CANNABIS
MEDICAL
36 MEDICAL CANNABIS
Pregnenolone and Signaling-Specific Inhibitor
In 2014, there was a huge step forward in our understanding of how our brains regulate cannabinoid signaling. Scientists found that pregnenolone, a naturally occurring steroid precursor, was a natural modulator of the CB1 receptor.
In response to CB1 receptor activation, our brains start synthesizing pregnenolone, which then blocks further CB1 receptor activation. When synthesis of pregnenolone was blocked in mice, all of the effects of THC were amplified.
Activation of the CB1 receptor stimulates multiple pathways of intracellular signaling. Interestingly, pregnenolone is able to block a specific signaling pathway, and thus is considered a “signaling-specific” inhibitor.
Pregnenolone is freely available to be sold in the US as a dietary supplement. So you would think that this would be an obvious choice for cannabis overdose. However, there are challenges with the absorption and stability of pregnenolone taken orally. Since little pregnenolone is absorbed and it is rapidly converted to other steroids, very little pregnenolone makes it to your brain intact.
One way to circumvent this is to take pregnenolone via the intranasal route. Intranasal administration resulted in high brain levels of pregnenolone and improved memory in mice. However, whether intranasal pregnenolone is effective for cannabis overdose in humans has not yet been demonstrated. If proven effective, this would be an excellent treatment option.