Executive Summary
Ä9-tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, induces persistent epigenetic modifications — DNA methylation changes, histone post-translational modifications, and altered non-coding RNA expression — that disrupt mesolimbic reward circuitry, impair neuroplasticity, and elevate risks of addiction, cognitive decline, and psychosis.

Cannabidiol (CBD), while pharmacologically distinct and non-intoxicating, offers only limited mitigation of these effects under conditions of repeated co-exposure, and THC-driven neuroadaptations dominate the epigenetic landscape of the mesolimbic system.

Evidence from preclinical rodent models and human cohort studies converges on the conclusion that these molecular “imprints” are often long-lasting, sometimes intergenerational, and only partially reversible with abstinence, providing a strong evidentiary basis for prevention-oriented, abstinence-focused policy in vulnerable populations such as adolescents and pregnant women.