Drug & supplement interaction

Black Seed + Diphenhydramine Hydrochloride, Naproxen Sodium

Diphenhydramine Hydrochloride, Naproxen Sodium brand name: Aleve PM.

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

Diphenhydramine Hydrochloride, Naproxen Sodium 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 Diphenhydramine Hydrochloride, Naproxen Sodium

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. Diphenhydramine Hydrochloride, Naproxen Sodium 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 Diphenhydramine Hydrochloride, Naproxen Sodium

Diphenhydramine Hydrochloride, Naproxen Sodium 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

Aleve PM pairs naproxen (a pain reliever) with diphenhydramine, the same drowsy antihistamine found in Benadryl and most nighttime sleep aids. That diphenhydramine is what makes you sleepy. Black seed has shown calming, sedative-like effects in animal studies, so the concern is simple: two things that relax the nervous system, stacked together, may add up.

In real life that could mean extra drowsiness, grogginess, dizziness, or feeling slow the next morning. Keep in mind this is theoretical and based only on lab and animal data, not strong human evidence, and a sprinkle of black seed as a spice is unlikely to matter. Concentrated supplement doses are the bigger question. If you take both, go easy and check with your pharmacist or doctor first.

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

ANTICOAGULANT/ANTIPLATELET DRUGS

2 of 3

Diphenhydramine Hydrochloride, Naproxen Sodium also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.

Theoretically, black seed may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro and animal research suggests that black seed extract can inhibit platelet aggregation and clotting, and increase bleeding time. In addition, decreased platelet counts have occurred in a human case report and in animal research.
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

Aleve PM combines naproxen (an anti-inflammatory pain reliever) with diphenhydramine (a sleep aid). The piece that matters here is the naproxen. Like other NSAIDs, naproxen already makes platelets a little less sticky and can irritate the stomach lining, so it carries some bleeding risk on its own.

Black seed, mostly studied in lab dishes and animals, seems to also slow down platelets and clotting and lengthen bleeding time. Stacking the two could, in theory, add up to a higher chance of bruising, nosebleeds, or stomach bleeding (watch for black or tarry stools). To be clear, this is weak, theoretical evidence, and food-amounts of black seed as a spice are unlikely to matter. Concentrated supplements are the concern. Check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Enomoto, S., Asano, R., Iwahori, Y., Narui, T., Okada, Y., Singab, A. N., and Okuyama, T. Hematological studies on black cumin oil from the seeds of Nigella sativa L. Biol.Pharm.Bull 2001;24(3):307-310. PubMed
  2. Al Jishi, S. A. and Abuo, Hozaifa B. Effect of Nigella sativa on blood hemostatic function in rats. J Ethnopharmacol. 2003;85(1):7-14. PubMed
  3. Awad, E. M. and Binder, B. R. In vitro induction of endothelial cell fibrinolytic alterations by Nigella sativa. Phytomedicine 2005;12(3):194-202. PubMed
  4. Wang X, Jiang A, Batra V. Severe thrombocytopenia associated with black seed oil and evening primrose oil. Cureus. 2020;12(6):e8390. PubMed
  5. Alkharfy K, Jan B, Alotaibi K, et al. Clopidogrel-herb Interactions: A Pharmacokinetic and Pharmacodynamic Assessment in a Rat Model. Curr Drug Metab 2021;22(12):969-977. PubMed
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

3 of 3

Diphenhydramine Hydrochloride, Naproxen Sodium 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 Aleve PM, which combines naproxen (a pain and inflammation reliever) and diphenhydramine (a sedating antihistamine for sleep). The naproxen half is partly broken down by a liver enzyme called CYP2C9. In a lab dish, a compound in black seed called thymoquinone slowed that enzyme down. If that happened in people, naproxen could build up a bit and lean toward its usual side effects, things like stomach upset, heartburn, or a higher chance of stomach irritation or bleeding.

I want to be honest though: this is only a theory based on test-tube work, and it has not been shown in real people. Food amounts of black seed are very unlikely to matter; concentrated supplements are less studied. If you'd like to use both, 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 912 moderate known drug interactions in our database — the Diphenhydramine Hydrochloride, Naproxen Sodium one above is among them. If you take anything else, check it against the full list below.

Moderate 912 No known interaction 1,918 (incl. Diphenhydramine Hydrochloride, Naproxen Sodium)
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 Diphenhydramine Hydrochloride, Naproxen Sodium

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 Diphenhydramine Hydrochloride, Naproxen Sodium, 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 Diphenhydramine Hydrochloride, Naproxen Sodium

This page covers Black Seed only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Diphenhydramine Hydrochloride, Naproxen Sodium page lists 378 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 Danshen (major).

By severity: 13 major · 320 moderate · 45 minor.

From our pharmacist’s overview on the Diphenhydramine Hydrochloride, Naproxen Sodium page

“Aleve PM combines naproxen, an NSAID, with the sedating antihistamine diphenhydramine, and its supplement list earns genuine care rather than a quick skim. Thirteen of the 378 ingredients on file rate major, and the two largest themes track the pill's two halves.”

Reviewed by 2 · Jul 18, 2026

Open the Diphenhydramine Hydrochloride, Naproxen Sodium 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 Diphenhydramine Hydrochloride, Naproxen Sodium 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 Diphenhydramine Hydrochloride, Naproxen Sodium 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%

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

29 days ago today
Medication Diphenhydramine Hydrochloride, Naproxen Sodium
Top 5%

#71 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
912Moderate
0Minor
1,917No known interaction
912 Moderate 1,917 No interaction
Moderate

912 interactions

Showing 60 of 912 moderate interactions — see all 912 on the Black Seed page.

No interaction 1,917 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 1,917 medications checked with no known interaction — see the full Black Seed list.

See the full Black Seed interactions page
See every supplement checked against Diphenhydramine Hydrochloride, Naproxen Sodium, 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 Diphenhydramine Hydrochloride, Naproxen Sodium supplement interactions › Every supplement checked against Diphenhydramine Hydrochloride, Naproxen Sodium, 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 Diphenhydramine Hydrochloride, Naproxen Sodium Together: Common Questions

Can you take Black Seed with Diphenhydramine Hydrochloride, Naproxen Sodium?
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 Diphenhydramine Hydrochloride, Naproxen Sodium?
Diphenhydramine Hydrochloride, Naproxen Sodium 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 Diphenhydramine Hydrochloride, Naproxen Sodium 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 Diphenhydramine Hydrochloride, Naproxen Sodium 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.