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Updated: Apr 8, 2026
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Chronic Intermittent Ethanol Vapor Exposure Paired with Two-Bottle Choice to Model Alcohol Use Disorder
Published on: June 23, 2023
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Roles for the endocannabinoid system in ethanol-motivated behavior
Angela N Henderson-Redmond1, Josée Guindon2, Daniel J Morgan3
1Department of Anesthesiology, Penn State University College of Medicine, Hershey, PA 17033, United States.
Summary
Targeting the endocannabinoid system may offer new treatments for alcohol use disorder. Modulating cannabinoid receptor 1 (CB1) shows promise in reducing alcohol consumption and relapse behaviors in preclinical models.
Area of Science:
- Neuroscience
- Pharmacology
- Addiction Research
Background:
- Alcohol use disorder (AUD) poses a major public health challenge with inadequate current treatments.
- The endocannabinoid system (ECS) plays a role in regulating ethanol-motivated behaviors.
- Chronic ethanol exposure alters the ECS, including down-regulation of cannabinoid receptor 1 (CB1).
Purpose of the Study:
- To explore the potential of targeting the endocannabinoid system for novel alcohol use disorder therapies.
- To investigate the role of CB1 receptor modulation in reducing ethanol consumption and related behaviors.
Main Methods:
- Review of preclinical rodent models and human neuroimaging studies (PET).
- Examination of the effects of CB1 inverse agonists (e.g., Rimonabant) and genetic CB1 deletion on ethanol intake and reward pathways.
- Analysis of chronic ethanol exposure effects on endocannabinoid levels and CB1 receptor function.
Main Results:
- Chronic ethanol exposure increases endocannabinoid levels, leading to CB1 receptor down-regulation and impaired signaling.
- PET studies show similar CB1 down-regulation in the brains of human alcoholic patients.
- Pharmacological or genetic blockade of CB1 receptors reduced ethanol drinking, dopamine release, and relapse behaviors in rodents.
Conclusions:
- The endocannabinoid system, particularly CB1 receptors, is a viable target for AUD treatment development.
- While CB1 antagonists have limitations, negative allosteric modulators and endocannabinoid catabolism inhibitors warrant further investigation for safer therapeutic strategies.
