Genetic Predisposition to Schizophrenia May Increase Risk of Psychosis From Cannabis Use

Summary: While cannabis users reported more psychotic experiences than non-users generally, the effect was more pronounced in those with a genetic risk factor for schizophrenia.

Source: CAMH

It has been long been known that cannabis users develop psychosis more often than non-users, but what is still not fully clear is whether cannabis actually causes psychosis and, if so, who is most at risk.

A new study published in Translational Psychiatry by researchers at the Centre for Addiction and Mental Health (CAMH) and King’s College London helps shed light on both questions.

The research shows that while cannabis users had higher rates of psychotic experiences than non-users across the board, the difference was especially pronounced among those with high genetic predisposition to schizophrenia.

“These results are significant because they’re the first evidence we’ve seen that people genetically prone to psychosis might be disproportionately affected by cannabis,” said lead author Dr. Michael Wainberg, Scientist the Krembil Centre for Neuroinformatics at CAMH.

“And because genetic risk scoring is still in its early days, the true influence of genetics on the cannabis-psychosis relationship may be even greater than what we found here.”

Using data from the UK Biobank, a large-scale biomedical database containing participants’ in-depth genetic and health information, the authors analyzed the relationship between genetics, cannabis use and psychotic experiences across more than 100,000 people.

Each person reported their frequency of past cannabis use, and whether they had ever had various types of psychotic experiences, such as auditory or visual hallucinations.

The researchers also scored each person’s genetic risk for schizophrenia, by looking at which of their DNA mutations were more common among schizophrenia patients than among the general population.

Overall, people who had used cannabis were 50 percent more likely to report psychotic experiences than people who had not. However, this increase was not uniform across the study group: among the fifth of participants with the highest genetic risk scores for schizophrenia, it was 60 percent, and among the fifth with the lowest scores, it was only 40 percent. In other words, people genetically predisposed to schizophrenia were at disproportionately higher risk for psychotic experiences if they also had a history of cannabis use.

This shows a brain
Overall, people who had used cannabis were 50 percent more likely to report psychotic experiences than people who had not. Image is in the public domain

Notably, because much less is known about the genetics of schizophrenia in non-white populations, the study’s analysis was limited to self-reported white participants.

“This study, while limited in scope, is an important step forward in understanding how cannabis use and genetics may interact to influence psychosis risk,” added senior author Dr. Shreejoy Tripathy, Independent Scientist at the Krembil Centre for Neuroinformatics, who supervised the study.

“The more we know about the connection between cannabis and psychosis, the more we can inform the public about the potential risks of using this substance. This research offers a window into a future where genetics can help empower individuals to make more informed decisions about drug use.”

About this psychosis research news

Source: CAMH
Contact: Hayley Chazan – CAMH
Image: The image is in the public domain

Original Research: Open access.
Cannabis, schizophrenia genetic risk, and psychotic experiences: a cross-sectional study of 109,308 participants from the UK Biobank” by Michael Wainberg, Grace R. Jacobs, Marta di Forti & Shreejoy J. Tripathy. Translational Psychiatry


Cannabis, schizophrenia genetic risk, and psychotic experiences: a cross-sectional study of 109,308 participants from the UK Biobank

Cannabis is known to produce acute, transient psychotic-like experiences. However, it is unclear whether cannabis disproportionately increases the risk of specific types of psychotic experiences and whether genetic predisposition influences the relationship between cannabis use and psychotic experiences.

In this cross-sectional study of 109,308 UK Biobank participants, we examined how schizophrenia polygenic risk modulates the association between self-reported cannabis use and four types of self-reported psychotic experiences (auditory hallucinations, visual hallucinations, persecutory delusions, and delusions of reference).

Cohort-wide, we found a strong, dose-dependent relationship between cannabis use and all four types of psychotic experiences, especially persecutory delusions. Cannabis users’ psychotic experiences tended to be earlier-onset and cause greater distress than non-users’, but were not more likely to lead to help-seeking.

Participants with high schizophrenia polygenic risk scores showed stronger associations between cannabis use and auditory hallucinations, visual hallucinations, and delusions of reference, as well as psychotic experiences overall. For instance, cannabis ever-use was associated with 67% greater adjusted odds of delusions of reference among individuals in the top fifth of polygenic risk, but only 7% greater adjusted odds among the bottom fifth.

Our results suggest that cannabis use is a predictive risk factor for psychotic experiences, including early-onset and distressing experiences. Individuals genetically predisposed to schizophrenia may be especially vulnerable to psychotic experiences as a result of using cannabis, supporting a long-postulated hypothesis.

This study exemplifies the utility of population-scale biobanks for elucidating gene-by-environment interactions relating substance use to neuropsychiatric outcomes and points to the translational potential of using polygenic risk scores to inform personalized harm reduction interventions.

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