Drug & supplement interaction

Black Seed + Fluoxetine

Fluoxetine brand names: Prozac, Sarafem.

Moderate Interaction
The bottom line Moderate

Fluoxetine falls into 2 drug categories that Black Seed can interact with; the most serious is rated moderate. Theoretically, combining serotonergic drugs with black seed might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders.

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

Black Seed and Fluoxetine

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

Why Are There 2 Interactions?

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

Moderate

SEROTONERGIC DRUGS

1 of 2

Why this applies to Fluoxetine

Fluoxetine falls under SEROTONERGIC DRUGS — the group Black Seed interacts with.

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

Here's the gist: fluoxetine (Prozac) already raises serotonin levels in your brain, which is exactly how it helps with depression, OCD, and the other conditions it treats. Black seed may nudge serotonin upward too, based mostly on animal studies and a single case report. Stacking the two could, in theory, push serotonin a little too high.

If that happens, watch for signs like agitation, a racing heart, sweating, shakiness, muscle twitching, or feeling confused. To be fair, this is weak, mostly theoretical evidence, and food-amount black seed in cooking is very unlikely to cause trouble. The concern is more about concentrated oil capsules taken daily. Don't stop either one on your own, but please run it by your pharmacist or doctor first.

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

2 of 2

Fluoxetine 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 idea behind this pairing. Black seed contains a compound called thymoquinone that, in lab dishes, seemed to slow down a liver enzyme (CYP2C9) that helps clear certain medicines. Fluoxetine is partly handled by this enzyme, so in theory black seed could let a bit more fluoxetine linger in your system. If that happened, you might notice stronger side effects like jitteriness, trouble sleeping, nausea, headache, or an upset stomach.

I want to be honest about how shaky this is. This concern comes only from test-tube work, not from real people, and the actual effect on CYP2C9 isn't clear. Food-amount black seed in cooking is very unlikely to matter. If you're considering concentrated supplement doses, just check with your pharmacist or doctor first.

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

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 Fluoxetine

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 Fluoxetine, 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 Fluoxetine

This page covers Black Seed only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Fluoxetine page lists 163 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), American Hellebore (major), Arsenic (major), Cesium (major) and Ephedra (major).

By severity: 8 major · 127 moderate · 28 minor.

From our pharmacist’s overview on the Fluoxetine page

“Grapefruit is the surprise at the top of fluoxetine's (Prozac) supplement list. In large amounts it can stretch the QT interval, the electrical pause between heartbeats, and fluoxetine, a widely prescribed antidepressant, can do the same, raising the odds of a dangerous rhythm.”

Reviewed by 2 · Jul 18, 2026

Open the Fluoxetine 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 Fluoxetine 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 Fluoxetine 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%

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

29 days ago today
Medication Fluoxetine
Top 1%

#25 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
Medication

About Fluoxetine

What Is Fluoxetine Used For?

Brand names: Prozac, Sarafem

Fluoxetine is approved to treat four conditions: major depressive disorder (MDD), obsessive-compulsive disorder (OCD), bulimia nervosa (a binge-eating and purging disorder), and panic disorder — with or without agoraphobia (fear of situations that feel hard to escape).

It works for adults across all four conditions, and for children and teens with depression (ages 8–18) and OCD (ages 7–17).

See full Fluoxetine drug information
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
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
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

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Pharmacist Counseling Corner

Taking Black Seed and Fluoxetine Together: Common Questions

Can you take Black Seed with Fluoxetine?
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 Seed and Fluoxetine?
Fluoxetine 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 Fluoxetine 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 Fluoxetine 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.