Genetic Predisposition vs Individual-Specific Processes in the Association Between Psychotic-like Experiences and Cannabis Use

Abstract

Importance: Previous research indicates that cannabis use is associated with psychotic-like experiences (PLEs). Yet is unclear whether this relationship is due to predispositional (i.e., shared genetic) or individual-specific (e.g., causal processes, such as cannabis use leading to PLEs) factors. Objective: To estimate genetic and environmental correlations between cannabis use and PLEs, and to examine PLEs in twins/siblings discordant for exposure to cannabis use to disentangle predispositional from individual-specific effects. Design: Cross-sectional diagnostic interviews and self-report data were collected from two separate population-based samples. Setting: Data from the Human Connectome Project (HCP) were collected between 2012–2015 and data from the Australian Twin Registry Sample 3 (ATR3) were collected between 2005–2009. Participants: The study included data from 1,188 HCP participants and 3,486 ATR3 participants, totaling 4,674 participants. Main Outcomes and Measures: Three cannabis involvement variables were examined: frequent use (i.e., ≥100 times), a DSM-IV lifetime cannabis use disorder (CUD) diagnosis, and current cannabis use. Genetic and environmental correlations between cannabis involvement and PLEs were estimated. Generalized linear mixed models examined PLE differences in twin/sibling pairs discordant for cannabis use. Results: Analyses were performed in 4,674 participants (mean age=30.51 years, 62.5% female). PLEs were associated with frequent use (β=0.11; 95% CI, 0.08–0.14), CUD (β=0.13; 95% CI, 0.09–0.16), and current cannabis use (β=0.07; 95% CI, 0.04–0.10), even after adjustment for covariates. Correlated genetic factors explained between 69.2–84.1% of this observed association. Even so, within discordant pairs of twins/siblings (Npairs: 308–324), PLEs were more common in cannabis exposed individuals relative to their relative who used cannabis to a lesser degree (βs≥.23, ps<.05; e.g., mean PLE score difference between frequent and infrequent cannabis-using relatives=0.27, Z=−5.41, p<.001). Conclusions: Despite the strong contribution of shared genetic factors, frequent and problem cannabis use also relates to PLEs via person-specific pathways. Policy discussions surrounding legalization should consider the impact of escalations in cannabis use on trait-like indices of vulnerability, like PLEs, which could contribute to pervasive psychological and interpersonal burden.

Factors Moderating the Association between Cannabis Use and Psychosis Risk: A Systematic Review

“…According to a 2019 study by Karcher et al, individuals who reported frequent lifetime cannabis use (defined as cannabis use >100 times lifetime) were diagnosed with a cannabis use disorder (CUD) and those who reported current cannabis use had an increased risk of 1.21 to 1.26 times of at least one psychotic-like experience. Moreover, psychotic-like experiences were associated with frequent cannabis use (β = 0.11, 95% CI 0.08-0.14), cannabis use disorder (β = 0.13, 95% CI 0.09-0.16), and current cannabis use (β = 0.07, 95% CI 0.04-0.10), even after adjustment for covariates (P < 0.05) [46]. Leadbeater and colleagues (2019) reported that more frequent cannabis use (β = 0.13, 95% CI 0.002-0.25, P < 0.05), as well as CUD (β = 0.51, 95% CI 0.01-1.01, P < 0.05), during adolescence were associated with psychotic symptoms at ages 22 and 23 [47].…”

The interplay between childhood trauma, cognitive biases, and cannabis use on the risk of psychosis in nonclinical young adults in Poland

“…Cannabis use has been repeatedly associated with the continuum of psychotic experiences, ranging from subthreshold psychotic symptoms to clinical high risk for psychosis. It has been demonstrated that PLEs are more prevalent among cannabis users in the general population when compared to nonusers [19][20][21][22][23][24]. Moreover, there is a dose-response relationship between the frequency of cannabis consumption and increased risk for psychosis [25,26].…”

Association of illicit drug use in adolescence with socioeconomic and criminal justice outcomes in adulthood: prospective findings from a UK national birth cohort

“…The associations between drug use and adult outcomes we observed might be direct, indirect or due to confounding. In support of a direct effect, discordant twin studies have found the cannabis-using twin was more likely to use other illicit drugs at a later date 6 7 and report psychotic-like experiences, 25 than the twin who did not. In the Christchurch birth cohort, associations between cannabis use with juvenile offending were attenuated after adjusting for affiliation with substance using or delinquent peers.…”