Pregnenolone Drug Interactions, Uses, Effectiveness, Safety & More
What is this page for?
First and foremost: how Pregnenolone interacts with medications. The heart of this page is the interaction list — every drug Pregnenolone is known to interact with, and how serious each one is.
But these pages have grown well beyond that into a full monograph — what Pregnenolone is, what people use it for and how strong the evidence is, its safety and side effects, and answers to the questions we’re asked most — written and reviewed by the clinical staff at HelloPharmacist. It’s educational information from our licensed clinical databases, not medical advice, and we don’t sell or endorse products. Our editorial policy
Check Pregnenolone against your medication
Add one medicationPregnenolone Drug Interactions: The Bottom Line
From the HelloPharmacist Editorial Team · Updated July 2026Based on the available evidence, the overall risk of a clinically significant Pregnenolone drug interaction is moderate rather than low, mainly because pregnenolone can influence sedative medicines and hormone therapies. None of the listed interactions are rated major, but none are minor either, and only one is backed by meaningful human evidence.
The best-documented concern involves benzodiazepines such as diazepam: early human research found that taking pregnenolone regularly may blunt their calming, sedative effect, likely because it acts on the same brain receptors. Because the body uses pregnenolone as a raw material to build steroid hormones, it could in theory strengthen hormone therapies including estrogens, progesterone, progestins, and testosterone. These hormone effects remain largely unproven, but they matter most for anyone whose treatment depends on steady hormone levels.
Most of the long list of interacting medications traces back to that theoretical hormone connection, not to proven harm in people. In fact, human studies found pregnenolone did not raise testosterone levels, and results for progesterone are mixed, so several predicted effects have not actually appeared when tested.
Based on HelloPharmacist’s Pregnenolone interaction data and reviewed under our editorial standards.
Drugs that interact with Pregnenolone
82 medications have a known interaction with Pregnenolone, graded by severity. Select any drug for the full evidence-based detail.
Don’t want to scroll the list? Just ask.
Tell us the medications you take and we’ll check each one against Pregnenolone using our pharmacist-reviewed interaction data.
AI summaries are generated from our Pregnenolone interaction data for education only — always confirm with your pharmacist. How we use AI
No drugs match “”.
What Severity, Likelihood & Evidence Mean
Severity — How Serious It Can Be
- Major. Clinically significant; generally best avoided, or used only under direct professional supervision.
- Moderate. May need monitoring, a dose adjustment, or separating the times you take each one.
- Minor. Generally not clinically significant, but still worth noting and mentioning to your pharmacist.
- No known interaction. Checked against our sources with nothing documented — not the same as proven safety.
Likelihood — How Well It’s Documented
- Likely. Well-controlled human studies have demonstrated the likely existence of this interaction
- Probable. Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
- Possible. Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists
- Unlikely. Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Where This Data Comes From
- Interaction records are evidence-graded and sourced from the Natural Medicines database (TRC Healthcare), the same reference used by pharmacists and hospitals.
- Each drug listed above links to the full report for that exact Pregnenolone combination — clinical detail, likelihood, evidence level, and citations.
- Content is reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.
The kinds of drugs Pregnenolone affects
Every type of medication (drug category) Pregnenolone is known to interact with. Open any category for the detail — or search your exact drug in the checker above.
Benzodiazepines
Concomitant use of pregnenolone may reduce the effects of benzodiazepines.
Very preliminary clinical research shows that chronic use of pregnenolone reduces sedative effects of diazepam when compared with chronic use of placebo. This effect may be related to the activity of pregnenolone at GABAA receptors.
Estrogens
Theoretically, taking pregnenolone might enhance the effects of estrogens.
Pregnenolone is a precursor for several steroid hormones, including estrogens.
Progesterone
Theoretically, taking pregnenolone might enhance the effects of progesterone.
In humans, some research shows that oral administration of pregnenolone can increase levels of progesterone. However, other research shows no effect on progesterone levels. It is possible the impact of pregnenolone on progesterone levels may be dose dependent.
Progestin
Theoretically, taking pregnenolone might enhance the effects of progestin.
Pregnenolone is a precursor for several steroid hormones, including progestin.
Testosterone
Theoretically, taking pregnenolone might enhance the effects of testosterone.
Pregnenolone is a precursor for several steroid hormones, including testosterone. However, preliminary clinical research shows that taking pregnenolone 30-500 mg orally daily for up to 8 weeks does not affect testosterone levels.
Pregnenolone: Uses, Safety & Side Effects
Pregnenolone is a hormone your body makes naturally and a building block for other hormones like cortisol, DHEA, estrogen, and testosterone. It is sold as a supplement for memory, mood, and anti-aging, but solid human evidence for these uses is very limited. Because it is a hormone, talk with your pharmacist or doctor before using it.

- Part used
- Naturally produced in the body; supplements are made synthetically (often from plant sterols like those in soy or wild yam)
- Common forms
- Capsules, tablets, sublingual tablets, creams
- Memory and cognitive support
- Anxiety and stress
- Anti-aging
- Fatigue and low energy
- Mood support
Popular and traditional uses — not proof it works. See “Uses & effectiveness” below for the evidence.
It is a hormone with limited human safety data, so use only under guidance from a healthcare professional.
Insufficient reliable information available; avoid using.
Read the full pregnancy detailInsufficient reliable information available; avoid using.
Read the full breastfeeding detailPregnancy & breastfeeding ratings are from Natural Medicines (Therapeutic Research Center). Safety guidance is general; always confirm with your pharmacist or doctor for your situation.
Overview
Pregnenolone is a hormone that your body makes naturally, mostly in the adrenal glands but also in the brain and other tissues. It is often called a "mother hormone" or precursor because your body can use it to make other hormones, including cortisol, progesterone, DHEA, testosterone, and estrogens.
As a supplement, pregnenolone is made in a lab, usually starting from plant sterols found in soy or wild yam. Important: your body does not automatically turn yam or soy into pregnenolone, so these foods alone do not raise your hormone levels.
People take pregnenolone hoping to improve memory, ease stress, boost mood and energy, and slow signs of aging. It comes as capsules, tablets, sublingual (under-the-tongue) products, and creams.
How it works
Pregnenolone sits near the top of the chain of hormone production. Your body can convert it into many other steroid hormones, which is why supplement makers suggest it might affect mood, memory, stress, and aging.
In the brain, pregnenolone and related compounds are studied as neurosteroids—substances that may influence nerve cell signaling and brain receptors involved in memory and stress. Much of this work comes from laboratory and animal studies, and it is not clear how well it applies to people taking a supplement by mouth.
Because it is a hormone precursor, taking pregnenolone could shift the balance of other hormones in ways that are hard to predict from person to person.
Does Pregnenolone work?
How to read these evidence grades
Natural Medicines’ 7-point scale. We show each rating’s label word-for-word.
For Pregnenolone, current evidence isn’t strong enough to rate any specific use. The conditions it has been studied for are listed below.
Also studied for 23 conditions — evidence insufficient to rate
Insufficient Reliable Evidence To Rate Aging
Although there has been interest in using oral pregnenolone for aging, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
Insufficient Reliable Evidence To Rate Alcohol use disorder
It is unclear if oral pregnenolone is beneficial in patients with alcohol use disorder.
Insufficient Reliable Evidence To Rate Alzheimer disease
Although there has been interest in using oral pregnenolone for Alzheimer disease, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
Insufficient Reliable Evidence To Rate Autism spectrum disorder
It is unclear if oral pregnenolone is beneficial in patients with autism spectrum disorder.
Insufficient Reliable Evidence To Rate Back pain
It is unclear if oral pregnenolone is beneficial in patients with back pain.
Insufficient Reliable Evidence To Rate Bipolar disorder
It is unclear if oral pregnenolone is beneficial in patients with bipolar disorder.
Insufficient Reliable Evidence To Rate Cocaine dependence
It is unclear if oral pregnenolone is beneficial in patients with cocaine dependence.
Insufficient Reliable Evidence To Rate Coronavirus disease 2019 (COVID-19)
Oral pregnenolone has only been evaluated in combination with other ingredients; its effect when used alone is unclear.
Insufficient Reliable Evidence To Rate Critical illness (trauma)
Although there has been interest in using oral pregnenolone for trauma, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
Insufficient Reliable Evidence To Rate Depression
Although there has been interest in using oral pregnenolone for depression, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
Insufficient Reliable Evidence To Rate Endometriosis
Although there has been interest in using oral pregnenolone for endometriosis, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
Insufficient Reliable Evidence To Rate Fatigue
Although there has been interest in using oral pregnenolone for fatigue, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
Insufficient Reliable Evidence To Rate Fibrocystic breast disease
Although there has been interest in using oral pregnenolone for fibrocystic breast disease, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
Insufficient Reliable Evidence To Rate Memory
Although there has been interest in using oral pregnenolone for memory, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
Insufficient Reliable Evidence To Rate Menopausal symptoms
Although there has been interest in using oral pregnenolone for menopausal symptoms, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
Insufficient Reliable Evidence To Rate Multiple sclerosis (MS)
Although there has been interest in using oral pregnenolone for MS, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
Insufficient Reliable Evidence To Rate Premenstrual syndrome (PMS)
Although there has been interest in using oral pregnenolone for PMS, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
Insufficient Reliable Evidence To Rate Psoriasis
Although there has been interest in using oral pregnenolone for psoriasis, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
Insufficient Reliable Evidence To Rate Schizophrenia
It is unclear if oral pregnenolone is beneficial in patients with schizophrenia.
Insufficient Reliable Evidence To Rate Scleroderma
Although there has been interest in using oral pregnenolone for scleroderma, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
Insufficient Reliable Evidence To Rate Seizures
Although there has been interest in using oral pregnenolone for seizures, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
Insufficient Reliable Evidence To Rate Stress
Although there has been interest in using oral pregnenolone for stress, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
Insufficient Reliable Evidence To Rate Systemic lupus erythematosus (SLE)
Although there has been interest in using oral pregnenolone for SLE, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
Source & disclaimer. Effectiveness ratings and evidence summaries are provided by Natural Medicines (Therapeutic Research Center) and shown as licensed. Where Natural Medicines hasn’t rated a use, HelloPharmacist’s pharmacists may add their own reviewed rating and evidence (each such entry is labeled). This is educational information, not medical advice — talk with your pharmacist or doctor before starting, stopping, or changing a supplement.
Safety & precautions
Pregnenolone has not been well studied for long-term safety in humans. Because it is a hormone that can be converted into estrogens, testosterone, and other steroids, it should be used cautiously.
People who should be especially careful—or avoid it unless a doctor advises otherwise—include those with hormone-sensitive conditions (such as certain breast, uterine, ovarian, or prostate cancers), those with a history of blood clots, and anyone with hormone-related disorders. People taking hormone therapy or with thyroid, adrenal, or pituitary problems should check with a healthcare provider first.
Pregnancy and breastfeeding: Avoid pregnenolone if you are pregnant or breastfeeding. There is not enough safety information, and hormone-altering products are best avoided during these times.
Always talk with your pharmacist or doctor before starting pregnenolone, especially if you take other medicines or have a chronic health condition.
Side effects
Because research is limited, the full side-effect profile is not well known. Reported or expected effects relate to its hormone activity and may include:
- Headache
- Irritability, anxiety, or trouble sleeping
- Acne or oily skin
- Unwanted hair growth or changes in body hair
- Menstrual changes in women
Higher doses may raise the chance of hormone-related effects. Stop and seek medical advice if you notice unusual symptoms. As with any hormone-related supplement, more serious effects are possible but not well documented.
Pregnenolone: Reported Adverse Effects
Documented safety reports on Pregnenolone from the evidence-graded Natural Medicines (TRC Healthcare) database, shown word-for-word from the licensed record.
Orally, pregnenolone is generally well tolerated.
Most Common Adverse Effects:
Orally: Acne, agitation, diarrhea, drowsiness, excitement, hair loss, skin abscess, sweating, tremor.
Acne Dermatologic
Orally, pregnenolone has been reported to cause skin abscesses, acne, and hair loss. A case of skin rash accompanied by a burning sensation on the back and sides of the hands has also been reported with oral pregnenolone use, possibly related to a photosensitivity reaction. The rash cleared on its own.
- Brown ES, Park J, Marx CE, et al. A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression. Neuropsychopharmacology 2014;39(12):2867-73.
- Meieran SE, Reus VI, Webster R, Shafton R, Wolkowitz OM. Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation. Psychoneuroendocrinology 2004;29(4):486-500.
Anorexia Psychiatric
Orally, pregnenolone has been reported to cause depressive affect and increased appetite. Increased excitement, agitation, increased motor activity, and anorexia have also been reported; however, it is not certain if these effects were due to pregnenolone.
- Fung LK, Libove RA, Phillips J, Haddad F, Hardan AY.Brief report: an open-label study of the neurosteroid pregnenolone in adults with autism spectrum disorder. J Autism Dev Disord 2014;44(11):2971-7.
- Meieran SE, Reus VI, Webster R, Shafton R, Wolkowitz OM. Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation. Psychoneuroendocrinology 2004;29(4):486-500.
Common cold Neurologic/CNS
Orally, pregnenolone has been reported to cause restlessness, tiredness, sweating, and a case of cold extremities. Sleep problems, drowsiness, and tremor have also been reported; however, it not certain if these effects were due to pregnenolone.
- Fung LK, Libove RA, Phillips J, Haddad F, Hardan AY.Brief report: an open-label study of the neurosteroid pregnenolone in adults with autism spectrum disorder. J Autism Dev Disord 2014;44(11):2971-7.
- Marx CE, Keefe RS, Buchanan RW, et al. Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia. Neuropsychopharmacology 2009;34(8):1885-903.
- Meieran SE, Reus VI, Webster R, Shafton R, Wolkowitz OM. Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation. Psychoneuroendocrinology 2004;29(4):486-500.
Constipation Gastrointestinal
Orally, pregnenolone may cause diarrhea. Constipation has also been reported after oral use; however, it is not certain if this effect was due to pregnenolone.
Pain Musculoskeletal
A case of muscle pain/stiffness has been reported after oral use of pregnenolone.
Sinusitis Pulmonary/Respiratory
A case of sinusitis has been reported after oral use of pregnenolone.
Adverse-effects data: Natural Medicines, Therapeutic Research Center
Dosing
There is no well-established or officially recommended dose for pregnenolone. Products vary widely in strength and form, and "more" is not safer with a hormone supplement.
If your healthcare provider agrees you should try it, follow the directions on the product label and use the lowest amount that seems reasonable. Do not assume a higher dose works better. Because dietary supplements are not tightly regulated, quality and labeling can differ between brands.
Check with your pharmacist or doctor before starting, and let them know about all other medicines and supplements you take.
Pregnenolone & Pregnancy
Pregnenolone & Breastfeeding
© 2026 Therapeutic Research Center
Pregnancy & lactation ratings: Natural Medicines, Therapeutic Research Center
References & further reading
The 6 references that drive our Pregnenolone monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.
- Devlin TM, ed. Textbook of Biochemistry With Clinical Correlations. third ed. New York: Wiley-Liss Inc., 1992.
- Fung LK, Libove RA, Phillips J, Haddad F, Hardan AY.Brief report: an open-label study of the neurosteroid pregnenolone in adults with autism spectrum disorder. J Autism Dev Disord 2014;44(11):2971-7. PubMed
- Brown ES, Park J, Marx CE, et al. A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression. Neuropsychopharmacology 2014;39(12):2867-73. PubMed
- Ritsner MS, Gibel A, Shleifer T, et al. Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial. J Clin Psychiatry 20 PubMed
- Meieran SE, Reus VI, Webster R, Shafton R, Wolkowitz OM. Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation. Psychoneuroendocrinology 2004;29(4):486-500. PubMed
- Marx CE, Keefe RS, Buchanan RW, et al. Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia. Neuropsychopharmacology 2009;34(8):1885-903. PubMed
This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.
Parts of this content are provided by the Therapeutic Research Center, LLC.
DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.
© 2021 Therapeutic Research Center, LLC
Brands that make products with Pregnenolone
84 brands in our database make a supplement containing Pregnenolone.
Supplement products with Pregnenolone
303 products in our database contain Pregnenolone. Open any to see its full ingredient list and every drug interaction we check.
Pregnenolone: Common Questions
What is Pregnenolone used for, and does it work?
Does Pregnenolone interact with prescription medications?
How are Pregnenolone interactions rated?
Is it safe to take Pregnenolone with my medications?
Where does this Pregnenolone interaction information come from?
What is Pregnenolone used for?
Is Pregnenolone safe to take?
Can I take Pregnenolone while pregnant or breastfeeding?
Does eating wild yam or soy raise my Pregnenolone levels?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
Products that contain Pregnenolone
A rotating sample of real supplements in our database that list Pregnenolone — open any to see its full ingredients and every drug interaction we check.
- Peak Male by Lean Factor
- Triple Hormone by Supplement Spot
- Pregnenolone 50 mg + 25 mg DHEA by Emerald
- DHEA Plus by DC
- Pregnenolone 150 mg by Supplement Spot
- Pregnenolone 100 mg by Double Wood Supplements
- Adrenal D-Stress by Patient One 1 MediNutritionals
- Pregnenolone by Karuna
- Pregnenolone Powder 20 mg by BulkSupplements.com
- Pregnenolone 10 mg by LifeLink
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