"Several limitations of the present study should also be addressed. The PET data used in this study were collected on a separate sample of young adults, not the 799 youths who underwent longitudinal neuroimaging. Given the invasive nature of PET imaging and its associated risks, it is not ethical to collect PET data on minors. We cannot state definitively that, in our sample of 799 participants, the areas exhibiting cannabis-related thinning in longitudinal MRI analysis were, in fact, high in CB1 receptor availability. Our present findings are also limited by the self-report nature of our cannabis use measure. As with any self-report measure, it is possible that participants were not honest regarding their cannabis use or that their estimates of past cannabis use were inaccurate. We also did not have information pertaining to the types of cannabis products used (eg, cannabis oil concentrates and other formulations). As in other longitudinal MRI studies, there is uncertainty with regard to the exact neurobiological mechanisms associated with MRI-assessed cortical thinning. Research suggests that MRI-assessed, age-related cortical thinning may reflect increased myelination of lower cortical layers as opposed to synaptic pruning and/or neuronal cell loss.57 Natu et al57 found good correspondence between MRI-assessed cortical thickness and histologic measurements of cortical thickness among young adults. This latter finding is critical given that we detected cannabis-related differences in cortical thickness at age 19 years and not at 14 years, suggesting that our MRI-assessed cortical thickness findings are associated with reduced cortical gray matter rather than increased myelination. The present study focused on cortical thickness development and did not examine potential cannabis-related outcomes within subcortical structures. Future studies may benefit from conducting similar analyses on subcortical regions, particularly those rich in CB1 receptors. Most important, given the observational nature of the present study, it is possible that the apparent association between cortical thinning and cannabis use reflects preexisting trajectories of brain maturation that were not caused by cannabis use. We cannot rule out the possibility that preexisting cognitive and/or behavioral differences are associated with neurodevelopmental trajectories from adolescence to early adulthood and that cannabis use is not causally related to cerebral cortical thickness development."
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.