Prenatal cannabis exposure linked to blunted brain response and psychotic-like symptoms in youth

An analysis of longitudinal data from the Adolescent Brain and Cognitive Development (ABCD) study has found that prenatal exposure to cannabis is associated with an increased likelihood of developing psychotic-like experiences in youth. These experiences were associated with reduced neural activation during reward anticipation in the brain’s reward-processing system, particularly in the striatum—a region involved in motivation and reward expectancy. This blunted response was more pronounced in children who had been exposed to cannabis in utero. The findings were published in Biological Psychiatry.

Psychotic-like experiences are subclinical symptoms that resemble features of psychosis but occur in individuals who do not meet the diagnostic criteria for a psychotic disorder. Such experiences may include hearing voices, holding unusual beliefs, experiencing paranoid thoughts, or feeling detached from reality. These symptoms are relatively common during adolescence, with many young people reporting at least one such experience during this developmental period.

In most cases, psychotic-like experiences are temporary and do not develop into a clinical disorder. However, frequent or distressing psychotic-like experiences have been linked to increased risk for future psychiatric conditions, including schizophrenia, depression, and anxiety. Factors associated with a heightened risk for psychotic-like experiences include genetic predisposition, childhood trauma, bullying, substance use, and high levels of stress. These experiences may also reflect normative developmental processes as adolescents navigate identity formation and shifts in cognitive and emotional regulation.

The study, led by Carolyn M. Amir and Carrie E. Bearden, tested the hypothesis that psychotic-like experiences are associated with diminished neural activity in reward-related brain regions—specifically the striatum and the ventromedial prefrontal cortex—during anticipation of a reward. The researchers also proposed that this association would be stronger in youth who had been exposed to cannabis in utero.

“Our lab has been really interested in mechanisms underlying the relationship between cannabis exposure and psychosis in adolescence. Particularly concerning is the rise in cannabis use during pregnancy—and the lack of data on how this might affect brain development,” explained Bearden, a professor and director of the Center for the Assessment and Prevention of Prodromal States (CAPPS) at the University of California, Los Angeles.

Prenatal cannabis exposure occurs when a pregnant individual uses cannabis, allowing compounds such as tetrahydrocannabinol (THC) to cross the placenta and affect fetal development. Previous studies have linked this exposure to outcomes such as reduced birth weight, neurodevelopmental alterations, and increased risk for cognitive and behavioral difficulties in childhood.

The current study analyzed data from children born between 2005 and 2009 who were enrolled in the ABCD study, a large-scale longitudinal investigation of brain development and health in U.S. youth. The sample included 11,368 participants with an average age of approximately 10 years at baseline.

To assess psychotic-like experiences, the researchers used the Prodromal Questionnaire – Brief Child Version, a validated tool designed to measure subclinical psychosis-related symptoms in youth. Information about prenatal cannabis exposure was based on retrospective reports provided by the child’s parent or caregiver. Neural responses were assessed using task-based functional MRI while participants completed the Monetary Incentive Delay task, which measures brain activation during reward anticipation.

The results showed that children with prenatal cannabis exposure were more likely to report psychotic-like experiences. Across the entire sample, greater severity of psychotic-like experiences was associated with reduced activation in the striatum during reward anticipation. This effect was significantly stronger among children with prenatal cannabis exposure.

The researchers also tested a mediation model to examine whether blunted neural responses to reward could help explain the link between prenatal cannabis exposure and psychotic-like experiences. The findings suggest that reduced striatal activation partially mediated this relationship, indicating that altered reward processing may be one pathway through which prenatal cannabis exposure increases risk for psychotic-like experiences.

Additionally, the study found that psychotic-like experiences were associated with higher levels of reward motivation and impulsivity, and that these associations were more pronounced among youth with prenatal cannabis exposure. In this group, participants scored higher on measures of reward drive, reward responsiveness, and multiple dimensions of impulsivity across several assessment time points.

“The big finding is that youth who were exposed to cannabis before they were born were more likely to report psychotic-like experiences as teenagers,” Bearden told PsyPost. “This also appeared in how their brains responded to a reward cue — a particular part of the brain, the ventral striatum, that’s normally very reactive in response to anticipating a reward like money, was less activated in children who had been exposed to cannabis prenatally. And that brain response, in turn, was associated with more distressing psychotic-like experiences.”

“I was quite surprised that, when controlling for all the possible confounds we could, this association persisted. That exposure during early development would be associated with brain and behavioral differences so many years later was unexpected.”

The study sheds light on the links between prenatal cannabis exposure and psychological outcomes later in adolescence. However, it should be noted that the design of this study does not allow any definitive causal inferences to be derived from the results.

Looking forward, “we are interested in looking at the relationship of early exposure to both psychotic-like experiences over time, as well as other mental health and substance use outcomes later in life (as more timepoint data from ABCD become available),” Bearden said. “We’re also planning prospective studies with more detailed information on cannabis use—such as potency, frequency, and type of use—and how that relates to both blood biomarkers of cannabinoids as well as symptoms over time.”

The paper, “Altered neurobehavioral reward response predicts psychotic-like experiences in youth exposed to cannabis prenatally,” was authored by Carolyn M. Amir, Dara G. Ghahremani, Sarah E. Chang, Ziva D. Cooper, and Carrie E. Bearden.

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