Home Ingredients Pregnenolone
CognitiveMood & Mental HealthMen's HealthWomen's Health

Pregnenolone

Evidence Level
Limited
2 Clinical Trials
5 Documented Benefits
2/5 Evidence Score

Pregnenolone is a steroid hormone precursor — synthesized from cholesterol in adrenals, gonads, and brain. Often called the 'mother of all steroid hormones' as it serves as precursor to: progesterone, cortisol, aldosterone, DHEA, testosterone, estrogens. Used in some integrative protocols for cognitive function, mood, and 'adrenal support' in perimenopause/menopause. Critical: hormone precursor, not 'just a supplement' — has hormonal effects requiring caution.

Studied Dose 10-100 mg/day (start LOW); some integrative practitioners use 5-30 mg; trials have used up to 500 mg/day for specific indications
Active Compound Pregnenolone (3β-hydroxypregn-5-en-20-one)

Benefits

Cognitive Function (Mixed Evidence)

Older 1940s research showed pregnenolone improved cognitive performance in industrial workers. Modern trials less consistent. trial in schizophrenia patients showed cognitive improvements with high-dose pregnenolone (500 mg/day). Mechanism: neurosteroid effects.

Supported by Trial 2

Bipolar Disorder Adjunct (Research)

trial of pregnenolone (500 mg/day) in bipolar depression showed reduced depression and anxiety vs placebo. Generated continuing research interest. Specific clinical context, not general use.

Supported by Trial 1, Trial 2

Schizophrenia Cognitive Symptoms (Research)

Multiple trials showing high-dose pregnenolone may improve negative and cognitive symptoms in schizophrenia. Adjunct only.

Supported by Trial 2

Joint Pain / Arthritis (Older Research)

1940s-50s research showed pregnenolone reduced arthritis symptoms. Largely abandoned as cortisone-type anti-inflammatories developed. Limited modern research.

Supported by Trial 2, Trial 1

Theoretical Anti-Aging / Hormone Precursor Support

Used in some integrative anti-aging protocols based on age-related decline in pregnenolone and downstream hormones. Insufficient evidence for anti-aging claims; reasonable mechanism but clinical translation unclear.

Supported by Trial 1, Trial 2

Mechanism of action

1

Steroidogenic Pathway Precursor

Pregnenolone is the first steroid hormone synthesized from cholesterol — by CYP11A1 (cholesterol side-chain cleavage enzyme). All other steroid hormones (progesterone, cortisol, aldosterone, DHEA, testosterone, estrogens) derive from pregnenolone. Supplementation increases substrate availability.

2

Direct Neurosteroid Activity

Pregnenolone (and pregnenolone sulfate) acts directly on GABA-A and NMDA receptors — neurosteroid effects independent of conversion to other hormones. May contribute to cognitive and mood effects.

3

Pregnenolone Sulfate (PS) Effects

Pregnenolone is sulfated in body to PS — a negative allosteric modulator of GABA-A and positive modulator of NMDA receptors. PS has alerting/cognitive effects; pregnenolone itself has more variable effects.

4

Variable Downstream Hormone Production

Supplemental pregnenolone is converted to varying amounts of progesterone, cortisol, DHEA, testosterone, estrogens depending on individual enzymatic activity. Effects differ between individuals — explains variable clinical responses.

Clinical trials

1
Pregnenolone for Bipolar Depression

Clinical trial of pregnenolone (500 mg/day) vs placebo in 80 bipolar depression patients for 12 weeks.

80 bipolar depression patients.

Significant reduction in depression and anxiety scores vs placebo. Generated interest in pregnenolone for mood disorders. Adjunctive — not replacement for evidence-based bipolar treatment.

2
Pregnenolone for Schizophrenia

Clinical trial of pregnenolone (up to 500 mg/day) vs placebo in 21 schizophrenia patients for 8 weeks.

21 schizophrenia patients.

Significant improvement in negative symptoms and cognitive function vs placebo. Adjunct to standard antipsychotic treatment. Subsequent trials have mixed results.

Side effects and drug interactions

Common Potential side effects

Variable — depends on individual conversion to downstream hormones.
Hormonal effects — acne, oily skin, hair changes, mood changes, menstrual irregularities, breast tenderness, libido changes (variable direction).
Insomnia or sedation (variable).
Headache.
Dizziness.
Cardiovascular: theoretical from increased steroid hormones.
GI distress.
Fluid retention.
Long-term effects of supplementation poorly studied.

Important Drug interactions

Hormone-containing medications — oral contraceptives, HRT, testosterone, progesterone — additive hormonal effects; consult.
Corticosteroids — pregnenolone is cortisol precursor; theoretical interactions.
Antipsychotics — pregnenolone studied as adjunct in schizophrenia but consult psychiatrist.
Antidepressants — theoretical interactions via neurosteroid effects.
Anticoagulants — theoretical via hormone effects; minor.
Pregnancy — pregnenolone is precursor to progesterone (which IS pregnancy-supporting) but supplementation in pregnancy not studied; avoid without obstetric guidance.
Hormone-sensitive cancers — pregnenolone converts to estrogens, testosterone, etc.; avoid without oncologist consultation.
Anesthesia — general anesthetic interactions theoretical; discontinue 2 weeks pre-surgery.

Featured in these supplement guides

Low Testosterone→

More Cognitive Ingredients

Cognitive
Vitamin B12
Vitamin B12, also known as cobalamin, is a water-soluble vitamin commonly supplemented as…
Cognitive
Longvida® Optimized Curcumin (Verdure Sciences)
Longvida® is a patented curcumin extract developed by Verdure Sciences using SLCP™ (Solid…
Cognitive
CurQfen® (Curcumin-Fenugreek FenuMat — Akay Bioactives)
CurQfen® is a patented curcumin complex from Curcuma longa rhizomes formulated with FENUMA…
Cognitive
Ashwagandha
Ashwagandha (Withania somnifera) is an adaptogenic herb from Ayurvedic tradition, widely u…

Frequently asked questions about Pregnenolone

What is pregnenolone used for?

Pregnenolone is a hormone the body makes from cholesterol and uses as a precursor to other hormones (including DHEA, progesterone, and cortisol). It is marketed for memory, mood, stress, and hormonal support, especially in aging.

What is pregnenolone good for?

It is used for cognitive and memory support, mood, and stress resilience, on the basis of its role as a master hormone precursor and neurosteroid. Human evidence is limited, and effects on downstream hormones are complex.

How much pregnenolone should I take?

Doses vary widely (often 10 to 50 mg); because it is a hormone precursor, it is best used cautiously and ideally with medical guidance and testing rather than guessing. Follow product labeling.

Is pregnenolone safe?

As a hormone precursor, it can influence other hormones and cause hormone-related side effects, so it should be used cautiously, especially by those with hormone-sensitive conditions. It is best taken under medical supervision; pregnant women should avoid it.

What is Pregnenolone?

Pregnenolone is a steroid hormone precursor — synthesized from cholesterol in adrenals, gonads, and brain. Often called the 'mother of all steroid hormones' as it serves as precursor to: progesterone, cortisol, aldosterone, DHEA, testosterone, estrogens.

What is the recommended dosage of Pregnenolone?

The clinically studied dose is 10-100 mg/day (start LOW); some integrative practitioners use 5-30 mg; trials have used up to 500 mg/day for specific indications Always follow the product label and check with a healthcare provider for personal advice.

Is Pregnenolone safe, and does it have side effects?

For most healthy adults, Pregnenolone is well tolerated at studied doses. Reported effects can include: Variable — depends on individual conversion to downstream hormones. Hormonal effects — acne, oily skin, hair changes, mood changes, menstrual irregularities, breast tenderness, libido changes (variable direction). It may also interact with some medications. Pregnenolone is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Pregnenolone interact with any medications?

Possible interactions include: Hormone-containing medications — oral contraceptives, HRT, testosterone, progesterone — additive hormonal effects; consult. Corticosteroids — pregnenolone is cortisol precursor; theoretical interactions. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Pregnenolone?

NutraSmarts rates the evidence for Pregnenolone as Limited (2 out of 5). It is backed by 2 clinical trials and 3 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(3 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Brown ES, Park J, Marx CE, Hynan LS, Gardner C, Davila D, Nakamura A, Sunderajan P, Lo A, Holmes T A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression. Neuropsychopharmacology. 2014;39(12):2867-73. doi: 10.1038/npp.2014.138.PubMedUsed to support: Human RCT testing pregnenolone 0–500 mg/day as adjunct in bipolar depression; significant improvement on depression scales vs. placebo. Supports the Bipolar Disorder Adjunct (Research) benefit.
  2. Kashani L, Shams N, Moazen-Zadeh E, Karkhaneh-Yousefi MA, Sadighi G, Khodaie-Ardakani MR, Rezaei F, Rahiminejad F, Akhondzadeh S Pregnenolone as an adjunct to risperidone for treatment of women with schizophrenia: A randomized double-blind placebo-controlled clinical trial. Journal of Psychiatric Research. 2017;94:70-77. doi: 10.1016/j.jpsychires.2017.06.011.PubMedUsed to support: Human RCT (n=40 women) showing add-on pregnenolone reduced total PANSS and negative symptom scores vs. placebo. Supports the Schizophrenia Cognitive Symptoms (Research) benefit.
  3. Kardashev A, Ratner Y, Ritsner MS Add-On Pregnenolone with L-Theanine to Antipsychotic Therapy Relieves Negative and Anxiety Symptoms of Schizophrenia: An 8-Week, Randomized, Double-Blind, Placebo-Controlled Trial. Clinical Schizophrenia & Related Psychoses. 2018;12(1):31-41..PubMedUsed to support: 8-week RCT showing pregnenolone plus L-theanine as antipsychotic adjunct significantly improved negative symptoms and anxiety in schizophrenia. Supports Schizophrenia Cognitive Symptoms and Cognitive Function benefits.