Disentangling the lasting effects of adolescent cannabinoid exposure

Cannabis is the most widely used illicit substance among adolescents, and adolescent cannabis use is associated with various neurocognitive deficits that can extend into adulthood. A growing body of evidence supports the hypothesis that adolescence encompasses a vulnerable period of development where exposure to exogenous cannabinoids can alter the normative trajectory of brain maturation. In this review, we present an overview of studies of human and rodent models that examine lasting effects of adolescent exposure. We include evidence from meta-analyses, longitudinal, or cross-sectional studies in humans that consider age of onset as a factor that contributes to the behavioral dysregulation and altered structural or functional development in cannabis users. We also discuss evidence from preclinical rodent models utilizing well-characterized or innovative routes of exposure, investigating the effects of dose and timing to produce behavioral deficits or alterations on a neuronal and behavioral level. Multiple studies from both humans and animals provide contrasting results regarding the magnitude of residual effects. Combined evidence suggests that exposure to psychoactive cannabinoids during adolescence has the potential to produce subtle, but lasting, alterations in neurobiology and behavior.