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

Nielsen, Suzanne and Picco, Louisa and Murnion, Bridin and Winters, Bryony and Matheson, Justin and Graham, Myfanwy and Campbell, Gabrielle and Parvaresh, Laila and Khor, Kok-Eng and Betz-Stablein, Brigid and Farrell, Michael and Lintzeris, Nicholas and Le Foll, Bernard (2022) Opioid-sparing effect of cannabinoids for analgesia: an updated systematic review and meta-analysis of preclinical and clinical studies. Neuropsychopharmacology, 47, pp. 1315-1330. doi: 10.1038/s41386-022-01322-4.

External website: https://www.nature.com/articles/s41386-022-01322-4

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 (ED) of morphine administered with delta-9-tetrahydrocannabinol was 3.5 times lower than the ED 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 or percentage change in pain scores; five studies found more adverse events with cannabinoids compared with placebo. 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, and 85% reported reduction. 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.


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