Sex Differences in the Neuropsychiatric Effects and Pharmacokinetics of Cannabidiol: A Scoping Review

Justin Matheson; Zoe Bourgault; Bernard Le Foll

doi:10.3390/biom12101462

Sex Differences in the Neuropsychiatric Effects and Pharmacokinetics of Cannabidiol: A Scoping Review

Biomolecules. 2022 Oct 12;12(10):1462. doi: 10.3390/biom12101462.

Authors

Justin Matheson¹, Zoe Bourgault^{1

2}, Bernard Le Foll^{1

2

3

4

5

6

7

8

9}

Affiliations

¹ Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, University of Toronto, 33 Ursula Franklin Street, Toronto, ON M5S 2S1, Canada.
² Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5S 1A8, Canada.
³ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5S 1A8, Canada.
⁴ Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5S 1A8, Canada.
⁵ Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada.
⁶ Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada.
⁷ Acute Care Program, Centre for Addiction and Mental Health, Toronto, ON M6J 1H4, Canada.
⁸ Department of Family and Community Medicine, University of Toronto, Toronto, ON M5G 1V7, Canada.
⁹ Waypoint Research Institute, Waypoint Centre for Mental Health Care, Penetanguishene, ON L9M 1G3, Canada.

Abstract

Cannabidiol (CBD) is a non-intoxicating cannabinoid compound with diverse molecular targets and potential therapeutic effects, including effects relevant to the treatment of psychiatric disorders. In this scoping review, we sought to determine the extent to which sex and gender have been considered as potential moderators of the neuropsychiatric effects and pharmacokinetics of CBD. In this case, 300 articles were screened, retrieved from searches in PubMed/Medline, Scopus, Google Scholar, PsycInfo and CINAHL, though only 12 met our eligibility criteria: eight studies in preclinical models and four studies in humans. Among the preclinical studies, three suggested that sex may influence long-term effects of gestational or adolescent exposure to CBD; two found no impact of sex on CBD modulation of addiction-relevant effects of Δ⁹-tetrahydrocannabinol (THC); two found antidepressant-like effects of CBD in males only; and one found greater plasma and liver CBD concentrations in females compared to males. Among the human studies, two found no sex difference in CBD pharmacokinetics in patient samples, one found greater plasma CBD concentrations in healthy females compared to males, and one found no evidence of sex differences in the effects of CBD on responses to trauma recall in patients with post-traumatic stress disorder (PTSD). No studies were identified that considered the role of gender in CBD treatment effects. We discuss potential implications and current limitations of the existing literature.

Keywords: addiction; cannabidiol; pharmacokinetics; psychiatry; sex differences.

Publication types

Review

MeSH terms

Adolescent
Cannabidiol* / pharmacology
Cannabidiol* / therapeutic use
Cannabinoids*
Dronabinol / pharmacology
Female
Humans
Male
Sex Characteristics
Stress Disorders, Post-Traumatic*

Substances

Cannabidiol
Dronabinol
Cannabinoids

Grants and funding

This research received no direct external funding. During the course of preparing this manuscript, J.M. received financial support from the Toronto Cannabis & Cannabinoid Research Consortium (TC3) and the Centre for Addiction and Mental Health (CAMH) Womenmind^TM Community.