SPS2-05 Effects of Chronic Alcohol Drinking on Endocannabinoids / CB1R System in Lungs of Alcohol Use Disorder Patients

Introduction

Alcohol misuse leads to tissue injury across multiple organs through mechanisms such as inflammation, metabolic disruption, and impaired repair, resulting in severe health consequences including increased risk and poor outcomes from respiratory infections. Recent evidence suggests that the endocannabinoid/cannabinoid receptor 1(CB1R) system, known for its role in injury and repair in the liver, gut, and heart, may also be relevant in alcohol-related lung disease. CB1R activation has been linked to lung injury and fibroinflammatory remodeling in pulmonary fibrosis as well as maladaptive responses in COVID-19 pneumonia. These findings indicate that overactivity of endocannabinoid/CB1R signaling may be involved in alcohol-induced lung tissue injury. Therefore, investigating the status of endocannabinoid/CB1R signaling could enhance our understanding of its pathological role in alcohol-associated lung vulnerability and related complications.

Methods

To investigate the effect of alcohol misuse on the endocannabinoid system in human lungs, we measured endocannabinoids anandamide (AEA) and 2-arachidonyl glycerol (2-AG) in bronchoalveolar lavage fluid (BALF) from individuals with alcohol use disorder (AUD) (n = 96, 87% male Age=45) and controls (n = 40, 65% male, Age =36) by using liquid chromatograph coupled triple quad mass spectrometry. AUD participants were divided into four study groups based on cigarette smoking status (current or none) and the period of alcohol abstinence prior to BALF collection (≤7 days or ≥ 8 days).

Results

Compared to control participants, AEA levels were significantly higher in the BALF of participants with AUD who were within 7 days of abstinence (both smokers and non-smokers). AEA levels in BALF from AUD participants collected at ≥ 8 days of abstinence were not significantly different from AEA levels in control subjects. In contrast, the endocannabinoid 2-AG were similar in AUD participants and controls, regardless of time since abstinence.

Conclusion

These findings suggest that alcohol misuse in AUD patients contributes to overactivity of the endocannabinoid/CB1R system, evidenced by increased AEA in the local lung microenvironment. These findings warranting further investigation of endocannabinoid/CB1R-directed interventions in alcohol-associated pulmonary vulnerability.

This abstract is funded by: National Institutes of Health (NIH) Intramural Research Program