"It has long been postulated that ongoing neurodevelopmental processes during adolescence may impart heightened vulnerability to cannabis exposure and increase the likelihood of long-term associations with cognition and behavior. Many animal studies have reported enduring effects of adolescent exposure to tetrahydrocannabinol (THC), the primary psychoactive substance in cannabis. Specifically, adolescent exposure to THC has been shown to decrease social behavior in adult rats46,47 as well as alter motivational processes.48 Rodent and primate studies have also demonstrated that adolescent exposure to THC results in working memory deficits in adulthood.49-52 Several rodent studies have also found that adolescent THC exposure results in lasting alterations in glutamatergic and γ-aminobutyric acidergic functioning.53,54 In humans, adolescent-onset cannabis users exhibit greater use-associated problems in adulthood relative to late-onset cannabis users.55,56 Findings from the present study may help to elucidate heightened vulnerability to the effects of cannabis use among adolescents. We found that the statistical map of age-related cortical change was significantly correlated with statistical maps of the time × cannabis interaction on cortical thickness as well as the main association of cannabis use with cortical thickness at 5-year followup. Taken together, these results suggest that, on average, cannabis use tended to qualify cortical thickness change within areas already undergoing the greatest degree of age-related change (from baseline to 5-year follow-up). This finding provides support for the association of cannabis use with ongoing maturational processes in the brain and a possible explanation for the heightened vulnerability to the cognitive outcomes of cannabis use among adolescents. More important, our imaging findings are consistent with recent animal research on adolescent THC exposure and prefrontal cortical maturation. Miller et al15 examined the association of adolescent THC exposure with prefrontal cortical maturation using a rat model. Researchers injected male rats with THC during the period of their adolescence, spanning 4 to 7 weeks of age. They found that adolescent THC exposure resulted in distinct proximate and long-term alterations of dendritic architecture. Specifically, THC exposure disrupted normal neurodevelopmental processes by inducing premature pruning of dendritic spines and atrophy of dendritic arbors in early adulthood. We hypothesize that the MR imaging (MRI)–assessed cannabis-related thinning revealed in our human study is underpinned by the same neurobiological phenomenon."


Albaugh MD, Ottino-Gonzalez J, Sidwell A, et al. Association of Cannabis Use During Adolescence With Neurodevelopment. JAMA Psychiatry. 2021;78(9):1031–1040. doi:10.1001/jamapsychiatry.2021.1258.