Faculty Collaboration Database

The therapeutic potential of the endocannabinoid system for the development of a novel class of antidepressants. Trends Pharmacol Sci 2009 Sep;30(9):484-93

Date

09/08/2009

Pubmed ID

19732971

DOI

10.1016/j.tips.2009.06.006

Scopus ID

2-s2.0-69549116206 (requires institutional sign-in at Scopus site)   141 Citations

Abstract

The endocannabinoid system is a neuromodulatory system which is known to regulate emotional, cognitive, neurovegetative and motivational processes. Substantial evidence has accumulated implicating a deficit in endocannabinoid in the etiology of depression; accordingly, pharmacological augmentation of endocannabinoid signaling could be a novel target for the pharmacotherapy of depression. Within preclinical models, facilitation of endocannabinoid neurotransmission evokes both antidepressant and anxiolytic effects. Similar to the actions of conventional antidepressants, enhancement of endocannabinoid signaling can enhance serotonergic and noradrenergic transmission; increase cellular plasticity and neurotrophin expression within the hippocampus; and dampen activity within the neuroendocrine stress axis. Furthermore, limbic endocannabinoid activity is increased by both pharmacological and somatic treatments for depression, and, in turn, appears to contribute to some of the neuroadaptive alterations elicited by these treatments. These preclinical findings support the rationale for the clinical development of agents which inhibit the cellular uptake and/or metabolism of endocannabinoids in the treatment of mood disorders.

Author List

Hill MN, Hillard CJ, Bambico FR, Patel S, Gorzalka BB, Gobbi G

Author

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antidepressive Agents
Cannabinoid Receptor Modulators
Clinical Trials as Topic
Depression
Drug Delivery Systems
Drug Design
Drug Evaluation, Preclinical
Endocannabinoids
Humans
Mood Disorders
Signal Transduction