Du nouveau pour protéger le cerveau du cannabis

Pregnenolone Can Protect the Brain from Cannabis Intoxication

1. Monique Vallée1,2,†, 
2. Sergio Vitiello1,2,*, 
3. Luigi Bellocchio1,2,*, 
4. Etienne Hébert-Chatelain1,2,*,
5. Stéphanie Monlezun3,*, 
6. Elena Martin-Garcia4, 
7. Fernando Kasanetz1,2, 
8. Gemma L. Baillie5,7,
9. Francesca Panin1,2, 
10. Adeline Cathala1,2, 
11. Valérie Roullot-Lacarrière1,2, 
12. Sandy Fabre3, 
13. Dow P. Hurst6,
14. Diane L. Lynch6, 
15. Derek M. Shore6, 
16. Véronique Deroche-Gamonet1,2, 
17. Umberto Spampinato1,2,
18. Jean-Michel Revest1,2, 
19. Rafael Maldonado4, 
20. Patricia H. Reggio6, 
21. Ruth A. Ross5,7, 
22. Giovanni Marsicano1,2,
23. Pier Vincenzo Piazza1,2,†‡

+Author Affiliations

1. ¹INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, France.
2. ²Université de Bordeaux, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, France.
3. ³Alienor Farma Parc Scientifique Unitec1, 2 Allée du Doyen Georges Brus, 33600 Pessac, France.
4. ⁴Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Parc de Recerca Biomédica de Barcelona, Calle Dr. Aiguader 88, Barcelona 08003, Spain.
5. ⁵Kosterlitz Centre for Therapeutics, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.
6. ⁶Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USA.
7. ⁷Present address: Department of Pharmacology and Toxicology, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8.

1. ↵‡Corresponding author. E-mail: pier-vincenzo.piazza@inserm.fr

1. ↵* These authors contributed equally to this work.
2. ↵† These authors equally supervised this work.

• ABSTRACT
• EDITOR'S SUMMARY

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.