Abstract
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.
Highlights
Adolescent-onset cannabis use is rising in the era of marijuana legalization
Using effect-size seed-based d mapping (SDM, known as signed differential mapping) [37], a coordinate-based meta-analytic approach on whole-brain voxel-based morphometry (VBM) studies comparing cannabis use (CU) and TD youth, our study aims were three-fold: [1] to identify brain regions of increased or decreased gray matter volume (GMV) in CU relative to TD youth, [2] to explore whether specific regional GMV differences in CU vs. TD youth are age-related, and [3] to determine if regional GMV differences in CU vs. TD youth are sex-dependent
The age-related metaregression showed that increasing mean age across adolescence was associated with a relative decrease in GMV in youth with CU vs. age-matched TD youth in the left superior temporal gyrus (L-STG: 85 voxel cluster; Montreal Neurologic Institute (MNI) peak coordinate: x = −54, y = −4, z = −12; SDM Zmap = −3.168, p = 0.0008)
Summary
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. While population-wide use of cannabis by adolescents has not changed appreciably in the past 10 years, recent studies point to increased prevalence of daily CU and expanded use of concentrates and vaped cannabis among U.S youth, along with increased prevalence of CU among different subgroups (e.g., college-aged young adults) [5]. This is problematic given growing literature that recreational use of cannabis, high- -9-THC-potency cannabis, during adolescence is associated with numerous adverse health outcomes including increased risk for psychiatric disorders, academic failure, and higher rates of morbidity and mortality [6, 7]
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