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The impact of cannabis on the adolescent compared to adult brain is of interest to researchers and society alike. From a theoretical perspective, adolescence represents a period of both risk and resilience to the harms of cannabis use and cannabis use disorders. The aim of this systematic review is to provide a critical examination of the moderating role of age on the relationship between cannabis use and cognition. To this end, we reviewed human and animal studies that formally tested whether age, adolescent or adult, changes the relationship between cannabis exposure and cognitive outcomes. While the results of this review do not offer a conclusive answer on the role of age, the novel review question, along with the inclusion of both human and animal work, has allowed for the formation of new hypotheses to be addressed in future work. First, general executive functioning seems to be more impaired in adolescent frequent cannabis users compared to adult frequent cannabis users. Second, age-effects may be most prominent among very heavy and dependent users. Third, craving and inhibitory control may not decrease as much post-intoxication in adolescents compared to adults. Lastly, adolescents’ vulnerability to reduced learning following cannabis use may not persist after sustained abstinence. If these hypotheses prove correct, it could lead to important developments in policy and prevention efforts. Electronic supplementary material The online version of this article (10.1007/s00406-019-00981-7) contains supplementary material, which is available to authorized users.

Rationale: Cannabis (CB) use and dependence are associated with regionally specific alterations to brain circuitry and substantial psychosocial impairment.Objectives: The objective of this study was to investigate the association between CB use and dependence, and the volumes of brain regions critically involved in goal-directed learning and behaviour—the orbitofrontal cortex (OFC) and caudate.Methods: In the largest multi-site structural imaging study of CB users vs healthy controls (HC), 140 CB users and 121 HC were recruited from four research sites. Group differences in OFC and caudate volumes were investigated between HC and CB users and between 70 dependent (CB-dep) and 50 non-dependent (CB-nondep) users. The relationship between quantity of CB use and age of onset of use and caudate and OFC volumes was explored.Results: CB users (consisting of CB-dep and CB-nondep) did not significantly differ from HC in OFC or caudate volume. CB-dep compared to CB-nondep users exhibited significantly smaller volume in the medial and the lateral OFC. Lateral OFC volume was particularly smaller in CB-dep females, and reduced volume in the CB-dep group was associated with higher monthly cannabis dosage.Conclusions: Smaller medial OFC volume may be driven by CB dependence-related mechanisms, while smaller lateral OFC volume may be due to ongoing exposure to cannabinoid compounds. The results highlight a distinction between cannabis use and dependence and warrant examination of gender-specific effects in studies of CB dependence.

Cannabis use disorders (CUDs) affect 13.1 million individuals worldwide. Brain morphology specific to CUDs may mediate the adverse behavioral outcomes of CUDs. We reviewed findings from 20 human neuroimaging studies on grey and white matter morphology in cannabis users that specifically included CUD assessments. There is evidence for CUD-specific morphological abnormalities within the striatum, medial temporal lobe, prefrontal cortex, cerebellum, and corpus callosum. Factors that may aggravate morphological abnormalities associated with CUDs include earlier onset age, higher lifetime exposure, and CUD-associated problems, while abstinence may result in (partial) recovery. These observations suggest that the neural substrates of compulsive cannabis use (e.g., striatum) may be distinct from those linked to cannabinoid exposure (e.g., hippocampus). The lack of studies examining individuals with a diagnosed CUD prevents drawing strong conclusions on CUD-specific morphological abnormalities. Comparing cannabis users with and without CUD is essential to delineate the neurobiology and inform new treatment strategies.