Drug & supplement interaction

Black Cohosh + Brexpiprazole

Brexpiprazole brand name: Rexulti.

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

Brexpiprazole falls into 2 drug categories that Black Cohosh can interact with; the most serious is rated moderate. Some research suggests that black cohosh might inhibit CYP2D6, but there is conflicting evidence.

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

Black Cohosh and Brexpiprazole

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. Brexpiprazole 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

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

1 of 2

Why this applies to Brexpiprazole

Brexpiprazole falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Black Cohosh interacts with.

Some research suggests that black cohosh might inhibit CYP2D6, but there is conflicting evidence.
Some clinical research suggests that black cohosh might modestly inhibit CYP2D6 and increase levels of drugs metabolized by this enzyme. However, contradictory clinical research shows a specific black cohosh product (Remifemin, Enzymatic Therapy) 40 mg twice daily does not significantly inhibit metabolism of a CYP2D6 substrate in healthy study volunteers. Until more is known, use black cohosh cautiously in patients taking drugs metabolized by CYP2D6.
Severity Moderate Likelihood Possible Evidence B

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 situation with these two together. Your body relies on a liver enzyme called CYP2D6 to break down brexpiprazole and clear it out. Black cohosh might slow that enzyme down a bit. If it does, brexpiprazole could clear more slowly and build up in your system. Brexpiprazole is an active drug (not a prodrug), so higher levels generally mean stronger effects and a bigger chance of side effects like drowsiness, restlessness, dizziness, weight gain, or feeling unusually sluggish.

That said, the evidence here is mixed. Some studies showed a modest effect, while others showed almost none, so this may not be a big deal for many people. Please don't stop or change either one on your own. Just check in with your pharmacist or doctor so they can keep an eye on how you feel.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77:415-26. PubMed
  2. Gurley BJ, Swain A, Hubbard MA, et al. Clinical assessement of CYP2D6-mediated herb-drug interactions in humans: Effects of milk-thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea. Mol Nutr Food Res 2008;52:755-63.
Moderate

SEROTONERGIC DRUGS

2 of 2

Brexpiprazole 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 idea behind this pairing. Black cohosh seems to nudge certain serotonin receptors in the brain, and brexpiprazole (Rexulti) also touches serotonin pathways as part of how it works. In theory, using them together could add up and slightly raise the chance of too much serotonin activity, sometimes called serotonin syndrome. Watch for things like restlessness, a racing heart, sweating, shivering, muscle twitching, or feeling confused.

I want to be honest about the strength of this concern. It rests mostly on lab work and a single case report involving different medications, so it is more of a theoretical caution than a proven problem. Brexpiprazole isn't a prodrug here, so we aren't expecting it to lose its effect. Still, before adding black cohosh, check with your pharmacist or doctor.

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 Brexpiprazole 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. Brexpiprazole)
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.

Everything else you take

See Every Supplement That Interacts With Brexpiprazole

This page covers Black Cohosh only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Brexpiprazole page lists 177 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), Indian Snakeroot (major), Lithium (major) and Rauvolfia Vomitoria (major).

By severity: 6 major · 130 moderate · 41 minor.

From our pharmacist’s overview on the Brexpiprazole page

“Brexpiprazole (Rexulti) treats schizophrenia and is added to antidepressants for depression, and its supplement list warrants real care before you add anything to it. The bulk of the 177 entries change how your liver clears the drug, so grapefruit can push levels up while St.”

Reviewed by 2 · Jul 18, 2026

Open the Brexpiprazole 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 Brexpiprazole 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 Brexpiprazole 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%

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

29 days ago today
Medication Brexpiprazole
Steady interest

#1,812 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 Brexpiprazole

What Is Brexpiprazole Used For?

Brand name: Rexulti

Brexpiprazole tablets are approved for two uses in adults: as an add-on (adjunctive) treatment alongside antidepressants for major depressive disorder (MDD), and as a treatment for schizophrenia. These uses apply to both the generic brexpiprazole tablets and Rexulti.

Rexulti has one additional approved use: treating agitation associated with dementia due to Alzheimer's disease in adults. Rexulti is also approved for schizophrenia in adolescents ages 13 and older. Note that Rexulti is not approved for dementia-related psychosis without agitation from Alzheimer's disease, and it is not meant to be used on an as-needed basis for Alzheimer's-related agitation.

See full Brexpiprazole 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 Brexpiprazole, 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 Brexpiprazole supplement interactions › Every supplement checked against Brexpiprazole, ranked by severity Brexpiprazole 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 Brexpiprazole Together: Common Questions

Can you take Black Cohosh with Brexpiprazole?
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 Brexpiprazole?
Brexpiprazole 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 Brexpiprazole 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 Brexpiprazole 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.