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

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Lazary J, Juhasz G, Hunyady L, Bagdy G

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

Trends Pharmacol Sci. 2011 May;32(5):270-80. doi: 10.1016/j.tips.2011.02.013. Epub 2011 Apr 16.

PubMed ID

21497918 [ View in PubMed

]

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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Rimonabant	Cytochrome P450 3A4	Protein	Humans	Unknown	Substrate	Details