Cannabis use altered DNA methylation in human and rat sperm, with changes in cancer and developmental pathways
A study found that cannabis use was associated with altered DNA methylation at nearly 4,000 sites in human sperm, with enrichment in Hippo Signaling and cancer pathways. The same pathways were affected in THC-exposed rat sperm, and cannabis use was also linked to lower sperm concentration.
Quick Facts
What This Study Found
Researchers compared DNA methylation in sperm from human cannabis users versus non-users, and from THC-exposed versus unexposed rats.
In human sperm, cannabis users differed from non-users by at least 10% methylation at 3,979 CpG sites.
Pathway analysis identified Hippo Signaling and Pathways in Cancer as enriched with altered genes (Bonferroni p < 0.02). These same two pathways were also enriched in THC-exposed rat sperm (p < 0.01), providing cross-species validation.
THC exposure levels in humans correlated significantly with methylation changes for 177 genes, suggesting a dose-response relationship.
There was substantial overlap between genes with altered methylation in rat sperm (this study) and genes previously reported as having altered methylation in the brains of rat offspring born to THC-exposed parents.
Cannabis use in humans was also associated with significantly lower sperm concentration.
Key Numbers
3,979 CpG sites differed by ≥10% between cannabis users and non-users. Hippo Signaling and Cancer pathways enriched (Bonferroni p < 0.02 in humans, p < 0.01 in rats). 177 genes showed dose-response correlation with THC levels. Cannabis use associated with lower sperm concentration.
How They Did This
Cross-sectional human comparison (cannabis users vs non-users) and controlled rat experiment (THC vs vehicle). DNA methylation by reduced representation bisulfite sequencing. Pathway analysis. Correlation of THC levels with methylation. Sperm concentration measurement.
Why This Research Matters
This is among the first studies to show that cannabis use alters the epigenetic signature of sperm in ways that affect developmental pathways, with potential implications for offspring. The cross-species replication strengthens the finding, and the overlap with offspring brain methylation patterns raises intergenerational concerns.
The Bigger Picture
Epigenetic changes in sperm could theoretically be transmitted to offspring, affecting their development. While this study cannot prove that paternal cannabis use harms children, the overlap between sperm methylation changes and offspring brain methylation patterns in rats is a serious signal that warrants further investigation.
What This Study Doesn't Tell Us
Human component is cross-sectional (cannabis users may differ in other ways). Small sample sizes in both human and rat studies. Methylation changes in sperm do not necessarily translate to functional changes in offspring. Reduced sperm concentration could have multiple causes.
Questions This Raises
- ?Do these sperm methylation changes reverse with cannabis cessation?
- ?Are offspring of cannabis-using fathers at measurable developmental risk?
- ?Which specific methylation changes are most functionally significant?
- ?Does the Hippo Signaling pathway disruption affect embryonic development?
Trust & Context
- Key Stat:
- 3,979 methylation sites altered in cannabis users' sperm, with cross-species validation in rats
- Evidence Grade:
- Moderate. Novel findings with cross-species validation and dose-response data, but small samples and inability to prove functional consequences in offspring limit conclusions.
- Study Age:
- Published in 2018. Paternal cannabis exposure epigenetics has become an active research area since this publication.
- Original Title:
- Cannabinoid exposure and altered DNA methylation in rat and human sperm.
- Published In:
- Epigenetics, 13(12), 1208-1221 (2018)
- Authors:
- Murphy, Susan K(11), Itchon-Ramos, Nilda(3), Visco, Zachary, Huang, Zhiqing, Grenier, Carole, Schrott, Rose, Acharya, Kelly, Boudreau, Marie-Helene, Price, Thomas M, Raburn, Douglas J, Corcoran, David L, Lucas, Joseph E, Mitchell, John T, McClernon, F Joseph, Cauley, Marty, Hall, Brandon J, Levin, Edward D, Kollins, Scott H
- Database ID:
- RTHC-01773
Evidence Hierarchy
A snapshot of a population at one point in time.
What do these levels mean? →Frequently Asked Questions
Could a father's cannabis use affect his future children?
This study found that cannabis alters DNA methylation in sperm, and some of these changes overlap with brain methylation patterns seen in rat offspring of THC-exposed parents. This raises the possibility of paternal transmission, but direct evidence of harm to human offspring has not been established.
What is the Hippo Signaling pathway?
Hippo Signaling is a pathway that controls organ size, cell growth, and tissue development. It plays critical roles during embryonic development. Disruption of this pathway in sperm DNA methylation could theoretically affect how genes are expressed during early development of offspring.
Read More on RethinkTHC
Cite This Study
https://rethinkthc.com/research/RTHC-01773APA
Murphy, Susan K; Itchon-Ramos, Nilda; Visco, Zachary; Huang, Zhiqing; Grenier, Carole; Schrott, Rose; Acharya, Kelly; Boudreau, Marie-Helene; Price, Thomas M; Raburn, Douglas J; Corcoran, David L; Lucas, Joseph E; Mitchell, John T; McClernon, F Joseph; Cauley, Marty; Hall, Brandon J; Levin, Edward D; Kollins, Scott H. (2018). Cannabinoid exposure and altered DNA methylation in rat and human sperm.. Epigenetics, 13(12), 1208-1221. https://doi.org/10.1080/15592294.2018.1554521
MLA
Murphy, Susan K, et al. "Cannabinoid exposure and altered DNA methylation in rat and human sperm.." Epigenetics, 2018. https://doi.org/10.1080/15592294.2018.1554521
RethinkTHC
RethinkTHC Research Database. "Cannabinoid exposure and altered DNA methylation in rat and ..." RTHC-01773. Retrieved from https://rethinkthc.com/research/murphy-2018-cannabinoid-exposure-and-altered
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.