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Updated: May 4, 2026

Brain Morphology of Cannabis Users With or Without Psychosis: A Pilot MRI Study
Published on: August 18, 2020
Pregnenolone can protect the brain from cannabis intoxication
Monique Vallée1, Sergio Vitiello, Luigi Bellocchio
1INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, France.
None:
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.
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