Caroline A Arout, Margaret Haney, Evan S Herrmann, Gillinder Bedi, Ziva D Cooper

Published in British Journal of clinical Pharmacology

 July 2021



Preclinical studies demonstrate that cannabidiol (CBD) elicits an antinociceptive response in animal models of neuropathic pain; in humans, limited data are available to support such analgesic effects. Few studies have examined CBD’s analgesic effects when administered without other compounds, and little is known regarding dose-dependent effects in non-cannabis users.


This double-blind, placebo-controlled, within-subject outpatient clinical laboratory study sought to determine the analgesic effects, abuse liability, safety and tolerability of acute CBD (0, 200, 400, and 800 mg PO) in healthy non-cannabis using volunteers (N=17; 8 men, 9 women). Outcomes included experimental pain threshold and pain tolerance using the Cold Pressor Test (CPT), subjective ratings of CPT ‘Painfulness’ and ‘Bothersomeness,’ subjective ratings of abuse liability and mood, and cardiovascular measures, which were assessed at baseline and several time points after drug administration. Data analyses included repeated measures analysis of variance (ANOVA) with planned comparisons.


CBD failed to consistently affect pain threshold and tolerance in the CPT relative to placebo. All doses of CBD increased ratings of ‘Painfulness’ compared to placebo (p < 0.01). Further, CBD had dose-dependent, modest effects on mood and subjective drug effects associated with abuse liability. Oral CBD was safe and well tolerated, producing small decreases in blood pressure (p < 0.01).


CBD did not elicit consistent dose-dependent analgesia and in fact increased pain on some measures. Future studies exploring CBD-induced pain relief should consider using a more extensive pain assessment paradigm in different participant populations.

Open Access


DOI: 10.1111/bcp.14973


Arout, C. A., Haney, M., Herrmann, E. S., Bedi, G., & Cooper, Z. D. (2021). The dose‐dependent analgesic effects, abuse liability, safety and tolerability of oral cannabidiol in healthy humans. British journal of clinical pharmacology.