever analgesic efficacy was there, was similar for neuropathic and non-neuropathic pain. Inhaled, oral, and oromucosal administration all provided statistically significant, but small, reductions in mean pain score. There were few adverse events attributed to cannabinoids, and, not surprisingly for the cannabis literature, the GRADE level of evidence was low to moderate. Pain intensity of chronic non-cancer patients was reduced by consumption of cannabinoids, but the effect sizes were small.3

This seemingly rather sophisticated review of available data seems to indicate that the analgesic effects of cannabinoids are limited in chronic pain patients. It is unusual that neuropathic pain did not respond better to cannabis, as it often does. Regardless, whether looking just at symptom relief or the societal implications of the opioid crisis, there is a lot of work to be done to assess the value of cannabis and cannabinoids in filling the gaps.

Resources

1. Capano A, Weaver R, Burkman E. Evaluation of the effects of CBD hemp extract on opioid use and quality of life indicators in chronic pain patients: a prospective cohort study. Postgrad Med. 2020;132(1):56-61. doi:10.1080/00325481.2019.1685298
2. Takakuwa KM, Hergenrather JY, Shofer FS, Schears RM. The Impact of Medical Cannabis on Intermittent and Chronic Opioid Users with Back Pain: How Cannabis Diminished Prescription Opioid Usage. Cannabis Cannabinoid Res. January 2020. doi:10.1089/can.2019.0039
3. Wong SSC, Chan WS, Cheung CW. Analgesic Effects of Cannabinoids for Chronic Non-cancer Pain: a Systematic Review and Meta-Analysis with Meta-Regression. J Neuroimmune Pharmacol Off J Soc NeuroImmune Pharmacol. March 2020. doi:10.1007/s11481-020-09905-y

 

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