PMID- 37179517 OWN - NLM STAT- MEDLINE DCOM- 20230612 LR - 20231120 IS - 1432-0738 (Electronic) IS - 0340-5761 (Print) IS - 0340-5761 (Linking) VI - 97 IP - 7 DP - 2023 Jul TI - Differential inflammatory profile in the lungs of mice exposed to cannabis smoke with varying THC:CBD ratio. PG - 1963-1978 LID - 10.1007/s00204-023-03514-3 [doi] AB - Cannabis contains cannabinoids including Delta(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC causes the psychoactive effects of cannabis, and both THC and CBD are thought to be anti-inflammatory. Cannabis is typically consumed by inhaling smoke that contains thousands of combustion products that may damage the lungs. However, the relationship between cannabis smoke exposure and alterations in respiratory health is poorly defined. To address this gap in knowledge, we first developed a mouse model of cannabis smoke exposure using a nose-only rodent inhalation exposure system. We then tested the acute effects of two dried cannabis products that differ substantially in their THC-CBD ratio: Indica-THC dominant (I-THC; 16-22% THC) and Sativa-CBD dominant (S-CBD; 13-19% CBD). We demonstrate that this smoke exposure regime not only delivers physiologically relevant levels of THC to the bloodstream, but that acute inhalation of cannabis smoke modulates the pulmonary immune response. Cannabis smoke decreased the percentage of lung alveolar macrophages but increased lung interstitial macrophages (IMs). There was also a decrease in lung dendritic cells as well as Ly6C(intermediate) and Ly6C(low) monocytes, but an increase in lung neutrophils and CD8(+) T cells. These immune cell changes were paralleled with changes in several immune mediators. These immunological modifications were more pronounced when mice were exposed to S-CBD compared to the I-THC variety. Thus, we show that acute cannabis smoke differentially affects lung immunity based on the THC:CBD ratio, thereby providing a foundation to further explore the effect of chronic cannabis smoke exposures on pulmonary health. CI - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Haidar, Zahraa AU - Haidar Z AD - Research Institute of the McGill University Health Centre, 1001 Decarie Blvd (EM22248), Montreal, QC, H4A3J1, Canada. AD - Meakins-Christie Laboratories, Montreal, QC, Canada. AD - Department of Medicine, McGill University, Montreal, QC, Canada. FAU - Traboulsi, Hussein AU - Traboulsi H AD - Research Institute of the McGill University Health Centre, 1001 Decarie Blvd (EM22248), Montreal, QC, H4A3J1, Canada. AD - Meakins-Christie Laboratories, Montreal, QC, Canada. AD - Department of Medicine, McGill University, Montreal, QC, Canada. FAU - Eidelman, David H AU - Eidelman DH AD - Research Institute of the McGill University Health Centre, 1001 Decarie Blvd (EM22248), Montreal, QC, H4A3J1, Canada. AD - Meakins-Christie Laboratories, Montreal, QC, Canada. AD - Department of Medicine, McGill University, Montreal, QC, Canada. FAU - Baglole, Carolyn J AU - Baglole CJ AUID- ORCID: 0000-0002-3107-0437 AD - Research Institute of the McGill University Health Centre, 1001 Decarie Blvd (EM22248), Montreal, QC, H4A3J1, Canada. Carolyn.baglole@mcgill.ca. AD - Meakins-Christie Laboratories, Montreal, QC, Canada. Carolyn.baglole@mcgill.ca. AD - Department of Medicine, McGill University, Montreal, QC, Canada. Carolyn.baglole@mcgill.ca. AD - Department of Pathology, McGill University, Montreal, QC, Canada. Carolyn.baglole@mcgill.ca. AD - Department of Pharmacology & Therapeutics, McGill University, Montreal, QC, Canada. Carolyn.baglole@mcgill.ca. LA - eng GR - 162273/CIHR/Canada GR - 162273/CIHR/Canada PT - Journal Article DEP - 20230514 PL - Germany TA - Arch Toxicol JT - Archives of toxicology JID - 0417615 RN - 19GBJ60SN5 (Cannabidiol) RN - 7J8897W37S (Dronabinol) RN - 0 (Smoke) RN - 0 (Hallucinogens) RN - 0 (Cannabinoid Receptor Agonists) SB - IM MH - Animals MH - Mice MH - *Cannabis MH - *Cannabidiol/toxicity MH - Dronabinol/toxicity/analysis MH - Smoke/adverse effects MH - CD8-Positive T-Lymphocytes MH - *Hallucinogens MH - Cannabinoid Receptor Agonists MH - Lung PMC - PMC10183104 OTO - NOTNLM OT - Cannabinoid OT - Cannabis OT - Cytokines OT - Inflammation OT - Macrophage OT - THC COIS- The authors declare that there is no conflict of interest. EDAT- 2023/05/14 13:10 MHDA- 2023/06/12 06:42 PMCR- 2023/05/14 CRDT- 2023/05/14 11:04 PHST- 2023/03/03 00:00 [received] PHST- 2023/04/26 00:00 [accepted] PHST- 2023/06/12 06:42 [medline] PHST- 2023/05/14 13:10 [pubmed] PHST- 2023/05/14 11:04 [entrez] PHST- 2023/05/14 00:00 [pmc-release] AID - 10.1007/s00204-023-03514-3 [pii] AID - 3514 [pii] AID - 10.1007/s00204-023-03514-3 [doi] PST - ppublish SO - Arch Toxicol. 2023 Jul;97(7):1963-1978. doi: 10.1007/s00204-023-03514-3. Epub 2023 May 14.