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Observational Study
. 2025 Apr 9;25(1):168.
doi: 10.1186/s12890-025-03634-9.

Cannabis smoking is associated with persistent epigenome-wide disruptions despite smoking cessation

Ana I Hernandez Cordero  1   2 , Xuan Li  1 , Chen Xi Yang  1 , Amirtha Ambalavanan  3 , Julie L MacIsaac  2   4 , Michael S Kobor  2   4 , Dany Doiron  5 , Wan Tan  1 , Jean Bourbeau  5 , Don D Sin  1   2   6 , Qingling Duan #  3   7 , Janice M Leung #  8   9   10 ; CanCOLD Collaborative Research Group
Collaborators, Affiliations
Observational Study

Cannabis smoking is associated with persistent epigenome-wide disruptions despite smoking cessation

Ana I Hernandez Cordero et al. BMC Pulm Med. .

Abstract

Background: The use of cannabis has been associated with both therapeutic and harmful effects. As with cigarette smoking, cannabis smoking may affect the epigenetic regulation (e.g., DNA methylation) of gene expression which could result in long term health effects. The study of DNA methylation in cannabis smoking has to date been restricted to young adults and there remains yet no evaluation of whether cannabis smoking cessation can reverse epigenetic disturbances. Here, we aimed to investigate the relationship between genome-wide DNA methylation and cannabis smoking.

Methods: We used peripheral blood from a subset of older adults within the Canadian Cohort of Obstructive Lung Disease (CanCOLD) cohort (n = 93) to conduct an epigenome-wide DNA methylation analysis that identified differential methylated positions (DMPs) associated with cannabis smoking at a false discovery rate < 0.05. Using these DMPs, we then identified differentially methylated genes (DMGs) that enriched pathways associated with both former and current cannabis smoking status.

Results: We found DMPs corresponding to 12,115 DMGs and 10,806 DMGs that distinguished the current and former cannabis smoking groups, respectively, from the never cannabis smoking group. 5,915 of these DMGs were shared between the current and former cannabis smoking groups. 50 enriched pathways were also shared between the current and former cannabis smoking groups, which were heavily represented by multiple aging- and cancer-related pathways.

Conclusions: Our findings indicate that in older adults, cannabis smoking is linked with epigenome-wide disruptions, many of which persist despite cannabis smoking cessation. Epigenetic modulation of genes associated with aging and cancer that remains even after quitting cannabis should serve as a caution that there may be long-lasting epigenetic injury with cannabis smoking.

Trial registration: NCT00920348.

Keywords: Cannabis; Epigenetics; Marijuana; Methylation; Smoking cessation.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Each institution at the study sites had ethics approval for the parent study [University of British Columbia and Providence Health Care Research Ethics Board, H08 - 01876 (Vancouver); Bio-REB09 - 162 (Saskatoon); Conjoint Health Research Ethics Board, ID21258 (Calgary); University Health Network Research Ethics Board, 06–0421-B (Toronto); 2009519 - 01H (Ottawa); DMED- 1240–09 (Kingston); McGill University Health Centre Research Ethics Board, 09–025-BMB-t (Montreal); CER20459 (Quebec City); Capital Health Research Ethics Board, CDHA-RS/2007–255 (Halifax)]. All participants provided written informed consent. This study adhered to the ethical principles of the Declaration of Helsinki. This specific study was approved by the University of British Columbia and Providence Health Care Research Ethics Board, certificate approval number H15 - 02166. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Differentially methylated positions (DMPs) associated with cannabis smoking. Volcano plots are shown for significant DMPs associated with a former cannabis smoking and b current cannabis smoking with never smoking status as the reference group. Compared to never smoking, hypomethylated DMPs are shown in blue and hypermethylated DMPs are shown in red. The x-axis represents the effect size for each CpG tested, where 0 represents 0% difference in methylation between groups, and 1 represents a 100% methylation difference
Fig. 2
Fig. 2
Differentially methylated pathways in former cannabis smoking. The top 50 enriched KEGG pathways are shown for the former cannabis smoking group. Color intensity (black to yellow) represents the level of significance. Abbreviations: false discovery rate – FDR; Kyoto Encyclopedia of Genes and Genomes – KEGG
Fig. 3
Fig. 3
Differentially methylated pathways in current cannabis smoking. The top 50 enriched KEGG pathways are shown for the current cannabis smoking group. Color intensity (black to yellow) represents the level of significance. Abbreviations: false discovery rate – FDR; Kyoto Encyclopedia of Genes and Genomes – KEGG
See this image and copyright information in PMC

References

    1. Bahji A, Stephenson C. International perspectives on the implications of cannabis legalization: a systematic review & thematic analysis. Int J Environ Res Public Health. 2019;16:3095. - PMC - PubMed
    1. Tramèr MR, Carroll D, Campbell FA, Reynolds DJM, Moore RA, McQuay HJ. Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ. 2001;323:16. - PMC - PubMed
    1. Schubert EA, Johnstone MT, Benson MJ, Alffenaar JC, Wheate NJ. Medicinal cannabis for Australian patients with chronic refractory pain including arthritis. Br J Pain. 2023;17:206–17. - PMC - PubMed
    1. Torres-Moreno MC, Papaseit E, Torrens M, Farré M. Assessment of efficacy and tolerability of medicinal cannabinoids in patients with multiple sclerosis: a systematic review and meta-analysis. JAMA Netw Open. 2018;1:e183485. - PMC - PubMed
    1. Stockings E, Zagic D, Campbell G, Weier M, Hall WD, Nielsen S, et al. Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence. J Neurol Neurosurg Psychiatry. 2018;89:741–53. - PubMed

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