A gene involved in dopamine regulation interacted with cannabis use to affect when psychosis first appeared

In 169 first-episode psychosis patients, cannabis use was associated with earlier onset, and the COMT Val158Met gene variant's effect on onset timing was only visible in non-users.

Pelayo-Terán, José María et al.·Psychiatry research·2010·Preliminary EvidenceCross-Sectional
RTHC-00440Cross SectionalPreliminary Evidence2010RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Cross-Sectional
Evidence
Preliminary Evidence
Sample
N=169

What This Study Found

Researchers examined 169 patients with first-episode schizophrenia spectrum disorders, looking at how the COMT gene (which regulates dopamine) interacted with cannabis use to affect when psychosis first appeared.

Cannabis users had significantly earlier onset of psychosis compared to non-users. The Met/Met genotype of COMT was associated with later onset, but only among patients who did not use cannabis.

Among cannabis users, the COMT genotype had no effect on onset timing. The authors concluded that cannabis use may override the protective delay effect of the Met allele, essentially eliminating the genetic advantage that would otherwise delay psychosis onset.

Key Numbers

169 Caucasian patients with first-episode psychosis. Cannabis-COMT interaction was significant for both DUP and age of onset. COMT genotype differences in onset were present only in non-users.

How They Did This

Cross-sectional study of 169 Caucasian patients with first-episode schizophrenia spectrum disorder. COMT Val158Met polymorphism was typed using PCR. Cannabis use was classified as regular versus sporadic/non-user. Multivariate ANCOVA tested effects on age of onset and duration of untreated psychosis (DUP), with gender as covariate.

Why This Research Matters

This was among the first studies to demonstrate gene-environment interaction between COMT and cannabis in the timing of psychosis onset, suggesting cannabis may neutralize genetic factors that would otherwise delay disease onset.

The Bigger Picture

This research contributed to understanding why some people develop psychosis earlier than others, identifying cannabis use as an environmental factor that could override genetic protective factors.

What This Study Doesn't Tell Us

Cross-sectional design examining only patients who already developed psychosis (no healthy controls). Cannot determine whether cannabis caused earlier onset or whether earlier-onset patients were more likely to use cannabis. Self-reported cannabis use may be unreliable.

Questions This Raises

  • ?Does cannabis accelerate psychosis onset through the dopamine pathway that COMT regulates?
  • ?Would these findings replicate in larger, more diverse samples?

Trust & Context

Key Stat:
COMT gene effect on psychosis timing visible only in non-cannabis-users
Evidence Grade:
Cross-sectional study of moderate size with genetic typing, but limited by lack of healthy controls and self-reported cannabis use.
Study Age:
Published in 2010. Gene-environment interaction research in psychosis has advanced substantially.
Original Title:
Catechol-O-Methyltransferase (COMT) Val158Met variations and cannabis use in first-episode non-affective psychosis: clinical-onset implications.
Published In:
Psychiatry research, 179(3), 291-6 (2010)
Database ID:
RTHC-00440

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study

A snapshot of a population at one point in time.

What do these levels mean? →

Frequently Asked Questions

What is the COMT gene?

COMT (Catechol-O-Methyltransferase) is a gene that controls an enzyme involved in breaking down dopamine in the brain. Different versions of this gene affect how quickly dopamine is cleared.

Does this mean cannabis causes earlier psychosis?

The study found an association between cannabis use and earlier psychosis onset, but the cross-sectional design could not prove causation. Other factors may explain why some patients both used cannabis and developed psychosis earlier.

Read More on RethinkTHC

Cite This Study

RTHC-00440·https://rethinkthc.com/research/RTHC-00440

APA

Pelayo-Terán, José María; Pérez-Iglesias, Rocío; Mata, Ignacio; Carrasco-Marín, Eugenio; Vázquez-Barquero, José Luis; Crespo-Facorro, Benedicto. (2010). Catechol-O-Methyltransferase (COMT) Val158Met variations and cannabis use in first-episode non-affective psychosis: clinical-onset implications.. Psychiatry research, 179(3), 291-6. https://doi.org/10.1016/j.psychres.2009.08.022

MLA

Pelayo-Terán, José María, et al. "Catechol-O-Methyltransferase (COMT) Val158Met variations and cannabis use in first-episode non-affective psychosis: clinical-onset implications.." Psychiatry research, 2010. https://doi.org/10.1016/j.psychres.2009.08.022

RethinkTHC

RethinkTHC Research Database. "Catechol-O-Methyltransferase (COMT) Val158Met variations and..." RTHC-00440. Retrieved from https://rethinkthc.com/research/pelayo-teran-2010-catecholomethyltransferase-comt-val158met-variations

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.