Pregnenolone
Also known as: Preg, 3beta-Hydroxypregn-5-en-20-one, P5
Lower numbers = closer to natural. Higher numbers = more enhanced.
Why this rating?
Pregnenolone is an endogenous steroid and the upstream precursor to essentially all steroid hormones, sold OTC as a supplement mainly for mood/cognition ("neurosteroid") claims. It is in hormone-precursor territory, but oral supplementation has not been shown to reliably raise downstream anabolic hormones or improve performance, and the mood/cognition evidence is weak. Rated 1 (basically natty) because, taken purely as a neurosteroid/mood supplement, it does not reliably move downstream anabolic hormones or physique/performance beyond a natural ceiling.
Overview
Pregnenolone is an endogenous steroid, synthesised from cholesterol, that sits at the very top of the steroid-hormone pathway. It is the precursor/metabolic intermediate for most steroid hormones (progestogens, androgens, estrogens, glucocorticoids and mineralocorticoids). It is also a neurosteroid with its own activity in the brain. In the US it is sold over-the-counter as a supplement, mainly promoted for mood, memory and cognition, claims that rest on weak, preliminary evidence.
Purpose & Use Cases
Neurosteroid / Mood & Cognition (Claimed)
Marketed to support mood, memory and cognition. Evidence is preliminary and weak. Treat these as unproven claims.
Hormone-Precursor Support (Claimed)
Promoted as an upstream "master" precursor to boost steroid-hormone levels, but oral supplementation has not been shown to reliably raise downstream hormones.
Benefits
- Endogenous neurosteroid that crosses the blood-brain barrier
- Upstream precursor to essentially all steroid hormones
- Available OTC in the US
- Generally well tolerated at supplement doses
Good to Know
The top of the steroid-hormone pyramid
Pregnenolone is made from cholesterol (via CYP11A1) and is the precursor to essentially every steroid hormone, progesterone, DHEA, testosterone, estrogen, cortisol and aldosterone all descend from it. That is the basis for the "master hormone precursor" marketing, but supplementing the top of the pathway does not reliably raise the hormones downstream.
A neurosteroid, marketed for the brain on thin evidence
Pregnenolone crosses the blood-brain barrier and acts in the brain (including as a negative allosteric modulator of the CB1 receptor), which is why it is sold for mood, memory and cognition. But the human evidence is preliminary and weak, and broader disease claims (MS, arthritis, cancer) are explicitly not backed by evidence.
OTC in the US, and not currently WADA-prohibited
It is widely sold over-the-counter as a supplement in the US (it was a rheumatoid-arthritis drug in the 1950s but is no longer used medically). Per USADA's substance reference, pregnenolone is not on the WADA Prohibited List and requires no Therapeutic Use Exemption, unlike its downstream relative DHEA, which IS banned. Separately, the FDA has issued warning letters calling pregnenolone an "unapproved new drug" for compounding/supplement purposes, a regulatory issue distinct from its anti-doping status.
Dosage Guidelines
| Experience Level | Dosage Range |
|---|---|
| Beginner | 5 – 25 mg/day |
| Intermediate | 25 – 50 mg/day |
| Advanced | 50 – 100 mg/day |
Clinical/research doses have gone well beyond typical supplement ranges: metabolic studies have used single doses of 50-100 mg and up to 400 mg, and a psychiatric proof-of-concept trial (Marx et al. 2009, Neuropsychopharmacology; PMID 19339966) titrated to a fixed 500 mg/day for 8 weeks and reported it as well tolerated. None of that constitutes validated dosing guidance for healthy adults, and oral pharmacokinetics are not well characterised. The ranges above reflect the far lower doses (5-100 mg/day) typically sold and used in OTC supplements. Because it is an upstream hormone precursor, more is not obviously better. It was approved as a medication for rheumatoid arthritis in the 1950s but is no longer used medically.
Oral pharmacokinetics are not well characterised; no reliable half-life has been established for pregnenolone taken as an oral supplement.
Side Effects
Hormonal / androgenic-estrogenic effects
uncommonAs an upstream steroid precursor it could in theory shift downstream hormone levels (e.g. acne, mood or menstrual changes), though oral dosing does not reliably move them.
Start low; discontinue if hormonal symptoms appear; consider bloodwork if using regularly.
Insomnia / overstimulation or drowsiness
uncommonBeing a neuroactive steroid, some users report changes in sleep, arousal or mood.
Adjust dose and timing; stop if it disrupts sleep.
Purity / dosing variability
uncommonAs an OTC supplement, label accuracy is not guaranteed.
Use reputable brands.
General Mitigation Strategies
Pregnenolone is generally well tolerated at supplement doses, but it is a hormone precursor, not an inert vitamin. Start low, and because unsubstantiated online claims (treating MS, arthritis, cancer) are not backed by evidence, do not use it in place of real treatment. Consider bloodwork if using it regularly.
Post Cycle Therapy (PCT)
Not a suppressive anabolic; no PCT protocol applies. As an upstream steroid precursor it is theoretically hormonally active, so anyone using it regularly should monitor how they feel and consider bloodwork.
How It Works
Pregnenolone is made from cholesterol by the mitochondrial enzyme cytochrome P450scc (CYP11A1) and is the entry point of steroidogenesis, feeding into progesterone, DHEA and the downstream sex and adrenal steroids. As a neurosteroid it is lipophilic and readily crosses the blood-brain barrier (its sulfate form does not), and it acts as a negative allosteric modulator of the CB1 cannabinoid receptor, with reported neuroprotective and myelination-supporting effects in preclinical work. Small clinical studies suggest it "may improve cognitive and memory function," but the human evidence remains preliminary.
Fundamentals
Reference on the practices relevant to Pregnenolone: how they are done and where they go wrong. Not a recommendation to use it.
Legal Status
Sold over-the-counter as a dietary supplement in the USA; no longer marketed as a prescription medication. The FDA has separately issued warning letters describing pregnenolone as an "unapproved new drug" that cannot legally be compounded or included in dietary supplements, even though it remains widely sold as one.
Legal status varies by country and changes over time. This is a general summary, not legal advice.
WADA Status
Per USADA's substance reference, pregnenolone is not on the WADA Prohibited List and no Therapeutic Use Exemption is required. As with any substance, the list is reviewed annually, so tested athletes should double-check current status on GlobalDRO.com before competing. Separately (and unrelated to anti-doping), the FDA has issued warning letters describing pregnenolone as an "unapproved new drug" that cannot legally be compounded or marketed in dietary supplements.