Cannabis Users Have Psychotic-Like Experiences via "Person-Specific" Pathways

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Researchers examined the genetic predisposition of cannabis users to determine whether it played a role in their psychotic-like experiences.
Researchers examined the genetic predisposition of cannabis users to determine whether it played a role in their psychotic-like experiences.

Cannabis use appears to be associated with psychotic-like experiences (PLEs) via person-specific pathways that are independent of genetic predisposition or environmental factors, per study data published in JAMA Psychiatry.

Investigators performed a cross-sectional analysis of twin and nontwin sibling pair data abstracted from the Human Connectome Project (n=1188) and the Australian Twin Registry Cohort (n=3486). Only individuals with a similarly aged full sibling (≤2 years' age difference) were included in analyses, and analyses of exposure effect were limited to same-sex sibling pairs.

For each sample, participants reported cannabis use per the semistructured Assessment for the Genetics of Alcoholism. In addition, answers to questions about mental health behaviors and adaptive functioning were used to construct a PLE diagnosis. For each cannabis-involvement measure, twin and nontwin sibling pairs were assigned to 4 groups: concordant cannabis-unexposed pairs, concordant exposed pairs, unexposed individuals from discordant pairs, and exposed individuals from discordant pairs.

The total cohort (n=4674) was 62.5% women, with a mean age of 30.5±3.2 years. Nearly a quarter (22.0%) of participants reported experiencing at least 1 PLE. Covariates associated with greater risk for PLEs included younger age, nontwin status, lower household income, lifetime regular smoking, and lifetime illicit drug use. Psychotic-like experiences were associated with frequent cannabis use, cannabis use disorder, and current cannabis use, even after adjustments for covariates.

Specifically, patients who reported frequent use, cannabis use disorder, and current use were 1.21 to 1.26 times more likely to report at least 1 PLE compared with their counterparts who reported lesser use or no use. Cannabis use and PLEs had a substantial genetic component, with genetic factors accounting for 69.2%, 84.1%, and 80.9% of the observed association between PLEs and frequent cannabis use, cannabis use disorder, and current cannabis use, respectively. The remainder of the covariances were attributable to individual-specific environmental factors.

PLEs were also more frequently reported by the exposed members of discordant sibling pairs and by members of concordant exposed pairs compared with unexposed members from discordant and concordant pairs (all P <.001). Among discordant pairs, cannabis-exposed individuals more frequently reported PLEs compared with their sibling with lesser exposure (P <.05). This observation suggests that cannabis use alone is a risk factor for PLEs and that genetic and environmental factors alone cannot account for PLE frequency. The likelihood of PLEs was significantly elevated in patients reporting regular tobacco smoking and use of illicit drugs.

Further research is necessary to elucidate the pathways through which cannabis use may affect psychosis. These data suggest that despite substantial genetic overlap, individual-specific characteristics may contribute to the association between cannabis use and PLEs. As such, targeting cannabis use in individuals may be key to mediating the risk for PLEs with increased genetic risk.

Investigators also note, "policy discussions surrounding legalization should consider the influence of escalations in cannabis use on traitlike indices of vulnerability, such as PLEs, which could contribute to pervasive psychological and interpersonal burden."

Reference

Karcher NR, Barch DM, Demers CH, et al. Genetic predisposition vs individual-specific processes in the association between psychotic-like experiences and cannabis use [published online October 17, 2018]. JAMA Psychiatry. doi: 10.1001/jamapsychiatry.2018.2546

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