A Meta-Analysis of fMRI Studies of Youth Cannabis Use: Alterations in Executive Control, Social Cognition/Emotion Processing, and Reward Processing in Cannabis Using Youth

Background: Adolescent cannabis use (CU) is associated with adverse health outcomes and may be increasing in response to changing cannabis laws. Recent imaging studies have identified differences in brain activity between adult CU and controls that are more prominent in early onset users. Whether these differences are present in adolescent CU and relate to age/developmental stage, sex, or cannabis exposure is unknown. Methods: A systematic review and subsequent effect-size seed-based d mapping (SDM) meta-analysis were conducted to examine differences in blood-oxygen-level-dependent (BOLD) response during fMRI studies between CU and non-using typically developing (TD) youth. Supplemental analyses investigated differences in BOLD signal in CU and TD youth as a function of sex, psychiatric comorbidity, and the dose and severity of cannabis exposure. Results: From 1371 citations, 45 fMRI studies were identified for inclusion in the SDM meta-analysis. These studies compared BOLD response contrasts in 1216 CU and 1486 non-using TD participants. In primary meta-analyses stratified by cognitive paradigms, CU (compared to TD) youth showed greater activation in the rostral medial prefrontal cortex (rmPFC) and decreased activation in the dorsal mPFC (dmPFC) and dorsal anterior cingulate cortex (dACC) during executive control and social cognition/emotion processing, respectively. In meta-regression analyses and subgroup meta-analyses, sex, cannabis use disorder (CUD) severity, and psychiatric comorbidity were correlated with brain activation differences between CU and TD youth in mPFC and insular cortical regions. Activation differences in the caudate, thalamus, insula, dmPFC/dACC, and precentral and postcentral gyri varied as a function of the length of abstinence. Conclusions: Using an SDM meta-analytic approach, this report identified differences in neuronal response between CU and TD youth during executive control, emotion processing, and reward processing in cortical and subcortical brain regions that varied as a function of sex, CUD severity, psychiatric comorbidity, and length of abstinence. Whether aberrant brain function in CU youth is attributable to common predispositional factors, cannabis-induced neuroadaptive changes, or both warrants further investigation.