# Impact of progesterone on stress-reactivity and cannabis use in cannabis using men and women

> **NIH NIH U54** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $400,841

## Abstract

ABSTRACT
Important sex differences exist in the behavioral, biologic, and clinical correlates of cannabis use disorder (CUD);
these sex differences are critical to consider in CUD treatment development. In particular, stress may be an
important intervention target for women using cannabis, as multiple studies have shown that women use
cannabis for coping and tension reduction more than men and are more likely to crave cannabis following stress.
Ovarian hormones have been identified as potential mechanisms of these stress-related disparities, and recent
clinical trials have begun to examine progesterone's utility as a possible pharmacotherapeutic agent in addictive
disorders. While progesterone has shown promise as a treatment for women with cocaine and tobacco use
disorders, it has not yet been tested in cannabis users. We propose to evaluate the impact of progesterone on
stress reactivity and cannabis use in 140 cannabis using individuals (70 men and 70 women). Participants will
complete a 3-week protocol combining naturalistic and laboratory-based methodologies. During the first week,
participants will be compensated to remain abstinent and will be randomly assigned to receive either daily
progesterone (200 mg twice daily) or matching placebo; additionally, stress and neutral cues will be delivered to
their mobile devices and they will also collect daily saliva samples for progesterone measurement. On the first
day of the second study week, participants will be exposed to a standardized laboratory stressor (Trier Social
Stress Task) to assess the effects of exogenous progesterone vs placebo on stress reactivity. At the completion
of the laboratory procedures, participants will no longer be compensated for abstinence but they will use their
mobile device to respond to stress and neutral cues, monitor stress/craving levels, and report cannabis use
(three times daily) for the next fourteen days. Throughout these two weeks, ovarian hormone levels will continue
to be collected daily (via saliva samples) to evaluate their impact on stress and cannabis use. The proposed
study has significant synergies with Projects 2 and 3, utilizing similar assessment and pharmacologic
interventions, respectively. Presently, little is known about sex differences in CUD; this study has the potential
to expand that knowledge landscape. Importantly, this project will also assess the effects of exogenous and
endogenous progesterone on the challenges posed by initial abstinence and/or daily stress, which could directly
inform gender-specific treatment development for CUD.

## Key facts

- **NIH application ID:** 9991815
- **Project number:** 5U54DA016511-18
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** AIMEE L MCRAE-CLARK
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $400,841
- **Award type:** 5
- **Project period:** 2002-09-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991815

## Citation

> US National Institutes of Health, RePORTER application 9991815, Impact of progesterone on stress-reactivity and cannabis use in cannabis using men and women (5U54DA016511-18). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9991815. Licensed CC0.

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