Pregnenolone is a naturally occurring steroid hormone synthesized from cholesterol in the body. Often referred to as the “mother hormone,” it serves as a precursor to many other hormones, including progesterone, estrogen, testosterone, cortisol, and DHEA. Pregnenolone capsules are used as a dietary supplement to support cognitive function, mood balance, hormone synthesis, and energy metabolism. It may also assist in managing stress and age-related hormonal decline.

Pregnenolone functions primarily as a prohormone, acting as a foundational building block for the synthesis of various steroid hormones. It influences the central nervous system by modulating neurotransmitter activity, particularly GABA and NMDA receptors, which are involved in mood regulation, memory, and stress responses. Additionally, pregnenolone has been shown to support mitochondrial energy production and promote neurogenesis, contributing to its role in cognitive enhancement and anti-aging support.

Pregnenolone should not be used by individuals with hormone-sensitive conditions such as breast, prostate, or uterine cancer unless directed by a healthcare provider. People with liver or kidney impairment, severe mood disorders, or a history of seizures should also exercise caution. It is advisable to monitor hormone levels during prolonged use to prevent hormonal imbalances. Always consult with a healthcare professional before beginning supplementation, especially if you are on hormone therapy or have a medical condition.

Pregnenolone may interact with medications that influence hormone levels, such as corticosteroids, hormone replacement therapy (HRT), or anti-estrogen drugs like tamoxifen. It may also affect the metabolism of certain psychiatric medications due to its impact on neurosteroid pathways. Combining pregnenolone with other hormone precursors or anabolic agents can amplify hormonal effects, potentially leading to adverse outcomes. Always discuss potential interactions with a healthcare provider if you are taking prescription drugs or other supplements.

Common side effects may include irritability, insomnia, anxiety, or acne due to hormonal fluctuations. In some individuals, pregnenolone can cause overstimulation or mood swings, particularly at higher doses. Rarely, it may contribute to headaches, palpitations, or skin rashes. Discontinuation or dose adjustment typically resolves mild side effects. If serious reactions occur, stop use and consult a healthcare professional.

Pregnenolone supplementation is not recommended during pregnancy or breastfeeding due to insufficient safety data. As it influences hormone levels, it may pose risks to fetal development or alter milk composition. Women who are pregnant, planning to become pregnant, or nursing should avoid using pregnenolone unless specifically advised and supervised by a healthcare provider.

Store this medication at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond-use date. Do not flush unused medications or pour down a sink or drain.

1. Burstein S, Gut M. Biosynthesis of Pregnenolone. Recent Prog Horm Res. 1971;27:303-49.
2. Strushkevich N, MacKenzie F, Cherkesova T, Grabovec I, Usanov S, Park HW. Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system. Proc Natl Acad Sci USA. 2011;108(25):10139-43.
3. M Schumacher, P Robel, E E Baulieu. Development and regeneration of the nervous system: a role for neurosteroids. Dev Neurosci. 1996;18(1-2):6-21.
4. Marx CE, Keefe RSE, et al. Proof-of-Concept Trial with the Neurosteroid Pregnenolone Targeting Cognitive and Negative Symptoms in Schizophrenia. Neuropsychopharmacology. 2009 Jul; 34(8): 1885–1903.
5. Vallée M, Mayo W, Moal ML. Role of pregnenolone, dehydroepiandrosterone and their sulfate esters on learning and memory in cognitive aging. Brain Res Brain Res Rev. 2001 Nov;37(1-3):301-12.
6. Murugan S, Jakka P, Namani S , Mujumdar V, Radhakrishnan G. The neurosteroid, pregnenolone promotes degradation of key proteins in the innate immune signalling to suppress inflammation. 2019;294(12):4596-4607.
7. Michael Ritsner, Rachel Maayan, Anatoly Gibel, Abraham Weizman. Differences in blood pregnenolone and dehydroepiandrosterone levels between schizophrenia patients and healthy subjects. Eur Neuropsychopharmacol. 2007;17(5):358-65.
8. Marx CE, Stevens RD, Shampine LJ, et al. Neuroactive steroids are altered in schizophrenia and bipolar disorder: relevance to pathophysiology and therapeutics. Neuropsychopharmacology. 2006;31(6):1249-63.
9. George MS, Guidotti A, Rubinow D, Pan B, Mikalauskas K, Post RM. CSF neuroactive steroids in affective disorders: pregnenolone, progesterone, and DBI. Biol Psychiatry. 1994;35(10):775-80.
10. Weill-Engerer S, David JP, Sazdovitch V. Neurosteroid quantification in human brain regions: comparison between Alzheimer’s and nondemented patients. J Clin Endocrinol Metab. 2002;87(11):5138-43.
11. Brown ES, Park J,1 Marx CE, et al. A Randomized, Double-Blind, Placebo-Controlled Trial of Pregnenolone for Bipolar Depression. Neuropsychopharmacology. 2014; 39(12): 2867–2873.
12. Plassart-Schiess E, Baulieu EE. Neurosteroids: recent findings. Brain Research Reviews. 2001;37(1-3):133-140.
13. Ducharme N, Banks WA, Morley JE, Robinson SM, Niehoff ML, and Mattern C. Brain distribution and behavioral effects of progesterone and pregnenolone after intranasal or intravenous administration. Eur J Pharmacol. 2010; 641(2-3):128–134.
14. Sripada RK, Marx CE, King AP, Rampton JC, Ho S, Liberzon I. Allopregnanolone Elevations Following Pregnenolone Administration are Associated with Enhanced Activation of Emotion Regulation Neurocircuits. Biol Psychiatry. 2013;73(11):1045–1053.
15. Schumacher M, Robel P, Baulieu EE. Development and regeneration of the nervous system: a role for neurosteroids. Dev Neurosci. 1996;18(1-2):6-21.
16. Mellon SH. Neurosteroid regulation of CNS development. Pharmacol Ther. 2007;116(1):107–124.
17. Baulieu EE, Robel P, Schumacher M. Neurosteroids: beginning of the story. Int Rev Neurobiol. 2001;46:1-32.
18. Baulieu EE. Neurosteroids: of the nervous system, by the nervous system, for the nervous system. Recent Prog Horm Res. 1997;52:1-32.
19. Fontaine-Lenoir V, Chambraud B, Fellous A, David S, Duchossoy Y, Baulieu EE, Robel P. Microtubule-associated protein 2 (MAP2) is a neurosteroid receptor. Proc Natl Acad Sci USA. 2006;103(12):4711–4716.
20. Wang M. Neurosteroids and GABA-A Receptor Function. Front Endocrinol (Lausanne). 2011;2:44.
21. Akk G, Bracamontes J, Steinbach JH. Pregnenolone sulfate block of GABAA receptors: mechanism and involvement of a residue in the M2 region of the α subunit. J Physiol. 2001;532(Pt 3):673–684.
22. Pertwee R.G. (2015) Endocannabinoids and Their Pharmacological Actions. In: Pertwee R. (eds) Endocannabinoids. Handbook of Experimental Pharmacology, vol 231.
23. Romieu P, Martin-Fardon R, Bowen WD, Maurice T. σ1 Receptor-Related Neuroactive Steroids Modulate Cocaine-Induced Reward. J Neurosci. 2003;23(9):3572–3576.
24. Kliewer SA, Lehmann JM, Milburn MV, Willson TM. The PPARs and PXRs: nuclear xenobiotic receptors that define novel hormone signaling pathways. Recent Prog Horm Res. 1999;54:345-67.
25. Ma Y, Liu D. Activation of Pregnane X Receptor by Pregnenolone 16 α-carbonitrile Prevents High-Fat Diet-Induced Obesity in AKR/J Mice. PLoS One. 2012;7(6):e38734.
26. Russo J, Russo IH. The Role of Estrogen in the Initation of Brest Cancer. J Steroid Biochem Mol Biol. 2006;102(1-5)89–96.
27. Yang B, Chen R, Liang X, Shi J, Wu X, Zhang Z, Chen X. Estrogen Enhances Endometrial Cancer Cells Proliferation by Upregulation of Prohibitin. J Cancer. 2019; 10(7):1616-1621.
28. Mungenast F, Thalhammer T. Estrogen Biosynthesis and Action in Ovarian Cancer. Front Endocrinol (Lausanne). 2014;5:192.
29. Bosland MC. The Role of Estrogens in Prostate Carcinogenesis: A Rationale for Chemoprevention. Rev Urol. 2005;7(Suppl 3):S4–S10.
30. Deroo BJ, Korach KS. Estrogen receptors and human disease. J Clin Invest. 2006;116(3):561–570.
31. Serdar E. Bulun SE, Monsavais D, Pavone ME, Dyson M, Xue Q, Attar E, Tokunaga H, Su EJ. Role of Estrogen Receptor-β in Endometriosis. Nat Med. 2012;18(7):1016–1018.
32. Howard BV, Rossouw JE. Estrogens and Cardiovascular Disease Risk Revisited: the Women’s Health Initiative. Curr Opin Lipidol. 2013;24(6):493–499.
33. Gilbert EL, Ryan MJ. Estrogen in Cardiovascular Disease during Systemic Lupus Erythematosus. Clin Ther. 2014;36(12):1901–1912.
34. Savolainen-Peltonen H, Rahkola-Soisalo P, Hoti F, Vattulainen P, Gissler M, Ylikorkala O, Mikkola TS. Use of postmenopausal hormone therapy and risk of Alzheimer’s disease in Finland: nationwide case-control study. BMJ. 2019;364:l665.
35. Velíšková J, Jesus GD, Kaur R, and Velíšek L. Females, their estrogens and seizures. Epilepsia. 2010; 51(Suppl 3):141–144.
36. Vacheron-Trystram MN, Cheref S, Gauillard J, Plas J. [A case report of mania precipitated by use of DHEA]. Encephale. 2002;28(6 Pt 1):563-566.
37. Dean CE. Prasterone (DHEA) and mania. Ann Pharmacother. 2000;34(12):1419-22.
38. Pure Encapsulations® pregnenolone 30mg capsules package insert. 2016.
39. Randel A. AACE Releases Guidelines for Menopausal Hormone Therapy. Am Fam Physician. 2012;86(9):864-868.
40. Mueck AO, Seeger H. Smoking, estradiol metabolism and hormone replacement therapy. Curr Med Chem Cardiovasc Hematol Agents. 2005;3(1):45-54.
41. Svartberg J, Jorde R. Endogenous testosterone levels and smoking in men. The fifth Tromsø study. Int J Androl. 2007;30(3):137-43.
42. Meieran SE, Reus VI, Webster R, Shafton R, Wolkowitz OM. Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation. Psychoneuroendocrinology. 2004;29(4):486-500.
43. Melchior CL, Ritzmann RF. Pregnenolone and pregnenolone sulfate, alone and with ethanol, in mice on the plus-maze. Pharmacol Biochem Behav. 1994;48(4):893-7.
44. Naylor JC, Kilts JD, Shampine LJ, et al. Effect of Pregnenolone vs Placebo on Self-reported Chronic Low Back Pain Among US Military Veterans. JAMA Netw Open. 2020;3(3):e200287.