Posted by Larry Hoover on January 6, 2003, at 9:45:56
There is an entirely novel regulatory pathway under study, based on research into the effects of cannabis on mood. The natural brain chemical which binds to the "cannabinoid receptor", known as anandamide, can be potentiated by blocking the enzyme responsible for its degradation, something like blocking the enzyme monoamine oxidase. Blocking this anandamide-degrading enzyme has similar effects to benzodiazepines in rodents.
Modulation of anxiety through blockade of anandamide hydrolysisSatish Kathuria1, Silvana Gaetani1, Darren Fegley1, Fernando Valiño1, Andrea Duranti2, Andrea Tontini2, Marco Mor3, Giorgio Tarzia2, Giovanna La Rana4, Antonio Calignano4, Arcangela Giustino5, Maria Tattoli5, Maura Palmery6, Vincenzo Cuomo6 & Daniele Piomelli1
The psychoactive constituent of cannabis, 9-tetrahydrocannabinol, produces in humans subjective responses mediated by CB1 cannabinoid receptors, indicating that endogenous cannabinoids may contribute to the control of emotion. But the variable effects of 9-tetrahydrocannabinol obscure the interpretation of these results and limit the therapeutic potential of direct cannabinoid agonists. An alternative approach may be to develop drugs that amplify the effects of endogenous cannabinoids by preventing their inactivation. Here we describe a class of potent, selective and systemically active inhibitors of fatty acid amide hydrolase, the enzyme responsible for the degradation of the endogenous cannabinoid anandamide. Like clinically used anti-anxiety drugs, in rats the inhibitors exhibit benzodiazepine-like properties in the elevated zero-maze test and suppress isolation-induced vocalizations. These effects are accompanied by augmented brain levels of anandamide and are prevented by CB1 receptor blockade. Our results indicate that anandamide participates in the modulation of emotional states and point to fatty acid amide hydrolase inhibition as an innovative approach to anti-anxiety therapy.
poster:Larry Hoover
thread:134705
URL: http://www.dr-bob.org/babble/20030106/msgs/134705.html