# Endocannabinoid Mechanisms in the Pathophysiology of Alcohol Use Disorders

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $399,480

## Abstract

PROJECT SUMMARY 
Alcohol  use  disorders  (AUDs)  manifest  from  a  convergence  of  characteristics  of  the  individual,  the 
environment,  and  the  alcohol  itself.    The  affective  disturbances  associated  with  alcohol  withdrawal  are 
examples  of  this  convergence  and  represent  a  critical  barrier  to  successful  treatment.  Reduction  of  these 
affective disturbances has been suggested to represent an important conceptual approach to reduce negative 
reinforcement-­based  alcohol  intake  in  dependent  individuals.  However,  treatment  of  these  affective 
disturbances is complicated by data indicating reduced efficacy of antidepressants such as selective-­serotonin 
reuptake  inhibitors  (SSRIs)  in  patients  with  AUDs,  and  that  these  traditional  treatments  can  actually  increase 
alcohol  intake  in  some  people;;  thus,  alternate  non-­monoamine-­based  treatment  approaches  for  affective 
symptoms  associated  with  AUDs  are  critically  needed.    Here  we  will  test  the  novel  hypothesis  that 
pharmacological augmentation of endogenous cannabinoid signaling could represent an effective treatment for 
negative  affective  states  associated  with  alcohol  withdrawal  including  anxiety  and  depression,  and  could 
thereby  facilitate  abstinence  in  patients  with  AUDs.  We  will  test  the  overall  hypothesis  that  2-­
arachidonoylglycerol  (2-­AG)-­mediated  endocannabinoid  signaling  reduces  anxiety  and  depressive-­like 
behaviors  associated  with  acute  and  protracted  alcohol  withdrawal  in  a  mouse  model  of  voluntary  alcohol 
consumption.  To  interrogate  the  underlying  mechanism  of  this  effect,  we  will  test  the  hypothesis  that  insula 
cortical-­extended  amygdala  circuits  are  hyperactive  during  alcohol  withdrawal  and  that  over  activation  of  this 
circuit is causally linked to the affective phenotypes observed during alcohol withdrawal. Finally, we will test the 
hypothesis  that  2-­AG-­mediated  inhibition  of  insula-­extended  amygdala  circuit  activity  represents  a  key 
mechanism by which endocannabinoid signaling reduces alcohol withdrawal-­induced anxiety and depressive-­
like  behaviors.    These  data  could  provide  new  insight  into  the  neural  circuit  mechanisms  responsible  for 
generating  negative  affective  states  associated  with  alcohol  withdrawal,  and  reveal  novel  neuromodulatory 
mechanisms  capable  of  counteracting  these  processes.  If  successful,  these  studies  could  support 
advancement of 2-­AG-­based pharmacological treatments for AUDs and co-­morbid affective disorders.

## Key facts

- **NIH application ID:** 9939409
- **Project number:** 5R01AA026186-04
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Sachin Patel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $399,480
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939409

## Citation

> US National Institutes of Health, RePORTER application 9939409, Endocannabinoid Mechanisms in the Pathophysiology of Alcohol Use Disorders (5R01AA026186-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9939409. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*