# Comorbidity of PTSD and Alcohol Dependence: Endocannabinoid Regulation

> **NIH VA IK2** · JOHN D DINGELL VA MEDICAL CENTER · 2020 · —

## Abstract

Thirty-one percent of the Vietnam-era Veterans have been diagnosed with posttraumatic stress disorder
(PTSD). Among those, 70% have also been diagnosed with an alcohol use disorder (AUD). Veterans with PTSD
use alcohol to cope with their distressing psychological symptoms such as anxiety. However, alcohol withdrawal
effects overlap with PTSD symptoms, thereby reinforcing alcohol consumption to alleviate the PTSD symptoms.
Studies have shown that individuals with comorbid PTSD and AUD have increased intensity of alcohol cravings
and relapse faster during withdrawal than those with AUD only. The cannabinoid (CB) system plays an important
role in both stress and alcohol dependence. Clinical studies have shown that individuals with PTSD have
dysregulated levels of the endocannabinoids, 2-arachidonolglycerol (2-AG) and anandamide (AEA). Animal
studies have also shown that both 2-AG and AEA concentrations and CB1 receptor protein levels are altered
after acute and chronic stress. While extensive research has shown that PTSD or AUD alone affects the CB
system, and different durations of ethanol withdrawal alone dysregulate the CB1 receptor, the role of the CB
system on the comorbidity of PTSD and alcohol dependence and withdrawal is yet unknown.
 This knowledge gap will be addressed in this application by elucidating the mechanism by which the
comorbidity of PTSD and ethanol dependence and withdrawal dysregulates cannabinoid functions that cause
negative health consequences outcomes for our Veterans. The central hypothesis of this project is that PTSD
comorbid with ethanol dependence and withdrawal will uniquely dysregulate CB signaling causing an increase
in ethanol consumption and anxiety behavior, and that a cannabinoidergic-based intervention will block this
effect.
 Mice will undergo traumatic stress using the single prolonged stress paradigm followed by chronic
intermittent ethanol vapor (CIEv) exposure, a model of ethanol dependence. After 4 cycles of CIEv with 5-days
of 2-bottle choice drinking tests during intervening weeks, mice will be withdrawn from ethanol for 7, 30, and 60
days. The following three Specific Aims will be tested to support the central hypothesis: 1) Evaluate the effects
of traumatic stress and ethanol dependence on ethanol consumption and anxiety behavior as a function of
ethanol withdrawal duration. 2) Examine changes in CB signaling associated with ethanol-induced withdrawal
behaviors as a factor of withdrawal duration. 3) Evaluate the efficacy of a selective CB1 agonist,
methanandamide, to block stress-induced ethanol dependence and withdrawal outcomes.

## Key facts

- **NIH application ID:** 9824468
- **Project number:** 5IK2RX002686-02
- **Recipient organization:** JOHN D DINGELL VA MEDICAL CENTER
- **Principal Investigator:** Veronica Piggott
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-10-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9824468

## Citation

> US National Institutes of Health, RePORTER application 9824468, Comorbidity of PTSD and Alcohol Dependence: Endocannabinoid Regulation (5IK2RX002686-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9824468. Licensed CC0.

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