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

  title={Psychotomimetic effects at initiation of cannabis use are associated with cannabinoid receptor 1 (CNR1) variants in healthy students},
  author={Marie-Odile Krebs and Yannick Morvan and Th{\'e}r{\`e}se M. Jay and Raphael Gaillard and Oussama Kebir},
  journal={Molecular Psychiatry},
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. Inconsistent results have been reported regarding the influence of variants in the catechol-O-methyltransferase (COMT) gene2,3… Expand
[Cannabis-induced cognitive and psychiatric disorders].
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This review combines data from human and experimental studies to show that long-term and heavy cannabis use during pregnancy can impair brain maturation and predispose the offspring to neurodevelopmental disorders, and suggests that endocannabinoid signaling can be an appealing druggable target to dampen neuronal activity if pre-existing pathologies associate with circuit hyperexcitability. Expand
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Cannabinoid receptor type 2 gene is associated with comorbidity of schizophrenia and cannabis dependence and fatty acid amide hydrolase gene is associated with cannabis dependence in the Spanish population.
The rs35761398 and rs12744386 polymorphisms in the CNR2 gene are genetic risk factors for schizophrenia in cannabis-dependent subjects and loss of heterozygosity for polymorphism rs324420 in the FAAH gene is a genetic risk factor for cannabis dependence in this population. Expand
Cannabinoid receptor gene polymorphisms and cognitive performance in patients with schizophrenia and controls.
Although limited, the data support the hypothesis that CNR1 variations may be associated with the pathogenesis of cognitive deficits of schizophrenia. Expand
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Delineating genetic risk factors in the various stages of cannabis use will provide insight into the biological mechanisms related to cannabis use, and highlight points of intervention prior to and following the development of dependence, as well as identify targets to aid drug development for treating problematic cannabis use. Expand
Exposure to cannabinoids can lead to persistent cognitive and psychiatric disorders
Cannabinoids are proposed in a wide array of medical indications. Yet, the evaluation of adverse effects in controlled clinical studies, following the evidence‐based model, has partly been bypassed.Expand
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A systematic review of association studies between schizophrenia (and its subphenotypes) and polymorphisms in the CNR1 gene, which encodes cannabinoid receptors classically implicated in schizophrenia pathophysiology, as well as to present unpublished results of an association study in a Brazilian population is performed. Expand
Genetic and Environmental Factors Associated with Cannabis Involvement
It is likely that the small effect sizes associated with variants related to cannabis involvement will only be robustly identified in substantially larger samples, and results of such large-scale efforts will provide valuable single variant targets for translational research in neurogenetic, pharmacogenetic, and non-human animal models. Expand
Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse
Recent advances in this important area of research are described, suggesting that heavy exposure to drugs of abuse is needed for neurotoxicity and for persistent emotional and cognitive alterations. Expand


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Findings argue against the widely held belief that the relative risk of developing psychosis following use of cannabis is dependent upon variation within catechol-methyl-transferase (COMT), and suggest that this harm is subgroup specific in the absence of robust evidence of replication. Expand
Gene-environment interactions underlying the effect of cannabis in first episode psychosis.
The present review will focus on the interaction between genes and cannabis exposure in the development of psychotic symptoms and schizophrenia and the biological mechanisms of cannabis. Expand
The incentive salience of alcohol: translating the effects of genetic variant in CNR1.
Individuals with the C allele may be more susceptible to changes in the mesocorticolimbic neurocircuitry that is involved in the attribution of incentive salience after repeated exposure to alcohol. Expand
Genetic variation underlying psychosis-inducing effects of cannabis: critical review and future directions.
The available evidence suggesting that differential sensitivity to the psychosis-inducing effects of cannabis may be related to underlying genetic liability is reviewed, and the concept of a biological interaction between cannabis use and one's underlying genetic vulnerability is supported. Expand
Moderation of the Effect of Adolescent-Onset Cannabis Use on Adult Psychosis by a Functional Polymorphism in the Catechol-O-Methyltransferase Gene: Longitudinal Evidence of a Gene X Environment Interaction
Findings provide evidence of a gene x environment interaction and suggest that a role of some susceptibility genes is to influence vulnerability to environmental pathogens. Expand
Confirmation that the AKT1 (rs2494732) Genotype Influences the Risk of Psychosis in Cannabis Users
Findings provide strong support for the initial report that genetic variation at rs2494732 of AKT1 influences the risk of developing a psychotic disorder in cannabis users. Expand
CNR1 Gene is Associated with High Neuroticism and Low Agreeableness and Interacts with Recent Negative Life Events to Predict Current Depressive Symptoms
The results represent the first evidence in humans that the CNR1 gene is a risk factor for depression––and probably also for co-morbid psychiatric conditions such as substance use disorders––through a high neuroticism and low agreeableness phenotype. Expand
Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review
There is now sufficient evidence to warn young people that using cannabis could increase their risk of developing a psychotic illness later in life, although evidence for affective outcomes is less strong. Expand
Human cannabinoid receptor 1: 5′ exons, candidate regulatory regions, polymorphisms, haplotypes and association with polysubstance abuse
Improved definition of the human CB1/Cnr1 locus and its variants is reported, finding that post-mortem brain samples of heterozygous individuals contain less mRNA transcribed from the TAG alleles than from other CB1 or Cnr1 haplotypes, andCB1/ Cnr 1 genomic variation thus appears to play roles in human addiction vulnerability. Expand
Allele-specific Differences in Activity of a Novel Cannabinoid Receptor 1 (CNR1) Gene Intronic Enhancer in Hypothalamus, Dorsal Root Ganglia, and Hippocampus*
Alleles of enhancer may be functionally linked to obesity and addictive behavior and further analysis of the different alleles of ECR1 may lead to a greater understanding of the role of CNR1 gene misregulation in these conditions as well as chronic inflammatory pain. Expand