Opioid-sparing effect of cannabinoids for analgesia: an updated systematic review and meta-analysis of preclinical and clinical studies

Abstract

Cannabinoid co-administration may enable reduced opioid doses for analgesia. This updated systematic review on the opioid-sparing effects of cannabinoids considered preclinical and clinical studies where the outcome was analgesia or opioid dose requirements. We searched Scopus, Cochrane Central Registry of Controlled Trials, Medline, and Embase (2016 onwards). Ninety-two studies met the search criteria including 15 ongoing trials. Meta-analysis of seven preclinical studies found the median effective dose (ED50) of morphine administered with delta-9-tetrahydrocannabinol was 3.5 times lower (95% CI 2.04, 6.03) than the ED50 of morphine alone. Six preclinical studies found no evidence of increased opioid abuse liability with cannabinoid administration. Of five healthy-volunteer experimental pain studies, two found increased pain, two found decreased pain and one found reduced pain bothersomeness with cannabinoid administration; three demonstrated that cannabinoid co-administration may increase opioid abuse liability. Three randomized controlled trials (RCTs) found no evidence of opioid-sparing effects of cannabinoids in acute pain. Meta-analysis of four RCTs in patients with cancer pain found no effect of cannabinoid administration on opioid dose (mean difference −3.8 mg, 95% CI −10.97, 3.37) or percentage change in pain scores (mean difference 1.84, 95% CI −2.05, 5.72); five studies found more adverse events with cannabinoids compared with placebo (risk ratio 1.13, 95% CI 1.03, 1.24). Of five controlled chronic non-cancer pain trials; one low-quality study with no control arm, and one single-dose study reported reduced pain scores with cannabinoids. Three RCTs found no treatment effect of dronabinol. Meta-analyses of observational studies found 39% reported opioid cessation (95% CI 0.15, 0.64, I2 95.5%, eight studies), and 85% reported reduction (95% CI 0.64, 0.99, I2 92.8%, seven studies). In summary, preclinical and observational studies demonstrate the potential opioid-sparing effects of cannabinoids in the context of analgesia, in contrast to higher-quality RCTs that did not provide evidence of opioid-sparing effects.

A review of studies evaluating medical cannabis for the chronic pain management

“…Opioids are widely prescribed for chronic pain, but in clinical practice it is recommended to delay or prevent the initiation of treatment with opioid analgesics, decrease the duration of treatment, reduce the dosage and adverse outcomes, without causing an unacceptable increase in pain. There is substantial interest in the opioid-sparing potential of cannabinoids in the context of pain management -cannabinoid co-administration may enable reduced opioid doses for analgesia, what was supported by results of preclinical and observational studies [12]. The trial performed by Zylla et al of early and delayed start medical cannabis also suggest that cannabis may improve pain management and minimise opioid utilisation.…”

Changes in Prescribed Opioid Dosages Among Patients Receiving Medical Cannabis for Chronic Pain, New York State, 2017-2019

“…A meta-analysis on the association of cannabinoids with reduced opioid use for analgesia found some support in observational studies but little evidence from clinical trials. 16 Several trials used cannabis-derived products for a short time, which may not reflect how patients actually use cannabis as an alternative therapy. 16 Medical cannabis (MC) programs present opportunities to investigate the potential therapeutic benefits of MC for pain management and its possible adjunctive use with opioid analgesics.…”

“… 16 Several trials used cannabis-derived products for a short time, which may not reflect how patients actually use cannabis as an alternative therapy. 16 …”

“…16 Several trials used cannabis-derived products for a short time, which may not reflect how patients actually use cannabis as an alternative therapy. 16 Medical cannabis (MC) programs present opportunities to investigate the potential therapeutic benefits of MC for pain management and its possible adjunctive use with opioid analgesics. Most MC programs regulate the licensure, cultivation, distribution, and sale of products and require patients to be authorized or certified by a health care practitioner to participate in the program.…”

“…Results showed individuals self-reported reduction in opioid use and improvement in pain management. A meta-analysis on the association of cannabinoids with reduced opioid use for analgesia found some support in observational studies but little evidence from clinical trials . Several trials used cannabis-derived products for a short time, which may not reflect how patients actually use cannabis as an alternative therapy …”