Epigenetic Effects of Cannabis Exposure

Abstract

The past decade has witnessed a number of societal and political changes that have raised critical questions about the long-term impact of marijuana (Cannabis sativa) that are especially important given the prevalence of its abuse and that potential long-term effects still largely lack scientific data. Disturbances of the epigenome have generally been hypothesized as the molecular machinery underlying the persistent, often tissue-specific transcriptional and behavioral effects of cannabinoids that have been observed within one's lifetime and even into the subsequent generation. Here, we provide an overview of the current published scientific literature that examined epigenetic effects of cannabinoids. Though mechanistic insights about the epigenome remain sparse, accumulating data in humans and animal models have begun to reveal aberrant epigenetic modifications in brain and the periphery linked to cannabis exposure. Expansion of such knowledge and causal molecular relationships could help provide novel targets for future therapeutic interventions.

Adolescent THC exposure in female rats leads to cognitive deficits through a mechanism involving chromatin modifications in the prefrontal cortex

“…15,16 However, hints on epigenetic effects of THC exposure are generally scarce, particularly regarding adolescent THC administration. 17 Despite the limited evi dence, the few studies addressing this topic, although based on very different experimental models, suggest that THC may principally act on the epigenome through the modula tion of the repressive histone marker H3K9me3. [18][19][20][21][22][23] Correspondence to: T. Rubino Background: Increasing cannabis consumption among adolescents, studies that link its early use with mental illnesses, and the political debate on cannabis legalization together call for an urgent need to study molecular underpinnings of adolescent brain vulnerability.…”

Chronic exposure to cannabinoids during adolescence causes long‐lasting behavioral deficits in adult mice

“…DNAme provides a stable and potentially heritable epigenetic component, moderates gene–environment interactions (Rotter et al , 2012) and participates in normal brain development (Wilson and Sengoku, 2013) and psychiatric disorders (Tuesta and Zhang, 2014; Watson et al , 2015). Most importantly, THC exposure has already been linked to DNAme changes (for review, see Szutorisz and Hurd, 2015), but the potential effects of DNAme alterations on remote cognitive performance after drug exposure have not been deeply explored.…”

Genetic and Environmental Factors Associated with Cannabis Involvement

“…Further, it will be important to understand the molecular and neural mechanisms through which such effects emerge (e.g. epigenetic modification (94), stress-related gene expression (95)). Indeed, such mechanistic understanding will facilitate the development of treatments that may target links within the etiologic chain.…”