Considering abuse liability and neurocognitive effects of cannabis and cannabis-derived products when assessing analgesic efficacy: a comprehensive review of randomized-controlled studies

ABSTRACT

Background: Pain is the most frequent indication for which medical cannabis treatment is sought.

Objectives: The clinical potential of cannabis and cannabis-derived products (CDPs) relies on their efficacy to treat an indication and potential adverse effects that impact outcomes, including abuse liability and neurocognitive effects. To ascertain the extent to which these effects impact therapeutic utility, studies investigating cannabis and CDPs for pain were reviewed for analgesic efficacy and assessments of abuse liability and neurocognitive effects.

Methods: A comprehensive review of placebo-controlled studies investigating cannabis and CDP analgesia was performed. Methods and findings related to adverse effects, abuse liability, and neurocognitive effects were extracted.

Results: Thirty-eight studies were reviewed; 29 assessed cannabis and CDPs for chronic pain, 1 for acute pain, and 8 used experimental pain tests. Most studies ascertained adverse effects through self-report (N = 27). Fewer studies specifically probed abuse liability (N = 7) and cognitive and psychomotor effects (N = 12). Many studies related to chronic and experimental pain (N = 18 and N = 5, respectively) found cannabis and CDPs to reduce pain. Overall, adverse effects were mild to moderate, and dose-related. Studies investigating the impact of cannabis and CDPs on abuse liability and neurocognitive endpoints were mostly limited to inhaled administration and confirmed dose-related effects.

Conclusion: Few studies investigating cannabis and CDP analgesia assess abuse liability and cognitive endpoints, adverse effects that impact the long-term clinical utility of these drugs. Future studies should include these measures to optimize research and clinical care related to cannabis-based therapeutics.

KEYWORDS:

• Cannabis
• cannabinoid
• analgesia
• abuse-liability
• cognitive effects

Acknowledgements

The authors acknowledge and appreciate the exceptional assistance of Gina Johnson in data collection.

Additional information

Funding

This research was supported by US National Institute on Drug Abuse Grant DA046614 and DA047296. ZDC and DA have no competing interests in relation to the work described. ZDC has received research funds and partial salary support from Insys Therapeutics. ZDC has served as a consultant to the following companies: GB Sciences and Beckley Canopy Therapeutics and has served on the scientific advisory board of FSD Pharma. DA is a scientific advisor to AXIM, Scriptyx, Tikun Olan and VIVO Cannabis and received speaker honorarium from Spectrum Cannabis.