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Psychotomimetic effects at initiation of cannabis use are associated with cannabinoid receptor 1 (CNR1) variants in healthy students

Molecular Psychiatry volume 19, pages 402–403 (2014)Cite this article

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Cannabis induces a diverse range of subjective experiences including relaxation, anxiety, euphoria, sadness, cognitive difficulties and psychotic-like symptoms. In addition, although cannabis use is associated with an overall twofold increased risk of subsequent psychotic disorders, all individuals are not at equal risk of developing psychosis when exposed to cannabis.1 Inconsistent results have been reported regarding the influence of variants in the catechol-O-methyltransferase (COMT) gene2,3 or in other genes of interest, such as brain-derived neurotrophic factor (BDNF), cannabinoid receptor 1 (CNR1)4,5 and more convincingly, v-Akt murine thymoma viral oncogene homolog 1 (AKT1).6 Inter-individual variability in subjective experience is already present at initiation of cannabis use and could reflect intrinsic personal characteristics. From a gene × environment perspective, we hypothesized that the propensity to experience psychotomimetic effects when first using cannabis (PEFU) is influenced by genetic factors. We conducted a large community-based survey profiling the subjective response to cannabis in unrelated healthy young students. We investigated the association of polymorphisms of interest in CNR1, AKT1, BDNF and COMT genes with PEFU and found a significant association with a functional haplotype block in CNR1.

We interviewed 3807 students (age=19.8±2.5 years) during their mandatory preventive health visit in a university medical center. 44% of them had used cannabis at least once in their lifetime. Subjective experiences during first use were assessed using a 17-item self-report questionnaire (5-level rating), which has a confirmed factorial structure including one grouping psychotic-like experiences: hallucinations (visual and/or auditory) and ideas of reference (see Supplementary Material for more details). High PEFU was defined as the experience of at least one of these psychotic symptoms ‘strongly‘ or ‘very strongly’ when first consuming cannabis. A psychologist directly screened a subsample of 1196 students for Caucasian origins and no personal or family psychiatric history (age=19.8±2 years). After giving their informed written consent, these subjects provided DNA using cheek swabs. Among this group, 45.5% had used cannabis at least once in their lifetime and described their first subjective experiences (n=544; age at initiation: 15.9±1.8 years) (see socio-demographic characteristics in Supplementary Table 1).

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Acknowledgements

This study was funded by the Wyeth Foundation and promoted by the Sainte-Anne Hospital. We thank Professor JF Dhainaut, Professor D Jore and the SIUMPPS’ staff (Dr J Rouvier and A Perufel), who made this study possible at Paris Descartes University, and the CERC’s staff (N Bendjemaa, M Johais) for data collection.

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Authors and Affiliations

  1. Université Paris Descartes,

    M O Krebs, Y Morvan, T Jay, R Gaillard & O Kebir

  2. INSERM, Laboratoire de Physiopathologie des Maladies Psychiatriques, Centre de Psychiatrie et Neurosciences, UMR 894,

    M O Krebs, Y Morvan, T Jay, R Gaillard & O Kebir

  3. PRES Paris Sorbonne Cité, Paris, France

    M O Krebs, Y Morvan, T Jay, R Gaillard & O Kebir

  4. Hôpital Sainte-Anne, Service Hospitalo-Universitaire, Faculté de Médecine Paris Descartes, Paris, France

    M O Krebs, R Gaillard & O Kebir

  5. Laboratoire Cognition, Santé, Socialisation, C2S, EA6291, Université de Reims Champagne-Ardenne, Reims, France

    Y Morvan

  6. GDR3557-Institut de Psychiatrie, Paris, France

    M O Krebs, Y Morvan, T Jay, R Gaillard & O Kebir

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  1. M O Krebs
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  2. Y Morvan
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Correspondence to M O Krebs.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website

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Krebs, M., Morvan, Y., Jay, T. et al. Psychotomimetic effects at initiation of cannabis use are associated with cannabinoid receptor 1 (CNR1) variants in healthy students. Mol Psychiatry 19, 402–403 (2014). https://doi.org/10.1038/mp.2013.188

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