Pregnenolone
Pregnenolone is an endogenous precursor to several neuroactive steroids. A four-week back-pain trial found a modest pain benefit, and small psychiatric trials reported selected positive endpoints. Oral studies confirm neurosteroid target engagement, but healthy mood, anxiety and cognitive results were largely null. No controlled evidence establishes hormone optimization, healthy performance or longevity.
Endogenous C21 steroid precursor with multiple downstream neurosteroids
- Oral pregnenolone, pregnenolone sulfate and allopregnanolone are different evidence targets.
- A 31-man acute trial changed neurosteroids and fMRI signals without improving anxiety, sedation, reaction time, accuracy or general neurocognition.
- The back-pain trial found a 0.56-point adjusted benefit on a 0 to 10 scale; five of seven interference domains were null.
- A 97-person PTSD trial and posted peri/menopausal-depression primary result were null.
- No deficiency-selected, hypogonadal, TRT-adjunct, modern performance or human-longevity trial was found.
- Human PK and long-term safety remain poorly characterized.
What is pregnenolone, and which neurosteroid evidence applies?
Pregnenolone is an endogenous neutral C21 steroid precursor. Oral parent pregnenolone can be converted to pregnenolone sulfate, progesterone, allopregnanolone and other steroids, but those metabolites have different receptor effects and cannot be treated as interchangeable products.
| Evidence target | What it shows | What it cannot show |
|---|---|---|
| Oral parent pregnenolone | Human absorption, conversion and clinical outcomes | The effect of directly applied pregnenolone sulfate |
| Pregnenolone sulfate | NMDA, GABA-A and TRPM3 mechanisms in cell or receptor systems | The dominant brain effect after an oral parent dose |
| Allopregnanolone and other metabolites | Possible downstream pathways after conversion | That raising a blood metabolite improves symptoms |
PubChem CID 8955 · pregnenolone identity
Government substance database
National Library of Medicine. PubChem Compound Summary for CID 8955, Pregnenolone.
Identifies pregnenolone as C21H32O2, molecular weight 316.5 g/mol, CID 8955.
- Participants / model
- Not applicable
- Treatment
- Not applicable
- Follow-up
- Living database record
- Study design
- Curated chemical identity record
Pregnenolone, pregnenolone sulfate, allopregnanolone, and downstream sex or adrenal steroids are distinct molecules.
Read the original sourceFDA · supplements are not preapproved like drugs
FDA consumer regulatory guidance
U.S. Food and Drug Administration. FDA 101: Dietary Supplements.
FDA explains that dietary supplements are regulated differently from prescription and over-the-counter drugs and are not FDA approved for safety and effectiveness before marketing.
- Participants / model
- US dietary-supplement marketplace
- Treatment
- Regulatory framework, not a pregnenolone intervention
- Follow-up
- Current web record
- Study design
- FDA regulatory guidance
This general supplement framework does not establish that every marketed pregnenolone product is lawful, equivalent, pure, or clinically effective.
Read the original sourcePregnenolone in US approval records
US drug approval status
openFDA Drugs@FDA records for pregnenolone.
No Drugs@FDA record matches pregnenolone as an exact active-ingredient name.
That exact-name result does not rule out differently named, historical, compounded, or non-drug products.
Read the original sourceCell mechanism · pregnenolone sulfate, not oral pregnenolone
Preclinical molecular and cellular study
Ming-Kuei Jang, Dale F. Mierke, Shelley J. Russek, and David H. Farb. Proceedings of the National Academy of Sciences of the United States of America. 2004. PMID 15150412.
Molecular and heterologous-expression experiments identified an NR2B-associated modulatory domain involved in pregnenolone sulfate effects on NMDA-receptor proton sensitivity.
- Participants / model
- Recombinant and cellular receptor systems
- Treatment
- Pregnenolone sulfate and receptor mutagenesis
- Follow-up
- Preclinical
- Study design
- Molecular pharmacology and cell study
Pregnenolone sulfate is a charged metabolite, not oral pregnenolone. Receptor effects in an expression system do not establish cognitive or mood outcomes in humans.
Read the original sourceDoes pregnenolone improve depression, anxiety, stress or sleep?
An 80-person bipolar trial found a positive clinician-rated time interaction and self-rated remission result. Its group main effect, clinician-rated remission, self-rated total score, anxiety and mania measures were null. Posted peri/menopausal-depression and PTSD primary comparisons were also null. Healthy trials changed brain or sleep physiology without establishing better mood, anxiety or sleep quality.
| Study | Result | Why the claim stays narrow |
|---|---|---|
| Bipolar depression: 80 randomized, 73 analyzed | HRSD time interaction p=0.025; HRSD remission 47.4% vs 51.4% null; self-rated remission 61% vs 37%, p=0.046 | Discordant instruments, baseline and sex imbalance, uneven completion |
| Peri/menopausal depression: 73 participants | Posted MADRS difference -2.46, p=0.29 | Primary result null; other outcomes descriptive |
| Veteran PTSD: 97 participants | CAPS-5 difference -1.24, 95% CI -5.89 to 3.41; p=0.596 | Depression, pain and pain interference also null |
| Healthy crossover: 17 completers | Mood, memory, subjective sleep and wellbeing null after four weeks | Diazepam substudy n=11 found sedation only; anxiety and amnesia null |
| Older sleep experiment | More slow-wave sleep and lower sigma power after one exposure | Primary abstract omits n, dose, route and allocation; no insomnia or durable benefit |
80 bipolar-depression participants · endpoint discordance
Randomized double-blind placebo-controlled adjunctive trial
E. Sherwood Brown, John Park, Christine E. Marx, et al. Neuropsychopharmacology. 2014. PMID 24917198.
Among 80 randomized and 73 with postbaseline data, HRSD treatment-by-week was p=0.025 but the group main effect and HRSD remission were null. IDS-SR total was null; IDS-SR remission was 61% versus 37% (p=0.046). Anxiety and mania measures did not differ.
- Participants / model
- 80 adults with bipolar disorder in a depressed mood state; 73 with postbaseline data
- Treatment
- Adjunctive oral pregnenolone versus placebo
- Follow-up
- 12 weeks
- Study design
- Randomized double-blind placebo-controlled add-on trial
- Funding
- Stanley Medical Research Institute
Small adjunctive trial with sex and baseline-depression imbalance, different completion proportions, and discordant clinician and self-report outcomes. One author disclosed a pending neurosteroid-use patent application.
Read the original source70-person dual-diagnosis trial · cognition null
Randomized double-blind placebo-controlled trial
E. Sherwood Brown et al. Human Psychopharmacology. 2010. PMID 20493557.
Among 70 enrolled and 60 analyzed, cognition was null. Depression and mania only trended in the main analysis; a depression result appeared in a post hoc completer analysis.
- Participants / model
- Adults with mood and substance-use disorders; 70 enrolled, 60 analyzed, 37 completed
- Treatment
- Oral pregnenolone titrated to 100 mg/day versus placebo
- Follow-up
- Eight weeks
- Study design
- Randomized double-blind placebo-controlled trial
Post hoc completer findings do not establish a general antidepressant effect.
Read the original source73-person depression registry · primary result null
Randomized sequential-parallel trial with posted results
ClinicalTrials.gov. NCT03505905. Pregnenolone for peri- and postmenopausal depression.
The combined posted MADRS treatment difference was -2.46 points, p=0.29. Anxiety, sleep, quality of life, menopausal symptoms, memory and executive outcomes were descriptive rather than confirmatory.
- Participants / model
- 73 participants with peri- or postmenopausal depression
- Treatment
- Oral pregnenolone up to 500 mg/day versus placebo
- Follow-up
- Sequential study periods
- Study design
- Randomized sequential-parallel clinical trial
The posted primary depression comparison was null. Descriptive secondary values are not treatment effects.
Read the original source97-veteran PTSD trial · CAPS-5 null
Randomized placebo-controlled trial with posted results
ClinicalTrials.gov. NCT03799562. Pregnenolone for PTSD.
CAPS-5 favored pregnenolone by -1.24 points, 95% CI -5.89 to 3.41, p=0.596. Depression, pain and pain interference were also null.
- Participants / model
- 97 veterans with PTSD
- Treatment
- Oral pregnenolone escalated to 250 mg twice daily versus placebo
- Follow-up
- Eight weeks
- Study design
- Randomized placebo-controlled trial
- Funding
- U.S. Department of Veterans Affairs
The primary PTSD outcome and several related clinical outcomes were null.
Read the original source17-completer healthy crossover · mood and memory null
Placebo-controlled crossover study
Meieran et al. Psychoneuroendocrinology. 2004. PMID 14749094.
Four weeks of 15 then 30 mg/day did not improve mood, memory, subjective sleep or wellbeing. In an 11-person diazepam substudy, sedation differed while amnesia was nonsignificant and anxiety unchanged.
- Participants / model
- Healthy adults; 17 completers; diazepam substudy n=11
- Treatment
- Oral pregnenolone versus placebo
- Follow-up
- Four weeks
- Study design
- Placebo-controlled crossover program
Small study with a tiny challenge substudy; direct healthy efficacy outcomes were null.
Read the original sourceAcute sleep architecture study
Human sleep experiment
Steiger et al. Neuropsychobiology. 1993. PMID 8395958.
The abstract reports increased slow-wave sleep and lower sigma power without nocturnal cortisol or growth-hormone changes.
- Participants / model
- Male volunteers; sample size not reported in the abstract
- Treatment
- Single pregnenolone exposure; dose and route not reported in the abstract
- Follow-up
- One night
- Study design
- Human sleep-architecture experiment
The abstract does not report sample size, dose, route, allocation, timing, or detailed methods. It does not establish insomnia or durable sleep benefit.
Read the original sourceDoes pregnenolone improve cognition in patients or healthy adults?
Small schizophrenia studies reported selected symptom, attention or working-memory benefits, sometimes only within the active arm. The larger 120-person trial found no benefit on its MCCB cognitive composite or negative symptoms. In healthy men, an acute 400 mg exposure changed neurosteroids and fMRI connectivity but not anxiety, sedation, reaction time, accuracy or general neurocognition.
| Population | Controlled result | Interpretation |
|---|---|---|
| Schizophrenia pilot: 21 randomized; 18 analyzed | SANS change 10.38 vs 2.33, p=0.048; BACS and MCCB composites null | Tiny, mostly male, single-site pilot with uncorrected subscales |
| Four-arm schizophrenia trial: 58 | Selected attention/working-memory findings at 30 mg but not 200 mg; symptoms and akathisia null | Nonmonotonic secondary pattern |
| Recent-onset schizophrenia: 60 | One between-arm visual-attention effect, d=0.42; several other headlines were within-arm changes | Two publications are one cohort, not two replications |
| Schizophrenia: 120 randomized; 111 analyzed | MCCB and negative symptoms null; functional capacity p=0.03, driven by communication | Secondary functional signal reported only in the abstract |
| Healthy acute fMRI: 31 men | Neurosteroids and imaging changed; behavioral, subjective and general cognitive measures null | Mechanistic target engagement, not healthy enhancement |
21-person pilot · negative-symptom signal, cognition null
Randomized double-blind placebo-controlled pilot trial
Christine E. Marx, Richard S. E. Keefe, Robert W. Buchanan, et al. Neuropsychopharmacology. 2009;34(8):1885 to 1903. PMID 19339966.
Twenty-one were randomized; 18 completed at least four weeks and 17 completed eight. SANS change was 10.38 versus 2.33 points (p=0.048), while BACS and MCCB cognitive composites were not different. CGI-I favored pregnenolone; CGI-S, PANSS, and quality of life were null.
- Participants / model
- 21 adults with schizophrenia or schizoaffective disorder on stable second-generation antipsychotics; one woman
- Treatment
- Adjunctive oral pregnenolone versus placebo after a two-week placebo lead-in
- Follow-up
- 8 randomized weeks
- Study design
- Single-site randomized double-blind placebo-controlled pilot
- Funding
- US Department of Veterans Affairs, NIH, and National Alliance for Research on Schizophrenia and Affective Disorders grants
Tiny single-VA pilot with one woman, mixed concomitant antipsychotics, LOCF, multiple exploratory tests, and uncorrected subscales. Authors disclosed neurosteroid patent applications and cognitive-test royalties.
Read the original source58-person four-arm trial · nonmonotonic cognitive signals
Randomized double-blind placebo-controlled trial
Ritsner et al. Journal of Clinical Psychiatry. 2010. PMID 20584515.
The 30 mg/day pregnenolone arm had selected attention and working-memory findings that the 200 mg/day arm did not reproduce; negative symptoms and akathisia were null.
- Participants / model
- 58 adults with schizophrenia across four treatment arms
- Treatment
- Oral pregnenolone at two doses, DHEA or placebo
- Follow-up
- Eight weeks
- Study design
- Randomized double-blind placebo-controlled four-arm trial
Secondary, nonmonotonic cognitive findings do not establish a dose-responsive general effect.
Read the original source60-person recent-onset cohort · selected outcomes
Randomized placebo-controlled trial and same-cohort analyses
Marx et al. 2014. PMID 24496044 and PMID 24548129.
Selected negative-symptom and visual-attention findings were reported, including a between-arm visual-attention effect of d=0.42; several other highlighted cognitive changes were within-arm tests.
- Participants / model
- 60 adults with recent-onset schizophrenia or schizoaffective disorder
- Treatment
- Adjunctive oral pregnenolone versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized placebo-controlled study with two same-cohort publications
- Funding
- Public research grants
The two publications are one cohort. Within-arm improvements are not placebo-controlled effects.
Read the original source120 schizophrenia participants · cognition primary null
Randomized placebo-controlled adjunctive trial
Christine E. Marx, Jimmy Lee, Mythily Subramaniam, et al. Psychopharmacology. 2014. PMID 25030803.
After 120 participants were randomized, modified intention-to-treat groups were 56 and 55. The MCCB cognitive composite did not improve versus placebo. UPSA-B functional capacity improved (p=0.03), driven in part by communication (p<0.001); negative-symptom scores were low at baseline and did not improve.
- Participants / model
- 120 adults with schizophrenia randomized; modified intention-to-treat n=111
- Treatment
- Adjunctive oral pregnenolone versus placebo
- Follow-up
- 8 weeks after placebo lead-in
- Study design
- Randomized placebo-controlled proof-of-concept trial
The cognitive composite and negative symptoms were null. The functional result was secondary and short-term. Only the primary abstract and indexed record were publicly readable, so claims remain limited to those materials.
Read the original source31-man acute trial · imaging changed, anxiety null
Randomized double-blind placebo-controlled mechanistic trial
Sripada et al. Neuropsychopharmacology. 2013. PMID 23348009.
A single 400 mg exposure raised pregnenolone and allopregnanolone and changed amygdala, insula and prefrontal connectivity. Anxiety, sedation, general neurocognition, reaction time and accuracy did not differ.
- Participants / model
- 31 healthy men; 16 pregnenolone and 15 placebo
- Treatment
- Single oral pregnenolone 400 mg versus placebo
- Follow-up
- Two hours before imaging
- Study design
- Randomized double-blind placebo-controlled fMRI study
- Funding
- National Institutes of Health and related public grants
Neural target engagement did not produce a same-day subjective or behavioral benefit.
Read the original source17-completer healthy crossover · mood and memory null
Placebo-controlled crossover study
Meieran et al. Psychoneuroendocrinology. 2004. PMID 14749094.
Four weeks of 15 then 30 mg/day did not improve mood, memory, subjective sleep or wellbeing. In an 11-person diazepam substudy, sedation differed while amnesia was nonsignificant and anxiety unchanged.
- Participants / model
- Healthy adults; 17 completers; diazepam substudy n=11
- Treatment
- Oral pregnenolone versus placebo
- Follow-up
- Four weeks
- Study design
- Placebo-controlled crossover program
Small study with a tiny challenge substudy; direct healthy efficacy outcomes were null.
Read the original sourceHow meaningful was the chronic low-back-pain result?
The four-week veteran trial found a statistically positive but modest mean pain result. One hundred were randomized, six were removed for placebo-lead-in noncompliance, 94 entered the baseline analysis and 83 completed the final visit. Adjusted daily pain favored pregnenolone by 0.56 points on a 0 to 10 scale; 51.2% versus 28.6% improved at least 20%. The averaged interference score and five of seven interference domains were null.
| Study | Positive result | Nulls and boundary |
|---|---|---|
| Durham VA back-pain RCT | Adjusted mean difference -0.56/10, p=0.02; responder OR 2.62, 95% CI 1.06 to 6.50 | Single center, 89.4% male, four weeks; averaged interference, depression, sleepiness, quality of life and cognition null |
| Veteran PTSD RCT | None | Pain and pain-interference comparisons null |
| 2026 AUD cue substudy: 60 | 300 mg arm lacked within-arm cue-related pain increases | 500 mg did not reproduce it; no direct active-vs-placebo analgesic contrast |
Veteran pain trial · small self-reported effect
Randomized double-blind placebo-controlled clinical trial
Jennifer C. Naylor, Jason D. Kilts, Lawrence J. Shampine, et al. JAMA Network Open. 2020. PMID 32119096. DOI 10.1001/jamanetworkopen.2020.0287.
One hundred were randomized; six were removed for placebo-lead-in noncompliance, leaving 94 in baseline analyses. Adjusted daily pain favored pregnenolone by 0.56/10 (p=0.02); at least 20% improvement occurred in 51.2% versus 28.6% (OR 2.62, 95% CI 1.06 to 6.50). Two of seven interference domains improved.
- Participants / model
- 100 Iraq- and Afghanistan-era veterans randomized; 94 after lead-in noncompliance; 89.4% male
- Treatment
- Adjunctive oral pregnenolone versus placebo
- Follow-up
- 1-week placebo lead-in plus 4-week randomized treatment
- Study design
- Randomized double-blind placebo-controlled single-center trial
The abstract reports 94 included while also giving randomized arms totaling 100; the full CONSORT flow resolves this as six lead-in noncompliance removals. Single-center, short, mostly male, with baseline pain imbalance and self-reported outcomes.
Read the original source97-veteran PTSD trial · CAPS-5 null
Randomized placebo-controlled trial with posted results
ClinicalTrials.gov. NCT03799562. Pregnenolone for PTSD.
CAPS-5 favored pregnenolone by -1.24 points, 95% CI -5.89 to 3.41, p=0.596. Depression, pain and pain interference were also null.
- Participants / model
- 97 veterans with PTSD
- Treatment
- Oral pregnenolone escalated to 250 mg twice daily versus placebo
- Follow-up
- Eight weeks
- Study design
- Randomized placebo-controlled trial
- Funding
- U.S. Department of Veterans Affairs
The primary PTSD outcome and several related clinical outcomes were null.
Read the original source60-person AUD substudy · dose-inconsistent within-arm findings
Randomized-trial laboratory substudy
PMID 42258258; DOI 10.1037/pha0000862.
The 300 mg arm lacked within-arm pain increases after stress and alcohol cues; the 500 mg arm did not reproduce that pattern.
- Participants / model
- 60 participants from an alcohol-use-disorder trial
- Treatment
- Oral pregnenolone 300 or 500 mg/day versus placebo
- Follow-up
- Week-two laboratory challenge
- Study design
- Same-program exploratory substudy
- Funding
- National Institutes of Health
Within-arm cue contrasts and dose inconsistency do not establish analgesia versus placebo.
Read the original sourceWhat does human target engagement prove?
Oral pregnenolone raises parent pregnenolone and several downstream neurosteroids. A 31-man experiment also changed amygdala, insula and prefrontal connectivity. These findings confirm biological exposure, but blood steroids and imaging signals are not validated substitutes for mood, memory, pain, sleep or functional benefit.
| Study | Measured change | Limit |
|---|---|---|
| Two healthy men, single exposure | Parent pregnenolone, pregnenolone sulfate and several downstream steroids rose over 24 hours | Too small for population PK |
| 31 healthy men, single exposure | Pregnenolone and allopregnanolone rose; task and resting-state fMRI changed | Behavioral and subjective endpoints were null; two imaging papers overlap |
| Seven-person CUD PK subset | Circulating pregnenolone higher after two weeks | Two or three people per group; absorption and elimination half-life could not be estimated |
Two-man oral conversion study · exploratory PK
Exploratory human exposure study
Freeman et al. Proceedings of the National Academy of Sciences. 2000. PMCID PMC23857.
Parent pregnenolone, pregnenolone sulfate and several downstream steroids rose during 24-hour sampling after one exposure.
- Participants / model
- Two healthy men aged 45 and 46
- Treatment
- Single oral pregnenolone 175 mg
- Follow-up
- 24 hours
- Study design
- Uncontrolled exploratory serial-sampling study
Two participants and sparse sampling cannot define population PK, a universal half-life or a clinical target.
Read the original source31-man acute trial · imaging changed, anxiety null
Randomized double-blind placebo-controlled mechanistic trial
Sripada et al. Neuropsychopharmacology. 2013. PMID 23348009.
A single 400 mg exposure raised pregnenolone and allopregnanolone and changed amygdala, insula and prefrontal connectivity. Anxiety, sedation, general neurocognition, reaction time and accuracy did not differ.
- Participants / model
- 31 healthy men; 16 pregnenolone and 15 placebo
- Treatment
- Single oral pregnenolone 400 mg versus placebo
- Follow-up
- Two hours before imaging
- Study design
- Randomized double-blind placebo-controlled fMRI study
- Funding
- National Institutes of Health and related public grants
Neural target engagement did not produce a same-day subjective or behavioral benefit.
Read the original sourceOverlapping healthy imaging cohort · not a replication
Resting-state fMRI analysis
Sripada et al. Frontiers in Human Neuroscience. 2014. PMID 24302681.
Resting-state connectivity changed after acute pregnenolone.
- Participants / model
- Healthy men from the same or overlapping acute imaging program
- Treatment
- Single oral pregnenolone exposure versus placebo
- Follow-up
- Acute
- Study design
- Resting-state fMRI analysis
- Funding
- Public research grants
This adds imaging analysis from an overlapping cohort, not an independent clinical replication.
Read the original sourceSeven-person PK subset · no half-life estimate
Exploratory clinical PK analysis
PMID 39598281; PMCID PMC11595496.
Circulating pregnenolone was higher after two weeks of 300 or 500 mg/day, but absorption and elimination half-life could not be estimated.
- Participants / model
- Seven participants from a cocaine-use-disorder trial; two or three per group
- Treatment
- Oral pregnenolone 300 or 500 mg/day versus placebo
- Follow-up
- Two weeks
- Study design
- Nested exploratory PK analysis
- Funding
- Public research grants
Extremely small groups and sparse sampling prevent a general PK estimate.
Read the original sourceCell mechanism · pregnenolone sulfate, not oral pregnenolone
Preclinical molecular and cellular study
Ming-Kuei Jang, Dale F. Mierke, Shelley J. Russek, and David H. Farb. Proceedings of the National Academy of Sciences of the United States of America. 2004. PMID 15150412.
Molecular and heterologous-expression experiments identified an NR2B-associated modulatory domain involved in pregnenolone sulfate effects on NMDA-receptor proton sensitivity.
- Participants / model
- Recombinant and cellular receptor systems
- Treatment
- Pregnenolone sulfate and receptor mutagenesis
- Follow-up
- Preclinical
- Study design
- Molecular pharmacology and cell study
Pregnenolone sulfate is a charged metabolite, not oral pregnenolone. Receptor effects in an expression system do not establish cognitive or mood outcomes in humans.
Read the original sourceDoes a low level, TRT use or precursor status justify supplementation?
No controlled trial selected people for a validated pregnenolone deficiency, enrolled hypogonadal men or tested pregnenolone as a TRT adjunct. Endogenous values vary with age, sex, menstrual state, timing and assay. In the schizophrenia pilot, pregnenolone raised several neurosteroids but did not raise total or free testosterone, cortisol, DHEA, estradiol or androstenedione. A product-independent half-life and Tmax remain unknown.
| Question | Evidence |
|---|---|
| Does oral exposure convert to metabolites? | Yes, in tiny PK and clinical subsets. |
| Does it predictably raise testosterone? | No. Total and free testosterone were null in the trial with a detailed steroid panel. |
| Do low baseline values identify responders? | No validated threshold or deficiency-selected efficacy trial was found. |
| Is there a universal half-life or best timing? | No. Endogenous baseline, formulation, conversion, analyte and assay change the curve. |
| Does it improve healthy performance or longevity? | Historical workplace reports were mixed and method-limited. No modern strength, endurance, body-composition, anti-aging or lifespan trial was found. |
Two-man oral conversion study · exploratory PK
Exploratory human exposure study
Freeman et al. Proceedings of the National Academy of Sciences. 2000. PMCID PMC23857.
Parent pregnenolone, pregnenolone sulfate and several downstream steroids rose during 24-hour sampling after one exposure.
- Participants / model
- Two healthy men aged 45 and 46
- Treatment
- Single oral pregnenolone 175 mg
- Follow-up
- 24 hours
- Study design
- Uncontrolled exploratory serial-sampling study
Two participants and sparse sampling cannot define population PK, a universal half-life or a clinical target.
Read the original source233-person reference study · no deficiency threshold
Cross-sectional hormone reference study
PMID 10369116; DOI 10.1515/CCLM.1999.072.
Endogenous pregnenolone varied nonlinearly with age, sex and menstrual state.
- Participants / model
- 233 healthy people aged 2 to 66
- Treatment
- No intervention
- Follow-up
- Cross-sectional
- Study design
- Hormone reference study
Observed population variation does not define a deficiency syndrome or show that supplementation improves outcomes.
Read the original source21-person pilot · negative-symptom signal, cognition null
Randomized double-blind placebo-controlled pilot trial
Christine E. Marx, Richard S. E. Keefe, Robert W. Buchanan, et al. Neuropsychopharmacology. 2009;34(8):1885 to 1903. PMID 19339966.
Twenty-one were randomized; 18 completed at least four weeks and 17 completed eight. SANS change was 10.38 versus 2.33 points (p=0.048), while BACS and MCCB cognitive composites were not different. CGI-I favored pregnenolone; CGI-S, PANSS, and quality of life were null.
- Participants / model
- 21 adults with schizophrenia or schizoaffective disorder on stable second-generation antipsychotics; one woman
- Treatment
- Adjunctive oral pregnenolone versus placebo after a two-week placebo lead-in
- Follow-up
- 8 randomized weeks
- Study design
- Single-site randomized double-blind placebo-controlled pilot
- Funding
- US Department of Veterans Affairs, NIH, and National Alliance for Research on Schizophrenia and Affective Disorders grants
Tiny single-VA pilot with one woman, mixed concomitant antipsychotics, LOCF, multiple exploratory tests, and uncorrected subscales. Authors disclosed neurosteroid patent applications and cognitive-test royalties.
Read the original sourceSeven-person PK subset · no half-life estimate
Exploratory clinical PK analysis
PMID 39598281; PMCID PMC11595496.
Circulating pregnenolone was higher after two weeks of 300 or 500 mg/day, but absorption and elimination half-life could not be estimated.
- Participants / model
- Seven participants from a cocaine-use-disorder trial; two or three per group
- Treatment
- Oral pregnenolone 300 or 500 mg/day versus placebo
- Follow-up
- Two weeks
- Study design
- Nested exploratory PK analysis
- Funding
- Public research grants
Extremely small groups and sparse sampling prevent a general PK estimate.
Read the original source1945 workplace reports · mixed and method-limited
Historical human performance reports
Psychosomatic Medicine. 1945. PMID 21005001 and PMID 21005002.
Some piece-work factory groups reported higher output, while fixed-wage output, waste and a five-person civilian replication were null.
- Participants / model
- Industrial workers, army pilots and a five-person civilian sample
- Treatment
- Study-specific oral pregnenolone exposures
- Follow-up
- Historical workplace and acute experiments
- Study design
- Historical controlled and observational reports
Wartime allocation, blinding, reporting and workplace conditions do not meet modern performance-trial standards. Work output is not strength, endurance or longevity.
Read the original sourceWhat do the trials say about safety?
Several small randomized studies were reasonably tolerated over weeks, but they cannot estimate uncommon or long-latency endocrine, reproductive, cardiovascular, psychiatric or hormone-sensitive outcomes. The PTSD record reported no serious adverse events; the cocaine-use-disorder study recorded one serious dizziness event in the 300 mg arm. Product equivalence and formal interaction data are limited.
| Record | Observed events | What remains unknown |
|---|---|---|
| PTSD, 97 participants | Any adverse event in 35/52 pregnenolone and 31/43 placebo; no serious events | Long-term and rare outcomes |
| Cocaine-use disorder, 55 participants | Nonserious events 12/20, 13/17 and 11/18 across 300 mg, 500 mg and placebo; one serious dizziness event at 300 mg | Small patient sample and uncertain generalizability |
| Back pain and psychiatric trials | Short-term tolerability broadly similar enough to continue study | Pregnancy, chronic exposure, hormone-sensitive disease and complex interactions |
97-veteran PTSD trial · CAPS-5 null
Randomized placebo-controlled trial with posted results
ClinicalTrials.gov. NCT03799562. Pregnenolone for PTSD.
CAPS-5 favored pregnenolone by -1.24 points, 95% CI -5.89 to 3.41, p=0.596. Depression, pain and pain interference were also null.
- Participants / model
- 97 veterans with PTSD
- Treatment
- Oral pregnenolone escalated to 250 mg twice daily versus placebo
- Follow-up
- Eight weeks
- Study design
- Randomized placebo-controlled trial
- Funding
- U.S. Department of Veterans Affairs
The primary PTSD outcome and several related clinical outcomes were null.
Read the original source55-person CUD pilot · choice changed, use days null
Randomized placebo-controlled pilot trial
PMID 40570771; NCT03953612.
Hypothetical cocaine-dollar choice was lower at 300 and 500 mg/day, but self-reported cocaine-use days did not differ significantly.
- Participants / model
- 55 adults with cocaine use disorder
- Treatment
- Oral pregnenolone 300 or 500 mg/day versus placebo
- Follow-up
- Eight weeks
- Study design
- Randomized placebo-controlled pilot
- Funding
- National Institutes of Health
Patient-specific experimental choice signal without a clinical use-days effect. One serious dizziness event occurred in the 300 mg arm.
Read the original sourceVeteran pain trial · small self-reported effect
Randomized double-blind placebo-controlled clinical trial
Jennifer C. Naylor, Jason D. Kilts, Lawrence J. Shampine, et al. JAMA Network Open. 2020. PMID 32119096. DOI 10.1001/jamanetworkopen.2020.0287.
One hundred were randomized; six were removed for placebo-lead-in noncompliance, leaving 94 in baseline analyses. Adjusted daily pain favored pregnenolone by 0.56/10 (p=0.02); at least 20% improvement occurred in 51.2% versus 28.6% (OR 2.62, 95% CI 1.06 to 6.50). Two of seven interference domains improved.
- Participants / model
- 100 Iraq- and Afghanistan-era veterans randomized; 94 after lead-in noncompliance; 89.4% male
- Treatment
- Adjunctive oral pregnenolone versus placebo
- Follow-up
- 1-week placebo lead-in plus 4-week randomized treatment
- Study design
- Randomized double-blind placebo-controlled single-center trial
The abstract reports 94 included while also giving randomized arms totaling 100; the full CONSORT flow resolves this as six lead-in noncompliance removals. Single-center, short, mostly male, with baseline pain imbalance and self-reported outcomes.
Read the original source80 bipolar-depression participants · endpoint discordance
Randomized double-blind placebo-controlled adjunctive trial
E. Sherwood Brown, John Park, Christine E. Marx, et al. Neuropsychopharmacology. 2014. PMID 24917198.
Among 80 randomized and 73 with postbaseline data, HRSD treatment-by-week was p=0.025 but the group main effect and HRSD remission were null. IDS-SR total was null; IDS-SR remission was 61% versus 37% (p=0.046). Anxiety and mania measures did not differ.
- Participants / model
- 80 adults with bipolar disorder in a depressed mood state; 73 with postbaseline data
- Treatment
- Adjunctive oral pregnenolone versus placebo
- Follow-up
- 12 weeks
- Study design
- Randomized double-blind placebo-controlled add-on trial
- Funding
- Stanley Medical Research Institute
Small adjunctive trial with sex and baseline-depression imbalance, different completion proportions, and discordant clinician and self-report outcomes. One author disclosed a pending neurosteroid-use patent application.
Read the original sourceFDA · supplements are not preapproved like drugs
FDA consumer regulatory guidance
U.S. Food and Drug Administration. FDA 101: Dietary Supplements.
FDA explains that dietary supplements are regulated differently from prescription and over-the-counter drugs and are not FDA approved for safety and effectiveness before marketing.
- Participants / model
- US dietary-supplement marketplace
- Treatment
- Regulatory framework, not a pregnenolone intervention
- Follow-up
- Current web record
- Study design
- FDA regulatory guidance
This general supplement framework does not establish that every marketed pregnenolone product is lawful, equivalent, pure, or clinically effective.
Read the original sourceWhat do recent, Chinese and Russian records add?
Recent studies concern specific patient groups. The 2025 cocaine-use report found lower hypothetical cocaine-dollar choice but no significant change in cocaine-use days; AUD heart-rate-variability and 2026 pain-cue reports are laboratory substudies of one program. Indexed Chinese and Russian records add reviews, biomarkers, and studies of other steroids; none reports a controlled local intervention of oral parent pregnenolone that changes the conclusion.
| Record | Finding | Boundary |
|---|---|---|
| Cocaine-use disorder, 2025 | Hypothetical cocaine-dollar choice lower at both doses; cocaine-use days null | Small pilot patient study |
| AUD HRV, 2025 | Treatment-by-imagery physiological interactions | Same program; no direct relapse or anxiety outcome |
| AUD pain, online 2026 | Dose-inconsistent within-arm cue findings | No active-vs-placebo analgesic effect |
| ASD placebo response, 2025 | Irritability fell 30.2% during placebo lead-in | Shows expectancy/study-contact sensitivity, not active efficacy |
| Ongoing AUD phase 2 | 150 planned; no results posted | Cannot contribute efficacy yet |
55-person CUD pilot · choice changed, use days null
Randomized placebo-controlled pilot trial
PMID 40570771; NCT03953612.
Hypothetical cocaine-dollar choice was lower at 300 and 500 mg/day, but self-reported cocaine-use days did not differ significantly.
- Participants / model
- 55 adults with cocaine use disorder
- Treatment
- Oral pregnenolone 300 or 500 mg/day versus placebo
- Follow-up
- Eight weeks
- Study design
- Randomized placebo-controlled pilot
- Funding
- National Institutes of Health
Patient-specific experimental choice signal without a clinical use-days effect. One serious dizziness event occurred in the 300 mg arm.
Read the original sourceAUD HRV substudy · physiological endpoint
Randomized-trial laboratory substudy
PMID 39779217; PMCID PMC11928267.
Treatment-by-imagery-condition interactions were reported for high-frequency HRV and LF/HF.
- Participants / model
- 55 participants from an alcohol-use-disorder trial
- Treatment
- Oral pregnenolone 300 or 500 mg/day versus placebo
- Follow-up
- Laboratory imagery challenge during treatment
- Study design
- Same-program randomized-trial substudy
- Funding
- National Institutes of Health
A physiological challenge endpoint does not establish less anxiety, relapse or disease burden.
Read the original source60-person AUD substudy · dose-inconsistent within-arm findings
Randomized-trial laboratory substudy
PMID 42258258; DOI 10.1037/pha0000862.
The 300 mg arm lacked within-arm pain increases after stress and alcohol cues; the 500 mg arm did not reproduce that pattern.
- Participants / model
- 60 participants from an alcohol-use-disorder trial
- Treatment
- Oral pregnenolone 300 or 500 mg/day versus placebo
- Follow-up
- Week-two laboratory challenge
- Study design
- Same-program exploratory substudy
- Funding
- National Institutes of Health
Within-arm cue contrasts and dose inconsistency do not establish analgesia versus placebo.
Read the original sourceASD lead-in analysis · symptoms fell before active treatment
Placebo lead-in analysis
PMID 40679745.
ABC irritability fell 30.2% during placebo lead-in before randomized pregnenolone exposure.
- Participants / model
- 25 autism-spectrum-disorder trial participants
- Treatment
- Placebo lead-in; no active pregnenolone comparison
- Follow-up
- Lead-in period
- Study design
- Placebo-response analysis
This informs interpretation of symptom change; it is not pregnenolone efficacy evidence.
Read the original sourceOngoing 150-person AUD trial · no results
Clinical trial registry
ClinicalTrials.gov. NCT05781009.
The recruiting phase 2 record plans 150 participants; no results are posted.
- Participants / model
- Adults with alcohol use disorder; planned n=150
- Treatment
- Oral pregnenolone 300 mg/day in divided doses versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized phase 2 trial
A recruiting no-results record cannot contribute efficacy or safety outcomes.
Read the original sourceStudies and sources
FDA · supplements are not preapproved like drugs
FDA consumer regulatory guidance
U.S. Food and Drug Administration. FDA 101: Dietary Supplements.
FDA explains that dietary supplements are regulated differently from prescription and over-the-counter drugs and are not FDA approved for safety and effectiveness before marketing.
- Participants / model
- US dietary-supplement marketplace
- Treatment
- Regulatory framework, not a pregnenolone intervention
- Follow-up
- Current web record
- Study design
- FDA regulatory guidance
This general supplement framework does not establish that every marketed pregnenolone product is lawful, equivalent, pure, or clinically effective.
Read the original sourcePregnenolone in US approval records
US drug approval status
openFDA Drugs@FDA records for pregnenolone.
No Drugs@FDA record matches pregnenolone as an exact active-ingredient name.
That exact-name result does not rule out differently named, historical, compounded, or non-drug products.
Read the original source80 bipolar-depression participants · endpoint discordance
Randomized double-blind placebo-controlled adjunctive trial
E. Sherwood Brown, John Park, Christine E. Marx, et al. Neuropsychopharmacology. 2014. PMID 24917198.
Among 80 randomized and 73 with postbaseline data, HRSD treatment-by-week was p=0.025 but the group main effect and HRSD remission were null. IDS-SR total was null; IDS-SR remission was 61% versus 37% (p=0.046). Anxiety and mania measures did not differ.
- Participants / model
- 80 adults with bipolar disorder in a depressed mood state; 73 with postbaseline data
- Treatment
- Adjunctive oral pregnenolone versus placebo
- Follow-up
- 12 weeks
- Study design
- Randomized double-blind placebo-controlled add-on trial
- Funding
- Stanley Medical Research Institute
Small adjunctive trial with sex and baseline-depression imbalance, different completion proportions, and discordant clinician and self-report outcomes. One author disclosed a pending neurosteroid-use patent application.
Read the original source120 schizophrenia participants · cognition primary null
Randomized placebo-controlled adjunctive trial
Christine E. Marx, Jimmy Lee, Mythily Subramaniam, et al. Psychopharmacology. 2014. PMID 25030803.
After 120 participants were randomized, modified intention-to-treat groups were 56 and 55. The MCCB cognitive composite did not improve versus placebo. UPSA-B functional capacity improved (p=0.03), driven in part by communication (p<0.001); negative-symptom scores were low at baseline and did not improve.
- Participants / model
- 120 adults with schizophrenia randomized; modified intention-to-treat n=111
- Treatment
- Adjunctive oral pregnenolone versus placebo
- Follow-up
- 8 weeks after placebo lead-in
- Study design
- Randomized placebo-controlled proof-of-concept trial
The cognitive composite and negative symptoms were null. The functional result was secondary and short-term. Only the primary abstract and indexed record were publicly readable, so claims remain limited to those materials.
Read the original sourceVeteran pain trial · small self-reported effect
Randomized double-blind placebo-controlled clinical trial
Jennifer C. Naylor, Jason D. Kilts, Lawrence J. Shampine, et al. JAMA Network Open. 2020. PMID 32119096. DOI 10.1001/jamanetworkopen.2020.0287.
One hundred were randomized; six were removed for placebo-lead-in noncompliance, leaving 94 in baseline analyses. Adjusted daily pain favored pregnenolone by 0.56/10 (p=0.02); at least 20% improvement occurred in 51.2% versus 28.6% (OR 2.62, 95% CI 1.06 to 6.50). Two of seven interference domains improved.
- Participants / model
- 100 Iraq- and Afghanistan-era veterans randomized; 94 after lead-in noncompliance; 89.4% male
- Treatment
- Adjunctive oral pregnenolone versus placebo
- Follow-up
- 1-week placebo lead-in plus 4-week randomized treatment
- Study design
- Randomized double-blind placebo-controlled single-center trial
The abstract reports 94 included while also giving randomized arms totaling 100; the full CONSORT flow resolves this as six lead-in noncompliance removals. Single-center, short, mostly male, with baseline pain imbalance and self-reported outcomes.
Read the original sourceCell mechanism · pregnenolone sulfate, not oral pregnenolone
Preclinical molecular and cellular study
Ming-Kuei Jang, Dale F. Mierke, Shelley J. Russek, and David H. Farb. Proceedings of the National Academy of Sciences of the United States of America. 2004. PMID 15150412.
Molecular and heterologous-expression experiments identified an NR2B-associated modulatory domain involved in pregnenolone sulfate effects on NMDA-receptor proton sensitivity.
- Participants / model
- Recombinant and cellular receptor systems
- Treatment
- Pregnenolone sulfate and receptor mutagenesis
- Follow-up
- Preclinical
- Study design
- Molecular pharmacology and cell study
Pregnenolone sulfate is a charged metabolite, not oral pregnenolone. Receptor effects in an expression system do not establish cognitive or mood outcomes in humans.
Read the original sourcePubChem CID 8955 · pregnenolone identity
Government substance database
National Library of Medicine. PubChem Compound Summary for CID 8955, Pregnenolone.
Identifies pregnenolone as C21H32O2, molecular weight 316.5 g/mol, CID 8955.
- Participants / model
- Not applicable
- Treatment
- Not applicable
- Follow-up
- Living database record
- Study design
- Curated chemical identity record
Pregnenolone, pregnenolone sulfate, allopregnanolone, and downstream sex or adrenal steroids are distinct molecules.
Read the original source21-person pilot · negative-symptom signal, cognition null
Randomized double-blind placebo-controlled pilot trial
Christine E. Marx, Richard S. E. Keefe, Robert W. Buchanan, et al. Neuropsychopharmacology. 2009;34(8):1885 to 1903. PMID 19339966.
Twenty-one were randomized; 18 completed at least four weeks and 17 completed eight. SANS change was 10.38 versus 2.33 points (p=0.048), while BACS and MCCB cognitive composites were not different. CGI-I favored pregnenolone; CGI-S, PANSS, and quality of life were null.
- Participants / model
- 21 adults with schizophrenia or schizoaffective disorder on stable second-generation antipsychotics; one woman
- Treatment
- Adjunctive oral pregnenolone versus placebo after a two-week placebo lead-in
- Follow-up
- 8 randomized weeks
- Study design
- Single-site randomized double-blind placebo-controlled pilot
- Funding
- US Department of Veterans Affairs, NIH, and National Alliance for Research on Schizophrenia and Affective Disorders grants
Tiny single-VA pilot with one woman, mixed concomitant antipsychotics, LOCF, multiple exploratory tests, and uncorrected subscales. Authors disclosed neurosteroid patent applications and cognitive-test royalties.
Read the original source70-person dual-diagnosis trial · cognition null
Randomized double-blind placebo-controlled trial
E. Sherwood Brown et al. Human Psychopharmacology. 2010. PMID 20493557.
Among 70 enrolled and 60 analyzed, cognition was null. Depression and mania only trended in the main analysis; a depression result appeared in a post hoc completer analysis.
- Participants / model
- Adults with mood and substance-use disorders; 70 enrolled, 60 analyzed, 37 completed
- Treatment
- Oral pregnenolone titrated to 100 mg/day versus placebo
- Follow-up
- Eight weeks
- Study design
- Randomized double-blind placebo-controlled trial
Post hoc completer findings do not establish a general antidepressant effect.
Read the original source73-person depression registry · primary result null
Randomized sequential-parallel trial with posted results
ClinicalTrials.gov. NCT03505905. Pregnenolone for peri- and postmenopausal depression.
The combined posted MADRS treatment difference was -2.46 points, p=0.29. Anxiety, sleep, quality of life, menopausal symptoms, memory and executive outcomes were descriptive rather than confirmatory.
- Participants / model
- 73 participants with peri- or postmenopausal depression
- Treatment
- Oral pregnenolone up to 500 mg/day versus placebo
- Follow-up
- Sequential study periods
- Study design
- Randomized sequential-parallel clinical trial
The posted primary depression comparison was null. Descriptive secondary values are not treatment effects.
Read the original source97-veteran PTSD trial · CAPS-5 null
Randomized placebo-controlled trial with posted results
ClinicalTrials.gov. NCT03799562. Pregnenolone for PTSD.
CAPS-5 favored pregnenolone by -1.24 points, 95% CI -5.89 to 3.41, p=0.596. Depression, pain and pain interference were also null.
- Participants / model
- 97 veterans with PTSD
- Treatment
- Oral pregnenolone escalated to 250 mg twice daily versus placebo
- Follow-up
- Eight weeks
- Study design
- Randomized placebo-controlled trial
- Funding
- U.S. Department of Veterans Affairs
The primary PTSD outcome and several related clinical outcomes were null.
Read the original source17-completer healthy crossover · mood and memory null
Placebo-controlled crossover study
Meieran et al. Psychoneuroendocrinology. 2004. PMID 14749094.
Four weeks of 15 then 30 mg/day did not improve mood, memory, subjective sleep or wellbeing. In an 11-person diazepam substudy, sedation differed while amnesia was nonsignificant and anxiety unchanged.
- Participants / model
- Healthy adults; 17 completers; diazepam substudy n=11
- Treatment
- Oral pregnenolone versus placebo
- Follow-up
- Four weeks
- Study design
- Placebo-controlled crossover program
Small study with a tiny challenge substudy; direct healthy efficacy outcomes were null.
Read the original sourceAcute sleep architecture study
Human sleep experiment
Steiger et al. Neuropsychobiology. 1993. PMID 8395958.
The abstract reports increased slow-wave sleep and lower sigma power without nocturnal cortisol or growth-hormone changes.
- Participants / model
- Male volunteers; sample size not reported in the abstract
- Treatment
- Single pregnenolone exposure; dose and route not reported in the abstract
- Follow-up
- One night
- Study design
- Human sleep-architecture experiment
The abstract does not report sample size, dose, route, allocation, timing, or detailed methods. It does not establish insomnia or durable sleep benefit.
Read the original source31-man acute trial · imaging changed, anxiety null
Randomized double-blind placebo-controlled mechanistic trial
Sripada et al. Neuropsychopharmacology. 2013. PMID 23348009.
A single 400 mg exposure raised pregnenolone and allopregnanolone and changed amygdala, insula and prefrontal connectivity. Anxiety, sedation, general neurocognition, reaction time and accuracy did not differ.
- Participants / model
- 31 healthy men; 16 pregnenolone and 15 placebo
- Treatment
- Single oral pregnenolone 400 mg versus placebo
- Follow-up
- Two hours before imaging
- Study design
- Randomized double-blind placebo-controlled fMRI study
- Funding
- National Institutes of Health and related public grants
Neural target engagement did not produce a same-day subjective or behavioral benefit.
Read the original sourceOverlapping healthy imaging cohort · not a replication
Resting-state fMRI analysis
Sripada et al. Frontiers in Human Neuroscience. 2014. PMID 24302681.
Resting-state connectivity changed after acute pregnenolone.
- Participants / model
- Healthy men from the same or overlapping acute imaging program
- Treatment
- Single oral pregnenolone exposure versus placebo
- Follow-up
- Acute
- Study design
- Resting-state fMRI analysis
- Funding
- Public research grants
This adds imaging analysis from an overlapping cohort, not an independent clinical replication.
Read the original source58-person four-arm trial · nonmonotonic cognitive signals
Randomized double-blind placebo-controlled trial
Ritsner et al. Journal of Clinical Psychiatry. 2010. PMID 20584515.
The 30 mg/day pregnenolone arm had selected attention and working-memory findings that the 200 mg/day arm did not reproduce; negative symptoms and akathisia were null.
- Participants / model
- 58 adults with schizophrenia across four treatment arms
- Treatment
- Oral pregnenolone at two doses, DHEA or placebo
- Follow-up
- Eight weeks
- Study design
- Randomized double-blind placebo-controlled four-arm trial
Secondary, nonmonotonic cognitive findings do not establish a dose-responsive general effect.
Read the original source60-person recent-onset cohort · selected outcomes
Randomized placebo-controlled trial and same-cohort analyses
Marx et al. 2014. PMID 24496044 and PMID 24548129.
Selected negative-symptom and visual-attention findings were reported, including a between-arm visual-attention effect of d=0.42; several other highlighted cognitive changes were within-arm tests.
- Participants / model
- 60 adults with recent-onset schizophrenia or schizoaffective disorder
- Treatment
- Adjunctive oral pregnenolone versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized placebo-controlled study with two same-cohort publications
- Funding
- Public research grants
The two publications are one cohort. Within-arm improvements are not placebo-controlled effects.
Read the original sourceTwo-man oral conversion study · exploratory PK
Exploratory human exposure study
Freeman et al. Proceedings of the National Academy of Sciences. 2000. PMCID PMC23857.
Parent pregnenolone, pregnenolone sulfate and several downstream steroids rose during 24-hour sampling after one exposure.
- Participants / model
- Two healthy men aged 45 and 46
- Treatment
- Single oral pregnenolone 175 mg
- Follow-up
- 24 hours
- Study design
- Uncontrolled exploratory serial-sampling study
Two participants and sparse sampling cannot define population PK, a universal half-life or a clinical target.
Read the original sourceSeven-person PK subset · no half-life estimate
Exploratory clinical PK analysis
PMID 39598281; PMCID PMC11595496.
Circulating pregnenolone was higher after two weeks of 300 or 500 mg/day, but absorption and elimination half-life could not be estimated.
- Participants / model
- Seven participants from a cocaine-use-disorder trial; two or three per group
- Treatment
- Oral pregnenolone 300 or 500 mg/day versus placebo
- Follow-up
- Two weeks
- Study design
- Nested exploratory PK analysis
- Funding
- Public research grants
Extremely small groups and sparse sampling prevent a general PK estimate.
Read the original source233-person reference study · no deficiency threshold
Cross-sectional hormone reference study
PMID 10369116; DOI 10.1515/CCLM.1999.072.
Endogenous pregnenolone varied nonlinearly with age, sex and menstrual state.
- Participants / model
- 233 healthy people aged 2 to 66
- Treatment
- No intervention
- Follow-up
- Cross-sectional
- Study design
- Hormone reference study
Observed population variation does not define a deficiency syndrome or show that supplementation improves outcomes.
Read the original source55-person CUD pilot · choice changed, use days null
Randomized placebo-controlled pilot trial
PMID 40570771; NCT03953612.
Hypothetical cocaine-dollar choice was lower at 300 and 500 mg/day, but self-reported cocaine-use days did not differ significantly.
- Participants / model
- 55 adults with cocaine use disorder
- Treatment
- Oral pregnenolone 300 or 500 mg/day versus placebo
- Follow-up
- Eight weeks
- Study design
- Randomized placebo-controlled pilot
- Funding
- National Institutes of Health
Patient-specific experimental choice signal without a clinical use-days effect. One serious dizziness event occurred in the 300 mg arm.
Read the original sourceAUD HRV substudy · physiological endpoint
Randomized-trial laboratory substudy
PMID 39779217; PMCID PMC11928267.
Treatment-by-imagery-condition interactions were reported for high-frequency HRV and LF/HF.
- Participants / model
- 55 participants from an alcohol-use-disorder trial
- Treatment
- Oral pregnenolone 300 or 500 mg/day versus placebo
- Follow-up
- Laboratory imagery challenge during treatment
- Study design
- Same-program randomized-trial substudy
- Funding
- National Institutes of Health
A physiological challenge endpoint does not establish less anxiety, relapse or disease burden.
Read the original source60-person AUD substudy · dose-inconsistent within-arm findings
Randomized-trial laboratory substudy
PMID 42258258; DOI 10.1037/pha0000862.
The 300 mg arm lacked within-arm pain increases after stress and alcohol cues; the 500 mg arm did not reproduce that pattern.
- Participants / model
- 60 participants from an alcohol-use-disorder trial
- Treatment
- Oral pregnenolone 300 or 500 mg/day versus placebo
- Follow-up
- Week-two laboratory challenge
- Study design
- Same-program exploratory substudy
- Funding
- National Institutes of Health
Within-arm cue contrasts and dose inconsistency do not establish analgesia versus placebo.
Read the original sourceASD lead-in analysis · symptoms fell before active treatment
Placebo lead-in analysis
PMID 40679745.
ABC irritability fell 30.2% during placebo lead-in before randomized pregnenolone exposure.
- Participants / model
- 25 autism-spectrum-disorder trial participants
- Treatment
- Placebo lead-in; no active pregnenolone comparison
- Follow-up
- Lead-in period
- Study design
- Placebo-response analysis
This informs interpretation of symptom change; it is not pregnenolone efficacy evidence.
Read the original sourceOngoing 150-person AUD trial · no results
Clinical trial registry
ClinicalTrials.gov. NCT05781009.
The recruiting phase 2 record plans 150 participants; no results are posted.
- Participants / model
- Adults with alcohol use disorder; planned n=150
- Treatment
- Oral pregnenolone 300 mg/day in divided doses versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized phase 2 trial
A recruiting no-results record cannot contribute efficacy or safety outcomes.
Read the original source1945 workplace reports · mixed and method-limited
Historical human performance reports
Psychosomatic Medicine. 1945. PMID 21005001 and PMID 21005002.
Some piece-work factory groups reported higher output, while fixed-wage output, waste and a five-person civilian replication were null.
- Participants / model
- Industrial workers, army pilots and a five-person civilian sample
- Treatment
- Study-specific oral pregnenolone exposures
- Follow-up
- Historical workplace and acute experiments
- Study design
- Historical controlled and observational reports
Wartime allocation, blinding, reporting and workplace conditions do not meet modern performance-trial standards. Work output is not strength, endurance or longevity.
Read the original sourceWhy is Pregnenolone in C tier?
C reflects oral target engagement, a modest four-week back-pain benefit and selected psychiatric secondary outcomes. Larger or posted studies often missed primary endpoints, and healthy cognition, mood and anxiety results were largely null. Baseline-guided replacement, testosterone optimization, healthy performance, longevity and long-term safety remain unestablished.