Pregnenolone
Pregnenolone
The 'master hormone' precursor that the body converts to DHEA, progesterone, cortisol, and other steroid hormones, supporting cognition and mood.
Pregnenolone is often called the 'mother of all hormones' because it's the precursor from which all other steroid hormones are made, including DHEA, progesterone, cortisol, estrogen, and testosterone. It's synthesized from cholesterol and declines with age. Beyond its role as a hormone precursor, pregnenolone itself has cognitive-enhancing and mood-supporting effects, particularly as a neurosteroid that modulates GABA receptors.
Mechanisms of Action
Hormone Precursor
Converts to multiple hormones
Neurosteroid Activity
Direct brain effects
GABA Modulation
Negative modulator of GABA-A
Recommended Dose
5-50mg daily
Loading: Start low (5-10mg) and increase gradually
Optimal Timing
- Morning (mimics natural production)
- With or without food
Can be taken without food
Best Form
Micronized pregnenolone capsules
Alternatives: Sublingual tablets, Topical cream
Micronized forms have better absorption. Sublingual bypasses first-pass metabolism. Start low.
Duration
Minimum: 4 weeks
Optimal: 12 weeks
Cycling: 8-12 weeks on, 4 weeks off; monitor hormone levels
Note: Start with low dose and assess response. Morning dosing aligns with natural hormone rhythms.
Personalized Dosage Calculator
Get a dosage recommendation tailored to your body weight, age, goals, and health profile.
Set up your health profile for personalized recommendations
Cognitive Enhancement
Improved memory and mental clarity
Mood Support
Better mood stability
Energy Support
Improved vitality and energy
Downstream Hormone Effects
Can affect multiple hormone levels
Natural levels decline with age; test levels before supplementing
Who Should NOT Take This
- Hormone-sensitive cancers
- Seizure disorders (may lower threshold)
Drug Interactions
May interact with hormone therapy
Both are steroid hormone precursors — combining may cause excessive hormone stimulation
May reduce sedative effects via GABA modulation
Possible Side Effects
Tip: Reduce dose
Tip: Reduce dose; may indicate progesterone conversion
Tip: Take in morning only
Warnings
- Affects multiple downstream hormones
- Test hormone levels before and during use
- Not recommended for those with hormone-sensitive conditions
Top studies from 40+ peer-reviewed papers
Cho M et al. • The Australian and New Zealand journal of psychiatry (2019)
“The comparative evaluation of efficacy and safety supported the use of anti-inflammatory adjuvant therapy over the use of antipsychotics alone.”
Key Findings:
- The comparative evaluation of efficacy and safety supported the use of anti-inflammatory adjuvant therapy over the use of antipsychotics alone.
- However, future studies could focus on patients with homogeneous clinical profile to figure out more detailed effects of anti-inflammatory therapy.
- Further research warranted to confirm findings
Heringa SM et al. • Schizophrenia research (2015)
“Estrogens and SERMs could be effective augmentation strategies in the treatment of women with schizophrenia, although potential side effects, partially associated with longer duration use, should be taken into account.”
Key Findings:
- Significant effects were found for estrogen action (k=10), regarding total symptoms (Hedges' g=0.63, p=0.001), positive (Hedges' g=0.42, p<0.001), and negative symptoms (Hedges' g=0.35, p=0.001).
- Testosterone augmentation in males (k=1) was beneficial only for negative symptoms (Hedges' g=0.82, p=0.027).
- Estrogens and SERMs could be effective augmentation strategies in the treatment of women with schizophrenia, although potential side effects, partially associated with longer duration use, should be taken into account.
- Future trials are needed to study long-term effects and effects on cognition.
Komatsu Y et al. • Pharmacopsychiatry (2024)
“Compared to the placebo, ulotaront, xanomeline/trospium chloride, vabicaserin, bitopertin, estradiol, cannabidiol, rimonabant, and D-serine showed efficacy for positive symptoms; roluperidone and pimavanserin were effective for negative symptoms; and encenicline, tropisetron, pregnenolone, tolcapone, BI 425809, and valacyclovir improved cognitive function.”
Key Findings:
- Systematic review examining Pregnenolone efficacy
- Published in Pharmacopsychiatry (2024)
- Further research warranted to confirm findings
Marx CE et al. • Journal of Clinical Psychopharmacology (2023)
“Pregnenolone (500mg/day) significantly reduced PTSD symptom severity and improved functioning in military veterans.”
Key Findings:
- Significant reduction in CAPS-5 total scores for PTSD symptoms
- Improved overall clinical global impression scores
- Well tolerated at 500mg/day with no significant adverse events vs placebo
Thavaraputta S et al. • European journal of endocrinology (2023)
“Women with anorexia nervosa have higher cortisol levels and lower DHEA-S and testosterone levels compared to women without anorexia nervosa.”
Key Findings:
- Women with anorexia nervosa have higher cortisol levels and lower DHEA-S and testosterone levels compared to women without anorexia nervosa.
- This finding is important to consider when evaluating low-weight women for disorders involving the adrenal axis, especially Cushing's syndrome.
- Further research warranted to confirm findings
Study Type Distribution
Goals This Supplement Supports
Related Goals
This information is for educational purposes only and is not intended as medical advice. Always consult a qualified healthcare provider before starting any supplement.