Allopregnanolone (allopreg for short) is a powerful neurosteroid that has been in the headlines recently ever since the deadly “post finasteride syndrome”. Allopreg is considered a neurosteroid that has numerous neuroprotective properties that range anywhere from the importance of the regulation of emotion and its therapeutical use in depression and anxiety may not only involve GABAergic mechanisms, but also includes enhancement of neurogenesis, myelination, neuroprotection, and regulatory effects on HPA axis function. When your body is under stress, allopregnanolone acts as the body’s natural tranquilizer or anti stress mechanism to help dampen the response [here]. It is highly involved in many mental disorders including mood disorders, depression, anxiety, sleep disorders and seizures. One of allopreg’s main role in the central nervous system is activating the GABA (A) receptor (taurine also does this) which provides many of those anti stress properties [here].
Now if you take a look at the chart above, you can see how finasteride (or any 5 alpha reductase inhibitor) can negatively impact the proper synthesis of not only allopregnanolone but also another important neurosteroid, tetrahydrodeoxycorticosterone (another anti stress mechanism). Allopreg is synthesized from progesterone which then gets converted into the direct precursor, 5a-DHP (5a-dihydroprogesterone). Through the series of coenzymes (NAD/NADH) allopreg is now established in the brain.
Now to put into perspective how powerful allopreg really is- it’s actually under development under the name “Ganaxolone” for the treatment of seizures, anxiety, epilepsy, Alzheimer’s, Parkinson’s etc. The difference is that Ganaxolone is allopreg’s synthetic brother [here].
Why are the mental effects (anxiety, memory loss, poor stress tolerance) of finasteride or any 5 alpha reductase inhibitor so severe? Well, there is a significant amount of 5AR expression in the brain and it fits in line with anything that disrupts that function like finasteride which absolutely destroys allopreg in the brain along with MANY other neurosteroid/steroids in the body besides just shutting down the conversion of DHT only. It was hard to find this study especially on male humans, but the results are pretty astounding [here].
This is only after 5 months, also keep in mind that the study notes 5mg of finasteride, but 1mg vs 5mg are pretty much the same in terms of 5AR inhibition in the body and brain [here].
As you can see, anything with a negative (-) number is taking a hit- allopreg being the absolute worse. So much for just being DHT only.
Alright, enough bashing 5ARi’s now it’s time to take a look at how to optimize allopregnanolone both for optimizing mental properties long term and also for anyone recovering from 5 alpha reductase inhibitors.
So as noted from the first master chart above that displays the entire hormone cascade, there a few different ways to increase neurosteroids in general but mainly allopreg:
- Oral pregnenolone at higher doses was shown to increase allopregnanolone significantly.
- Caffeine was shown to increase pregnenolone, progesterone and allopreg in the brain [here]. The trick with caffeine is to take it after eating food and enough sugar to avoid the stress (cortisol) response when lack of glucose is available.
- Progesterone, which is one of allopreg’s precursors can raise allopreg levels [here]. If you are a male, probably wouldn’t go to high on the dose to avoid any potential anti androgenic effects or just simply supplement with oral pregnenolone instead to let your body regulate the conversion of progesterone synthesis.
- Supplementing with the direct precursor to allopreg, 5a-DHP works pretty damn well too. It’s hard to find, but one legit vendor does offer it [here]. I have experimented with 5a-DHP on my pet rat and the effects seem almost identical to a benzodiazepine- without the foggy memory issues which means that it is getting directly converted into allopreg.
- Glycine is another amino acid that can increase allopreg [here]. I found doses 6+ grams was best used before bed.
Another quick tip is whichever method you decide to take, supplementing with a small amount of niacinamide concurrently with any method will help enhance the conversion of neurosteroid activity by increasing the coenzyme (NAD/NADH) [here].
Allopreg in the bio-identical form is not available from any legit vendors after doing some quick searching around- mostly vendors looking to sell to a business (commercial use). Leveraging the precursors would actually be safer in optimizing serum allopreg levels since your body can regulate it better.