Drug & supplement interaction

Black Seed + Amitriptyline, Perphenazine

Amitriptyline, Perphenazine brand names: Triavil, Etrafon, Etrafon-A, Etrafon-Forte.

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

Amitriptyline, Perphenazine falls into 3 drug categories that Black Seed can interact with; the most serious is rated moderate. Theoretically, concomitant use with drugs that have sedative properties may cause additive effects.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Black Seed and Amitriptyline, Perphenazine

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

Why Are There 3 Interactions?

Black Seed interacts with whole categories of medication. Amitriptyline, Perphenazine falls into 3 of those categories, so it can interact with Black Seed in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CNS DEPRESSANTS

1 of 3

Why this applies to Amitriptyline, Perphenazine

Amitriptyline, Perphenazine falls under CNS DEPRESSANTS — the group Black Seed interacts with.

Theoretically, concomitant use with drugs that have sedative properties may cause additive effects.
Animal research suggests that black seed may have CNS depressant effects.
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

This combination pill pairs amitriptyline (a tricyclic antidepressant) with perphenazine (an antipsychotic), and both already tend to make people drowsy on their own. The concern here is simple: black seed appears to have its own mild calming, sedative-type effects, so stacking it on top could add to that sleepiness rather than create a brand new problem.

In practical terms, you might notice more drowsiness, grogginess, dizziness, or a foggy head, especially when standing up or driving. I'll be honest though, this caution rests on lab and animal research, not solid human studies, so it's a theoretical add-on effect. Food-amount black seed as a spice is unlikely to matter much; concentrated supplement doses are the bigger question. Please check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Al Naggar, T. B., Gomez-Serranillos, M. P., Carretero, M. E., and Villar, A. M. Neuropharmacological activity of Nigella sativa L. extracts. J Ethnopharmacol. 2003;88(1):63-68. PubMed
Moderate

SEROTONERGIC DRUGS

2 of 3

Amitriptyline, Perphenazine also falls under SEROTONERGIC DRUGS.

Theoretically, combining serotonergic drugs with black seed might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders.
Animal research suggests that black seed can increase brain serotonin levels. In one case report, a 35-year-old man undergoing endoscopic surgery experienced immediate postoperative serotonin syndrome that was likely associated with the use of black seed oil 600 mg daily starting 4 days before surgery, and precipitated by the use of serotonergic pain medications, including fentanyl and oxycodone. Monitor patients for signs of serotonin syndrome and other serotonergic side effects if using black seed with serotonergic drugs.
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

The combo pill you asked about pairs amitriptyline (a tricyclic antidepressant) with perphenazine (an antipsychotic). The piece that matters here is amitriptyline, since it raises serotonin in the brain. There's a theory that black seed may nudge serotonin levels up too, so taking both together could, in rare cases, add up and raise the small risk of serotonin syndrome. Watch for things like agitation, a racing heart, sweating, shakiness, muscle twitching, or feeling unusually hot or confused.

I want to keep this in perspective: this is based on one case report and animal data, so the evidence is weak. Food amounts of black seed as a spice are very unlikely to matter; concentrated oil capsules are the bigger question mark. Please run it by your pharmacist or doctor before adding black seed.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Akhondian, J., Parsa, A., and Rakhshande, H. The effect of Nigella sativa L. (black cumin seed) on intractable pediatric seizures. Med Sci Monit. 2007;13(12):CR555-CR559.
  2. Perveen T, Haider S, Zuberi NA, et al. Increased 5-HT levels following repeated administration of Nigella sativa L. (Black Seed) oil produce antidepressant effects in rats. Sci Pharm 2013;82:161-70. PubMed
  3. Warner ME, Warner PA, Sprung J, Warner MA. Black seed oil and perioperative serotonin syndrome: A case report. A A Pract. 2019;13(11):420-422. PubMed
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

3 of 3

Amitriptyline, Perphenazine also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Theoretically, black seed might increase levels of drugs metabolized by CYP2C9.
In vitro research suggests that thymoquinone, a constituent of black seed, can decrease the metabolism of phenytoin by a mechanism possibly related to the inhibition of CYP2C9. The effect of black seed on CYP2C9 is unclear. This has not been shown in humans.
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 gist with this combo (Triavil, which pairs amitriptyline with perphenazine): black seed might slow down a liver enzyme called CYP2C9, and in theory that could let some of this medication build up a bit higher than usual. If that happened, you could notice more of amitriptyline's typical effects, things like drowsiness, dry mouth, constipation, blurry vision, dizziness on standing, or a faster heartbeat.

I want to be honest, though: this is only a theoretical concern from lab testing, not something proven in people, and these drugs lean more on other enzymes anyway. Food-amount black seed in cooking is very unlikely to matter. If you're using concentrated black seed capsules or oil, just run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Wang Z, Wang X, Wang Z, et al. Potential herb-drug interaction risk of thymoquinone and phenytoin. Chem Biol Interact. 2022;353:109801. 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 Seed Also Interacts With Other Medications

Black Seed has 911 moderate known drug interactions in our database — the Amitriptyline, Perphenazine one above is among them. If you take anything else, check it against the full list below.

Moderate 911 No known interaction 1,919 (incl. Amitriptyline, Perphenazine)
Taking anything else?

Check Another of Your Medications Against Black Seed

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

From our Q&A

Questions About Black Seed or Amitriptyline, Perphenazine

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 Seed or Amitriptyline, Perphenazine, 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 Amitriptyline, Perphenazine

This page covers Black Seed only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Amitriptyline, Perphenazine page lists 311 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), American Hellebore (major), Arsenic (major) and Beer (major).

By severity: 19 major · 235 moderate · 57 minor.

From our pharmacist’s overview on the Amitriptyline, Perphenazine page

“Alcohol is the risk I'd flag first for anyone taking amitriptyline with perphenazine (Triavil, Etrafon). Beer and wine both carry major ratings here, and 78 of the 311 ingredients on file deepen the drowsiness this antidepressant and antipsychotic combination already causes, sometimes to the point of slowed breathing.”

Reviewed by 2 · Jul 18, 2026

Open the Amitriptyline, Perphenazine interaction page

One more smart check

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

We hold 226 real supplement products containing Black Seed, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Black Seed. Your product may carry other ingredients that interact with Amitriptyline, Perphenazine too, on top of Black Seed — 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 Seed and Amitriptyline, Perphenazine 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 Seed
Top 25%

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

29 days ago today
Medication Amitriptyline, Perphenazine
Top half

#1,335 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 Seed

What is Black Seed?

Black Seed
  • Respiratory support (asthma, allergies, cough)
  • Digestive upset
  • Immune support
  • Blood sugar and cholesterol support
  • General inflammation

Black seed (Nigella sativa) is a traditional spice and remedy that has been studied for asthma, blood sugar, cholesterol, and blood pressure, with early research showing some promise but no firmly proven benefits. It is generally well tolerated in food amounts, but supplement-strength doses are less studied, so talk to your pharmacist or doctor before using it—especially if you are pregnant, breastfeeding, or take other medicines.

Read the full Black Seed monograph & all interactions
Keep checking

Other Drugs & Black Seed

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

0Major
911Moderate
0Minor
1,918No known interaction
911 Moderate 1,918 No interaction
Moderate

911 interactions

Showing 60 of 911 moderate interactions — see all 911 on the Black Seed page.

No interaction 1,918 drugs checked — show the list

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

Showing the 60 most looked-up of 1,918 medications checked with no known interaction — see the full Black Seed list.

See the full Black Seed interactions page
See every supplement checked against Amitriptyline, Perphenazine, 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 Seed monograph › Uses, safety, and every drug interaction in one place Amitriptyline, Perphenazine supplement interactions › Every supplement checked against Amitriptyline, Perphenazine, 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 Seed and Amitriptyline, Perphenazine Together: Common Questions

Can you take Black Seed with Amitriptyline, Perphenazine?
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 Seed and Amitriptyline, Perphenazine?
Amitriptyline, Perphenazine belongs to more than one drug category, and Black Seed 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 Seed and Amitriptyline, Perphenazine 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 Amitriptyline, Perphenazine and Black Seed?

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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.