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), 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.
authors.affiliation: INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Vallée
authors.forename: Sergio
authors.initials: S
authors.lastname: Vitiello
authors.forename: Luigi
authors.initials: L
authors.lastname: Bellocchio
authors.forename: Etienne
authors.initials: E
authors.lastname: Hébert-Chatelain
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Monlezun
authors.forename: Elena
authors.initials: E
authors.lastname: Martin-Garcia
authors.forename: Fernando
authors.initials: F
authors.lastname: Kasanetz
authors.forename: Gemma L
authors.initials: GL
authors.lastname: Baillie
authors.forename: Francesca
authors.initials: F
authors.lastname: Panin
authors.forename: Adeline
authors.initials: A
authors.lastname: Cathala
authors.forename: Valérie
authors.initials: V
authors.lastname: Roullot-Lacarrière
authors.forename: Sandy
authors.initials: S
authors.lastname: Fabre
authors.forename: Dow P
authors.initials: DP
authors.lastname: Hurst
authors.forename: Diane L
authors.initials: DL
authors.lastname: Lynch
authors.forename: Derek M
authors.initials: DM
authors.lastname: Shore
authors.forename: Véronique
authors.initials: V
authors.lastname: Deroche-Gamonet
authors.forename: Umberto
authors.initials: U
authors.lastname: Spampinato
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Revest
authors.forename: Rafael
authors.initials: R
authors.lastname: Maldonado
authors.forename: Patricia H
authors.initials: PH
authors.lastname: Reggio
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Ross
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marsicano
authors.forename: Pier Vincenzo
authors.initials: PV
authors.lastname: Piazza
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D063387:Cannabinoid Receptor Antagonists / Q000008:administration & dosage; D002188:Cannabis / Q000633:toxicity*; D013759:Dronabinol / Q000633:toxicity*; D008297:Male; D002189:Marijuana Abuse / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D011284:Pregnenolone / Q000008:administration & dosage* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000037:antagonists & inhibitors*
chemical_list: D063387:Cannabinoid Receptor Antagonists; D043884:Receptor, Cannabinoid, CB1; D011284:Pregnenolone; D013759:Dronabinol