Pregnenolone administration can help stop or limit the “high” from cannabis consumption

Pregnenolone administration can help stop or limit the “high” from cannabis consumption

Yes you read that right, you can take cannabis and avoid or limit its mental effects. To some this may sound like something they would not want to do, but for many cannabis users out there it is a very important finding, especially to those using it medically and wanting to avoid its mental effects.
This is a very important finding as it can help many people with various medical issues utilizing all the great things cannabis does for them at higher doses while avoiding excessive or generally unwanted mental effects from this amazing plant. From simple over sensitivity to cannabis or general increases of anxiety with administration of it, to people dealing with life threatening conditions such as cancer that often calls for very high doses of cannabis daily, these findings open the door to having better control over your cannabis use and its related effects.

But what the heck is pregnenolone some of you may ask?

Pregnenolone is an endogenous steroid and precursor used in the biosynthesis of most of the steroid hormones you would normally find in the human body, such as; progestogens, androgens, estrogens and glucocorticoids. Pregnenolone is synthetized in the mitochondria from cholesterol when high levels of steroid synthesis are required in the body. Steroid hormones play very important roles in the regulation of physiological activities such as food-intake, wakening, sleep, reproduction and sexual behavior, and also play a major role in the regulation of mood and memory.
It is sort of a “mother hormone” and although once seen as an inactive precursor to them, it is now coming to light it has actions all on its own without the need of converting to other hormones as mentioned above. Pregnenolone levels in the body play a major role in the regulation of mood, cognitive activities and their decline associated with aging-related conditions. So although this article is geared about its importance in relation to cannabis use, I want to make it clear it does so much more than simply give you a tool to control cannabis’s mental effects and is a very important compound for a variety of reasons.
It has been noted in research that “this negative feedback mediated by pregnenolone reveals an unknown paracrine/autocrine loop protecting the brain from CB1 receptor over-activation that could open an unforeseen novel approach for the treatment of cannabis intoxication and addiction.”

Something I also find pretty interesting is that it has been noted in research that simple cannabis administration raises pregnenolone levels without any sort of pregnenolone administration! It is my opinion/theory that since we already have our own “endo-cannabinoid” system and related receptors (CB1, CB2 and a suspected CB3) that our bodies have evolved a regulatory system on their own in regards to control of our own endo-cannabinoids and their effects. So I guess in a way it is not that surprising that adding additional pregnenolone to the system would potentiate its effect on people consuming cannabis both recreationally and medically. In a recent study it was noted, “The increase in pregnenolone induced by THC (around 1500%) was several fold higher and longer lasting (2h) than the one induced by the other drugs (around 300% and 30 min)” This clearly shows that just cannabis administration will heighten pregnenolone levels, as a mechanism of regulation in my opinion.

But what about straight pregnenolone administration along with cannabis?

Well here is a few points from recent research that should answer that question; “The injection of pregnenolone reversed the effects of AMG, inhibited the effects of THC per se, but had no effect in animals that did not receive THC. These data show that THC-induced production of pregnenolone exerts a negative feed-back on CB1 receptor activity”, “Pregnenolone administration (2–6 mg/kg) blocked THC-induced food-intake in Wistar rats and in C57BL/6N mice, and blunted the memory impairment induced by THC in mice.”, “THC, administered intravenously at escalating cumulative doses (0.15, 0.3, 0.6, 1.2 mg/kg) infused at one minute intervals (9), induced a significant increase in extracellular NAc dopamine levels (Fig. 4F) and in the firing activity of VTA neurons (Fig. 4F,G). Both effects were blunted by pre-treatment with pregnenolone (2m/kg)”, “results presented here provide an example of an unforeseen paracrine/autocrine loop, through which brain steroids can control the activity of a GPCR. Thus, CB1 receptor stimulation increases brain pregnenolone levels, which in turn exerts a negative feedback on the activity of the CB1 receptor antagonizing most of the known behavioral and somatic effects of THC.” and “Signaling-pathway specific allosteric inhibitors, such as pregnenolone, should be better tolerated because: 1. they do not produce an inhibition of all CB1 receptor activities and 2. their insurmountable effects cannot be overcome by increasing drug intake.”
This is just some of the studies out there showing the direct impact of pregnenolone has with cannabis. It has been noted various times recently that “Pregnenolone inhibits behavioral and neurobiological effects of cannabinoids drugs.”

But what does all this mean to the cannabis user?
Well if you get the “munchies” from a particular strain you like other wise or have a general issue with more hunger than you prefer and/or have an issue controlling diet, this may be a helpful compound to supplements with. If you tend to get anxiety from cannabis at times, then this can to help to control that my limiting the effects of administered cannabis. And on a larger more important note (in my opinion) people that want to consume massive amounts of cannabis and/or concentrates due to medical issues such as cancer, can now do so while limiting mental effects that would otherwise be too much for them or limit their productivity.

All in all this is a very important finding and opens the door to more optimal cannabis use for not just recreational use, but medical uses as well.


Pregnenolone Can Protect the Brain from Cannabis Intoxication.
Pregnenolone Can Protect the Brain from Cannabis Intoxication Science 03 Jan 2014:Vol. 343, Issue 6166, pp. 94-98DOI: 10.1126/science.1243985
Cannabis, a complex plant: different compounds and different effects on individuals. Zerrin Atakan.