How to Take Pregnenolone: Dosage, Timing, Duration

Pregnenolone supplement labels offer different amounts, and forums — even more varied "regimens." However, pregnenolone is a precursor of all steroid hormones and a neurosteroid, so its use should not be selected by trial and error. The editorial team does not give individual recommendations but explains which amounts were studied in randomized trials, for what purpose, for how long, and what of this can and cannot be transferred to everyday life.

Why there is no "standard dose" of pregnenolone

Unlike vitamins or minerals, no recommended daily intake has been established for pregnenolone, and in most countries there are no registered medicinal products based on it with official instructions. Therefore any "standard dose" on a label is a manufacturer's decision, not a clinical recommendation.

The second reason is the lack of a clear goal. In clinical studies pregnenolone was studied as a supplement to the treatment of specific psychiatric conditions. For healthy people and athletes there are no proven indications, and therefore there is no scientifically justified amount "for recovery" or "for concentration."

The third reason is the individual variability of metabolism. Pregnenolone can be converted into progesterone, allopregnanolone, DHEA, and further into sex hormones, and which pathway the greater part of the molecule takes differs from person to person.

Because of these circumstances, the editorial team regards amounts from studies only as reference information that helps to understand the context, not as an instruction for action.

Amounts in clinical studies

The range of amounts in randomized studies is very wide. In the study by Ritsner and colleagues, patients with schizophrenia and schizoaffective disorder received 30 mg of pregnenolone per day for eight weeks as a supplement to antipsychotics.

In the pilot study by Marx and colleagues, the amount was gradually increased to 500 mg per day, also as a supplement to the main treatment of schizophrenia. Brown and colleagues in the study of bipolar depression also used a gradual increase to 500 mg per day.

Thus, amounts that differ by more than an order of magnitude appear in the scientific literature, and all of them were used in special populations under the supervision of doctors. The content of typical commercial capsules, which usually contain several tens of milligrams, does not correspond to any specific proven protocol for healthy people.

It is also important that in these studies the levels of neurosteroids in the blood were assessed, the mental state and adverse reactions were monitored. Independent use is deprived of all these safety mechanisms.

Timing and regimen

The body's own synthesis of adrenal steroids follows a circadian rhythm with a peak in the morning. Many manufacturers advise taking pregnenolone in the first half of the day, explaining this precisely by the physiological rhythm and by the fact that in some people it may cause agitation and worse falling asleep.

At the same time, the metabolite allopregnanolone has a sedative action, so in some people the opposite reaction is possible — drowsiness. This is another argument in favor of the fact that the reaction to pregnenolone is difficult to predict in advance.

Pregnenolone is a fat-soluble steroid molecule. There are few special studies of the effect of food on its absorption in humans, so the scientific literature does not formulate specific requirements regarding intake before or after food.

In clinical studies the daily amount was often divided into two doses, especially at high amounts. For independent use such detailing makes no sense without medical indications and monitoring.

Duration and laboratory monitoring

Randomized studies of pregnenolone lasted mostly from eight to twelve weeks. Data on the safety of use over many months or years in healthy people are absent, so prolonged continuous use has no scientific justification.

If a doctor decides that pregnenolone is appropriate, it is reasonable to measure the baseline levels of the hormones it may affect: progesterone, DHEA-S, testosterone, estradiol. Repeat tests after a few weeks show whether the readings go beyond the norm.

The doctor must be informed about taking pregnenolone before any hormonal examination, because the supplement may distort the results and lead to erroneous conclusions.

The effect should be assessed by predefined criteria. If after a few weeks there is no objective benefit, there are no grounds to continue use.

Common mistakes

The first mistake is to transfer amounts from psychiatric studies to healthy people. 500 mg per day was used in patients with severe disorders under constant supervision, and this does not mean that such an amount is safe or beneficial for an athlete.

The second mistake is to combine pregnenolone with DHEA, prohormones, and other "hormonal boosters." The total effect on steroid metabolism becomes unpredictable, and when side effects appear it is impossible to establish their cause.

The third mistake is to disregard contraindications: hormone-dependent tumors, pregnancy, epilepsy, bipolar disorder, taking hormonal and psychotropic drugs.

• do not start use without consulting a doctor and basic tests;
• do not go by amounts from psychiatric studies;
• do not combine with other steroid precursors;
• do not take it in the evening if sleep worsens;
• stop use if acne, cycle changes, anxiety, or insomnia appear.

Editorial conclusions

There is no scientifically justified "standard dose" of pregnenolone for healthy people and athletes: in studies the amounts ranged from 30 to 500 mg per day and concerned patients with psychiatric disorders.

The studies lasted 8–12 weeks, so long-term safety is unknown. Use makes sense only for specific indications, with tests and medical supervision.

The most important thing is not to transfer data from clinical studies to independent use and not to combine pregnenolone with other hormonal agents.

We also recommend reading "Side Effects of Pregnenolone," "The Benefits of Pregnenolone for Athletes: The Evidence Base," and "How to Take DHEA: Dosage, Timing, Duration."

References

1. Ritsner MS, Gibel A, Shleifer T, et al. Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial. J Clin Psychiatry. 2010;71(10):1351–1362.
2. Marx CE, Keefe RS, Buchanan RW, et al. Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia. Neuropsychopharmacology. 2009;34(8):1885–1903.
3. Brown ES, Park J, Marx CE, et al. A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression. Neuropsychopharmacology. 2014;39(12):2867–2873.
4. Miller WL, Auchus RJ. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev. 2011;32(1):81–151.
5. Vallée M, Vitiello S, Bellocchio L, et al. Pregnenolone can protect the brain from cannabis intoxication. Science. 2014;343(6166):94–98.
6. Roberts E. Pregnenolone — from Selye to Alzheimer and a model of the pregnenolone sulfate binding site on the GABA_A receptor. Biochem Pharmacol. 1995;49(1):1–16.