Drug & supplement interaction

Black Cohosh + Tramadol, Acetaminophen

Tramadol, Acetaminophen brand name: Tramacet.

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

Tramadol, Acetaminophen falls into 3 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
Interactions3
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Black Cohosh and Tramadol, Acetaminophen

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Black Cohosh interacts with whole categories of medication. Tramadol, Acetaminophen falls into 3 of those categories, so it can interact with Black Cohosh in 3 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 3

Why this applies to Tramadol, Acetaminophen

Tramadol, Acetaminophen 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 wrinkle with Tramacet: the tramadol part actually relies on an enzyme called CYP2D6 to turn it into its stronger, pain-relieving form. So tramadol is a bit of a prodrug. If black cohosh slows down CYP2D6 (and the research here is mixed), it could mean less of that active form, so you might notice your pain isn't controlled as well. The acetaminophen half isn't really affected by this.

Honestly, the evidence is shaky and one study showed a popular black cohosh product had no meaningful effect. I wouldn't lose sleep over it, but if you take both and find your pain relief slipping, mention it to your pharmacist or doctor before changing anything.

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

HEPATOTOXIC DRUGS

2 of 3

Tramadol, Acetaminophen also falls under HEPATOTOXIC DRUGS.

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 simple version: this isn't about black cohosh changing how your Tramacet works or how strong it feels. Instead, both products are processed by the liver, and the acetaminophen half of Tramacet is well known for being hard on the liver if you take too much. Black cohosh has a handful of rare reports linking it to liver trouble too, so the worry is that stacking two things that can stress the liver might add up.

I'll be honest, this is mostly a theoretical caution based on scattered case reports, not strong proof. Still, watch for yellowing skin or eyes, dark urine, belly pain, or unusual tiredness, and check with your pharmacist or doctor before combining them, especially if you drink alcohol or have liver concerns.

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

3 of 3

Tramadol, Acetaminophen 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 about Tramacet: the tramadol part of it nudges up serotonin levels in your brain, on top of its pain-relieving action. Black cohosh appears to tickle some of the same serotonin receptors. So in theory, taking the two together could stack up that serotonin activity a bit more than either one alone.

If serotonin climbs too high, you can run into what's called serotonin syndrome. Watch for things like agitation, a racing heart, sweating, shivering, muscle twitching, or feeling confused. That said, I want to keep this in perspective. The evidence here is weak, mostly lab-based with one isolated case report involving different drugs. It's worth a quick chat with your pharmacist or doctor before combining them, especially if you take other serotonin-affecting medicines.

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 Tramadol, Acetaminophen 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. Tramadol, Acetaminophen)
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 Tramadol, Acetaminophen

This page covers Black Cohosh only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Tramadol, Acetaminophen page lists 280 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), Asarabacca (major), Beer (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 12 major · 224 moderate · 44 minor.

From our pharmacist’s overview on the Tramadol, Acetaminophen page

“The combinations I worry about most with tramadol and acetaminophen (Tramacet) involve anything that deepens drowsiness or strains the liver. Tramadol is an opioid, so sedating supplements like kava, along with alcohol in any form, can slow breathing on top of adding sleepiness, which is why this list deserves genuine care rather than…”

Reviewed by 2 · Jul 18, 2026

Open the Tramadol, Acetaminophen 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 Tramadol, Acetaminophen 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 Tramadol, Acetaminophen 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%

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

29 days ago today
Medication Tramadol, Acetaminophen
Top 25%

#372 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
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 Tramadol, Acetaminophen, 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 Tramadol, Acetaminophen supplement interactions › Every supplement checked against Tramadol, Acetaminophen, ranked by severity 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 Tramadol, Acetaminophen Together: Common Questions

Can you take Black Cohosh with Tramadol, Acetaminophen?
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 3 interactions listed for Black Cohosh and Tramadol, Acetaminophen?
Tramadol, Acetaminophen 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 Tramadol, Acetaminophen 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

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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.