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Pregnenolone Research Snapshot

Research Snapshot

Pregnenolone

A synthesis of the peer-reviewed evidence for Pregnenolone across inflammation, cognition, mood and memory, graded by scientific consensus and reviewed by our Scientific Advisory Board.

57 studies analyzed 4 benefit areas Reviewed by the SAB Updated Jul 2026

See the Research

Inflammation

Does pregnenolone have anti-inflammatory properties?

Evidence from 10 studies

Yes
90%
9 studies
Possibly
0%
0 studies
No
10%
1 study

What the research shows

Pregnenolone has significant anti-inflammatory properties, acting through various mechanisms to reduce inflammation and oxidative stress. Its potential applications in cardioprotection, liver protection, and neuroimmune regulation highlight its therapeutic promise in managing inflammatory conditions.

View the top studies
Pregnenolone Inhibits Doxorubicin-Induced Cardiac Oxidative Stress, Inflammation, and Apoptosis—Role of Matrix Metalloproteinase 2 and NADPH Oxidase 1 d antioxidant activity in animal models.

Pharmaceuticals | M. Morsy et al. | 5 | 2023

Randomized Control Trial (RCT) , Animal Trial

Pregnenolone demonstrated anti-inflammatory and antioxidant activity in animal models.

Pregnenolone protects the liver against doxorubicin-induced cellular injury by anti-inflammatory, antioxidant, and antiapoptotic mechanisms: role of Keap1/Nrf2/HO-1 and P-glycoprotein.

European review for medical and pharmacological sciences | M. Morsy et al. | 2 | 2023

Randomized Control Trial (RCT) , Animal Trial

Pregnenolone protects the liver against doxorubicin-induced hepatotoxicity by anti-inflammatory, antioxidant, and antiapoptotic mechanisms.

The neurosteroid pregnenolone promotes degradation of key proteins in the innate immune signaling to suppress inflammation

The Journal of Biological Chemistry | Subathra Murugan et al. | 46 | 2019

In Vitro Trial

Pregnenolone promotes degradation of key proteins in innate immune signaling to suppress inflammation and maintain immune homeostasis in various inflammatory conditions.

Synthesis and anti-inflammatory activity of novel steroidal chalcones with 3β-pregnenolone ester derivatives in RAW 264.7 cells in vitro

Steroids | Xiaorui Cai et al. | 11 | 2021

In Vitro Trial

Pregnenolone-derived compounds showed significant anti-inflammatory activity, suggesting potential as a therapeutic anti-inflammatory drug candidate.

Cognition

Does Pregnenolone have cognitive enhancing effects?

Evidence from 16 studies

Yes
75%
12 studies
Possibly
6%
1 study
No
19%
3 studies

What the research shows

Pregnenolone and its sulfate form exhibit cognitive enhancing effects, particularly in memory enhancement and synaptic plasticity. These effects are evident in animal studies and show potential in human clinical settings, especially concerning age-related cognitive decline and certain psychiatric conditions. Further research is needed to fully understand its mechanisms and therapeutic potential.

View the top studies
Pregnenolone sulfate as a modulator of synaptic plasticity

Psychopharmacology | Conor C. Smith et al. | 0 | 2014

Very Rigorous Journal , Systematic Review

Pregnenolone sulfate (PregS) acts as a cognitive enhancer and modulator of neurotransmission, affecting excitatory N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic transmission.

Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group

The Journal of clinical psychiatry | M. Ritsner et al. | 92 | 2010

Randomized Control Trial (RCT) , Highly Cited

Low-dose pregnenolone augmentation demonstrated significant improvement in attention and working memory performance of schizophrenia and schizoaffective disorder patients.

Memory-enhancing effects in male mice of pregnenolone and steroids metabolically derived from it.

Proceedings of the National Academy of Sciences of the United States of America | J. Flood et al. | 439 | 1992

Non-Randomized Control Trial , Animal Trial , Highly Cited

Pregnenolone and its derivatives improve memory retention in male mice through the facilitation of transcription of immediate-early genes.

Promnestic effects of intranasally applied pregnenolone in rats

Neurobiology of Learning and Memory | Laila Abdel-Hafiz et al. | 7 | 2016

Non-Randomized Control Trial , Animal Trial

Intranasally applied pregnenolone (IN-PREG) has cognitive enhancing properties in rats, including memory-enhancing and resistance to extinction.

Mood

Does Pregnenolone influence mood?

Evidence from 15 studies

Yes
53%
8 studies
Possibly
40%
6 studies
No
7%
1 study

What the research shows

Overall, pregnenolone shows potential as a mood-enhancing agent, particularly in the context of bipolar depression and mood disorders with a history of substance use. Its effects are likely mediated through neurosteroid pathways and dopaminergic activity, although further research is needed to fully understand its mechanisms and efficacy across different populations.

View the top studies
A Randomized, Double-Blind, Placebo-Controlled Trial of Pregnenolone for Bipolar Depression

Neuropsychopharmacology | E. Brown et al. | 85 | 2014

Randomized Control Trial (RCT) , Very Rigorous Journal , Highly Cited

Pregnenolone may improve depressive symptoms in patients with bipolar disorder and can be safely administered.

Pregnenolone for cognition and mood in dual diagnosis patients

Psychiatry Research | I. Osuji et al. | 33 | 2010

Randomized Control Trial (RCT) , Rigorous Journal

Pregnenolone use may be associated with some improvement in manic and depressive symptoms, but not cognition in depressed patients with a history of substance use.

Microtubule associated protein 2 in bipolar depression: Impact of pregnenolone.

Journal of affective disorders | Shivani Daftary et al. | 13 | 2017

Randomized Control Trial (RCT) , Rigorous Journal

Pregnenolone treatment is associated with a change in serum MAP2 levels, which correlates positively with changes in self-reported depressive symptom scores.

GABAergic neuroactive steroids: a new frontier in bipolar disorders?

Behavioral and Brain Functions : BBF | M. Carta et al. | 65 | 2012

Literature Review

Pregnenolone derivative neurosteroids like allopregnanolone have significant mood-stabilizing effects and play a role in mood disorders.

Memory

Does Pregnenolone support the processes that contribute to the building of memory?

Evidence from 16 studies

Yes
75%
12 studies
Possibly
19%
3 studies
No
6%
1 study

What the research shows

Pregnenolone and pregnenolone sulfate significantly support memory-building processes through various mechanisms, including gene transcription facilitation, enhancement of synaptic plasticity, and modulation of neurotransmitter systems. These effects are particularly pronounced in specific brain regions and may offer therapeutic potential for age-related cognitive decline and other memory disorders.

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Pregnenolone sulfate enhances post-training memory processes when injected in very low doses into limbic system structures: the amygdala is by far the most sensitive.

Proceedings of the National Academy of Sciences of the United States of America | J. Flood et al. | 180 | 1995

Non-Randomized Control Trial , Animal Trial , Highly Cited

Pregnenolone sulfate enhances post-training memory processes when injected into the amygdala, making it the most potent memory enhancer yet reported.

Memory-enhancing effects in male mice of pregnenolone and steroids metabolically derived from it.

Proceedings of the National Academy of Sciences of the United States of America | J. Flood et al. | 439 | 1992

Non-Randomized Control Trial , Animal Trial , Highly Cited

Pregnenolone and its derivatives improve memory retention in male mice through the facilitation of transcription of immediate-early genes.

Neurosteroids: deficient cognitive performance in aged rats depends on low pregnenolone sulfate levels in the hippocampus.

Proceedings of the National Academy of Sciences | Monique Vallée et al. | 318 | 1997

Non-Randomized Control Trial , Animal Trial , Highly Cited

Pregnenolone sulfate levels in the hippocampus play a physiological role in preserving and/or enhancing cognitive abilities in aged rats, possibly via an interaction with central cholinergic systems.

The synthetic enantiomer of pregnenolone sulfate is very active on memory in rats and mice, even more so than its physiological neurosteroid counterpart: Distinct mechanisms?

Proceedings of the National Academy of Sciences of the United States of America | Y. Akwa et al. | 143 | 2001

Non-Randomized Control Trial , Animal Trial , Highly Cited

Pregnenolone sulfate (PREGS) supports memory function, with its synthetic enantiomer having a 10 times higher potency than the natural steroid.

Reviewed by Experts

Reviewed by the Scientific Advisory Board

Every research snapshot is checked by our independent Scientific Advisory Board: physicians, botanists and pharmacology researchers who verify the evidence grading and its interpretation.

Kerry Hughes

M.Sc., RH(AHG), FDN-P

Ethnobotanist & herbalist; Berkeley Herbal Center; principal at EthnoPharm.

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Lance Dreher

PhD, Nutritional Counseling

Performance nutrition & conditioning; four decades of applied training science.

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Dr. Lindsey Faucette

DO, FAAFP

Board-certified in Family & Integrative Medicine; Touro University College of Osteopathic Medicine.

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Francisco Chacon

PhD, Plant Biology

Botanical natural products & phytochemistry researcher, Penn State University.

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How We Grade Consensus

For each benefit we retrieve the relevant peer-reviewed literature and classify every study by whether its findings support (Yes), partially or conditionally support (Possibly), or do not support (No) the claim. The donut shows the share of studies in each category; N is the number of studies analyzed for that benefit.

Grades reflect the weight and direction of the current evidence, not a guarantee of outcome, and the interpretation is verified by the Scientific Advisory Board.

Data sourced from published, peer-reviewed research. Citations link to the original studies. These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. Last reviewed Jul 2026 · Meet the Scientific Advisory Board.