# Effect of sex differences and concurrent cannabis use on stress-related psychobiological mechanisms associated with smoking cessation and relapse

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $348,822

## Abstract

Abstract
Smoking cessation interventions (pharmacological and behavioral) and policy actions have reduced overall
smoking rates. However, there remain significant populations for whom success rates are lower than predicted,
most notably smokers who use other substances and those with psychiatric disorders. Cannabis, the most
prevalent illicit drug in the U.S. and among tobacco users, may increase risk for relapse to cigarette smoking.
Stress is one of the most commonly reported precipitants of smoking and relapse for both tobacco and
cannabis users. Systems involved in the stress response, including the hypothalamic-pituitary-adrenocortical
(HPA), endocannabinoid, and sympathetic systems, play a critical role in regulating mood and the reinforcing
effects of drug use. Research from our current and previous funding periods has shown that cigarette smokers
exhibit: 1) enhanced basal HPA activity; 2) blunted cortisol response to multiple stressors; 3) disrupted opioid
regulation of the stress response; 4) association of attenuated stress response and early smoking relapse; and
5) sex differences in patterns of predictors of relapse-- men exhibit consistent hormonal prediction, while
women show consistent withdrawal symptoms predictive of smoking relapse. It is not known whether the
altered stress response observed in smokers is further exacerbated by cannabis co-use. How these systems
are modified by withdrawal and influence risk for relapse is also unknown. Research to elucidate sex
differences in these factors is particularly lacking. We propose to elucidate stress-related psychobiological
mechanisms associated with concurrent cannabis use that impede successful smoking cessation and which,
when identified, can be used as metrics to identify and tailor interventions. We will therefore conduct this
research to: 1) Define the impact of concurrent cannabis use on the psychobiological mechanisms of the stress
response in smokers who are interested in quitting but still smoking ad libitum, 2) determine the impact of
abstinence from cannabis use, in conjunction with abstinence from cigarette smoking, on stress response in
smokers who are interested in tobacco cessation, 3) examine the extent to which stress response during ad
libitum smoking and during abstinence from tobacco, or from tobacco and cannabis, predict affective
disturbance and smoking relapse over three months, and 4) identify sex differences in diurnal patterns and the
stress response during ad libitum smoking and withdrawal in smokers and co-users, and establish the extent to
which these differences predict relapse. The proposed work will build on our previous research to set the stage
for interventions that involve a personalized medicine approach to predicting smoking relapse. This will enable
the development and testing of targeted, sex-specific, just-in-time interventions to address the impact of stress
and co-use of cannabis on smoking cessation.

## Key facts

- **NIH application ID:** 9977992
- **Project number:** 5R01DA027232-08
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Mustafa al'Absi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $348,822
- **Award type:** 5
- **Project period:** 2010-09-30 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977992

## Citation

> US National Institutes of Health, RePORTER application 9977992, Effect of sex differences and concurrent cannabis use on stress-related psychobiological mechanisms associated with smoking cessation and relapse (5R01DA027232-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9977992. Licensed CC0.

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