Even without clinical schizophrenia, genetic liability for the disorder predicted more paranoia, depression, social withdrawal, and cognitive difficulties from cannabis use.
Psychiatric geneticists, cannabis researchers, and clinicians screening for psychosis risk.
beta=0.22, p=5.2e-7for association between schizophrenia polygenic risk and cannabis-related cognitive difficulties
What the researchers found
Polygenic risk for schizophrenia was significantly associated with cannabis-related paranoia, depression/anhedonia, social withdrawal, and cognitive difficulties, with cognitive difficulties showing the strongest association (beta=0.22, p=5.2e-7).
Why it matters
This suggests genetic vulnerability to schizophrenia makes people more susceptible to negative cannabis experiences, even before any clinical illness develops, which could serve as an early warning marker.
The numbers in context
4,832 subjects analyzed (3,128 European, 1,704 African ancestry). 70% had CUD. Schizophrenia PRS most strongly associated with cognitive difficulties (beta=0.22, p=5.2e-7). Replicated in independent sample (n=1,446).
How the study worked
Genetic association study using polygenic risk scores for schizophrenia in the COGA study sample, with independent replication. Controlled for cannabis use duration, CUD severity, and age at first use.
Who was studied
4,832 subjects from the COGA study (74% with alcohol use disorders, 70% with CUD) plus 1,446 replication sample.
What this study cannot tell us
Sample ascertained for alcohol use disorders may not represent general population. Self-reported cannabis experiences. Polygenic scores capture only a fraction of genetic risk.
How to read the evidence
Genetic association study with independent replication; strong evidence for the genetic link.
When this study was published
Recent genetic study using established COGA cohort data.
The bigger picture
This study bridges genetics and subjective cannabis experience, suggesting that individual differences in cannabis response have a genetic basis and that negative cannabis experiences may signal underlying schizophrenia vulnerability.
Replication
Key finding replicated in independent sample; strong genetic evidence.
Funding
Not specified in abstract
Conflicts of interest
Not specified in abstract
Questions still open
- Could self-reported cannabis experiences be used as a clinical screening tool for schizophrenia risk?
- Do these genetic effects interact with cannabis potency or frequency of use?
Read the original research
Associations Between Cannabis Use, Polygenic Liability for Schizophrenia, and Cannabis-related Experiences in a Sample of Cannabis Users.
Schizophrenia bulletin, 49(3), 778-787
Citation
Johnson, Emma C; Colbert, Sarah M C; Jeffries, Paul W; Tillman, Rebecca; Bigdeli, Tim B; Karcher, Nicole R; Chan, Grace; Kuperman, Samuel; Meyers, Jacquelyn L; Nurnberger, John I; Plawecki, Martin H; Degenhardt, Louisa; Martin, Nicholas G; Kamarajan, Chella; Schuckit, Marc A; Murray, Robin M; Dick, Danielle M; Edenberg, Howard J; D'Souza, Deepak Cyril; Di Forti, Marta; Porjesz, Bernice; Nelson, Elliot C; Agrawal, Arpana. (2023). Associations Between Cannabis Use, Polygenic Liability for Schizophrenia, and Cannabis-related Experiences in a Sample of Cannabis Users.. Schizophrenia bulletin, 49(3), 778-787. https://doi.org/10.1093/schbul/sbac196