Cannabis users with a genetic predisposition to schizophrenia more likely to experience psychotic symptoms

By Dr. Sanchari Sinha Dutta, Ph.D.Reviewed by Danielle Ellis, B.Sc.Apr 24 2023

A study published in the journal Schizophrenia Bulletin highlights that genetic risk factors for schizophrenia can increase the possibility of experiencing cannabis-related subclinical psychotic symptoms in regular cannabis users. 

Study: Associations Between Cannabis Use, Polygenic Liability for Schizophrenia, and Cannabis-related Experiences in a Sample of Cannabis Users. Image Credit: StunningArt / Shutterstock 

Background

Excessive cannabis use is known to associate with psychotic-like experiences, schizophrenia symptoms, cognitive impairment, and emotional distress. Studies have shown that the administration of psychoactive constituents of cannabis can induce acute psychotic-like experiences, including unusual thoughts, paranoia, disorganized thinking, and in some rare cases, auditory and visual hallucinations.

The risk of developing schizophrenia symptoms due to cannabis use is partly influenced by genetic factors. Recent evidence has shown that individuals with higher genetic susceptibility to schizophrenia have a higher risk of developing psychotic-like experiences due to cannabis intake.   

In the current study, scientists have investigated whether genetic risk for schizophrenia is associated with cannabis intake-related psychotic-like experiences, including hallucination, paranoia, depression, cognitive difficulties, and impaired social interaction.

Study design

The study was conducted on a total of 4,832 individuals partially ascertained for alcohol use disorder. Among enrolled participants, 74% met the lifetime criteria for alcohol use disorder, and 70% met the lifetime criteria for cannabis use disorder.

Five self-reported cannabis-related experiences were assessed in the study, including hallucination (audio, visual, and olfactory), paranoia, depression, cognitive difficulties, and impaired social interaction. Polygenic risk scores for schizophrenia were calculated using recent databases.

Statistical analyses were conducted to determine whether polygenic risk for schizophrenia is associated with cannabis-related experiences in individuals who reported using cannabis at least 11 times.

Important observations

A high prevalence (70%) of cannabis use disorder was observed in the study population. Among them, 40% had mild, 25% had moderate, and 35% had severe cannabis use disorder. The average age of first-time cannabis use was 16 years. About 75% of the enrolled participants reported using other illicit drugs.

A significant positive association was observed between polygenic risk for schizophrenia and cannabis-related paranoia, depression, impaired social interaction, and cognitive difficulties. This association remained unchanged even after adjusting for duration of daily cannabis use, cannabis use disorder, and age at first-time cannabis use. Conversely, cannabis-related hallucination showed the lowest association with polygenic risk for schizophrenia.

A significant association between lifetime diagnosis of cannabis use disorders and earlier age at first-time cannabis use was observed with reporting of cannabis-related experiences. Except for hallucination and paranoia, all other cannabis-related experiences showed significant associations with the duration of daily cannabis use. Moreover, a strong association was observed between the severity of cannabis use disorder and endorsing a higher number of cannabis-related experiences.

The analysis conducted after adjusting for cannabis use disorder showed a strong association between polygenic risk scores for schizophrenia and all cannabis-related experiences except hallucination. Polygenic risk scores also showed a significant association with endorsing a higher number of cannabis-related experiences. The highest association of schizophrenia polygenic risk score was observed with cannabis-related cognitive difficulties.  

The analysis conducted after adjusting for age at first-time cannabis use and diagnosis of alcohol use disorder revealed a strong association between polygenic risk score for schizophrenia and all cannabis-related experiences except paranoia.

The study also included a separate group of 1,446 individuals with opioid use disorder and genetically unrelated control individuals with minimal or no lifetime opioid misuse. In this study group, no significant association was observed between polygenic risk score for schizophrenia and cannabis-related experiences. However, the patterns of associations were similar to that observed in individuals with alcohol use disorder and cannabis use disorder.

Study significance

The study reveals that regular cannabis users with higher pre-existing genetic susceptibility to schizophrenia are at higher risk of experiencing cannabis-related psychotic experiences, including hallucination, paranoia, depression, cognitive difficulties, and social withdrawal. Moreover, excessive and early-onset cannabis users are more likely to report unusual cannabis-related experiences.

As mentioned by the scientists, the study involved ascertained individuals with a high prevalence of cannabis use disorder and use of other illicit drugs. This makes it unclear whether these findings can be generalized to the population at large.