Pregnenolone monosulfate sodium salt is a powerful neurosteroid, the main precursor of various steroid hormones including steroid ketones. Pregnenolone monosulfate sodium salt can protect the brain from cannabis intoxication. Pregnenolone monosulfate sodium salt acts as a signaling-specific inhibitor of the cannabinoid CB1 receptor. Pregnenolone monosulfate sodium salt also inhibits the effects of tetrahydrocannabinol (THC) that are mediated by the CB1 receptors.

Pregnenolone likely acts as a signaling-specific negative allosteric modulator binding to a site distinct from that occupied by orthosteric ligands. Pregnenolone does not modify agonist binding but only agonist efficacy. The effect of THC is obviously attenuated when slices are pre-treated with Pregnenolone 100 nM (15.1±1.8 % of inhibition). These effects are likely due to a pre-synaptic action of Pregnenolone. Thus, Pregnenolone blocks the increase in the paired-pulse ratio induced by THC but does not modify either the amplitude or the decay time of miniature EPSC [1].

Injections of Pregnenolone (2 and 4mg/kg) before each self-administration session reduce the intake of WIN 55,212-2 and decrease the break-point in a progressive ratio schedule. Pregnenolone administration (2-6 mg/kg) blocks THC-induced food-intake in Wistar rats and in C57BL/6N mice and blunts the memory impairment induced by THC in mice, but it does not modify these behaviors per se [1].