# Sex Differences in the Interface between Cannabis Use and Stress among Emerging Adults

> **NIH NIH U54** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2024 · $298,716

## Abstract

PROJECT SUMMARY/ABSTRACT
Among the physiological systems most important to brain development in emerging adulthood is the
endocannabinoid system, which among other roles facilitates cognitive and behavioral processing, including the
underpinnings of stress management and resiliency. Sex differences in endocannabinoid system development
have been identified, and emerging evidence indicates a bidirectional relationship between stress exposure and
the endocannabinoid system during emerging adulthood. Repeated exposure to exogenous cannabinoids, such
as those administered via cannabis use, perturbates endocannabinoid system development, which may
adversely affect the programming of future coping in a manner that differs by sex. Use of cannabis, which exerts
its psychoactive effects via delta-9-tetrahydrocannabinol binding to endocannabinoid receptors, is more common
among emerging adults than in any other age group. Many regular users develop a maladaptive, impairing
pattern of use characterized as cannabis use disorder (CUD). A constellation of preliminary evidence suggests
several factors disproportionately complicate CUD in females compared to males; the salience of these factors
in emerging adulthood indicates that this developmental stage deserves focused sex differences research to
inform clinical management. A central running thread is the importance of stress and stress-reactivity across
endocannabinoid system development, cannabis use, CUD, cannabis withdrawal, and relapse to cannabis use.
We propose an experiment that combines rigorous ecological momentary assessment (EMA), controlled human
laboratory procedures, and innovative bioassay collection. Emerging adult cannabis users with CUD (ages 18-
25, N=148, 1:1 female to male ratio) will undergo 3 days of reinforced abstinence with EMA monitoring of
cannabis withdrawal and stress-related symptoms, followed by a standardized laboratory stress induction
paradigm. Blood levels of endocannabinoid system markers will be assessed before and after the abstinence
period; during the lab session, self-report measures and biomarkers of stress reactivity will be collected. Double-
blind cannabidiol (CBD) versus placebo dosing before the laboratory stress paradigm will allow for examination
of effects on stress response during withdrawal. Prior work indicates CBD administration reduces stress
response in general populations and preliminary research suggests this effect may extend to cannabis users;
this has not been rigorously applied to induced stress amid cannabis withdrawal in emerging adults with CUD, a
context particularly important for females with CUD who often report using cannabis to cope with stress.
Following the laboratory session, EMA monitoring will resume as participants return to ad libitum cannabis use,
providing the opportunity to test associations between stress reactivity and time to resumption of use. The
proposed study is designed to elucidate sex differences and guide the developm...

## Key facts

- **NIH application ID:** 10898732
- **Project number:** 5U54DA016511-22
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Kevin M. Gray
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $298,716
- **Award type:** 5
- **Project period:** 2002-09-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898732

## Citation

> US National Institutes of Health, RePORTER application 10898732, Sex Differences in the Interface between Cannabis Use and Stress among Emerging Adults (5U54DA016511-22). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10898732. Licensed CC0.

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