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Published Online: 18 August 2023

Sex Differences in the Association Between Cumulative Use of Cannabis and Cognitive Function in Middle Age: The Coronary Artery Risk Development in Young Adults Study

Publication: Cannabis and Cannabinoid Research


Background: Cannabis use may impair cognitive function (CF) differently in men and women, due to sex-specific differences in neurobiological mechanisms and environmental risk factors.
Objective: Assess sex differences in the association between cumulative exposure to cannabis and cognitive performance in middle age.
Methods: We studied participants from the Coronary Artery Risk Development in Young Adults (CARDIA) Study, including Black and White men and women 18–30 years old at baseline followed over 30 years. Our cross-sectional analysis of CF scores at year 30 was stratified by sex. We computed categories of cumulative exposure in “cannabis-years” (1 cannabis-year=365 days of use) from self-reported use every 2 to 5 years over 30 years. At years 25 and 30, we assessed CF with the Rey Auditory Verbal Learning Test (verbal memory), the Digit Symbol Substitution Test (processing speed), and the Stroop Interference Test (executive function). At year 30, additional measures included Category and Letter Fluency Test (verbal ability) and the Montreal Cognitive Assessment (global cognition). We computed standardized scores for each cognitive test and applied multivariable adjusted linear regression models for self-reported cumulative cannabis use, excluding participants who used cannabis within 24 h. In a secondary analysis, we examined the association between changes in current cannabis use and changes in CF between years 25 and 30.
Results: By year 30, 1,352 men and 1,793 women had measures of CF; 87% (N=1,171) men and 84% (N=1,502) women reported ever cannabis use. Men had a mean cumulative use of 2.57 cannabis-years and women 1.29 cannabis-years. Self-reported cumulative cannabis use was associated with worse verbal memory in men (e.g., −0.49 standardized units [SU] for ≥5 cannabis-years of exposure; 95% CI=−0.76 to −0.23), but not in women (SU=0.02; 95% CI=−0.26 to 0.29). Other measures of CF were not associated with cannabis. Changes in current cannabis use between years 25 and 30 were not associated with CF in men or women.
Conclusions: Self-reported cumulative cannabis exposure was associated with worse verbal memory in men but not in women. Researchers should consider stratified analyses by sex when testing the association between cannabis and cognition.

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An abstract and a poster have been presented at the SGAIM (Swiss Society of General Internal Medicine) Spring Congress 2021 ( Target Journal: Cannabis and Cannabinoids Research—“Call for Papers: Sex and Gender Differences: Focus on Cannabis and Cannabinoids.”


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Cite this article as: Pasquier B, Yaffe K, Levine DA, Rana JS, Pletcher MJ, Tal K, Sidney S, Auer R, Jakob J (2023) Sex differences in the association between cumulative use of cannabis and cognitive function in middle age: the coronary artery risk development in young adults study, Cannabis and Cannabinoid Research X:X, 1–17, DOI: 10.1089/can.2022.0343.

Information & Authors


Published In

cover image Cannabis and Cannabinoid Research
Cannabis and Cannabinoid Research
PubMed: 37594767


Published online: 18 August 2023




Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.
Kristine Yaffe
Department of Psychiatry, Neurology, Epidemiology and Biostatistics, University of California, San Francisco, California, USA.
Deborah A. Levine
Department of Internal Medicine and Cognitive Health Services Research Program, University of Michigan, Ann Arbor, Michigan, USA.
Jamal S. Rana
Department of Cardiology, Kaiser Permanente Northern California, Oakland, California, USA.
Mark J. Pletcher
Department of Psychiatry, Neurology, Epidemiology and Biostatistics, University of California, San Francisco, California, USA.
Kali Tal
Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.
Stephen Sidney
Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.
Reto Auer
Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.
University General Medicine and Public Health Centre, University of Lausanne, Lausanne, Switzerland.
Julian Jakob* [email protected]
Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.
Department of Paediatrics, University Hospital Bern, Inselspital, Bern, Switzerland.


Address correspondence to: Julian Jakob, MD, Institute of Primary Health Care (BIHAM), University of Bern, Mittelstrasse 43, 3012 Bern, Switzerland. [email protected]

Authors' Contributions

Conception and design of the study were carried out by B.P., R.A., and J.J. Acquisition, analysis, and interpretation of the data were contributed by B.P., K.Y., D.A.L., J.S.R., M.J.P., S.S., R.A., and J.J. Drafting of the article was done by B.P., K.T., R.A., and J.J. Critical revision of the article for important intellectual content was carried out by B.P., K.Y., D.A.L., J.S.R., M.J.P., K.T., S.S., R.A., and J.J. Final approval of the version to be published was taken care by B.P., K.Y., D.A.L., J.S.R., M.J.P., S.S., R.A., and J.J.

Author Disclosure Statement

All authors have no reported conflict of interest. All authors had access to the data.

Funding Information

The CARDIA study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201800005I and HHSN268201800007I), Northwestern University (HHSN268201800003I), University of Minnesota (HHSN268201800006I), and Kaiser Foundation Research Institute (HHSN268201800004I). This article was reviewed by CARDIA for scientific content.

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