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Cannabis Users With Genetic Markers for Schizophrenia Are More Likely to Have Psychotic Episodes, Study Finds

By Leo Bear-McGuinness

Published: Apr 16, 2021   
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When it comes to the drug’s less desirable effects, cannabis has long been associated with psychosis. But the relationship between the two has never been clear. Does cannabis cause psychosis in otherwise healthy users? Or does it trigger psychotic episodes in users who are already predisposed to the mental health disorder?

Well, a new genetics study has shed some more light on the issue. Published in Translational Psychiatry, the paper found that, while cannabis consumers have higher rates of psychotic experiences than non-consumers, the difference was indeed more pronounced among those with a high genetic predisposition to schizophrenia.

Hidden in the genes

To get their findings, the researchers at the Centre for Addiction and Mental Health, Canada, and King's College London, UK, first trawled through the UK Biobank, a large database containing the genetic and health information of more than half a million people.

From this database, the researchers identified 109,308 participants (61,047 female, 48,261 male, all of “unrelated White British ancestry”) who had provided information on their levels of cannabis use and number of psychotic experiences, but lacked a diagnosis of any psychotic disorder.

After analyzing these data, the team concluded that there was a strong and consistent relationship between self-reported cannabis use frequency and all types of self-reported psychotic experiences.

Among people who had never used cannabis, around 4 percent reported some kind of psychotic episode. This kind of proportion rose to 7 percent among participants who admitted to consuming cannabis, and further increased to 8.4 percent and 9.6 percent among those who consumed cannabis weekly and daily, respectively.

Cannabis consumers were also more likely to report psychotic experiences earlier in their lives and at more frequent rates than non-users.

The researchers also assigned each participant a polygenic risk score (PRS) for schizophrenia by looking at which of their DNA mutations were more common among schizophrenia patients compared to the general population. After analyzing these PRSs, the team found that cannabis consumers with higher genetic risk scores were more likely to experience auditory and visual hallucinations, delusions, and psychotic experiences in general.

“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,” Dr Michael Wainberg, lead author of the paper and scientist at the Centre for Addiction and Mental Health, said in a statement. “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.”

But despite these novel conclusions, Wainberg and his colleagues note that their research still hasn’t firmly elucidated the relationship between cannabis and psychosis. A genetic predisposition to schizophrenia may in fact, in the researchers’ own words, “lead individuals to use cannabis, perhaps due to dysfunction in reward circuitry induced by these genetic factors or as a means of self-medicating to reduce negative symptoms, anxiety, or insomnia.”

The data on cannabis use and psychotic episodes were also self-reported and limited to white participants – factors that may limit the study’s conclusions.

“This study, while limited in scope, is an important step forward in understanding how cannabis use and genetics may interact to influence psychosis risk,” Dr Shreejoy Tripathy, an independent scientist at the Centre for Addiction and Mental Health, said in a statement.

Cannabis and psychosis

People who experience episodes of psychosis usually have their first during their late teens and early twenties. These events are characterized by a “loss of contact with reality,” which manifests in visual hallucinations and delusional thinking. Around 100,000 adolescents and young adults in the US experience first episodes of psychosis (FEP) each year.

Cannabis is the most widely used drug among patients with FEP, and previous medical research has concluded that cannabis use may approximately double the overall risk of young people developing their first episode. 

Another study published in 2019 found a strong association between a certain genetic polymorphism (the FAAH SNP) and a greater risk of presenting an FEP in people with a history of cannabis use. This association was not reflected in the data of those who did not use cannabis.

But while cannabis use is associated with worse psychosis outcomes, the cannabinoid cannabidiol (CBD) has actually been shown by researchers at King’s College London to have anti-psychotic properties in young people experiencing distressing psychotic symptoms. 


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