# Allopregnanolone

Category: Hormones

Also known as: 3α-hydroxy-5α-pregnan-20-one

Allopregnanolone is a neurosteroid—a steroid acting predominantly on the brain—synthesized from progesterone via the sequential actions of 5-alpha-reductase and 3α-hydroxysteroid dehydrogenase (3α-HSD). It functions primarily as a potent positive allosteric modulator of GABAA…

12 passages · 3 authors · 2015–2024 · Most-cited: [Georgi Dinkov](https://bioenergeticoracle.com/md/voices/georgi-dinkov/index.md)

Canonical page: https://bioenergeticoracle.com/concepts/allopregnanolone

## Synthesis

**Allopregnanolone** is a **neurosteroid**—a steroid acting predominantly on the brain—synthesized from progesterone via the sequential actions of **5-alpha-reductase** and **3α-hydroxysteroid dehydrogenase** (3α-HSD). [Source 4, 7, 11] It functions primarily as a potent *positive allosteric modulator of GABAA receptors*, producing sedative, anxiolytic, and antidepressant effects. [Source 1, 2, 10] Unlike its precursor progesterone, allopregnanolone is considered devoid of classical hormonal activity through nuclear receptors such as the progesterone, estrogen, androgen, or glucocorticoid receptors, making it similar to pregnenolone in its neurosteroid profile. [Source 1, 2] The FDA-approved drug brexanolone (Zulresso) is simply an intravenous formulation of allopregnanolone for postpartum depression, though the steroid itself is openly sold as a research chemical. [Source 1, 2, 7]

Peat argued that supplementing progesterone reliably increases brain allopregnanolone concentrations, with a small oral dose tripling its levels, and that pregnenolone supplementation also raises it. [Source 6] He viewed the pharmaceutical monopolization of allopregnanolone as a reductionist approach, noting that the drug industry profits from isolating a single metabolite when the parent steroid, progesterone, achieves the same effect. [Source 6] Dinkov has written that the antidepressant effect of exogenous allopregnanolone is likely only partially explained by GABA agonism, as pure GABA agonists like benzodiazepines lack antidepressant properties; he suggests that at micromolar concentrations achieved through supplementation, allopregnanolone may also stimulate *thyroid synthesis and metabolism*. [Source 2] He further notes that the first SSRI, fluoxetine (Prozac), was discovered to increase the activity and expression of 3α-HSD, leading to the hypothesis that allopregnanolone is the true antidepressant agent. [Source 7, 11]

Dinkov has emphasized that allopregnanolone is one of the most powerful protective steroids in the brain, alongside its precursors pregnenolone and progesterone, and that **5-alpha-reductase** is the crucial enzyme for its synthesis. [Source 3] He has linked allopregnanolone deficiency during pregnancy to autism in offspring, interpreting this deficiency as an indirect marker of an *energetic production deficiency* in the mother, since steroid synthesis depends on adequate energy metabolism. [Source 4] The steroid has also been described as neuroregenerative, synaptogenic, and a free radical scavenger, with clinical trials showing that once-weekly low-dose intravenous administration (as low as 4 mg) can reduce brain atrophy and increase neurogenesis in Alzheimer’s disease patients, though higher doses plateaued or reduced neurogenesis. [Source 5, 10] Its pro-dopamine effects, including increased dopamine release and dopaminergic response, have been documented in animal studies. [Source 5]

In practical application, Dinkov reports that allopregnanolone has a much more potent sedative effect than progesterone and was historically used as a general anesthetic. [Source 8, 9, 12] He has noted that at higher doses, it produces the social disinhibition and mood improvement of alcohol without the hepatic side effects. [Source 9] While Peat expressed that he did not see what allopregnanolone could do that progesterone could not, he considered it acceptable to try, and Dinkov has characterized it as a relatively benign steroid with no known hormone-imbalancing effects, making it a candidate for conditions like post-finasteride syndrome where 5-alpha-reductase activity is impaired. [Source 8, 9, 12] The synthesis pathway requires that progesterone first be converted to **5α-dihydroprogesterone** by 5-alpha-reductase before 3α-HSD can produce allopregnanolone; once progesterone undergoes 3α-HSD reduction directly, the resulting C-3-ol steroid cannot be processed by 5-alpha-reductase, though the bidirectional nature of 3α-HSD allows for potential reconversion. [Source 11]

## People also ask

### How does allopregnanolone differ from progesterone in its effects?

Allopregnanolone is a neurosteroid that acts primarily as a potent GABAA receptor modulator, producing strong sedative and anxiolytic effects, whereas progesterone has broader hormonal activity through nuclear receptors. Peat argued that progesterone supplementation reliably increases allopregnanolone levels and achieves similar therapeutic outcomes.

### Why might allopregnanolone help with depression when benzodiazepines do not?

Dinkov suggests the antidepressant effect is only partially explained by GABA agonism, as pure GABA agonists like benzodiazepines lack this property. He proposes that at micromolar concentrations, allopregnanolone may also stimulate thyroid synthesis and metabolism.

### What role does 5-alpha-reductase play in allopregnanolone production?

The enzyme 5-alpha-reductase is crucial for converting progesterone into 5α-dihydroprogesterone, the necessary intermediate before 3α-HSD can produce allopregnanolone. Impaired 5-alpha-reductase activity, as in post-finasteride syndrome, can therefore limit allopregnanolone synthesis.

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## Cited passages

Passage numbers match the `[Source N]` markers in the synthesis above.

### Source 1 — IdeaLabs Forum Q&A — AlloP

Georgi Dinkov · Forum Q&A · Jun 22, 2021

> **Georgi Dinkov:** (2021-06-23) You can buy allopregnanolone openly, without restrictions, from many chemical companies in the US. See below for some links. We are selling it exactly as they are - as a lab product. 5α-Pregnan-3α-ol-20-one solid | Sigma-Aldrich 5α-Pregnan-3α-ol-20-one solid; CAS Number: 516-54-1; Synonyms: Allopregnanolone,3α-OH-DHP,Allopregnan-3α-ol-20-one,Brexanolone,3α-Hydroxy-5α-pregnan-20-one; find Sigma-Aldrich-P8887 MSDS, related peer-reviewed papers, technical documents, similar products & more at Sigma-Aldrich www.sigmaaldrich.com 404 Not Found Allopreganolone supplier | CAS 516-54-1 | Focus Biomolecules Allopregnanolone (516-54-1) is an endogenous neurosteroid which acts as a positive allosteric modulator of GABAA receptors. focusbiomolecules.com Abcam completes $340m strategic acquisition and expands kit capacity and capability – Abcam Limited www.biovision.com
>
> **Dr. B:** (2021-06-23) is brexanolone just a patented form or what is the exact ingredients in brexanolone besides allopregnanolone? if you google brexanolone a wikipedia page for allopregnenolone comes up

### Source 2 — IdeaLabs Forum Q&A — AlloP

Georgi Dinkov · Forum Q&A · Jun 22, 2021

> **Georgi Dinkov:** (2021-06-23) Can't talk about risks/safety. That is against FDA rules. All I can say is that studies so far do not demonstrate suppression of endogenous synthesis of other steroids of neurotransmitters. There are no reports of hormonal effects either. Unlike progesterone, 5a-DHP, etc allopregnanolone seems to be similar to pregnenolone - i.e. mostly a neurosteroid, devoid of "classical" hormonal effects through receptors such as PR, ER, AR, GR, etc.
>
> **Mufasa:** (2021-06-23) Does that also mean that it can not alter the menstrual cycle if taken at the wrong time of month like progesterone does?
>
> **Georgi Dinkov:** (2021-06-23) I can't legally make statements on this topic, but AFAIK the clinical trial with Brexanolone did not report issues with the menstrual cycle.
>
> **Dr. B:** (2021-06-23) Mate does this not apply for things for lab usage. seems very restricted "In the United States, brexanolone is a Schedule IV controlled substance.[7][6] Allopregnanolone is available only through a restricted program called the Zulresso REMS Program that requires the drug to be administered by a healthcare provider in a certified healthcare facility. The REMS requires that patients be enrolled in the program prior to administration of the drug" also "Exogenous progesterone, such as oral progesterone, elevates allopregnanolone levels in the body with good dose-to-serum level correlations.[57] Due to this, it has been suggested that oral progesterone could be described as a prodrug of sorts for allopregnanolone"

### Source 3 — Generative Energy #7: Polyunsaturated Fats in The Real Organism

Danny Roddy · Interview · Oct 1, 2015 · https://www.youtube.com/watch?v=ngdmdtrwyas

> **Georgi Dinkov:** Allopregnanolone is one of the most powerful steroids - protective steroids - in the brain together with its precursors pregnenolone, progesterone, there's also pregnenolone, premenedione, there are a number of steroids that are all derived from pregnenolone and 5-alpha reductase is a crucial enzyme into converting them from one to the other, and without that enzyme we're inhibiting strongly; essentially means suboptimal brain function, which the designers of the drug freely admitted upon applying for approval of the FDA, they said that for unknown reasons at that time, the drug causes severe depressive symptoms in the majority of the population that was studied.

### Source 4 — Georgi's Background, and Prenatal, Neonatal Development with Georgi Dinkov

Georgi Dinkov · Interview · Oct 27, 2019

> **David Butterworth:** Wow. All right. This one you posted on your, you started posting stuff on a personal blog of yours. Allopregnanolone deficiency during pregnancy causes autism.
>
> **Georgi Dinkov:** That's right. So allopregnanolone is a steroid. It's a neurosteroid, and neurosteroid means a steroid that has actions predominantly on the brain. There are several of them, and the better known ones are pregnenolone, progesterone, DHEA, and allopregnanolone. And allopregnanolone just happens to be synthesized from progesterone, and progesterone is synthesized from pregnenolone. So because progesterone is so important for pregnancy, right? If you have a deficiency of progesterone, pregnancy cannot be carried to term, right? So allopregnanolone, deficiency of allopregnanolone immediately suggests a deficiency of progesterone and consequently a deficiency of pregnenolone. And the synthesis of steroids, just like everything else in the organism, also depends on energy. So an allopregnanolone deficiency is an indirect way of saying there is an energetic... production deficiency in the organism of the mother but specifically it can manifest in many different ways right it's not you can be you can if you don't produce enough energy that can hit any of the systems that depend on energy production for proper functioning in this case it happens to be the synthesis of allopregnanolone of the all of the neurosteroids right So allopregnanolone has this beneficial effect, has an anabolic effect on the brain. FDA recently approved allopregnanolone as an actual treatment for postpartum depression for the mothers. And since depression is thought to mostly originate in the brain, you can immediately see that apparently allopregnanolone has these greatly beneficial effects on the brain. And since autism is also considered a brain condition, you can immediately see how the deficiency of allopregnanolone, since it's so important for the mother, well, the presumption is probably it will be important for the fetus as well because...

### Source 5 — IdeaLabs Forum Q&A — 5α-DHP

Georgi Dinkov · Forum Q&A · Nov 23, 2016

> **CoolTweetPete:** (2017-02-17) My rat loves this product. He's sleeping great and feels basically impervious to stress. Also lost some weight and just looks generally healthier. Anecdotally, I recall hearing an endocrinologist Dr Mark Gordon on a podcast a year or two ago. He was working on treating veterans with hormones to alleviate PTSD. He mentioned many of them had traumatic brain injury which had resulted in hormone deficiencies. He specifically mentioned allopregnanolone (which synthesizes from 5a-DHP) being neuroregenerative, synaptogenic, (regenerates synapses), and a free radical scavenger in the brain. Cool discovery for those of us that have banged our noggins in the past.
>
> **1kT:** (2017-02-21) Regarding 5a-DHP's pro-dopamine effects: Allopregnanolone plays a role in the modulation of dopamine and acts pro-dopamine. Allopregnanolone protects against dopamine-induced striatal damage after in vitro ischaemia via interaction at GABA A receptors. - PubMed - NCBI The neurosteroid allopregnanolone increases dopamine release and dopaminergic response to morphine in the rat nucleus accumbens. - PubMed - NCBI Dopamine is involved in the antidepressant-like effect of allopregnanolone in the forced swimming test in female rats. - PubMed - NCBI Allopregnanolone Increase in Striatal N-Methyl-D-aspartic Acid Evoked [3H]Dopamine Release Is Estrogen and Progesterone Dependent
>
> **Georgi Dinkov:** (2017-02-21) Thanks for this. In that case, it may be better to take 5a-DHP in the morning (similar to the dopamine agonists like lisuride or bromocriptine) to avoid disrupting the circadian rhythm.

### Source 6 — Postpartum depression, brain, aging, and reductionism

Ray Peat · Newsletter · 2019

> The drug is allopregnanolone, the main metabolite of progesterone in the brain. Taking progesterone reliably increases the brain content of allopregnanolone, with a small oral dose of progesterone tripling (196% increase) the concentration of allopregnanolone (Andréen, et al., 2006). Supplementing pregnenolone also increases allopregnanolone.
>
> The approval of the “New Drug,” Zulresso, was possible because of the recognized commitment of the FDA, the insurance industry, and a large part of the medical profession, to the idea that each disease can be treated by a specific drug, and that the only way to have confidence that the right drug has been chosen, is to permit a monopoly that will justify the investment needed for research. The FDA has been committed to the privatization of generic drugs for many years; for example, a cheap drug, gamma hydroxybutyrate, Oxybate, was given a New Drug monopoly, as Xyrem, leading to an astronomical price increase. Monopoly profits are a powerful reinforcer for a reductionist approach to medicine, especially for a centralized, official, reductionism. When some older methods of treating sickness are used instead of “Evidence-Based” treatments, doctors risk losing their license. Some doctors still prefer to use reasoning, rather than authority, to guide their practice. When medical reasoning fails, it’s usually because the facts taken into account are mistaken. The basic assumption of medical reductionism is that the parts of a system can be understood and defined, and that those definitions can be trusted as a basis for pathophysiological reasoning. To the extent that the interests of the drug industry have guided research, publication, and education, the facts, the “basic sciences,” have to be reconsidered.
>
> Whenever a major industry sells a substance, with profits of billions of dollars, reasoning involving that substance should begin with a skeptical and detailed investigation of the substance, in as many different contexts as possible.
>
> The problems that occur in the months after having a baby have, historically, been treated in a great variety of ways. Chamomile tea (Chang and Chen, 2016), massage, and counseling seem to be effective.

### Source 7 — New IdeaLabs Product – 3α-Dihydroprogesterone (3α-DHP)

Georgi Dinkov · Article · Oct 1, 2024 · https://haidut.me/?p=2691

> As many of my readers know, the medical industry has been quietly increasing its interest in and clinical trials with so-called “neurosteroids”, most of them members of the pregnane family. I think the term “neurosteroid” as used by mainstream medicine is a misnomer as it is used selectively for only a few of all the known steroids, despite the fact that virtually all of them have been demonstrated to have a central (brain) effect. For example, currently the label “neurosteroid” is applied almost exclusively to steroids such as pregnenolone, progesterone, allopregnanolone and various of their synthetic derivatives, though steroid families such as estrogens, androgens, mineralo/gluco-corticoids, and even thyroid hormones have all been demonstrated to have potent and rapid central effects as well, with indisputable influence on mood, cognition, various neurological conditions, traumas (e.g. TBI) and even cancer.
>
> Recently, the FDA approved the progesterone derivative allopregnanolone (3α, 5α-tetrahydroprogesterone), commonly known as Allo or AlloP, as a treatment for post-partum depression. In addition, multiple companies are running clinical trials with that steroid for wide range of other conditions including dementia (e.g. Alzheimer Disease), anxiety disorders, autism, psychotic states (e.g. schizophrenia), post-traumatic stress disorder (PTSD), and even direct brain damage states such as traumatic brain injury (TBI) as well as its chronic form known as chronic traumatic encephalopathy (CTE). As of now, the only condition for which AlloP has been approved is postpartum depression with expectations that the steroid will soon be also approved for depression of any origin. The currently approved formulation is through IV infusion, but some of the new formulations currently being tested are meant for oral use, and use a preparation very close to the ideas of Dr. Peat for using long-chain fats and vitamin E to circumvent first-pass metabolism of any steroid and ensure most of the steroid gets absorbed through the lymphatic system. As such, selling AlloP has become very legally risky.

### Source 8 — #60: PUFA as a Mitochondrial Toxin | Vitamin D, Inflammation, and Aging | Iron, Copper, and Anemia with Georgi Dinkov

Georgi Dinkov · Interview · Jun 21, 2021 · https://open.spotify.com/episode/2o7YVyFGyWgLnNX6MpyqLD

> **Georgi Dinkov:** Uh, but now with a pandemic and everything, again, quote unquote pandemic, uh, a lot of people under a lot of stress and probably self-medicating with less than, um, optimal substances. Um, You should be able to help yourself by simply upping your pregnenolone and vitamin D intake. Well, speaking of allopregnenolone. Oh, forgot. Coming this week, we will release allopregnenolone. Totally slipped my mind. We'll replace the 5-alpha-dihydroprogesterone with allopregnenolone. Way too many people complained and got Pete involved to say like, God, you know, you shouldn't be supplementing this thing because it's like it can block progesterone's effects or like decrease its effects. But allopregnanolone is pretty safe. I don't know of any study that has shown any hormone imbalancing effects of it. It's pretty benign in terms of upsetting the hormonal balance. And a lot of people have asked for it because a lot of people just struggle with post-finasteride syndrome, BFS. They cannot get hold of androgens like dihydrotestosterone or other strong androgen agonists. And they're basically, you know, they're asking for allopregnanolone because it's already preformed. And in those people, 5-alpha dihydroprogesterone, several people emailed me and said, like, it helps, but I have to keep taking it. And also, it loses its effectiveness over time. However, one of them managed to get allopregnanolone from a chemical company and said that it cured his PFS. Let's see. I'm not making any claims. By the way, PFS is not a recognized condition by the FDA, so it should be less of a problem to talk about trying to help it.

### Source 9 — #60: PUFA as a Mitochondrial Toxin | Vitamin D, Inflammation, and Aging | Iron, Copper, and Anemia with Georgi Dinkov

Georgi Dinkov · Interview · Jun 21, 2021 · https://open.spotify.com/episode/2o7YVyFGyWgLnNX6MpyqLD

> **Georgi Dinkov:** The only reason we're releasing it is to replace the 5-alpha DHP, which people seem to be wary about. And Pete has said that he would rather not use it long-term because he thinks it can interfere or at least create an imbalance of basically progesterone's effects. But I think when people emailed him about allopregnanolone, he said it can be tried, but he just didn't see what it can do that progesterone couldn't. So we're just replacing whatever we have with a hopefully less risky steroid.
>
> **Danny Roddy:** Well, isn't that also a new drug by pharma? Like, isn't that a little bit risky?
>
> **Georgi Dinkov:** It is, but we're going to release it in relatively low amounts and be dissolved into coferol. So I'm hoping that it's not going to compete with big pharma. They're administering it as an infusion, and it's a relatively large dose in order to trigger the immediate antidepressant effects. I think they're using like a couple of hundred milligrams. And the reason it's done is infusion because at such dosages, you get knocked out. So you have to be under the supervision of a doctor, I guess, because if they inject you or infuse you with 100 milligrams of allopregnanolone, you'll be so drunk. Oh, speaking of which, you want to get the social effects of alcohol without the side effects. a higher dosage of progesterone or any of the steroids derived from it, especially allopregnanolone, will pretty much overlap with the social effects, the drunkenness, the disincubation, the improvement in mood, but without most of the negative side effects of alcohol, especially on the liver.

### Source 10 — Allopregnanolone found safe, may slow brain atrophy from Alzheimer’s

Georgi Dinkov · Article · May 5, 2022 · https://haidut.me/?p=1820

> A great new study, which is one of the very few to examine the safety and effectiveness of allopregnanolone in humans. The trial was conducted in patients with Alzheimer Disease (AD) and aimed to establish the safety of various doses of once-weekly allopregnanolone administration, as well as any potential benefits on brain morphology in AD patients. The route of administration was IV and the doses tried were 2mg, 4mg, 6mg, 10mg, and 14mg. All groups received their respective doses once weekly for 12 weeks. The outcome of the safety arm was that allopregnanolone is safe in doses up to 10mg for males and 14mg for females. The main side effect from the therapy was sedation, which is to be expected of a strong GABA agonist such as allopregnanolone. The other good news is that administration of these low doses (as low as 4mg once weekly) of allopregnanolone once weekly led to reduced brain atrophy in the AD patients, increased neurogenesis, white matter integrity and functional connectivity in the AD patients. However, at higher doses some of the benefits plateaued and there was even reduction in neurogenesis. Based on the follow-up trial with 4mg once weekly dose, my guess is that the 4mg weekly dose was the optimal in terms of benefit, while also being safe and virtually free of side effects. The trial is now into its long-term phase trying to determine if chronic allopregnanolone administration can actually fully stop or (hopefully) even reverse the AD pathology.
>
> [references]

### Source 11 — 3α-DHP — IdeaLabs Lab/R&D Chemical

Georgi Dinkov · Product · Oct 1, 2024 · https://idealabs.ecwid.com/3%CE%B1-DHP-p698093046

> The currently approved formulation is through IV infusion, but some of the new formulations currently being tested are meant for oral use, and use a preparation very close to the ideas of Dr. Peat for using long-chain fats and vitamin E to circumvent first-pass metabolism of any steroid and ensure most of the steroid gets absorbed through the lymphatic system. As such, selling AlloP has become very legally risky.
>
> Interestingly enough, the first commercial antidepressant of the SSRI class known as fluoxetine (Prozac) was found to increase the activity and expression of an enzyme called 3α-hydroxysteroid dehydrogenase (3α-HSD), which is one of the major steps in synthesizing allopregnanolone from progesterone.
>
> [references]
>
> Since levels of allopregnanolone have been consistently found to increase after fluoxetine administration, and allopregnanolone levels were found to be universally low in people with depression (as well as many other brain/mood conditions) the hypothesis was that it was allopregnanolone that was the true antidepressant, with fluoxetine functioning only as a trigger for the synthesis of that "neurosteroid".
>
> [references]
>
> However, this hypothesis is incomplete since fluoxetine was found to increase activity and expression of mostly 3α-HSD, and while this MAY results in higher allopregnanolone levels it does not guarantee it, since the cascade has to also pass through the enzyme 5α-reductase (5-AR) in order to synthesize allopregnanolone. In fact, the steps of allopregnanolone synthesis are as follows: progesterone -> 5α-dihydroprogesterone (5-AR activity) -> allopregnanolone (3α-reductase activity). If fluoxetine selectively increases the activity of only 3α-HSD, then the only thing that can be said for sure is that fluoxetine would increase the levels of a steroid that takes progesterone as input and produces a 3α-reduced steroid, which is a steroid with a hydroxyl group (OH) on position C-3, in the alpha configuration.

### Source 12 — #60: PUFA as a Mitochondrial Toxin | Vitamin D, Inflammation, and Aging | Iron, Copper, and Anemia with Georgi Dinkov

Georgi Dinkov (with Georgi Dinkov) · Interview · Jun 21, 2021 · https://open.spotify.com/episode/2o7YVyFGyWgLnNX6MpyqLD

> **Danny Roddy:** Well, this gets into a whole can of worms, but whenever somebody comes on a forum and is like, hey, guys, I'm cured of XYZ, I'm always like... They're usually back within a month or two or whatever. And so then they turn into lurking. You can tell them like, you know, commenting here and there.
>
> **Georgi Dinkov:** I just, we'll see. We'll see. I've tried it. It has a much more potent sedative effect than progesterone does. And in fact, it was used as a general anesthetic and some steroids derived from it. They were used and developed as general anesthetics back in the early 20th century. For whatever reason, they didn't catch up as general anesthetics, but I think they're still used in the veterinary medicines in some countries in the world to actually replace the general anesthesia that normally you get. put under whatever toxic drug by actually administering allopregnanolone or steroids closely related to it.
>
> **Danny Roddy:** Yeah, let me just be extremely clear here. I'm not negating that person's experiencing. I'm saying I think PFS is way more complicated than a lot of people think. And a person working a job they hate or familial things or being alone, I think all those types of things factor into this like continued sense of hopelessness that... And like we talked about earlier, I strongly don't believe that there's single bullet approaches to things like that. It's like systemic dysfunction that existed before the person took finasteride that was probably made even worse by the finasteride. And so, again, not that single bullet approach where, oh, I was just missing X, Y, Z, you know?

_Generated 2026-07-20 from the Bioenergetic Oracle corpus._