# Psychopharmacological effects of cannabidiol on responses to stress and nicotine withdrawal

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2024 · $652,290

## Abstract

Summary
Despite advances in tobacco smoking cessation interventions (pharmacological and behavioral), most
smokers do not succeed at quitting, creating a major public health burden. Stress is one of the most
commonly reported precipitants of tobacco craving and relapse. Tobacco withdrawal is associated with
escalation of negative affect symptoms; our research has found multiple stress-related physiological and
hormonal alterations during withdrawal that predict relapse. Modifying these stress-related biobehavioral
changes may prove useful in reducing effects of stress. Cannabidiol (CBD) is a phytocannabinoid of
cannabis with low abuse liability that has received increased attention in the retail market and cannabis
research. Although CBD is aggressively marketed for addressing stress, little research has been done to
characterize CBD’s physiological and mood effects, their implications in managing tobacco withdrawal
symptoms, and the mechanism by which CBD may influence these symptoms. Our research will address
these timely issues. This application builds on our current and previous funding periods (PI: al’Absi,
R01DA027232) demonstrating that stress-related hormonal changes during tobacco withdrawal predict
relapse. We have shown that tobacco dependence is linked with: 1) enhanced basal hypothalamic-pituitary-
adrenocortical (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 relapse; and 5)
sex differences in changes during withdrawal and predictors of relapse; hormonal responses are better
predictors of relapse in men, while withdrawal symptoms and craving are stronger predictors of relapse in
women. Our recent research has also documented blunted emotion regulation among cannabis users. In
the new cycle, we plan to conduct a multi-site, multi-group, multi-dose, double blind, within-subject study.
We will address the following specific aims: 1) Determine the acute effect of CBD on the psychobiological
mechanisms of the stress response in healthy participants; 2) Examine how tobacco dependence influences
the acute effect of CBD on psychobiological mechanisms of the stress response; 3) Determine the effect of
CBD on tobacco withdrawal-related changes in psychobiological mechanisms of the stress response in
tobacco users; 4) Explore sex differences in the psychobiological mechanisms of the stress response and
acute effects of CBD in dependent tobacco users. This research is the first to examine CBD's effect during
exposure to acute stress and tobacco withdrawal using relevant measures that are known to be sensitive to
acute stress and to tobacco withdrawal. The research builds on important preliminary results and uses
rigorous, reproducible procedures.

## Key facts

- **NIH application ID:** 10804182
- **Project number:** 2R01DA027232-09A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Dustin Clark Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $652,290
- **Award type:** 2
- **Project period:** 2010-09-30 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10804182

## Citation

> US National Institutes of Health, RePORTER application 10804182, Psychopharmacological effects of cannabidiol on responses to stress and nicotine withdrawal (2R01DA027232-09A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10804182. Licensed CC0.

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