Cannabidiol Effect on Anxiety Symptoms and Stress Response in Individuals With Cocaine Use Disorder: Exploratory Results From a Randomized Controlled Trial

J Addict Med. 2022 Sep-Oct;16(5):521-526. doi: 10.1097/ADM.0000000000000959. Epub 2022 Feb 8.


Objectives: Individuals with a cocaine use disorder (CUD) are more likely to present anxiety, which in turn negatively impacts substance use outcomes. Some evidence suggests that cannabidiol (CBD) presents anxiolytic properties and could be a treatment for substance use disorders. This study explores CBD's effect on stress biomarker (cortisol) and anxiety symptoms in people with CUD.

Methods: Exploratory analyses were conducted using data from a randomized, double-blind, placebo-controlled trial evaluating CBD's efficacy to treat CUD. We randomized 78 individuals with CUD into receiving a daily oral dose up to 800 mg CBD (n = 40) or placebo (n = 38). The trial was divided into 2 phases: an inpatient detoxification lasting 10 days and an outpatient follow-up lasting 12 weeks. Anxiety symptoms and stress response were assessed using a visual analog scale, the Beck Anxiety Inventory, and cortisol levels at multiple time points throughout the study. We also measured anxiety after a stressful and a cocaine-cue scenarios. We used generalized estimating equations models and multiple linear regression to assess CBD's effects on anxiety and cortisol levels.

Results: Both treatment groups had similar mean anxiety scores according to the Beck Anxiety Inventory ( P = 0.27) and the visual analog scale ( P = 0.18). CBD did not decrease anxiety after a stressful ( P = 0.14) and a cocaine ( P = 0.885) scenarios compared with placebo. No statistically significant group difference was found in cortisol levels ( P = 0.76).

Conclusions: We found no evidence for 800 mg of CBD to be more efficacious than placebo for modulating anxiety symptoms and cortisol levels in individuals with CUD.

Trial registration: NCT02559167.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Anxiety Agents* / therapeutic use
  • Anxiety / drug therapy
  • Cannabidiol* / pharmacology
  • Cannabidiol* / therapeutic use
  • Cocaine*
  • Double-Blind Method
  • Humans
  • Hydrocortisone
  • Substance-Related Disorders* / drug therapy


  • Anti-Anxiety Agents
  • Cannabidiol
  • Cocaine
  • Hydrocortisone

Associated data


Grants and funding