A specific polymorphism in the cannabinoid receptor 1 gene (CNR1 rs1049353) was found at different frequencies across groups with cannabis-induced psychosis, cannabis use without psychosis, and schizophrenia—suggesting genetic susceptibility varies.
Psychiatric geneticists, researchers studying cannabis and psychosis, and clinicians interested in personalized risk assessment.
What the researchers found
Not everyone who uses cannabis develops psychosis, and not everyone with schizophrenia has used cannabis. This study investigated whether a specific genetic variation might help explain who is vulnerable.
The researchers genotyped 120 people at an Indian medical college, divided into four groups: cannabis-induced psychosis (CIP), cannabis users without psychosis, schizophrenia unrelated to cannabis, and healthy controls. They focused on the CNR1 gene—which codes for the CB1 cannabinoid receptor—specifically the rs1049353 single nucleotide polymorphism.
The genetic analysis found that the prevalence of this CNR1 polymorphism differed across the groups, though the abstract doesn't detail the specific genotype distributions. The demographic analysis showed no significant differences in education, employment, religion, or other socioeconomic factors between groups, suggesting the genetic finding isn't confounded by obvious social variables.
This is the same genetic variant studied in RTHC-00180 (in the context of diabetic kidney disease), demonstrating that a single cannabinoid receptor polymorphism may influence multiple disease pathways—psychosis vulnerability here, kidney disease progression there.
Why it matters
If genetic testing could identify who is at elevated risk for cannabis-induced psychosis, it could inform personalized prevention. The 10-fold risk for genetically vulnerable individuals identified in RTHC-00201 needs a molecular explanation—variants like rs1049353 are candidate mechanisms. This line of research could eventually lead to genetic screening that identifies high-risk individuals before they ever use cannabis.
The numbers in context
N = 120 (30 per group). 4 groups: cannabis-induced psychosis, cannabis use without psychosis, schizophrenia without cannabis, healthy controls. CNR1 rs1049353 genotyped by RT-PCR. No significant demographic differences between groups.
How the study worked
Cross-sectional genetic study at SCB Medical College, Cuttack, India. 120 participants in 4 groups (30 each): cannabis-induced psychosis, cannabis use without psychosis, schizophrenia without cannabis, and healthy controls. Genotyping of CNR1 rs1049353 by real-time PCR. Standardized demographic and clinical data collection.
Who was studied
N=120 patients with varying cannabis use and psychosis status from SCB Medical College, Cuttack, India.
What this study cannot tell us
Small sample size (30 per group) limits statistical power. Single-center study in India may not generalize to other populations where allele frequencies differ. Only one SNP examined out of many possible variants. Cross-sectional design can't establish causation. The abstract doesn't report specific genotype frequencies or effect sizes. Cannabis exposure history isn't standardized (dose, duration, potency vary).
How to read the evidence
Small cross-sectional genetic study—hypothesis-generating for the gene-environment interaction but not definitive proof of genetic causation.
When this study was published
Published in 2025 with data from an Indian population, adding genetic diversity to cannabinoid receptor research.
The bigger picture
This adds genetic precision to the psychosis-cannabis literature. RTHC-00201 quantified the risk (4-fold, 10-fold with genetic vulnerability). RTHC-00193 showed THC and CBD push psychosis in opposite directions. RTHC-00163 found the cannabis-psychosis link disappeared after adjusting for other substances. This study asks the next question: which specific genes determine individual vulnerability? The CNR1 rs1049353 variant is a promising candidate—the same variant studied for kidney disease in RTHC-00180, suggesting CB1 receptor function affects multiple organ systems.
Replication
Not stated in abstract.
Funding
Not reported in abstract.
Conflicts of interest
Not reported in abstract.
Questions still open
- Does rs1049353 genotype predict psychosis risk prospectively, or only correlate with it cross-sectionally? Would combining multiple SNPs improve prediction beyond a single variant? Could pharmacogenomic screening for CNR1 variants become part of clinical practice?
Read the original research
Genetic Insights into Cannabis-induced Psychosis: Role of CNR1 Gene Mutation (rs1049353) and Implications- A Cross-sectional Study.
Indian journal of psychological medicine, 02537176251377498
The Indian Journal of Psychological Medicine is a peer-reviewed journal focusing on mental health research.
Citation
Sahoo, Sujata; Swain, Sarada Prasanna; Samal, Abhishek; Jena, Mamta; Das, Pragyna Paramita. (2025). Genetic Insights into Cannabis-induced Psychosis: Role of CNR1 Gene Mutation (rs1049353) and Implications- A Cross-sectional Study.. Indian journal of psychological medicine, 02537176251377498. https://doi.org/10.1177/02537176251377498
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