Low-dose Allopregnanolone Induces Relief From Depression In Just 24 Hours

haidut

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I posted a few studies on the powerful mood boosting effects of allopregnanolone in relation to its precursor 5a-DHP. The precursor 5a-DHP converts into allopregnanolone with almost 100% efficiency as it is the the only pathway through which it can be metabolized downstream.
All successful antidepressants of the SSRI class are capable of stimulating allopregnanolon synthesis in the brain. SSRI drugs devoid of this capability are ineffective as antidepressants and a few of them have already been withdrawn. The pharma industry is keenly aware of the terrible side effects SSRI drugs produce in most people and have been in hot pursuit of a synthetic derivative of allopregnanolone that can be patented and approved as treatment for depression. One such derivative (Ganaxolone) is already in clinical trials for depression and intractable seizures. However, the results from animal studies suggest that allopregnanolone itself is probably more effective ans safer than the synthetic derivatives and as such human studies with it continue. These new studies below show that allopregnanolone (also known as brexanolone) is capable of rapidly reliving depression in humans within 24h of administration. Perhaps even more importantly, the response rate was 70% in active group vs just 9% in placebo (which is almost unheard of rate of response in psychotropic drugs research) and the improvements in mood were sustained over at least 30 days.
The human dose used was low and in the range of 25mcg/kg - 65mcg/kg. The route of administration was IV, so for an oral route a factor of 10x needs to be applied, so the oral dose range becomes 250mcg/kg - 650mcg/kg or in other words 0.25mg/kg - 0.65mg/kg. For most people this means an oral dose of 2mg - 5mg allopregnanolone should be enough to replicate the design of the study.

Open‐label, proof‐of‐concept study of brexanolone in the treatment of severe postpartum depression
Medscape: Medscape Access

"...An investigational formulation of allopregnanolone, a metabolite of progesterone, in which dosing replicates soaring levels of the hormone that occur during the height of pregnancy, appears to lead to rapid improvement of symptoms of severe postpartum depression. Results of an open-label phase 2 study show that following 60-hour intravenous administration of the drug, known as brexanolone, the majority of patients experienced significant improvement in depressive symptoms. The improvement began at 24 hours and was sustained at 30 days. "The rapid onset of response, the robust treatment effect size and durability of the response we are seeing with this treatment are quite different from anything else available for postpartum depression," said Samantha Meltzer-Brody, MD, MPH, an associate professor in the Department of Psychiatry at the University of North Carolina (UNC) at Chapel Hill and director of the Perinatal Psychiatry Program at the UNC Center for Women's Mood Disorders."
 

Diokine

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I gave a very depressed friend 6 drops of Stressnon and he said it was like a switch was flipped - he immediately (within 5 minutes) felt much better.
 

TubZy

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Switch 5a-dhp to pure allopreg so you can do away with that cancer disclaimer for 5a-dhp lol
 

tankasnowgod

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Switch 5a-dhp to pure allopreg so you can do away with that cancer disclaimer for 5a-dhp lol

I've been putting 5 drops of 5A-DHP on my forehead the past couple nights. Felt better today than I have in a few weeks.
 

TubZy

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I've been putting 5 drops of 5A-DHP on my forehead the past couple nights. Felt better today than I have in a few weeks.

I agree it does work but it is inconsistent and tolerance builds fast, I think since it is a precursor rather than straight allopreg so your body will put a cap on the enzyme after a while when it senses there is enough in the circulating in the brain.

Pure allopreg, your brain cant really control the dosage leading to higher saturation levels for people who need it.
 

Dhair

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I agree it does work but it is inconsistent and tolerance builds fast, I think since it is a precursor rather than straight allopreg so your body will put a cap on the enzyme after a while when it senses there is enough in the circulating in the brain.

Pure allopreg, your brain cant really control the dosage leading to higher saturation levels for people who need it.
I'm not sure this is true. At least not in my experience.
Higher doses of 5a-DHP made me extremely depressed, anxious, and borderline suicidal. Significant increases in allopreg aren't good for everyone.
 
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TubZy

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I'm not sure this is true. At least not in my experience.
Higher doses of 5a-DHP made me extremely depressed, anxious, and borderline suicidal. Significant increases in allopreg aren't good for everyone.

Do you have low allopreg to begin with? If not, allopreg is on a U shaped curve so that is no surprise. So raising the precursor of allopreg with already normal levels could bump you with opposite effects (if you take too much). I was talking in reference to PFS people who have severely low neurosteroid levels. I have taken up to 100mg of 5a-DHP with no sign of effects at times, same with other PFS people and the euphoric great effect wears off after a few days . I personally like 5a-DHP I wish the great effect would happen everytime. It seems there is a lower homeostatis set in the brain for that enzyme.

The one thing that did make a pretty big difference was pairing it with diamant.
 
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haidut

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I gave a very depressed friend 6 drops of Stressnon and he said it was like a switch was flipped - he immediately (within 5 minutes) felt much better.

Yeah, I think lower dose pregnenolone is really good at going down the 5-AR pathway. The human studies with depression and other mood issues showed best effects from 30mg - 50mg daily (orally), so for StressNon that would probably be less than 12 drops daily, as you did.
 

haidut

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Switch 5a-dhp to pure allopreg so you can do away with that cancer disclaimer for 5a-dhp lol

I was actually going to go with allo as a supplement but the company behind Ganaxolone managed to shut down a competitor who used allopregnanolone acetate and also petitioned a judge to rule allopregnanolone as being a drug. There has been no decision on it yet but there is a reason I went with 5a-DHP and not allo :):
 

haidut

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haidut

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I agree it does work but it is inconsistent and tolerance builds fast, I think since it is a precursor rather than straight allopreg so your body will put a cap on the enzyme after a while when it senses there is enough in the circulating in the brain.

Pure allopreg, your brain cant really control the dosage leading to higher saturation levels for people who need it.

Higher dose allopregnanolone will be metabolized downstream and eventually into androsterone. Peat said once using a precursor is always preferable as long as you can guarantee it won't go into other pathways. In the case of 5a-DHP it can only convert into allopregnanolone. But I hear you on the saturation, if the dose is too high it can get excreted by the liver at a faster rate as Peat said it happens with all consistent use of any steroid. That's why breaks of a few days are probably needed periodically for any steroid.
 

TubZy

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I was actually going to go with allo as a supplement but the company behind Ganaxolone managed to shut down a competitor who used allopregnanolone acetate and also petitioned a judge to rule allopregnanolone as being a drug. There has been no decision on it yet but there is a reason I went with 5a-DHP and not allo :)

If they are trying that hard then you know how legit allopreg actually is for all kinds of medical conditions lol.
 

TubZy

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Higher dose allopregnanolone will be metabolized downstream and eventually into androsterone. Peat said once using a precursor is always preferable as long as you can guarantee it won't go into other pathways. In the case of 5a-DHP it can only convert into allopregnanolone. But I hear you on the saturation, if the dose is too high it can get excreted by the liver at a faster rate as Peat said it happens with all consistent use of any steroid. That's why breaks of a few days are probably needed periodically for any steroid.

If higher doses of allopreg can be converted to androsterone, I'm assuming the high doses of androsterone can work back upstream and convert into allopreg, right? I know some steroids can do that and androsterone can do that with DHT too.

I do agree with you, I guess the saturation point would be that the tissue was so deprived of allopreg and 5AR in the brain in general for such a long time (finasteride) that the cells and enzymes become desensitized just like how cells can become desensitized to T3 when in a hypothyroid type state for a long time, bigger doses of T3 can help resensitize the cells again.

For example, instead of using T4 you would need pure T3, and sometimes much higher doses than expected. Where many cases T4 doesn't work when already in a hypothyroid state due to the conversion it has to undergo.

5a-DHP (T4) vs allopreg (T3)
 

haidut

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If higher doses of allopreg can be converted to androsterone, I'm assuming the high doses of androsterone can work back upstream and convert into allopreg, right? I know some steroids can do that and androsterone can do that with DHT too.

I do agree with you, I guess the saturation point would be that the tissue was so deprived of allopreg and 5AR in the brain in general for such a long time (finasteride) that the cells and enzymes become desensitized just like how cells can become desensitized to T3 when in a hypothyroid type state for a long time, bigger doses of T3 can help resensitize the cells again.

For example, instead of using T4 you would need pure T3, and sometimes much higher doses than expected. Where many cases T4 doesn't work when already in a hypothyroid state due to the conversion it has to undergo.

5a-DHP (T4) vs allopreg (T3)

I suspect that androsterone (and DHT) can indeed raise allopregnanolone levels and this is probably one of the main reasons for heir antidepressant effects. The other one being their strong pro-thyroid effect as well.
 

TubZy

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I suspect that androsterone (and DHT) can indeed raise allopregnanolone levels and this is probably one of the main reasons for heir antidepressant effects. The other one being their strong pro-thyroid effect as well.

Well, that is exactly in line with my experience but dosage was the only issue. When I was taking up to 900mg of androsterone (logged) a day I felt pretty awesome, but when I take lower doses of androsterone in the 10-20mg, I feel worse like almost identical to taking DHEA only.

Maybe because at higher doses the androsterone dumps more into allopreg and DHT while the lower doses of mainly going only DHT route.
 
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900mg of androsterone (logged) a day
 
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