Association of Cannabis Use During Adolescence With Neurodevelopment

Abstract

for the IMAGEN Consortium IMPORTANCE Animal studies have shown that the adolescent brain is sensitive to disruptions in endocannabinoid signaling, resulting in altered neurodevelopment and lasting behavioral effects. However, few studies have investigated ties between cannabis use and adolescent brain development in humans.OBJECTIVE To examine the degree to which magnetic resonance (MR) imaging-assessed cerebral cortical thickness development is associated with cannabis use in a longitudinal sample of adolescents. DESIGN, SETTING, AND PARTICIPANTS Data were obtained from the community-based IMAGEN cohort study, conducted across 8 European sites. Baseline data used in the present study were acquired from March 1, 2008, to December 31, 2011, and follow-up data were acquired from January 1, 2013, to December 31, 2016. A total of 799 IMAGEN participants were identified who reported being cannabis naive at study baseline and had behavioral and neuroimaging data available at baseline and 5-year follow-up. Statistical analysis was performed from October 1, 2019, to August 31, 2020.MAIN OUTCOMES AND MEASURES Cannabis use was assessed at baseline and 5-year follow-up with the European School Survey Project on Alcohol and Other Drugs. Anatomical MR images were acquired with a 3-dimensional T1-weighted magnetization prepared gradient echo sequence. Quality-controlled native MR images were processed through the CIVET pipeline, version 2.1.0. RESULTSThe study evaluated 1598 MR images from 799 participants (450 female participants [56.3%]; mean [SD] age, 14.4 [0.4] years at baseline and 19.0 [0.7] years at follow-up). At 5-year follow-up, cannabis use (from 0 to >40 uses) was negatively associated with thickness in left prefrontal (peak: t 785 = -4.87, cluster size = 1558 vertices; P = 1.10 × 10 −6 , random field theory cluster corrected) and right prefrontal (peak: t 785 = -4.27, cluster size = 1551 vertices; P = 2.81 × 10 −5 , random field theory cluster corrected) cortices. There were no significant associations between lifetime cannabis use at 5-year follow-up and baseline cortical thickness, suggesting that the observed neuroanatomical differences did not precede initiation of cannabis use. Longitudinal analysis revealed that age-related cortical thinning was qualified by cannabis use in a dose-dependent fashion such that greater use, from baseline to follow-up, was associated with increased thinning in left prefrontal (peak: t 815.27 = -4.24, cluster size = 3643 vertices; P = 2.28 × 10 −8 , random field theory cluster corrected) and right prefrontal (peak: t 813.30 = -4.71, cluster size = 2675 vertices; P = 3.72 × 10 −8 , random field theory cluster corrected) cortices. The spatial pattern of cannabis-related thinning was associated with age-related thinning in this sample (r = 0.540; P < .001), and a positron emission tomography-assessed cannabinoid 1 receptor-binding map derived from a separate sample of participants (r = −0.189; P < .001). Analysis revealed that thinning in right prefrontal cortices, from baseline to ...

Age- and Sex-Related Cortical Gray Matter Volume Differences in Adolescent Cannabis Users: A Systematic Review and Meta-Analysis of Voxel-Based Morphometry Studies

“…Our GMV results are consistent with a previous study showing that CUD status influences cortical maturation of the L-STG in adolescents with and without early-onset psychosis (EOP) who were initially scanned at age 16 and then again 18-months later ( 45 ). Cannabis exposure starting early and persisting throughout the middle-to-late adolescent periods is associated with greater cortical thinning in PFC regions by young adulthood ( 46 ). Moreover, greater duration of CU and higher cumulative cannabis exposure is associated with smaller volumes and thinner cortices in temporal and frontal regions of chronic CU adults who started using in early adolescence ( 15 , 19 , 20 , 27 ).…”

“…These explanations are not mutually exclusive. In fact, recent evidence has emerged that partially supports both models [e.g., shared genetic factors ( 74 ); premorbid OPFC volumes predicting cannabis initiation in adolescence ( 75 ); and cannabis-induced neuroadaptive changes ( 44 , 46 )] suggesting complex bidirectional relationships. The ongoing ABCD study should aid in clarifying the nature, directionality, and mediators and moderators of cannabis-brain morphology relationships emerging during adolescence.…”

Chronic adolescent exposure to cannabis in mice leads to sex-biased changes in gene expression networks across brain regions

“…The frequent use of cannabis during adolescence has been linked to deleterious long-term consequences in humans, including an elevated likelihood of earlier onset of schizophrenia, cannabis use disorders and addiction 30,[61][62][63][64][65][66][67][68] . We found coexpression modules that both respond to THC treatment and are enriched in genes relevant to human cognitive traits, schizophrenia, and CUD.…”

“…We found coexpression modules that both respond to THC treatment and are enriched in genes relevant to human cognitive traits, schizophrenia, and CUD. These modules are involved in pathways already reported to be implicated in the development of psychiatric disorders, such as synaptic transmission, dopaminergic transmission, axon guidance, MAPK regulation, chromatin organization and immune functions [61][62][63][64][65][66][67] . We have also identified novel pathways that link chronic adolescent THC exposure to schizophrenia, such as sumoylation and glycosaminoglycan metabolism in females and inositol metabolism in males.…”

Use of Marijuana: Effect on Brain Health: A Scientific Statement From the American Heart Association

“…In a longitudinal study including 1598 MRIs done in adolescents at baseline and the 5-year follow-up, a dose-dependent association was observed between cannabis use and PFC thinning. 41 On the other hand, although a meta-analysis found that regular cannabis consumption was associated with smaller hippocampal (standardized mean difference, 0.14 [95% CI, 0.02–0.27]), medial orbitofrontal cortex (standardized mean difference, 0.30 [95% CI, 0.15–0.45]), and lateral orbitofrontal cortex (standardized mean difference, 0.19 [95% CI, 0.07–0.32]) volumes relative to nonuse, brain volumes were not associated with cannabis use duration and dosage. 42 Other large studies have reported null effects.…”