Pregnenolone can protect the brain from cannabis intoxication

Monique Vallée, Sergio Vitiello, Luigi Bellocchio, Stephanie Monlezun, Elena Martin-Garcia, Fernanado Kasanetz, Gemma Louise Baillie, Francesca Panin, Adeline Cathala, Valerie Roullot-Lacarriere, Sandy Fabre, Dow P. Hurst, Diane Lynch, Derek M Shore, Veronique Deroche-Gamonet, Umberto Spampinato, Jean-Michel Revest, Rafael Maldonado, Patricia H. Reggio, Ruth Alexandra RossGiovanni Marsicano (Corresponding Author), Pier Vincenzo Piazza (Corresponding Author)

Research output: Contribution to journalArticlepeer-review

233 Citations (Scopus)


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), ∆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.
Original languageEnglish
Pages (from-to)94-98
Number of pages5
Issue number6166
Early online date3 Jan 2014
Publication statusPublished - 3 Jan 2014


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