# Impact of Dual Alcohol and Cannabis Use on Lung

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2022 · $185,951

## Abstract

Project Summary/Abstract
In the US, mortality attributable to alcohol consumption continues to climb, while cannabis use and associated
disorders are also becoming increasingly prevalent. Concurrent cannabis use is reported by an estimated 11%
of regular alcohol consumers, and cannabis use has been linked to increased frequency and quantity of
alcohol consumption. Harmful alcohol use can heighten the risk of respiratory infections, particularly
community-acquired pneumonia (CAP). However, how dual alcohol and cannabis consumption influences CAP
risk is unknown, and their combined impact on pulmonary immune cell function is not established. Through
investigations facilitated by the Colorado Pulmonary-Alcohol Research Collaborative (CoPARC), a NIAAA-
supported R24 Research Resource, we seek to unravel how dual alcohol and cannabis use exacerbate the
risk of developing pulmonary infections, including CAP. Our preliminary studies indicate that harmful alcohol
and cannabis exposures alter expression of genes that are critical for pathogen recognition in both airway
epithelial cells (AECs) and alveolar macrophages (AMs). The focus of this proposal is to gain detailed insights
into how the combination of harmful alcohol and cannabis use alter fundamental immune cell functions in
pathogen recognition and clearance. Specific Aim 1 will establish the molecular signature of dual alcohol and
cannabis misuse in human AECs and AMs. Studies will be performed with bronchoscopically obtained cells
(AECs and AMs) and fluid from four participant types in the CoPARC biorepository, including those with
alcohol use disorders (AUDs), with and without cannabis use; cannabis users; and control participants. RNA-
seq will be performed to gain detailed insights into immunomodulatory changes associated with substance use.
Additionally, the relationship of substance use on mucus secretion markers and inflammatory mediators will be
assessed in BAL fluid. In Specific Aim 2, we will establish cooperativity between alcohol and cannabinoid (CB)
receptor agonists on cellular responses to pathogens and pathogen components in human BEAS-2B cell lines
(bronchial epithelium) and THP1 monocyte-derived macrophages (Macs). Cells will be treated with ± alcohol ±
specific CB receptor agonists, and outcome measures will include efficiency in neutralizing and killing bacteria,
modulation of TLR responsiveness, expression of immunomodulatory cytokines, and expression of MUC5AC
and epithelial barrier disruption. Further functional outcomes will be studied in BEAS-2B cell lines and Macs
subjected to human BAL fluid from the four participant types (as for Aim 1). Through these mutually linked
aims, we will gain valuable insights into dual alcohol- and cannabis-imposed alterations in pathogen
recognition.

## Key facts

- **NIH application ID:** 10471332
- **Project number:** 5R21AA028871-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** ELLEN L BURNHAM
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $185,951
- **Award type:** 5
- **Project period:** 2021-08-20 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10471332

## Citation

> US National Institutes of Health, RePORTER application 10471332, Impact of Dual Alcohol and Cannabis Use on Lung (5R21AA028871-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10471332. Licensed CC0.

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