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Expert Opin Drug Discov. 2015 Jan;10(1):17-36. doi: 10.1517/17460441.2014.966680. Epub 2014 Dec 9.

Drug discovery strategies that focus on the endocannabinoid signaling system in psychiatric disease.

Author information

1
Drexel University, Department of Pharmacology and Physiology , Mail Stop 400, New College Building, 245 N. 15th Street, Philadelphia, PA 19102 , USA rrw47@drexel.edu.

Abstract

INTRODUCTION:

The endocannabinoid (eCB) system plays an important role in the control of mood, and its dysregulation has been implicated in several psychiatric disorders. Targeting the eCB system appears to represent an attractive and novel approach to the treatment of depression and other mood disorders. However, several failed clinical trials have diminished enthusiasm for the continued development of eCB-targeted therapeutics for psychiatric disorders, despite the encouraging preclinical data and promising preliminary results obtained with the synthetic cannabinoid nabilone for treating post-traumatic stress disorder.

AREAS COVERED:

This review describes the eCB system's role in modulating cell signaling within the brain. There is a specific focus on eCB's regulation of monoamine neurotransmission and the stress axis, as well as how dysfunction of this interaction can contribute to the development of psychiatric disorders. Additionally, the review provides discussion on compounds and drugs that target this system and might prove to be successful for the treatment of mood-related psychiatric disorders.

EXPERT OPINION:

The discovery of increasingly selective modulators of CB receptors should enable the identification of optimal therapeutic strategies. It should also maximize the likelihood of developing safe and effective treatments for debilitating psychiatric disorders.

KEYWORDS:

CB1 receptors; anxiety; clinical trials; depression; hypothalamic–pituitary–adrenal axis; monoamines; post-traumatic stress disorder; stress response

PMID:
25488672
PMCID:
PMC4696509
DOI:
10.1517/17460441.2014.966680
[Indexed for MEDLINE]
Free PMC Article

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