A genetic variant in the P2RX7 gene may increase risk of psychotic experiences among cannabis users | Research

The takeaway

A genome-wide study identified a genetic variant in P2RX7 associated with higher levels of psychotic experiences in regular cannabis users, replicated in an independent cohort and supported by in vitro experiments.

Genetics researchers, psychiatrists, people interested in cannabis and psychosis risk

P2RX7 variant rs7958311 linked to psychotic experiences in cannabis users (p = 1.10 x 10^-7)

What the researchers found

A SNP in the P2RX7 gene (rs7958311) was associated with increased psychotic-like experiences in regular cannabis users (p = 1.10 x 10^-7) and was replicated in the IMAGEN cohort (p = 0.020). In vitro, THC and CBD reduced the P2X7 receptor's immune response in a genotype-dependent manner.

Why it matters

This identifies a specific genetic pathway that may explain why some cannabis users develop psychotic symptoms while others do not, potentially opening doors for targeted prevention.

The numbers in context

Discovery: rs7958311 association p = 1.10 x 10^-7 (N = 1,262). Replication: p = 0.020 (N = 1,217). P2X7 receptor immune response was reduced by THC and CBD in a genotype-dependent manner.

How the study worked

Genome-wide environment-interaction study (GWEIS) in 1,262 individuals without psychiatric disorders, enriched for extremes of cannabis use and psychotic-like experiences. Replication in the IMAGEN cohort (n = 1,217). Functional validation through in vitro monocyte experiments.

What this study cannot tell us

Discovery p-value did not reach genome-wide significance (5 x 10^-8); enriched sampling design may limit generalizability; in vitro immune findings may not fully reflect brain-level effects.

How to read the evidence

Genome-wide study with independent replication and functional validation, though the primary finding narrowly missed genome-wide significance.

When this study was published

Published in 2020.

The bigger picture

Most cannabis users do not develop psychosis. Identifying genetic variants that increase vulnerability could eventually allow for personalized risk assessment.

Questions still open

Could P2RX7 antagonists reduce psychosis risk in genetically vulnerable cannabis users? How does this genetic variant interact with other known risk factors like COMT or AKT1?

Common questions

Does this mean there is a "psychosis gene" for cannabis users?

Not exactly. The P2RX7 variant identified appears to increase vulnerability to psychotic experiences specifically when combined with cannabis use. It is one of likely many genetic factors that interact with cannabis exposure.

What does P2RX7 do in the brain?

The P2X7 receptor is involved in neurotransmission, synaptic plasticity, and immune regulation. It has been previously linked to psychiatric disorders, and this study suggests cannabinoids interact with it in a genotype-dependent way.

Read the original research

Cannabinoids and psychotic symptoms: A potential role for a genetic variant in the P2X purinoceptor 7 (P2RX7) gene.

Brain, behavior, and immunity, 88, 573-581

View on PubMed ↗Publisher’s paper ↗

Citation

Boks, Marco P; He, Yujie; Schubart, Chris D; Gastel, Willemijn van; Elkrief, Laurent; Huguet, Guillaume; Eijk, Kristel van; Vinkers, Christiaan H; Kahn, René S; Paus, Tomás; Conrod, Patricia; Hol, Elly M; de Witte, Lot D. (2020). Cannabinoids and psychotic symptoms: A potential role for a genetic variant in the P2X purinoceptor 7 (P2RX7) gene.. Brain, behavior, and immunity, 88, 573-581. https://doi.org/10.1016/j.bbi.2020.04.051