# Gender and Sex Hormone Influences on Cannabis Use Disorder Remission

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2022 · $431,010

## Abstract

PROJECT SUMMARY/ABSTRACT
Cannabis use disorder (CUD) is prevalent and associated with significant clinical sequelae. Effective treatment
for CUD may be complicated by gender and sex differences in the behavioral, biological, and clinical correlates
of CUD. Women demonstrate more severe withdrawal, more rapid progression from first use to CUD, and
greater likelihood of comorbid psychiatric disorder, while men tend to initiate use earlier and have higher
lifetime prevalence rates of CUD. In other addictive disorders, such as alcohol use disorder, clinical trial
endpoints are sex/gender specific. However, to date, no work has focused on whether different clinically
relevant endpoints may be needed for men and women with CUD. An expert workgroup recently concluded
that reduced cannabis use is a viable alternative endpoint to abstinence in CUD trials, particularly in the
context of changing patient preferences and growing cannabis legalization. However, the amount of reduction
necessary for remission from CUD is unknown and may differ for men and women. An emerging literature
suggests that ovarian hormones play a key role in drug use. Preclinical and clinical research suggests that
endogenous progesterone attenuates drug sensitivity and behavior. Recent clinical studies investigating
exogenous progesterone as a potential pharmacotherapy have shown that it attenuates the subjective and
physiological effects of cocaine and tobacco in drug-dependent individuals. Presently, little is known regarding
the interface of progesterone and CUD, and if fluctuations in progesterone levels may impact ability to reduce
cannabis use. This proposal addresses a key gap in CUD treatment research by empirically-deriving the
threshold of cannabis quantity and frequency of use below which most individuals in CUD treatment can
achieve CUD remission. Importantly, the roles of gender and ovarian hormones in CUD outcomes are
considered and gender-specific endpoints will be derived. Treatment-seeking adults who meet criteria for CUD
(N=224, ages 18+, 50% female) will receive 8 weeks of a psychosocial intervention, including computerized
CBT4CBT. CUD symptoms and detailed information on cannabis use will be collected from participants during
the 8-week treatment period and during a three month follow-up (1, 2, and 3 month follow-up visits).
Participants will complete daily electronic diaries to enhance assessment of self-reported cannabis quantity
and frequency of use, corroborated by weekly assessment of a urinary cannabis metabolite, 11-nor-9-carboxy-
Δ⁹-tetrahydrocannabinol. Daily saliva samples will be collected for assessment of progesterone. Analyses will
examine whether the threshold for cannabis reduction necessary to achieve remission from CUD differs by
gender and the effect of variation in progesterone on successful cannabis reduction. The establishment of
gender-specific reduction endpoints will have both real-world clinical treatment implications as well as enable
f...

## Key facts

- **NIH application ID:** 10435554
- **Project number:** 5R01DA054617-02
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** AIMEE L MCRAE-CLARK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $431,010
- **Award type:** 5
- **Project period:** 2021-07-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10435554

## Citation

> US National Institutes of Health, RePORTER application 10435554, Gender and Sex Hormone Influences on Cannabis Use Disorder Remission (5R01DA054617-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10435554. Licensed CC0.

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