Pharmacodynamic effects following co-administration of cannabinoids and opioids: A scoping review of human experimental studies

Pain Med. 2024 Apr 1:pnae024. doi: 10.1093/pm/pnae024. Online ahead of print.


Background: Cannabinoids are increasingly used in the management of chronic pain. Although analgesic potential has been demonstrated, cannabinoids interact with a range of bodily functions that are also influenced by chronic pain medications, including opioids.

Objective: We performed a scoping review of literature on the pharmacodynamic effects following co-administration of cannabinoids and opioids.

Methods: We systematically searched EMBASE, PubMed, and PsycINFO for studies that experimentally investigated the co-effects of cannabinoids and opioids in human-subjects. Available evidence was summarized by clinical population and organ system. A risk of bias assessment was performed.

Results: A total of sixteen studies met inclusion criteria. Study populations included patients with chronic non-cancer and cancer pain on long-term opioid regimens and healthy young adults without prior exposure to opioids who were subject to experimental nociceptive stimuli. Commonly administered cannabinoid agents included Δ9-tetrahydrocannabinol and/or cannabidiol. Co-administration of cannabinoids and opioids did not consistently improve pain outcomes; however, sleep and mood benefits were observed in chronic pain patients. Increased somnolence, memory and attention impairment, dizziness, gait disturbance, and nauseousness and vomiting were noted with co-administration of cannabinoids and opioids. Cardiorespiratory effects following co-administration appeared to vary according to duration of exposure, population type, and prior exposure to cannabinoids and opioids.

Conclusions: The available evidence directly investigating the pharmacodynamic effects following co-administration of cannabinoids and opioids for non-analgesic outcomes is scarce and suffers from a lack of methodological reporting. As such, further research in this area with comprehensive methodologic reporting is warranted.