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Allopregnenelone the missing ingredient?


Senior Member
It's kind of a tricky thing to raise because when you take it's precursors, such as progesterone or cortisol, you end up raising and potentially unbalancing many other hormones.

It seems progesterone is the closest you can get...

Endogenously produced allopregnanolone exerts a pivotal neurophysiological role by fine-tuning of GABAA receptor and modulating the action of several positive allosteric modulators and agonists at GABAA receptor.[2] The 21-hydroxylated derivative of this compound, tetrahydrodeoxycorticosterone (THDOC), is an endogenous inhibitory neurosteroid with similar properties to those of allopregnanolone, and the 3β-methyl analogue of allopregnanolone, ganaxolone, is under development to treat epilepsy and other conditions, including post-traumatic stress disorder (PTSD).[1]


Ganaxolone (INN, also known as CCD-1042 and 3α-Hydroxy-3β-methyl-5α-pregnan-20-one) is a CNS-selective GABAAmodulator that acts on well-characterized targets in the brain known to have anxiolytic and anticonvulsant effects.[1] Ganaxolone protects against seizures in diverse animal models, including the pentylenetetrazol, 6 Hz and amygdala kindling models.[2][3][4]Ganaxolone is a positive allosteric modulator of the action of the GABAA receptor and, unlike benzodiazepines, there does not appear to be tolerance to the anticonvulsant effects of ganaxolone.[1][5]

Ganaxolone is designed to modulate both synaptic and extrasynaptic GABAA receptors to calm over-excited neurons.[1][10]


So what's the point drob31?

I think cortisol and DHEA aren't the only two culprits when pregnenelone is low.

Furthermore, pregnenelone steal may be occuring because of low cortisol, but cortisol itself may be diverting down a specific pathway, and also starves the body of allopregnenolone, since progesterone reserves are used up.

Perhaps the pregnenelone is stolen to begin with for production of cortisol and non-allopregnenelone metabolites because inflammation in the body.


Senior Member
I supplement both Progesteron and Hydrocortison, hopefully preventing Pregnenolone steal.

If I take too much Prog. it's converted (back) into Pregnenolone and it's the most wonderful feeling! I get so sleepy and I sleep so soundly and restoring. I'd love to take Pregnenolone on its own. If I'd only dare...

(Too much cortisol never ends up in Pregnenolone (in me anyway). I just get extremely hungry and active.)

I don't know my levels of Pregnenolone.
I do know DHEAs is low but that's of little clinical significance my dr. tells me. I once supplemented DHEA and I felt great, probably because it was used to make Testosterone.

Something else to consider: my CYP2C19*17 is faulty. This liver enzym syphons away any Progesteron it finds in the blood. Causing Prog. deficiency in both male and female alike. No matter what adrenal state or Pregnenolone levels they have.
Oral supplementation poses a problem in people who are homozygous for this gene. It breaks down substrates (like Prog. and Test.) way too fast, we need much higher doses.
But for drugs that need this enzym to convert them into active ingredients we need much lower doses because it will flood the blood with it (for example blood thinners).

Here's an interesting site telling you which enzymes are needed to handle which drugs: http://www.drugbank.ca/