Drug & supplement interaction

Black Cohosh + Protriptyline

Protriptyline brand name: Vivactil.

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

Black Cohosh has a moderate interaction with Protriptyline. Combining serotonergic drugs with black cohosh might cause additive serotonergic effects.

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

Black Cohosh and Protriptyline

Here is the interaction we found between these two, with the evidence behind it.

Moderate

SEROTONERGIC DRUGS

Why this applies to Protriptyline

Protriptyline falls under SEROTONERGIC DRUGS — the group Black Cohosh interacts with.

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 connection worth knowing about. Protriptyline (Vivactil) is a tricyclic antidepressant that raises serotonin levels in the brain. Black cohosh appears to nudge certain serotonin receptors too. Put them together and you could, in theory, get a bit too much serotonin activity at once. That's why this pairing is flagged as a possible cause of serotonin syndrome, which can show up as agitation, a racing heart, sweating, shakiness, muscle twitching, or confusion.

That said, the evidence here is thin. It rests mainly on lab work plus one case report involving different antidepressants, so the real-world risk with protriptyline isn't well proven. Still, since these effects can stack, I'd check with your pharmacist or doctor before adding black cohosh rather than starting it on your own.

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 Protriptyline one above is one of them. If you take anything else, check it against the full list below.

Moderate 635 Minor 16 No known interaction 2,179 (incl. Protriptyline)
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 Protriptyline

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 Protriptyline, 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 Protriptyline

This page covers Black Cohosh only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Protriptyline page lists 93 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Henbane (major), Lithium (major), Scopolia (major) and 5-htp (moderate).

By severity: 4 major · 71 moderate · 18 minor.

From our pharmacist’s overview on the Protriptyline page

“Protriptyline (Vivactil) is an older tricyclic antidepressant, and I read its supplement list with genuine care because so much of it piles onto what the drug already does. Four of the 93 ingredients on file rate major, and those deserve your attention before anything else.”

Reviewed by 2 · Jul 18, 2026

Open the Protriptyline 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 Protriptyline 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 Protriptyline 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%

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

29 days ago today
Medication Protriptyline
Top half

#743 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 Protriptyline

What Is Protriptyline Used For?

Brand name: Vivactil

Protriptyline Hydrochloride tablets are used to treat symptoms of mental depression in patients who are under close medical supervision. Because it has activating (energizing) properties rather than sedating ones, it may be especially useful for people with depression who feel withdrawn or have very low energy.

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

Can you take Black Cohosh with Protriptyline?
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.
How serious is the Black Cohosh and Protriptyline 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 Protriptyline 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.