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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.
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Introduction: Adolescent-onset cannabis use is rising in the era of marijuana legalization. Recent imaging studies have identified neuroanatomical differences between adult cannabis users and controls that are more prominent in early-onset users. Other studies point to sex-dependent effects of cannabis. Methods: A systematic review following PRISMA guidelines and subsequent effect-size seed-based d mapping (SDM) meta-analyses were conducted to investigate relationships between age (across the 12-to-21-year-old developmental window), sex, and gray matter volume (GMV) differences between cannabis using (CU) and typically developing (TD) youth. Results: Our search identified 1,326 citations, 24 of which were included in a qualitative analysis. A total of 6 whole-brain voxel-based morphometry (VBM) studies comparing regional GMV between 357 CU [mean (SD) age = 16.68 (1.28); 71% male] and 404 TD [mean (SD) age = 16.77 (1.36); 63% male] youth were included in the SDM-meta-analysis. Meta-analysis of whole-brain VBM studies identified no regions showing significant GMV difference between CU and TD youth. Meta-regressions showed divergent effects of age and sex on cortical GMV differences in CU vs. TD youth. Age effects were seen in the superior temporal gyrus (STG), with older-aged CU youth showing decreased and younger-aged CU youth showing increased STG GMV compared to age-matched TD youth. Parallel findings in the STG were also observed in relation to duration of CU (years) in supplemental meta-regressions. Regarding sex effects, a higher proportion of females in studies was associated with increased GMV in the middle occipital gyrus in CU vs. TD youth. Conclusions: These findings suggest that GMV differences between CU and TD youth, if present, are subtle, and may vary as a function of age, cumulative cannabis exposure, and sex in young people. Whether age- and sex-related GMV differences are attributable to common predispositional factors, cannabis-induced neuroadaptive changes, or both warrant further investigation.
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Objective: Addictive disorders start during adolescence for most individuals, and developmental differences in brain maturation and response to treatments are present. Recent studies in adults have identified associations between addiction treatment response and regional and circuit specific brain dysfunction, suggesting candidate neural treatment targets. The purpose of this systematic review and meta-analysis was to qualitatively and quantitatively summarize findings from structural and functional neuroimaging studies that examine neural correlates of treatment response in adolescents and young adults with addictive disorders. Methods: A systematic review and meta-analysis of peer-reviewed studies was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies were selected if they included individuals aged 13-26 with a DSM-IV or DSM-5 (Diagnostic and Statistical Manual, Fourth and Fifth Edition) addictive disorder diagnosis, used neuroimaging, administered a treatment/intervention, and reported within- or between-subject contrasts in brain structure or activity across treatment/intervention and a control condition or brain-behavior correlations with treatment-outcome variables. Quantitative meta-analyses used an activation-likelihood estimation (ALE) approach. Results: Out of 3177 citations, 27 studies were included in the qualitative analysis. Qualitative analyses revealed anatomical, connectivity, and functional brain-behavior associations with response to addiction interventions across a broad array of cortical and subcortical brain regions and associated networks. Eighteen functional magnetic resonance imaging studies involving 354 participants and 88 brain foci were included in the ALE meta-analysis. Despite significant heterogeneity in study design and methods, six ALE activation clusters localized to the anterior cingulate cortex, inferior frontal gyrus, supramarginal gyrus, middle temporal gyrus, precuneus, and putamen showed consistent brain-behavior associations with treatment-outcome variables. Conclusions: Cortical and subcortical brain regions involved in cognition, emotion regulation, decision-making, reward, and self-reference are associated with treatment response in addicted youth. These results are consistent with findings in the adult literature and suggest overlapping neural treatment targets across developmental stages.