Background: Evidence suggests that cannabinoids, by interacting with the opioid system, could reduce opioid doses while maintaining an effective analgesic effect of opioids in patients with pain. However, cannabinoid dosing that could be associated with a reduction in opioid use is not well known.
Objectives: we conducted this systematic review to determine whether medical cannabis is effective in reducing opioid use for pain management and to assess the doses of cannabinoids associated with potential opioid dose reduction.
Methods:
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.
Studies inclusion criteria: Randomized controlled trials (RCT) and longitudinal observational studies assessing the effect of cannabinoids on opioid use in patients with acute or chronic pain. Studies not providing a measure of the used cannabinoids dosing were excluded.
Study selection and data extraction: Two reviewers independently assessed studies titles, abstracts, and full text of potentially eligible articles and extracted the data.
Exposure: Tetrahydrocannabinol (THC), Cannabidiol (CBD), and other cannabinoids with dosing and routes of administration.
Outcomes: Change in opioid doses (total doses or % of patients achieving a pre-specified dose reduction) and opioid discontinuation.
Data Synthesis and Analysis: Data were synthesized for acute and chronic pain separately and discussed according to the type of cannabinoids and dosing plan.
Results: Fifteen studies (including seven RCTs) satisfied the inclusion criteria. Eight studies (six observational studies 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 of opioid use following cannabis initiation. 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 and the low quality of studies. Further studies are thus needed to elucidate this important question in the context of the opioid crisis and the increasing use of cannabinoids for pain.
