Francis Rodriguez Bambico1, Gabriella Gobbi. 1. McGill University, Neurobiological Psychiatry Unit, Department of Psychiatry, Research and Training Building, 1033 Pine Avenue West, Montréal Québec, H3A 1A1, Canada.
Abstract
BACKGROUND: Major depression has the highest rate of prevalence and incidence of morbidity among all mental disoders. The limited efficacies of current antidepressant treatments necessitate the development of alternative pharmacotherapies. Recent preclinical findings suggesting that cannabinoid CB(1) receptor agonists and endocannabinoid enhancers possess antidepressant-like properties, and clinical evidence that the CB(1) antagonist rimonabant increases the risk of depression and suicidality, support the notion that the endocannabinoid system represents a novel target in the treatment of mood disorders. OBJECTIVE/ METHODS: To compare the mechanism of endocannabinoid enhancers and CB(1) agonists with current antidepressants and provide a rationale for a role of the endocannabinoid system in the pathology and treatment of mood disorders. RESULTS/ CONCLUSION: CB(1) agonists and fatty acid amide hdyrolase (FAAH) inhibitors share mechanisms with other antidepressants: the ability to enhance central serotonergic and noradrenergic transmission and promote neurogenesis in the hippocampus. FAAH inhibitors, compared with direct CB(1) agonists, exhibit distinct pharmacological properties that quell adverse cannabinoid effects and widen the therapeutic window. Since the endocannabinoid system also plays a role in peripheral functions, side effects need to be addressed.
BACKGROUND: Major depression has the highest rate of prevalence and incidence of morbidity among all mental disoders. The limited efficacies of current antidepressant treatments necessitate the development of alternative pharmacotherapies. Recent preclinical findings suggesting that cannabinoidCB(1) receptor agonists and endocannabinoid enhancers possess antidepressant-like properties, and clinical evidence that the CB(1) antagonist rimonabant increases the risk of depression and suicidality, support the notion that the endocannabinoid system represents a novel target in the treatment of mood disorders. OBJECTIVE/ METHODS: To compare the mechanism of endocannabinoid enhancers and CB(1) agonists with current antidepressants and provide a rationale for a role of the endocannabinoid system in the pathology and treatment of mood disorders. RESULTS/ CONCLUSION:CB(1) agonists and fatty acid amide hdyrolase (FAAH) inhibitors share mechanisms with other antidepressants: the ability to enhance central serotonergic and noradrenergic transmission and promote neurogenesis in the hippocampus. FAAH inhibitors, compared with direct CB(1) agonists, exhibit distinct pharmacological properties that quell adverse cannabinoid effects and widen the therapeutic window. Since the endocannabinoid system also plays a role in peripheral functions, side effects need to be addressed.
Authors: Arpana Agrawal; Elliot C Nelson; Andrew K Littlefield; Kathleen K Bucholz; Louisa Degenhardt; Anjali K Henders; Pamela A F Madden; Nicholas G Martin; Grant W Montgomery; Michele L Pergadia; Kenneth J Sher; Andrew C Heath; Michael T Lynskey Journal: Arch Gen Psychiatry Date: 2012-07
Authors: Zhen Zhang; Wei Wang; Peng Zhong; Sarah J Liu; Jonathan Z Long; Li Zhao; Hai-Qing Gao; Benjamin F Cravatt; Qing-Song Liu Journal: Hippocampus Date: 2014-08-27 Impact factor: 3.899