Pregnenolone

Q: Does pregnenolone improve memory?

Not in the trials cited here: composite cognitive scores did not improve in two schizophrenia trials, and no trial tested healthy people.

Q: Does pregnenolone help schizophrenia?

Add-on trials were mixed. A 2026 meta-analysis found an initial small pooled benefit (effect size 0.20) but warned that heterogeneity and publication bias weakened results for several of the agents it studied, and a 2017 trial in 82 women found no significant change in total symptom scores.

Q: Does pregnenolone help anxiety or stress?

Only in people with substance use disorders: 500 mg/day reduced stress-induced anxiety in a 30-person cocaine trial, and 300 mg/day did so in a 43-person alcohol trial. No trial tested general anxiety.

Q: Is pregnenolone safe?

It was well tolerated at up to 500 mg/day for 4–12 weeks in supervised trials; long-term safety is unknown.

Q: How much pregnenolone was studied?

Trials used 30 mg/day up to 500 mg/day. In one schizophrenia trial 30 mg/day helped while 200 mg/day did not.

Q: Does pregnenolone interact with medicines?

No interaction studies have been published in the sources we checked. It feeds steroid-hormone production, so effects alongside hormone medicines or DHEA are unknown, and psychiatric trials gave it on top of existing medicines under supervision.

Q: What does pregnenolone do?

It is converted into other neurosteroids. Small add-on trials found some symptom or craving improvements in schizophrenia, bipolar depression, back pain and cocaine or alcohol use disorder; other measures did not change.

Also called 3β-hydroxypregn-5-en-20-one, PREG, neurosteroid precursor.

Best grade C across 10 graded outcomes Other Last checked Oct 21, 2026

The short answer

From 13 sources

Pregnenolone is a neurosteroid that the body converts into other neurosteroids. Small add-on trials of 30–500 mg/day in schizophrenia, bipolar depression, back pain and cocaine or alcohol use disorder were mixed: some symptom and craving scores improved, while cognition mostly did not. It was well tolerated over 4–12 weeks. No trials cover healthy people, pregnancy or long-term use.

Every graded outcome on this page

10 rows · line = participants

Grade CCognition, functional capacity and negative symptoms in schizophrenia (add-on)Schizophrenian 111
Grade CChronic low back pain in military veterans (add-on)Low back painn 94
Grade CTotal symptom scores in women with schizophrenia (add-on to risperidone)Schizophrenian 82
Grade CDepressive symptoms in bipolar depression (add-on)Bipolar depressionn 73
Grade DNegative symptoms in recent-onset schizophrenia (add-on)Schizophrenian 60
Grade DPositive symptoms, attention and working memory in schizophrenia (add-on)Schizophrenian 58
Grade DProvoked craving and cocaine use in cocaine use disorderCraving and anxietyn 55
Grade DStress- and cue-induced craving and anxiety in alcohol use disorderCraving and anxietyn 43
Grade DStress- and cue-induced craving and anxiety in cocaine use disorderCraving and anxietyn 30
Grade DNegative symptoms and cognition in schizophrenia (add-on)Schizophrenian 18
7 more graded outcomes, in the evidence chapter

Key facts

What it is: A neurosteroid; treatment raises allopregnanolone (acts on GABA-A receptors) and pregnenolone sulfate (modulates NMDA receptors)²
Studied doses: 30 mg/day to 500 mg/day, as add-on therapy for 4–12 weeks^8,3,4,5
Cognition: Two schizophrenia trials found no improvement in composite cognitive scores^1,2
Back pain: In 94 veterans, pain diary scores fell 0.56 points more than placebo (0–10 scale) over 4 weeks⁵
Tolerability: Described as well tolerated in six of the ten trials cited here; the other four abstracts do not comment^1,2,3,4,5,8

What it is

Pregnenolone is a neurosteroid; the body converts it into other neurosteroids such as allopregnanolone.

How it works

Proposed

Pregnenolone is converted into other neurosteroids. In trials, supplementation raised serum pregnenolone, allopregnanolone (a GABA-A receptor enhancer) and pregnenolone sulfate (a positive NMDA receptor modulator), and some symptom changes correlated with these rises. Learning and memory effects come from rodent studies.^2,1,4

Forms

Form

The form on this page
Form	Elemental %	Absorption (human data)	GI tolerance	Studied for
Oral pregnenolone capsules	Varies^4,6Not applicable (whole compound or extract; no elemental fraction)	Supplementation raised serum pregnenolone and produced large changes in other neurosteroid levels that were not seen with placebo.^4,6	Well tolerated at 30–500 mg/day for 4–12 weeks in the cited trials.^8,3,4,5	Add-on trials in schizophrenia, bipolar depression, back pain and cocaine or alcohol use disorder

What the human research says

Human trials only, one row per outcome. The form line shows what each trial actually tested. Grades follow our evidence-grading policy.

Trial map

10 graded outcomes, largest study first

10 graded outcomes: 5 improved, 4 mixed, 1 no effect. The largest, a 2014 randomized trial of 111 people on cognition, functional capacity and negative symptoms in schizophrenia (add-on), found mixed results.

By sizeTable

1Cognition, functional capacity and negative symptoms in schizophrenia (add-on)

Mixed · Grade C · RCT, 111 people, 2014

Adults with schizophrenia (Singapore)

Dose, result and source

Every graded outcome on this page, largest study first
Outcome	Found	People	Study	Who was studied
Cognition, functional capacity and negative symptoms in schizophrenia (add-on)	Mixed	111	Grade C · RCT, 2014	Adults with schizophrenia (Singapore)
Chronic low back pain in military veterans (add-on)	Improved	94	Grade C · RCT, 2020	Iraq- and Afghanistan-era US veterans aged 18–65 with chronic low back pain
Total symptom scores in women with schizophrenia (add-on to risperidone)	No effect	82	Grade C · RCT, 2017	Female inpatients with chronic schizophrenia starting risperidone (Iran)
Depressive symptoms in bipolar depression (add-on)	Mixed	73	Grade C · RCT, 2014	Adults with bipolar disorder in a depressed phase
Negative symptoms in recent-onset schizophrenia (add-on)	Improved	60	Grade D · RCT, 2014	Out- and inpatients with recent-onset schizophrenia or schizoaffective disorder and suboptimal antipsychotic response
Positive symptoms, attention and working memory in schizophrenia (add-on)	Mixed	58	Grade D · RCT, 2010	Adults with chronic schizophrenia or schizoaffective disorder on antipsychotics (two centres)
Provoked craving and cocaine use in cocaine use disorder	Improved	55	Grade D · Pilot RCT, 2025	Treatment-seeking men and women with cocaine use disorder
Stress- and cue-induced craving and anxiety in alcohol use disorder	Improved	43	Grade D · RCT, 2023	Treatment-seeking adults with alcohol use disorder
Stress- and cue-induced craving and anxiety in cocaine use disorder	Improved	30	Grade D · RCT, 2022	Treatment-seeking adults with cocaine use disorder
Negative symptoms and cognition in schizophrenia (add-on)	Mixed	18	Grade D · Pilot RCT, 2009	Adults with schizophrenia or schizoaffective disorder on stable second-generation antipsychotics

Every graded row

10 rows

Form tested

Showing 10 of 10 outcomes. Human trials only.

Grade CCognition, functional capacity and negative symptoms in schizophrenia (add-on)SchizophreniaMixedRCT
n 111 · 2014

Mixed No change in composite cognitive scores vs placebo; functional capacity (UPSA-B) improved more with pregnenolone (p=0.03). Negative symptoms were low at baseline and did not improve further.

Design: RCT, n = 111, 2014
Population: Adults with schizophrenia (Singapore)
Form: Pregnenolone
Dose: Dose not stated in the abstract
Duration: 8 weeks
Source: Reference 2 · PubMed 25030803 (opens PubMed)

Grade CChronic low back pain in military veterans (add-on)Low back pain−0.56 points (0–10 scale)RCT
n 94 · 2020

Improved Pain diary scores improved more than with placebo (least-squares mean change −0.56 points; P=.02), as did pain interference with work and activity.

Design: RCT, n = 94, 2020
Population: Iraq- and Afghanistan-era US veterans aged 18–65 with chronic low back pain
Form: Pregnenolone
Dose: 100 mg/day (1 week), 300 mg/day (1 week), then 500 mg/day (2 weeks)
Duration: 4 weeks
Source: Reference 5 · PubMed 32119096 (opens PubMed)

Grade CTotal symptom scores in women with schizophrenia (add-on to risperidone)SchizophreniaNo effectRCT
n 82 · 2017

No effect The primary outcome, change in PANSS total score, did not differ from placebo (mean difference −9.41, 95% CI −20.24 to 1.41; p = 0.087). Negative and general symptom differences did not survive correction for multiple testing.

Design: RCT, n = 82, 2017
Population: Female inpatients with chronic schizophrenia starting risperidone (Iran)
Form: Pregnenolone
Dose: 50 mg/day
Duration: 8 weeks
Source: Reference 9 · PubMed 28688338 (opens PubMed)

Grade CDepressive symptoms in bipolar depression (add-on)Bipolar depressionMixedRCT
n 73 · 2014

Mixed The clinician-rated depression scale (HRSD) improved more than with placebo, but the self-rated scale did not; remission was higher (61% vs 37%) on the self-rated scale only.

Design: RCT, n = 73, 2014
Population: Adults with bipolar disorder in a depressed phase
Form: Pregnenolone
Dose: Titrated to 500 mg/day
Duration: 12 weeks
Source: Reference 4 · PubMed 24917198 (opens PubMed)

Grade DNegative symptoms in recent-onset schizophrenia (add-on)SchizophreniaImprovedRCT
n 60 · 2014

Improved Negative symptom scores fell more than with placebo (effect size d=0.79); other symptoms, functioning and side effects did not differ.

Design: RCT, n = 60, 2014
Population: Out- and inpatients with recent-onset schizophrenia or schizoaffective disorder and suboptimal antipsychotic response
Form: Pregnenolone
Dose: 50 mg/day
Duration: 8 weeks
Source: Reference 3 · PubMed 24548129 (opens PubMed)

Grade DPositive symptoms, attention and working memory in schizophrenia (add-on)SchizophreniaMixedRCT
n 58 · 2010

Mixed At 30 mg/day, positive symptoms and extrapyramidal side effects fell and attention and working memory improved more than with placebo; 200 mg/day did not differ from placebo. Negative symptoms did not improve with any treatment.

Design: RCT, n = 58, 2010
Population: Adults with chronic schizophrenia or schizoaffective disorder on antipsychotics (two centres)
Form: Pregnenolone
Dose: 30 mg/day or 200 mg/day (a third arm took DHEA 400 mg/day)
Duration: 8 weeks
Source: Reference 8 · PubMed 20584515 (opens PubMed)

Grade DProvoked craving and cocaine use in cocaine use disorderCraving and anxietyImprovedPilot RCT
n 55 · 2025

Improved Stress- and cue-induced craving rose with placebo but not with pregnenolone (p < .001). The 300 mg group used less cocaine than placebo (p = .047) and the 500 mg group; the drop in days of use was not significant (p = .122).

Design: Pilot RCT, n = 55, 2025
Population: Treatment-seeking men and women with cocaine use disorder
Form: Pregnenolone
Dose: 300 or 500 mg/day
Duration: 8 weeks
Source: Reference 11 · PubMed 40570771 (opens PubMed)

Grade DStress- and cue-induced craving and anxiety in alcohol use disorderCraving and anxietyImprovedRCT
n 43 · 2023

Improved Both doses reduced stress- and alcohol cue-induced craving versus placebo; stress-induced anxiety fell only at 300 mg/day. Cortisol/ACTH responses were normalised.

Design: RCT, n = 43, 2023
Population: Treatment-seeking adults with alcohol use disorder
Form: Pregnenolone
Dose: 300 or 500 mg/day
Duration: Laboratory testing in week 2 of an 8-week pilot trial
Source: Reference 10 · PubMed 36445398 (opens PubMed)

Grade DStress- and cue-induced craving and anxiety in cocaine use disorderCraving and anxietyImprovedRCT
n 30 · 2022

Improved Both doses reduced stress- and cue-induced craving; anxiety and stress-induced heart rate and blood pressure fell only at 500 mg/day.

Design: RCT, n = 30, 2022
Population: Treatment-seeking adults with cocaine use disorder
Form: Pregnenolone
Dose: 300 or 500 mg/day
Duration: 8 weeks (lab testing after 2 weeks)
Source: Reference 6 · PubMed 36358943 (opens PubMed)

Grade DNegative symptoms and cognition in schizophrenia (add-on)SchizophreniaMixedPilot RCT
n 18 · 2009

Mixed Negative symptoms (SANS) improved more than with placebo (p=0.048); composite cognitive scores did not differ.

Design: Pilot RCT, n = 18, 2009
Population: Adults with schizophrenia or schizoaffective disorder on stable second-generation antipsychotics
Form: Pregnenolone capsules
Dose: Fixed escalating doses up to 500 mg/day
Duration: 8 weeks
Source: Reference 1 · PubMed 19339966 (opens PubMed)

What the numbers add up to

Each point is worked out from the data and the sources numbered on this page, with the arithmetic shown under it. It adds no new data and is not medical advice.

Mixed results on the main outcome

Four of the ten trials had mixed results, with one measure or dose improving and another not, and a fifth found no change in its primary outcome.^1,2,4,8,9

Small effect on back pain

The back-pain benefit was about half a point on a 0–10 scale over placebo after 4 weeks.⁵

Lower dose was not worse

In the two trials that compared doses head to head, the lower dose did as well or better: 30 mg beat 200 mg in schizophrenia, and 300 mg beat 500 mg on cocaine use.^8,11

Studied doses

Doses used in research, shown against the official limits. They describe the studies, not a recommendation for you.

Studied doses in research, not advice. These are amounts used in research, not personal advice. Your clinician or pharmacist can say what fits you.

Doses studied in human trials

Doses studied in human trials ranged from 30 mg/day for 8 weeks to 500 mg/day for up to 12 weeks, always as add-on therapy in people with psychiatric conditions, back pain or cocaine or alcohol use disorder. In one schizophrenia trial, 30 mg/day helped while 200 mg/day did not. The craving trials’ authors describe 300–500 mg/day as supraphysiologic. These are research doses, not recommendations.^8,3,4,5,6,10

Interactions and safety

Published interactions only: each row cites a source. No row means none was found in our sources, not that a combination is safe.

Interactions

0 agents

None found in our sources.

Check with what you take

Kept on this device only

Add what you take. We list every interaction our evidence profiles cite between Pregnenolone and your picks, and between your picks.

Add a supplement or medicine

Most cited:

Add a supplement or medicine you take to check it against Pregnenolone.

Starting from one medicine? The interaction checker rates how serious each pair is, on a curated list of 19 entries for 11 medicines. This cabinet has no severity rating: it lists every interaction row our supplement pages cite.

Who should be careful

5 groups

Pregnancy and breastfeeding: No cited trial studied these groups, so safety in pregnancy and breastfeeding is unknown; because it feeds steroid-hormone production, effects there cannot be assumed to be neutral (inferred).^{1,2,3,4,5,6,7}
Hormone-sensitive conditions: Pregnenolone synthesis is the first step in making all of the body’s steroid hormones, and trials showed large shifts in downstream neurosteroids; effects on sex hormones were not reported in these abstracts (caution for hormone-sensitive conditions inferred).^7,2,4
People on psychiatric medicines: All psychiatric trials gave pregnenolone on top of existing medicines under supervision; this does not show it is safe to combine without a clinician (inferred).^1,3,4
Medicines and other hormones: No drug-interaction studies have been published, and NIH fact sheets, LiverTox and LactMed have no pregnenolone entry. Because it is the starting point for the body’s steroid hormones, use alongside hormone medicines or DHEA is untested (inferred).⁷
Competitive athletes: In an administration study, oral and skin-applied pregnenolone changed the carbon-isotope ratio of a urinary steroid that doping labs use as a reference; the authors proposed it be considered a masking agent.¹³

How the body handles pregnenolone

2 notes

It is a starting point for other neurosteroids.

Downstream steroids: In bipolar depression, large baseline-to-exit changes in neurosteroid levels were seen with pregnenolone but not placebo.⁴
Blood levels and response: Rises in serum pregnenolone and allopregnanolone predicted better cognitive scores in one pilot, and serum changes correlated with functional gains in women in a larger trial.^1,2

How to read the label

What to check on the Supplement Facts panel.

How to read the label

2 checks

Label dose vs studied dose

Trials used 30 mg/day up to 500 mg/day; the higher doses were reached by escalating over weeks.^8,3,5

Populations studied

Every trial cited here enrolled people with a psychiatric condition, chronic pain or a substance use disorder; none tested memory or mood in healthy people.^{1,2,3,4,5,6,8,9,10,11}

Have the bottle? Photograph its Supplement Facts panel and see each line, pregnenolone included, beside the doses and forms the trials used in Label X-Ray.

Frequently asked questions

Short answers to common questions; the numbers link to the sources below.

Common questions

7 answers

Does pregnenolone improve memory?

Not in the trials cited here: composite cognitive scores did not improve in two schizophrenia trials, and no trial tested healthy people.^1,2

Does pregnenolone help schizophrenia?

Add-on trials were mixed. A 2026 meta-analysis found an initial small pooled benefit (effect size 0.20) but warned that heterogeneity and publication bias weakened results for several of the agents it studied, and a 2017 trial in 82 women found no significant change in total symptom scores.^12,9

Does pregnenolone help anxiety or stress?

Only in people with substance use disorders: 500 mg/day reduced stress-induced anxiety in a 30-person cocaine trial, and 300 mg/day did so in a 43-person alcohol trial. No trial tested general anxiety.^6,10

Is pregnenolone safe?

It was well tolerated at up to 500 mg/day for 4–12 weeks in supervised trials; long-term safety is unknown.^4,5

How much pregnenolone was studied?

Trials used 30 mg/day up to 500 mg/day. In one schizophrenia trial 30 mg/day helped while 200 mg/day did not.^8,3,4,5

Does pregnenolone interact with medicines?

No interaction studies have been published in the sources we checked. It feeds steroid-hormone production, so effects alongside hormone medicines or DHEA are unknown, and psychiatric trials gave it on top of existing medicines under supervision.^7,1,3,4

What does pregnenolone do?

It is converted into other neurosteroids. Small add-on trials found some symptom or craving improvements in schizophrenia, bipolar depression, back pain and cocaine or alcohol use disorder; other measures did not change.^{2,3,4,5,10,11}

Sources

13 sources: trial abstracts, NIH fact sheets and reference databases. Numbers in the text link here.

Sources cited on this page

13 sources

1Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia.Pilot RCT Neuropsychopharmacology, 2009 · PMID 19339966
2Proof-of-concept randomized controlled trial of pregnenolone in schizophrenia.RCT Psychopharmacology (Berl), 2014 · PMID 25030803
3Pregnenolone treatment reduces severity of negative symptoms in recent-onset schizophrenia: an 8-week, double-blind, randomized add-on two-center trial.RCT Psychiatry Clin Neurosci, 2014 · PMID 24548129
4A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression.RCT Neuropsychopharmacology, 2014 · PMID 24917198
5Effect of Pregnenolone vs Placebo on Self-reported Chronic Low Back Pain Among US Military Veterans: A Randomized Clinical Trial.RCT JAMA Netw Open, 2020 · PMID 32119096
6Pregnenolone Reduces Stress-Induced Craving, Anxiety, and Autonomic Arousal in Individuals with Cocaine Use Disorder.RCT Biomolecules, 2022 · PMID 36358943
7Genetic defects in pregnenolone synthesis.Review Pediatr Endocrinol Rev, 2012 · PMID 23330251
8Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial.RCT J Clin Psychiatry, 2010 · PMID 20584515
9Pregnenolone as an adjunct to risperidone for treatment of women with schizophrenia: A randomized double-blind placebo-controlled clinical trial.RCT J Psychiatr Res, 2017 · PMID 28688338
10Pregnenolone effects on provoked alcohol craving, anxiety, HPA axis, and autonomic arousal in individuals with alcohol use disorder.RCT Psychopharmacology (Berl), 2023 · PMID 36445398
11Pregnenolone reduces provoked craving and cocaine use in men and women with cocaine use disorder: A pilot trial.Pilot RCT Drug Alcohol Depend, 2025 · PMID 40570771
12Efficacy and safety of anti-inflammatory drug-assisted treatment of symptoms in patients with schizophrenia: a meta-analysis.Meta-analysis BMC Psychiatry, 2026 · PMID 41559638
13Investigations on changes in ¹³C/¹²C ratios of endogenous urinary steroids after pregnenolone administration.PK study Drug Test Anal, 2011 · PMID 21538944

What changed

Every dated change to this page: what changed, who made it and why.

Change log

4 entries

Dated changes to this page
Date	Change	Who and why
Oct 21, 2026evidence, studied doses, who should be careful, FAQ, label guide, insights	Added four trials (PMIDs 20584515, 28688338, 36445398, 40570771), a 2026 meta-analysis in the FAQ (PMID 41559638) and an anti-doping note (PMID 21538944); studied doses now start at 30 mg/day; tolerability count, summary and insights updated. Interaction check: NIH ODS, NCCIH, LiverTox, LactMed and MedlinePlus have no pregnenolone entry and no published drug-interaction study was found, so the interactions list stays empty with a note under who should be careful. Fact-checked against the sources; corrected: the 2026 meta-analysis answer no longer says bias weakened results for every agent studied (the abstract says several).	Writer: Kymata Health EditorialTrigger: A–Z page audit
Oct 14, 2026all	Independent adversarial review: sourced the steroid-precursor point (pregnenolone synthesis is the first step in all steroid-hormone biosynthesis, PMID 23330251) and strengthened the pregnancy and hormone-sensitive cautions; noted that the cocaine-trial authors call 300–500 mg/day supraphysiologic.	Writer: Kymata Health EditorialTrigger: review
Oct 14, 2026all	Adversarial review pass: every evidence row, key fact, interaction, safety note and FAQ re-read against its PubMed abstract or source page, and every number machine-checked against the cited source text. Retraction, expression-of-concern and withdrawn checks on all PMIDs: none flagged. Fixes: definition limited to sourced facts; tolerability count corrected to five of six abstracts; 2009 trial typed as a pilot RCT.	Writer: Kymata Health EditorialTrigger: review
Oct 14, 2026all	Initial editorial evidence review (first draft). Every PMID checked against NCBI E-utilities esummary (titles and years taken from the record) and the abstract read for each cited row. Studied doses are reported as research doses, not dosing advice.	Writer: Kymata Health EditorialTrigger: new page

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