Drug & supplement interaction

Black Seed + Benzhydrocodone, Acetaminophen

Benzhydrocodone, Acetaminophen brand name: Apadaz.

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

Benzhydrocodone, Acetaminophen falls into 2 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
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Black Seed and Benzhydrocodone, Acetaminophen

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. Benzhydrocodone, Acetaminophen 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

CNS DEPRESSANTS

1 of 2

Why this applies to Benzhydrocodone, Acetaminophen

Benzhydrocodone, Acetaminophen 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

Here's the simple version: Apadaz contains an opioid pain reliever (benzhydrocodone) plus acetaminophen. Opioids already slow down your brain and nervous system, which is why they can make you drowsy, foggy, slow to breathe, or just plain sleepy. The concern with black seed is that, in animal studies, it seemed to have its own calming, sedative-like effect on the nervous system. Stack the two together and the theory is you could feel more of that sedation than you bargained for.

I want to be honest about the evidence though: this is based on lab and animal research, not real people, so it's a theoretical caution rather than a proven problem. Food-amount black seed (as a spice) is unlikely to matter much. Concentrated supplement doses are the bigger question mark. Please run it by your pharmacist or doctor before combining them, and never adjust your pain medicine on your own.

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 2

Benzhydrocodone, Acetaminophen 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

Here's the short version: black seed (Nigella sativa) may nudge serotonin levels up in the brain, and opioids like the benzhydrocodone in Apadaz can also raise serotonin activity. Stack the two together and there's a small, mostly theoretical chance of too much serotonin, called serotonin syndrome. Signs to watch for include agitation, a racing heart, sweating, shivering, muscle twitching, or feeling confused or restless.

I want to be honest about the evidence here: this is based mainly on animal studies and a single case report, so it's a possible concern, not a proven one. Food-amount black seed used as a spice is unlikely to matter. Concentrated oil capsules are the bigger question mark. Don't stop either one on your own, just loop in your pharmacist or doctor before combining them.

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

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 Benzhydrocodone, Acetaminophen 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. Benzhydrocodone, Acetaminophen)
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 Benzhydrocodone, Acetaminophen

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 Benzhydrocodone, Acetaminophen, 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 Benzhydrocodone, Acetaminophen

This page covers Black Seed only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Benzhydrocodone, Acetaminophen page lists 299 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: 14 major · 239 moderate · 46 minor.

Open the Benzhydrocodone, Acetaminophen 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 Benzhydrocodone, Acetaminophen 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 Benzhydrocodone, 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 Seed
Top 25%

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

29 days ago today
Medication Benzhydrocodone, Acetaminophen
Steady interest

#2,311 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 Benzhydrocodone and Acetaminophen

What Is Benzhydrocodone and Acetaminophen Used For?

Brand name: Apadaz

Apadaz is indicated for the short-term management of acute pain — up to 14 days — that is severe enough to require an opioid and for which non-opioid treatments have not worked or are not expected to work. It combines benzhydrocodone (a prodrug that converts to the opioid hydrocodone) with acetaminophen.

Because of serious risks including addiction, abuse, and misuse, Apadaz is reserved for patients who have not tolerated or have not gotten adequate relief from alternative pain treatments. It should not be used for an extended period of time unless the pain remains severe enough to require an opioid and alternatives remain inadequate.

See full Benzhydrocodone and Acetaminophen 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
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 Benzhydrocodone, 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 Seed monograph › Uses, safety, and every drug interaction in one place Benzhydrocodone, Acetaminophen supplement interactions › Every supplement checked against Benzhydrocodone, Acetaminophen, ranked by severity Benzhydrocodone and Acetaminophen 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 Seed and Benzhydrocodone, Acetaminophen Together: Common Questions

Can you take Black Seed with Benzhydrocodone, 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 2 interactions listed for Black Seed and Benzhydrocodone, Acetaminophen?
Benzhydrocodone, Acetaminophen 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 Benzhydrocodone, 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.