These findings support the hypothesis that heavy alcohol use in adolescence has an adverse influence on the hippocampus, potentially affecting subsequent memory performance. Additionally, marijuana, in combination with alcohol use, could have some neuroprotective effects, but further studies are warranted to examine this hypothesis. An alternative explanation is that alcohol and marijuana use may create opposing mechanisms (e.g., neuroinflammation and myelination suppression), so that macromorphometric variables may actually appear normal. Microstructural hippocampal changes related to marijuana use may include increased glial proliferation and white matter density as well as reduced gray matter, resulting in relatively normal hippocampal volumes despite functional pathology. Alternatively, heavy adolescent marijuana use may subtly interfere with synaptic pruning processes, resulting in larger gray matter volumes, particularly in the left hippocampus 32, 34.
