Cannabis Use and Endocannabinoid Receptor Genes: A Pilot Study on Their Interaction on Brain Activity in First-Episode Psychosis
Maitane Oscoz-Irurozqui, Carmen Almodóvar-Payá, Maria Guardiola-Ripoll, Amalia Guerrero‐Pedraza, Noemí Hostalet, Raymond Salvador, María Isabel Huéscar Carrión, Teresa Maristany, Edith Pomarol‐Clotet, Mar Fatjó‐Vilas
International Journal of Molecular Sciences April 19, 2023 DOI: 10.3390/ijms24087501 (opens in new tab) via OpenAlex
Summary
AI-generated from the abstractIn patients with first-episode psychosis, cannabis use and genetic variants in cannabinoid receptor genes jointly affect brain activity in regions linked to reward, including the caudate nucleus, cingulate cortex, and orbitofrontal cortex. The study genotyped 40 patients (half cannabis users, half non-users) for two single-nucleotide polymorphisms in the CNR1 and CNR2 genes and measured brain activity with fMRI during a working-memory task. Interaction models showed that cannabis use combined with specific genotypes influenced activation in these areas, suggesting a joint role for cannabis and genetic background in brain function during early psychosis.
Study at a glance
| Characteristics | Case-only design Pilot study Peer reviewed |
|---|---|
| Sample size | 40 |
| Population | Patients with first-episode psychosis |
| Topics | Cannabis |
| Keywords | Psychosis Endocannabinoid system Cannabinoid receptor Orbitofrontal cortex |
| Citations | 2 |
| Key finding | Cannabis use and CNR1 and CNR2 genotypes jointly influence brain activity in the caudate nucleus, cingulate cortex, and orbitofrontal cortex in first-episode psychosis. |
Abstract
The role of both cannabis use and genetic background has been shown in the risk for psychosis. However, the effect of the interplay between cannabis and variability at the endocannabinoid receptor genes on the neurobiological underpinnings of psychosis remains inconclusive. Through a case-only design, including patients with a first-episode of psychosis (n = 40) classified as cannabis users (50%) and non-users (50%), we aimed to evaluate the interaction between cannabis use and common genetic variants at the endocannabinoid receptor genes on brain activity. Genetic variability was assessed by genotyping two Single Nucleotide Polymorphisms (SNP) at the cannabinoid receptor type 1 gene (CNR1; rs1049353) and cannabinoid receptor type 2 gene (CNR2; rs2501431). Functional Magnetic Resonance Imaging (fMRI) data were obtained while performing the n-back task. Gene × cannabis interaction models evidenced a combined effect of CNR1 and CNR2 genotypes and cannabis use on brain activity in different brain areas, such as the caudate nucleus, the cingulate cortex and the orbitofrontal cortex. These findings suggest a joint role of cannabis use and cannabinoid receptor genetic background on brain function in first-episode psychosis, possibly through the impact on brain areas relevant to the reward circuit.