A placebo-controlled investigation of the analgesic effects, abuse liability, safety and tolerability of a range of oral cannabidiol doses in healthy humans

Br J Clin Pharmacol. 2022 Jan;88(1):347-355. doi: 10.1111/bcp.14973. Epub 2021 Jul 23.


Aims: 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 noncannabis users.

Methods: 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 orally) in healthy noncannabis-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.

Results: 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 < .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 < .01).

Conclusion: 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.

Keywords: abuse liability; analgesia; cannabidiol; cannabinoids; pain.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Analgesia*
  • Analgesics / adverse effects
  • Cannabidiol* / pharmacology
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Pain / chemically induced
  • Pain / drug therapy
  • Pain Measurement


  • Analgesics
  • Cannabidiol