Drug & supplement interaction

Black Cohosh + Valproic Acid

Valproic Acid brand names: Depakene, Depacon, Valproate.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Valproic Acid falls into 2 drug categories that Black Cohosh can interact with; the most serious is rated moderate. Theoretically, taking black cohosh with hepatotoxic drugs may increase the risk of liver damage.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Black Cohosh and Valproic Acid

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Black Cohosh interacts with whole categories of medication. Valproic Acid falls into 2 of those categories, so it can interact with Black Cohosh in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

HEPATOTOXIC DRUGS

1 of 2

Why this applies to Valproic Acid

Valproic Acid falls under HEPATOTOXIC DRUGS — the group Black Cohosh interacts with.

Theoretically, taking black cohosh with hepatotoxic drugs may increase the risk of liver damage.
There is concern that black cohosh might be linked to cases of liver failure and autoimmune hepatitis.
Severity Moderate Likelihood Possible Evidence D

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.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the thing to keep in mind with this pairing: both black cohosh and valproic acid can each be tough on the liver on their own. Valproic acid (Depakene) is already known to occasionally raise liver enzymes, and in rare cases cause more serious liver injury. Black cohosh has its own rare reports of liver problems too. Stack them together and the worry is simply that you're putting two potential stressors on the same organ at once.

I want to be honest about the evidence here, it's mostly anecdotal and theoretical, not proven. Still, watch for signs like unusual tiredness, yellowing of your skin or eyes, dark urine, or pain on your right side. Please check with your pharmacist or doctor before combining these, since you may already be getting liver bloodwork on valproic acid.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Whiting PW, Clouston A, Kerlin P. Black cohosh and other herbal remedies associated with acute hepatitis. Med J Aust 2002;177:440-3. PubMed
  2. Lontos S, Jones RM, Angus PW, Gow PJ. Acute liver failure associated with the use of herbal preparations containing black cohosh. Med J Aust 2003;179:390-1.. DOI
  3. Cohen SM, O'Connor AM, Hart J, et al. Autoimmune hepatitis associated with the use of black cohosh: a case study. Menopause 2004;11:575-7. PubMed
  4. Vitetta L, Thomsen M, Sali A. Black cohosh and other herbal remedies associated with acute hepatitis. Med J Aust 2003;178:411-2.. PubMed
  5. Cohen B, Schardt D. Center for Science in the Public Interest. Letter to Food and Drug Administration. Commissioner Mark McClellan, MD, PhD. March 4, 2004.
  6. Levitsky J, Alli TA, Wisecarver J, Sorrell MF. Fulminant liver failure associated with the use of black cohosh. Dig Dis Sci 2005;50:538-9. PubMed
  7. MHRA. Black cohosh (Cimicifuga racemosa) - risk of liver problems. Herbal Safety News July 2006. Available at: http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&useSecondary= true&ssDocName=CON2024131&ssTargetNodeId=663.
  8. Lynch CR, Folkers ME, Hutson WR. Fulminant hepatic failure associated with the use of black cohosh: a case report. Liver Transpl 2006;12:989-92. PubMed
  9. Brar HS, Marathi R. Case of cholestatic drug-induced liver injury (DILI) associated with black cohosh. BMJ Case Rep 2021;14(5):e240408. PubMed
Moderate

SEROTONERGIC DRUGS

2 of 2

Valproic Acid also falls under SEROTONERGIC DRUGS.

Combining serotonergic drugs with black cohosh might cause additive serotonergic effects.
Black cohosh might increase the risk of serotonin syndrome when combined with other serotonergic drugs. Black cohosh acts as an agonist at several serotonin receptor subtypes and might interact with other serotonergic medications. In one case, a 55-year-old female who had been on stable treatment with sertraline 50 mg and duloxetine 60 mg daily developed serotonin syndrome after taking black cohosh extract 40 mg daily for 3 days.
Severity Moderate Likelihood Possible Evidence D

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.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the thing to keep in mind: this interaction is filed because black cohosh may nudge serotonin pathways in the brain, and the concern is combining it with other serotonin-active drugs. The honest part is that valproic acid is not really a classic serotonergic medication. It works mainly by boosting a calming brain chemical called GABA, not serotonin, so it doesn't fit this interaction the way an antidepressant would.

On top of that, the evidence here is weak (lab and animal data, plus one case involving very different drugs). I wouldn't expect black cohosh to change how your valproic acid controls seizures, mood, or migraines. The bigger shared concern is actually the liver, since both can occasionally stress it. Please check with your pharmacist or doctor before combining them, especially if you have any liver issues.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Dernbach MR, Carpenter JE, Shah N, Carter GB. Black Cohosh Interactions with Prescription Medications Associated with Serotonin Toxicity and Rhabdomyolysis: A Case Report. J Emerg Med 2024;66(5):e592-e596. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction 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.
  • PossibleInteraction 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.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Black Cohosh Also Interacts With Other Medications

Black Cohosh has 635 moderate, 16 minor known drug interactions in our database — the Valproic Acid one above is among them. If you take anything else, check it against the full list below.

Moderate 635 Minor 16 No known interaction 2,179 (incl. Valproic Acid)
Taking anything else?

Check Another of Your Medications Against Black Cohosh

Covers the 2,830 medications we’ve checked against Black Cohosh. Pick one to open its full report.

From our Q&A

Questions About Black Cohosh or Valproic Acid

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Black Cohosh or Valproic Acid, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Valproic Acid

This page covers Black Cohosh only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Valproic Acid page lists 173 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Kava (major).

By severity: 9 major · 147 moderate · 17 minor.

From our pharmacist’s overview on the Valproic Acid page

“Anyone taking valproic acid (Depakene, Depacon) for seizures or bipolar disorder should treat this list with genuine care. Of the 173 supplements and herbs on file, nine are rated major.”

Reviewed by 2 · Jul 18, 2026

Open the Valproic Acid interaction page

One more smart check

Taking Black Cohosh as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,472 real supplement products containing Black Cohosh, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Black Cohosh. Your product may carry other ingredients that interact with Valproic Acid too, on top of Black Cohosh — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Black Cohosh and Valproic Acid Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Black Cohosh
Top 25%

#148 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Valproic Acid
Top half

#838 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Black Cohosh

What is Black Cohosh?

Black Cohosh
  • Hot flashes and night sweats
  • Other menopause symptoms
  • Mood changes during menopause
  • Premenstrual syndrome (PMS)
  • Menstrual cramps

Black cohosh is a North American plant most often used to ease menopause symptoms like hot flashes, but the research is mixed and far from settled. It is generally well tolerated for short-term use, though rare reports of liver problems mean you should talk with your pharmacist or doctor before trying it, especially if you have liver disease.

Read the full Black Cohosh monograph & all interactions
Medication

About Valproic Acid

What Is Valproic Acid Used For?

Brand names: Depakene, Depacon, Valproate

Valproic acid capsules (brands Valproic and Valproic Acid) and valproic acid oral solution (brand Valproic Acid) are both used to treat epilepsy. Specifically, they are approved for complex partial seizures (either alone or with other seizure types) as monotherapy or add-on therapy, and for simple and complex absence seizures as sole therapy or add-on therapy.

Both forms are intended for adults and pediatric patients. Always follow your prescriber's guidance on which product and regimen is right for you.

See full Valproic Acid drug information
Keep checking

Other Drugs & Black Cohosh

Browse every other medication we’ve checked against Black Cohosh — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
635Moderate
16Minor
2,178No known interaction
635 Moderate 16 Minor 2,178 No interaction
Moderate

635 interactions

Showing 60 of 635 moderate interactions — see all 635 on the Black Cohosh page.

Minor

16 interactions

No interaction 2,178 drugs checked — show the list

We also checked Black Cohosh against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,178 medications checked with no known interaction — see the full Black Cohosh list.

See the full Black Cohosh interactions page
See every supplement checked against Valproic Acid, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

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

Keep exploring
Black Cohosh monograph › Uses, safety, and every drug interaction in one place Valproic Acid supplement interactions › Every supplement checked against Valproic Acid, ranked by severity Valproic Acid drug information › The full plain-English guide to this medication Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Black Cohosh and Valproic Acid Together: Common Questions

Can you take Black Cohosh with Valproic Acid?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Black Cohosh and Valproic Acid?
Valproic Acid belongs to more than one drug category, and Black Cohosh interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Black Cohosh and Valproic Acid interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Valproic Acid and Black Cohosh?

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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.