Like there is no smoke without fire, another study has linked cannabis use to unwanted epigenetic alterations. We’ve seen that cannabis exposure alters DNA methylation in prenatal mouse brains (influencing subsequent behavior), the sperm of rats and humans (priming an autism spectrum disorder-like profile), and human adult brains (impacting brain function), and now epigenetic aging has added fuel to the flames. Do these studies suggest that risk-free cannabis use has gone up in smoke?
A talented team led by Joseph P. Allen and Jessica J. Connelly (University of Virginia) evaluated how long-term cannabis exposure impacts epigenetic aging as measured through DNA methylation profiles. They assessed links between cannabis use (assessed yearly) and epigenetic aging (measured at age 30) through a prospective longitudinal study of over 150 participants aged between 13 and 30 from the southeastern USA. The team evaluated epigenetic aging in blood samples using DNA methylation-based epigenetic clocks and co-analyzed additional parameters as other possible confounding/associated factors.
So, let’s hear more from Allen and colleagues about this seventeen-year, multi-method, prospective study of cannabis smoking in a diverse community sample:
- Lifetime levels of marijuana use predict accelerated epigenetic aging measured by DNAmGrimAge and DunedinPoAm
- Predictions remain after accounting for cigarette smoking, which causes additional epigenetic acceleration
- Prior health problems, varying family incomes, gender, personality traits, and lifetime history of anxiety/depressive symptoms fail to explain the link between cannabis use and accelerated epigenetic age
- Higher cannabis use associates with more significant epigenetic age acceleration, indicating a dose-response effect
- More recent cannabis use also strongly associates with epigenetic age acceleration, indicating a recency-of-use effect
- Epigenetic effects of smoke inhalation among cannabis users likely mediate these links
- Hypomethylation at a CpG site associated with the aryl hydrocarbon receptor repressor gene (previously linked to effects of smoking) appears to fully mediate the effects of cannabis use on accelerated epigenetic aging
While these findings suggest the association of accelerated epigenetic aging with cannabis use, prospective longitudinal datasets such as these cannot fully establish causal links. However, the team hopes to advance research in this field by exploring additional epigenetic mechanisms, the effects of cannabis quantity, quality, and potency, and the impact of other forms of cannabis ingestion (other than smoking) to fully delineate how cannabis affects the epigenome and healthy aging.
Has risk-free cannabis use truly gone up in smoke? To find out more, see Drug and Alcohol Dependence, February 2022.