Pregnenolone can protect the brain from cannabis intoxication.

Monique Vallée, Sergio Vitiello, Luigi Bellocchio, Etienne Hébert-Chatelain, Stéphanie Monlezun, Elena Martin-Garcia, Fernando Kasanetz, Gemma L. Baillie, Francesca Panin, Adeline Cathala, Valérie Roullot-Lacarrière, Sandy Fabre, Dow P. Hurst, Diane L. Lynch, Derek M. Shore, Véronique Deroche-Gamonet, Umberto Spampinato, Jean-Michel Revest, Rafael Maldonado, Patricia H. Reggio, Ruth A. Ross, Giovanni Marsicano, Pier Vincenzo Piazza
Science. 2014-01-02; 343(6166): 94-98
DOI: 10.1126/science.1243985

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Erratum in
Science. 2014 Feb 28;343(6174):969.

Comment in
Nat Rev Neurosci. 2014 Feb;15(2):66-7.

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),
Δ(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.


Auteurs Bordeaux Neurocampus