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 Ross; Giovanni  Marsicano; Pier Vincenzo  Piazza

doi:10.1126/science.1243985

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 journal › Article › peer-review

233 Citations (Scopus)

Abstract

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 language	English
Pages (from-to)	94-98
Number of pages	5
Journal	Science
Volume	343
Issue number	6166
Early online date	3 Jan 2014
DOIs	https://doi.org/10.1126/science.1243985
Publication status	Published - 3 Jan 2014

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Vallée, M., Vitiello, S., Bellocchio, L., Monlezun, S., Martin-Garcia, E., Kasanetz, F., Baillie, G. L., Panin, F., Cathala, A., Roullot-Lacarriere, V., Fabre, S., Hurst, D. P., Lynch, D., Shore, D. M., Deroche-Gamonet, V., Spampinato, U., Revest, J.-M., Maldonado, R., Reggio, P. H., ... Piazza, P. V. (2014). Pregnenolone can protect the brain from cannabis intoxication. Science, 343(6166), 94-98. https://doi.org/10.1126/science.1243985

Vallée, M, Vitiello, S, Bellocchio, L, Monlezun, S, Martin-Garcia, E, Kasanetz, F, Baillie, GL, Panin, F, Cathala, A, Roullot-Lacarriere, V, Fabre, S, Hurst, DP, Lynch, D, Shore, DM, Deroche-Gamonet, V, Spampinato, U, Revest, J-M, Maldonado, R, Reggio, PH, Ross, RA, Marsicano, G & Piazza, PV 2014, 'Pregnenolone can protect the brain from cannabis intoxication', Science, vol. 343, no. 6166, pp. 94-98. https://doi.org/10.1126/science.1243985

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title = "Pregnenolone can protect the brain from cannabis intoxication",

abstract = "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.",

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AU - Kasanetz, Fernanado

AU - Baillie, Gemma Louise

AU - Panin, Francesca

AU - Cathala, Adeline

AU - Roullot-Lacarriere, Valerie

AU - Fabre, Sandy

AU - Hurst, Dow P.

AU - Lynch, Diane

AU - Shore, Derek M

AU - Deroche-Gamonet, Veronique

AU - Spampinato, Umberto

AU - Revest, Jean-Michel

AU - Maldonado, Rafael

AU - Reggio, Patricia H.

AU - Ross, Ruth Alexandra

AU - Marsicano, Giovanni

AU - Piazza, Pier Vincenzo

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AB - 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.

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ER -

Pregnenolone can protect the brain from cannabis intoxication

Abstract

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