Posted by SLS on July 24, 2006, at 7:07:16
In reply to Re: Cannabinoids, posted by linkadge on July 23, 2006, at 16:31:53
The "MAOI" of Cannabinoids:
It appears that the inhibition of the catabolization of anandamide produces antidepressant effects throught the moduclation of monoaminergic systems. This mechanism obviates the need to get "high" because it doesn't use agonist ligands.
- Scott-----------------------------------------------
Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18620-5. Epub 2005 Dec 13.* Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2465.
Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis.Gobbi G, Bambico FR, Mangieri R, Bortolato M, Campolongo P, Solinas M, Cassano T, Morgese MG, Debonnel G, Duranti A, Tontini A, Tarzia G, Mor M, Trezza V, Goldberg SR, Cuomo V, Piomelli D.
Department of Psychiatry, McGill University, Montreal, QC, Canada H1N 3V2.
Although anecdotal reports suggest that cannabis may be used to alleviate symptoms of depression, the psychotropic effects and abuse liability of this drug prevent its therapeutic application. The active constituent of cannabis, delta9-tetrahydrocannabinol, acts by binding to brain CB1 cannabinoid receptors, but an alternative approach might be to develop agents that amplify the actions of endogenous cannabinoids by blocking their deactivation. Here, we show that URB597, a selective inhibitor of the enzyme fatty-acid amide hydrolase, which catalyzes the intracellular hydrolysis of the endocannabinoid anandamide, exerts potent antidepressant-like effects in the mouse tail-suspension test and the rat forced-swim test. Moreover, URB597 increases firing activity of serotonergic neurons in the dorsal raphe nucleus and noradrenergic neurons in the nucleus locus ceruleus. These actions are prevented by the CB1 antagonist rimonabant, are accompanied by increased brain anandamide levels, and are maintained upon repeated URB597 administration. Unlike direct CB1 agonists, URB597 does not exert rewarding effects in the conditioned place preference test or produce generalization to the discriminative effects of delta9-tetrahydrocannabinol in rats. The findings support a role for anandamide in mood regulation and point to fatty-acid amide hydrolase as a previously uncharacterized target for antidepressant drugs.
PMID: 16352709 [PubMed - indexed for MEDLINE]
poster:SLS
thread:669631
URL: http://www.dr-bob.org/babble/20060724/msgs/669943.html