Pregnenolone is a fascinating hormone precursor, being the first step in almost all hormone synthesis! Most hormones are derived from cholesterol, and the first hormone generated from cholesterol, is pregnenolone. This means that taking pregnenolone is great for enhancing overall hormone synthesis, such as DHEA, testosterone and dihydrotestosterone. This also means that pregnenolone can enhance the efficacy of virtually any testosterone booster, such as tongkat ali or Cistanche tubulosa!
Another fascinating aspect of pregnenolone is that it is a potent neurosteroid which can modulate cognitive function and mood. One of the most interesting targets of pregnenolone is the sigma-1 receptor, where it acts as an agonist! This is quite a legendary, albeit elusive nootropic target, so the fact that pregnenolone acts as an agonist here is quite a big deal! Pregnenolone also converts to pregnenolone sulfate, which retains the sigma-1 agonist activity and gains NMDA positive allosteric modulator activity. More interestingly, pregnenolone also converts to allopregnanolone, which is a potent modulator of GABAA receptors. Overall, supplementation of pregnenolone will lead to a wide array of positive cognitive effects, in addition to hormonal effects!
Pregnenolone can be considered to be the “master” steroid hormone, as it is the precursor to virtually all steroid hormones. Below is an image which will help visualize this.
Figure 1. Steroidogenic Enzymes
As can be seen in figure 1, all steroid hormone synthesis starts from cholesterol. The first step in this process is that cholesterol is converted to pregnenolone via the cholesterol side-chain cleavage enzyme. From here, pregnenolone can be converted to progesterone, which later yields the corticosteroids. Alternatively, pregnenolone can be converted to DHEA and androstenediol which later yields testosterone, and dihydrotestosterone. With this all in mind, pregnenolone is clearly the main precursor steroid hormone that drives all steroidogenesis.
Besides being a master steroid hormone precursor, pregnenolone also acts as a potent neurosteroid and neurosteroid precursor. Via this mechanism, pregnenolone affects a plethora of neurotransmitter systems, most interestingly of which is the sigma-1 receptor where it acts as an agonist. By converting to progesterone, pregnenolone also acts as a precursor to allopregnanolone which is another potent neurosteroid. Allopregnanolone acts most strongly on GABAA receptors.
As we covered above in some detail, pregnenolone is basically a master regulator of steroid hormone synthesis, as it is the precursor to almost all of them. This means that when you take a dose of pregnenolone, you can expect increases in virtually all steroid hormones. However, this is also where dosing becomes critical, because you do not get linear increases in all of the steroid hormones! In fact, escalating doses of pregnenolone starts to shut off the production of androstenedione, DHEA and 17-OH-Pregnenolone while continuously driving progesterone synthesis. This occurs in this exact order too, escalating doses of pregnenolone first start to shut off androstenedione synthesis, after which DHEA synthesis gets shut off, and lastly, 17-OH-Pregnenolone synthesis gets shut off. Consulting Figure 1, this means that testosterone synthesis then also gets gradually shut off. However, progesterone keeps getting produced.
Due to the fact that escalating doses of pregnenolone gradually start to produce only progesterone, this means that in lower doses pregnenolone is pro-androgenic while in higher doses, it may even be anti-androgenic! This is why our product is dosed very low at 5 mg. This may seem strange at first when looking around at other pregnenolone products which are often dosed in the 100 mg+ range. However, we hope that this explanation has highlighted just how important a low dose of pregnenolone is, since we are shooting for pro-androgenic effects, rather than potentially anti-androgenic effects!
So, what can you expect from a low dose of pregnenolone? The 5 mg dose of pregnenolone allows you to bypass the first rate limiting step of androgen synthesis, which is the conversion of cholesterol to pregnenolone. Based on this, we now have a unique opportunity to enhance the synthesis of androgens above baseline. This will help enhance mood, confidence, vitality and muscle strength. In addition to this, it will work very nicely together with other testosterone boosters, such as tongkat ali, Cistanche tubulosa and Primavie shilajit since all of them require pregnenolone in order to generate testosterone.
In addition to the pro-androgenic effects, pregnenolone also has direct effects in the brain, due to its activity as a steroid hormone, but also as a neurosteroid precursor. The two main neurosteroids that pregnenolone can yield are pregnenolone sulfate and allopregnanolone. Considering all three together, they have a diverse effect on many different nootropic targets. For example, pregnenolone sulfate acts as a positive allosteric modulator of the NMDA receptor. Activation of the NMDA receptor is one of the main processes during long term potentiation (LTP). Thus, by acting as a NMDA positive allosteric modulator, pregnenolone sulfate can enhance LTP, thereby enhancing memory encoding. This is further backed up by pregnenolone, and pregnenolone sulfate's ability to activate the sigma-1 receptor. Together with positive allosteric modulation of the NMDA receptor, this produces potent nootropic effects. In addition to this, sigma-1 agonism also produces significant mood enhancing effects. These mood enhancing effects are further amplified by allopregnanolone which acts as a positive allosteric modulator of GABAA receptors, while also helping to enhance neuroplasticity. Taken together, it is clear to see that pregnenolone supplementation has enormous nootropic and mood enhancing potential too!
The Testosterone Stack: Pregnenolone + Tongkat Ali Extract Capsules
Tongkat ali likely needs no introduction at this point, it has quickly become one of the gold standards in the world of testosterone boosters. However, for tongkat ali to boost testosterone, it still requires the presence of steroid hormone precursors. Thus, in order to further enhance the efficacy of tongkat ali, providing a dose of pregnenolone will do wonders!
The Nootropic Stack: Pregnenolone + OmegaTAU Capsules
Since pregnenolone is an endogenous neurosteroid which is highly important for cognitive function, we thought it would be a great idea to stack it with Omega-TAU which provides other endogenous compounds that are critical for cognitive function. Together, they make for a very well rounded nootropic stack that ticks most boxes!
The Mood Stack: Pregnenolone + High Potency Saffron Extract Capsules
The mood effects of pregnenolone are quite uplifting and calming, and we have found that they mesh perfectly with the mood elevating properties of saffron. Taken together, they feel like sunshine in a bottle!
As a dietary supplement, take one 5mg tablet of Pregnenolone daily.
To gain more insight, see the Pregnenolone reviews and experiences below.
Nootropics Depot offers 120ct. or 365ct. jars of high-quality Pregnenolone. Nootropics Depot’s Pregnenolone has been lab-tested and verified for both product purity and identity.
Attention: These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.