ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1539813
This article is part of the Research TopicThe toxicology of cannabis and cannabis-based productsView all 8 articles
Cannabinoids and Alcohol Co-Exposure Modulate Pathogen-Induced Pulmonary Immune Responses
Provisionally accepted
DeJana Parker1
Vijay Sivaraman2*- 1University of Michigan, Ann Arbor, Michigan, United States
- 2North Carolina Central University, Durham, United States
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Both alcohol and cannabinoid misuse cause substantial societal problems individually, and cannabis is the most popular illicit drug used simultaneously with alcohol. The role of endocannabinoids (eCB) and cognate receptors in the regulation of inflammation is clinically relevant, however, the role of cannabinoid receptors (CBRs) specifically in pulmonary inflammation and associated lung pathobiology remains elusive. For this study, we investigated the effects of binge cannabinoid exposure on pathogen-induced pulmonary inflammation. We also describe a binge ethanol+cannabinoid adolescent mouse model of pathogen-induced pulmonary inflammation by Klebsiella pneumoniae (K.pneumoniae) infection. We show that adolescent cannabinoid exposure primes the lung to more severe inflammation in adulthood and this response is mitigated by cannabinoid antagonists. We also show that ethanol and cannabinoid pre-exposure followed by microbial challenge yielded CBR-dependent pulmonary immune activation via dangerassociated molecular pattern (DAMP) release. This research may shed light on CB signaling as it relates to DAMPs and can provide a framework for developing potential novel therapeutics in polysubstance use disorders.
Keywords: Cannabinoids, alcohol, pulmonary inflammation, Polysubstance misuse, Immune responses
Received: 04 Dec 2024; Accepted: 04 Jun 2025.
Copyright: © 2025 Parker and Sivaraman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Vijay Sivaraman, North Carolina Central University, Durham, United States
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