番茄社区

The association between cannabis use and "psychotic-like experiences" appeared to be largely influenced by genetic predisposition, according to a cross-sectional study.

Across a sample of twin and non-twin sibling pairs, frequent cannabis users were more likely to report psychotic-like experiences than their relatives who used cannabis less frequently (β=0.08-0.13, P<0.001), reported Nicole Karcher, PhD, of Washington University in St. Louis, and colleagues.

Specifically within non-twin relatives, those who used cannabis more frequently were more likely to undergo psychotic-like experiences (β=0.23-0.41, P<0.05), they wrote in .

However, cannabis involvement -- frequent or current use; cannabis use disorders -- was also tied to greater number of psychotic-like experiences, the authors pointed out.

Genetic factors accounted for 69.2% to 84.1% of the association between frequent, current, and dependent cannabis use and psychotic-like experiences, and this heritability remained significant after adjusting for covariates, although it was reduced. The remainder can likely be attributed to individual-specific environmental factors, they stated.

"The relationship between cannabis use and psychotic-like experiences is vastly shared genetic contributions, but even when you take into account those genetic factors, there are some person-specific factors," Karcher told 番茄社区. "Previously, researchers have largely focused on psychotic disorders like schizophrenia, whereas very little research has been done on subthreshold psychotic experiences and their relationship to cannabis use."

In past research, it has been unclear what proportion of this association can be contributed to shared genetic or individual-specific factors. Some studies have found psychosis tends to follow cannabis use, suggesting a causal relationship. However, researchers noted that they are unable to discount the role of environmental factors, like early-life exposures, in this association.

The relationship between cannabis use and psychotic-like events could be caused by both genetic and individual-specific factors, which is a "frequently untested possibility," the authors stated.

Karcher's group used the U.S. Human Connectome Project (HCP) and the Australian Twin Registry Cohort (ATR3) to collect data for a combined 4,674 individuals, including 758 pairs of monozygotic twins, 780 pairs of dizygotic twins, and 195 same-sex sibling pairs with no more than 2 years' age difference.

Data collection in these projects differed somewhat, particularly with regard to psychotic-like experiences: in the HCP, prevalence of such experiences was determined from the Achenbach Adult Self-Report instrument that measures adaptive functioning and mental health-related behaviors; in the ATR3 group, it came from answers to four questions, including whether participants heard voices or saw things that other people did not, and whether they had thoughts or did things others would consider strange. Cannabis involvement (frequent, dependence, and current use) was measured in both groups with results from the Semi-structured Assessment for the Genetics of Alcoholism.

Overall, the samples were 65.5% female with an average age 30.5. Although race/ethnicity data were not available for the Australian study, the majority of participants in the U.S. survey were white (73.7%). Similar numbers of the study population reported cannabis use in each of the three measures (15.2% frequent, 14.2% dependent, 14.1% current users).

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). Lower household incomes, younger age, non-twin status, and lifetime alcohol and illicit drug use were also associated with greater psychotic-like events. Age at onset of cannabis use and sex were not related to psychotic-like events (β=0.013, P=0.44; β≤0.13, P>0.21).

Karcher said heavy cannabis use releases dopamine in the brain, and since dopamine dysfunction can lead to psychotic symptoms, this could be one potential mechanism behind this association. She called for additional research to definitively determine why this association persists, but noted that the current results could support potential intervention mechanisms, such as providing educational materials or creating guidelines for cannabis use in these vulnerable populations.

"At the end of the day, I'm in clinical psychology," she said. "Targeting or reducing cannabis use in individuals who are at risk might be a really important method of treatment."

Study limitations include the lack of certain data in this analysis, including age at first psychotic-like event and potential confounders such as stressful life events. The study was also underpowered to determine nuanced sex differences and whether an independent association existed between tobacco use and psychotic-like events.

Additionally, several factors varied across the two datasets, including the definition of current cannabis use and exclusion guidelines for patients with certain kinds of psychotic-like events. Lastly, the researchers acknowledged they were unable to test for associations with variability in amount smoked, or for varying strengths of tetrahydrocannabinol.

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