Dosing of Cannabinoids Associated with an Opioid-Sparing Effect: A Systematic Review of Longitudinal Studies.

Objective: To assess cannabinoid dosing that could be associated with a reduction in opioid use. Design: Systematic review conducted according to the PRISMA statement. Data Sources: PubMed, Embase, Web of Science, and PsycINFO were searched up to December 10, 2022. Review/Analysis Methods: We included randomized controlled trials (RCT) and longitudinal observational studies assessing cannabinoids effect on opioid use in patients with acute or chronic pain. Two reviewers independently assessed the studies for inclusion and extracted the data. Tetrahydrocannabinol (THC), Cannabidiol (CBD), and other cannabinoids with dosing were the exposures. Change in opioid doses and opioid discontinuation were the outcomes. Results: Fifteen studies (including seven RCTs) were included. Eight studies (six observational and two RCTs) were conducted among patients with chronic pain including three with cancer-related pain. Seven studies involved patients with acute pain (five RCTs).In chronic non-cancer pain patients, two observational studies that assessed THC and CBD in combination (average daily dose 17mg/15mg), and one that assessed a CBD-rich extract (31.4 mg/day), showed a significant reduction in opioid use. Of the three studies conducted on patients with cancer, only the observational study that assessed nabilone (average 1.7 mg/day) showed a significant reduction in opioid use. In patients with acute pain, only two observational studies that assessed dronabinol (5mg and 5-10 mg/day for four days) showed a significant reduction in opioid use. Conclusion: The opioid-sparing effect of cannabinoids remains uncertain based on current evidence. However, attention could be paid to cannabinoid doses associated with opioid reduction in included observational studies.