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Shared Predisposition in the Association Between Cannabis Use and Subcortical Brain Structure.

David Pagliaccio, Deanna M Barch, Ryan Bogdan, Phillip K Wood, Michael T. Lynskey, Andrew C Heath, Arpana Agrawal

JAMA Psychiatry October 2015 DOI: 10.1001/jamapsychiatry.2015.1054 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Cross-sectional study Peer reviewed
Sample size 483
Population Participants aged 22-35 years from the Human Connectome Project, including twins and siblings, with 262 reporting lifetime cannabis exposure
Measures Semi-Structured Assessment for the Genetics of Alcoholism
Topics Cannabis
Key findings Lifetime cannabis exposure was associated with smaller left amygdala (about 2.3%) and right ventral striatum (about 3.5%) volumes, but the amygdala difference was largely explained by shared genetic factors and did not differ between siblings discordant for use. The authors conclude that amygdala volume differences in cannabis users are attributable to common predispositional factors, with little support for causal influences.

Abstract

Prior neuroimaging studies have suggested that alterations in brain structure may be a consequence of cannabis use. Siblings discordant for cannabis use offer an opportunity to use cross-sectional data to disentangle such causal hypotheses from shared effects of genetics and familial environment on brain structure and cannabis use. To determine whether cannabis use is associated with differences in brain structure in a large sample of twins/siblings and to examine sibling pairs discordant for cannabis use to separate potential causal and predispositional factors linking lifetime cannabis exposure to volumetric alterations. Cross-sectional diagnostic interview, behavioral, and neuroimaging data were collected from community sampling and established family registries from August 2012 to September 2014. This study included data from 483 participants (22-35 years old) enrolled in the ongoing Human Connectome Project, with 262 participants reporting cannabis exposure (ie, ever used cannabis in their lifetime). Cannabis exposure was measured with the Semi-Structured Assessment for the Genetics of Alcoholism. Whole-brain, hippocampus, amygdala, ventral striatum, and orbitofrontal cortex volumes were related to lifetime cannabis use (ever used, age at onset, and frequency of use) using linear regressions. Genetic (ρg) and environmental (ρe) correlations between cannabis use and brain volumes were estimated. Linear mixed models were used to examine volume differences in sex-matched concordant unexposed (n = 71 pairs), exposed (n = 81 pairs), or exposure discordant (n = 89 pairs) sibling pairs. Among 483 study participants, cannabis exposure was related to smaller left amygdala (approximately 2.3%; P = .007) and right ventral striatum (approximately 3.5%; P < .005) volumes. These volumetric differences were within the range of normal variation. The association between left amygdala volume and cannabis use was largely owing to shared genetic factors (ρg = -0.43; P = .004), while the origin of the association with right ventral striatum volumes was unclear. Importantly, brain volumes did not differ between sex-matched siblings discordant for use (fixed effect = -7.43; t = -0.93, P = .35). Both the exposed and unexposed siblings in pairs discordant for cannabis exposure showed reduced amygdala volumes relative to members of concordant unexposed pairs (fixed effect = 12.56; t = 2.97; P = .003). In this study, differences in amygdala volume in cannabis users were attributable to common predispositional factors, genetic or environmental in origin, with little support for causal influences. Causal influences, in isolation or in conjunction with predispositional factors, may exist for other brain regions (eg, ventral striatum) or at more severe levels of cannabis involvement and deserve further study.

Comparable studies

Other cross-sectional and survey studies on cannabis, most cited first.

Study Year Design Participants
Cannabis use before age 15 and subsequent executive functioning 104 chronic cannabis users (49 early-onset before age 15, 55 late-onset after age 15)... 2011 Observational cross-sectional study n = 148
Patterns of simultaneous polysubstance use in drug using university students Drug-using university students 2006 Cross-sectional survey n = 149
Persisting Reductions in Cannabis, Opioid, and Stimulant Misuse After Naturalistic Psychedelic Use: An Online Survey Online survey respondents 2020 Cross-sectional survey
User perceptions of the benefits and harms of hallucinogenic drug use: A web-based questionnaire study Users of hallucinogenic drugs who completed a web-based questionnaire 2010 Cross-sectional survey n = 600
Illicit Use of LSD or Psilocybin, but not MDMA or Nonpsychedelic Drugs, is Associated with Mystical Experiences in a Dose-Dependent Manner Adults recruited from the MAPS website and newsletter, most reporting use of various... 2012 Cross-sectional survey n = 337

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