期刊
SCIENCE
卷 343, 期 6166, 页码 94-98出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1243985
关键词
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资金
- INSERM
- University Victor Segalen-Bordeaux2
- Structure Federative de Recherche Neurosciences (SFRn) de l'Universite de Bordeaux
- Region Aquitaine funds
- EU-FP7 (REPROBESITY) [HEALTH-F2-2008-223713]
- European Research Council (ENDOFOOD) [ERC-2010-StG-260515]
- Fondation pour la Recherche Medicale
- Agence Nationale pour la Recherche
- U.S. National Institutes of Health (NIH) [DA-03672, DA-003934, DA-09789, RO1 DA003934, KO5 DA021358]
Pregnenolone is considered the inactive precursor of all steroid hormones, and its potential functional effects have been largely uninvestigated. The administration of the main active principle of Cannabis sativa (marijuana), Delta(9)-tetrahydrocannabinol (THC), substantially increases the synthesis of pregnenolone in the brain via activation of the type-1 cannabinoid (CB1) receptor. Pregnenolone then, acting as a signaling-specific inhibitor of the CB1 receptor, reduces several effects of THC. This negative feedback mediated by pregnenolone reveals a previously unknown paracrine/autocrine loop protecting the brain from CB1 receptor overactivation that could open an unforeseen approach for the treatment of cannabis intoxication and addiction.
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