Personalized medicine can pave the way for the safe use of CB 1 receptor antagonists

Judit Lazary, Gabriella Juhasz, Laszlo Hunyady, Gyorgy Bagdy

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Antagonists of cannabinoid type-1 (CB 1) receptors have been explored as therapeutic agents for obesity and addiction. However, use of rimonabant (the first marketed CB 1 receptor antagonist) has been suspended due to its anxiogenic and depressive side effects (including suicide risk). Recent genomic studies provide evidence that variants of the CB 1 receptor gene (CNR1) alone or in combination with the gene of the serotonin transporter (SLC6A4) contribute to the development of anxiety and/or depression, suggesting that high-risk individuals could be identified through genetic testing. In this review, we argue that identification of high-risk individuals by a combination of genomic screening, previous risk phenotype, and environmental risk factors offers a promising method for the safe use of centrally acting CB 1 receptor antagonists. We summarize endocannabinoid signaling in pathways related to anxiety and depression, identify the serotonergic system as the most likely candidate to mediate the side effects of CB 1 receptor antagonists, and propose that poloymorphisms in CNR1, SLC6A4 and certain CYP 450 enzymes could help to identify individuals who may benefit from treatment with CB 1 receptor antagonist without psychiatric side effects. © 2011 Elsevier Ltd. All rights reserved.
    Original languageEnglish
    Pages (from-to)270-280
    Number of pages10
    JournalTrends in pharmacological sciences
    Volume32
    Issue number5
    DOIs
    Publication statusPublished - May 2011

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