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

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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.

Original languageEnglish
Pages (from-to)270-280
Number of pages11
JournalTrends in Pharmacological Sciences
Volume32
Issue number5
DOIs
Publication statusPublished - May 2011

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Cannabinoid Receptor Antagonists
Precision Medicine
Cannabinoids
Medicine
rimonabant
Anxiety
Genes
Depression
Cannabinoid Receptors
Endocannabinoids
Serotonin Plasma Membrane Transport Proteins
Genetic Testing
Suicide
Psychiatry
Screening
Obesity
Phenotype
Testing
Enzymes
Therapeutics

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

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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.",
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