# Examining the Role of Circulating Endocannabinoids in Predicting Alcohol Relapse Risk and Resiliency

> **NIH NIH R21** · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $255,156

## Abstract

Project Summary
Approximately 14,500,000 Americans meet diagnostic criteria for current alcohol use disorder (AUD), and the
deaths of 88,000 Americans are attributed to alcohol misuse annually. There is an urgent need to bring our
current scientific understanding of the neurobiology of AUD to bear on the challenges of developing novel
treatments and biomarkers of relapse risk for individuals with AUD. The purpose of this new 2-year exploratory
R21 research project is to examine the role of circulating endogenous cannabinoids (eCBs) in predicting
alcohol relapse risk and resiliency, using archival, de-identified, longitudinal clinical research data and
associated plasma specimens frozen and maintained at -80 degrees. Clinical and eCB data were collected
from 300 individuals (69% male, mean age 40.3 yrs) with AUD who completed human laboratory studies
assessing reactivity to affective priming and in vivo alcohol cue exposure. The eCB signaling system is a
neuromodulatory system known to buffer stress-like responses. Pre-clinical evidence suggests that repeated
excessive alcohol consumption is associated with the blunting of the "on demand" release of eCBs which
provide an important source of inhibitory influence in brain stress signaling and mood homeostasis. Deficient
eCB tone as a result of chronic alcohol misuse may thus reflect the critical loss of signaling elements that
contribute to alcohol-related motivational pathologies, i.e., negative affect, craving, insomnia and relapse.
Circulating levels of eCBs have been found to be lower in humans with major depression, posttraumatic stress
disorder and following exposure to chronic stress. Unknown, however, is what role the eCB system plays in
stress-related relapse associated with alcohol use disorder. The purpose of this proposal is to test the
hypothesis that circulating eCB levels will identify individuals having heightened relapse risk or resiliency as
reflected in responsivity to affective priming and in vivo alcohol cue exposure in a human laboratory model of
craving and relapse risk in AUD. To test this hypothesis, Specific Aim 1 is designed to determine if eCB levels
(AEA, 2AG, PEA, OEA) in AUD subjects obtained at the time of cue testing vary in relation to reactivity to
alcohol cues, with high reactivity representing a heightened risk for relapse, and low reactivity representing
resiliency to relapse risk, and Specific Aim 2 is designed to determine if baseline eCB concentrations predict
subsequent eCB levels. The present proposal will provide key information linking craving driven by negative
emotional states to circulating eCBs. Significant association could provide a marker for vulnerability for craving
and/or resilience to craving either of which could provide a framework for a future clinical trial outlining key
markers for recovery and/or a clinical trial of medications to treat AUD by engaging the eCB system.

## Key facts

- **NIH application ID:** 9957492
- **Project number:** 1R21AA028321-01
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** BARBARA J MASON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $255,156
- **Award type:** 1
- **Project period:** 2020-04-10 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9957492

## Citation

> US National Institutes of Health, RePORTER application 9957492, Examining the Role of Circulating Endocannabinoids in Predicting Alcohol Relapse Risk and Resiliency (1R21AA028321-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9957492. Licensed CC0.

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