Drug & supplement interaction

Annatto + Esketamine

Esketamine brand name: Spravato.

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Sep 20, 2026
The bottom line No known interaction

We found no known interaction between Annatto and Esketamine in our sources. Absence of a documented interaction is not the same as proven safety, and does not guarantee one does not exist. Do not start, stop, or change a medication or supplement based on this page; confirm with your pharmacist or doctor first.

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Interaction report

Annatto and Esketamine

We checked these two against our interaction database. Here is what we found.

No Known Interaction Found

We did not find a documented interaction between Esketamine and Annatto in our sources. This does not guarantee that the combination is completely free of risk — there is often limited research on supplements and herbal products, especially around drug interactions.

If you decide to take both, the practical routine is simple: add one new thing at a time and note the date you started it. If the combination is going to disagree with you, it usually shows in the first days to a couple of weeks — and a start date turns “I’ve been feeling off” into something a pharmacist can actually work with. Do not stop a prescribed medicine on your own.

Always talk with your pharmacist or doctor before making changes to your medications or supplements, particularly if you take several medications or have an ongoing health condition.

Annatto safety at a glance

Annatto overall Use caution Generally recognized as safe as a food coloring, but supplement use is not well studied and it can cause allergies in some people.
Pregnancy Use caution Food amounts are likely fine, but concentrated supplement doses are not well studied, so avoid them unless your doctor approves.
Breastfeeding Use caution Food amounts are likely fine, but there is not enough safety information on supplement doses, so use caution.

Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Esketamine and Annatto? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
How we checked

Why No Interaction Is Listed for Esketamine

Interactions in our licensed database are recorded against drug classes, not just single drug names. Esketamine is filed under 2 classifications — tricyclic antidepressants (tcas), antidepressant drugs. Annatto has documented interactions with 1 drug class — the most serious being antidiabetes drugs (moderate) — and none of Esketamine’s classifications are among them.

Classification data comes from our licensed Natural Medicines dataset. A medication can belong to classes beyond those recorded there, so this describes how the check was run — it is not a safety guarantee.

Keep it in perspective

Annatto Does Interact With Other Medications

Annatto has 86 moderate known drug interactions in our database — Esketamine isn’t one of them. If you take anything else, check it against the full list below.

Moderate 86 No known interaction 2,744 (incl. Esketamine)
Taking anything else?

Check Another of Your Medications Against Annatto

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

What to actually watch for

What Annatto Itself Has Been Linked To

This is not an interaction — nothing below involves Esketamine. It is the side-effect record for Annatto on its own, from the licensed Natural Medicines monograph. If something new turns up after you add Annatto, this list is the first place to look. 2 entries are worth acting on rather than waiting out — marked below.

  • A severe allergic reaction / An allergic reaction Worth acting on Additional detail

    “Orally, annatto leaf seems to be well tolerated. Rarely, annatto has been reported to cause constipation. When used as a coloring agent, annatto has been reported to cause allergic reactions, including anaphylaxis.”

    Annatto · Natural Medicines adverse-effect record, reported in constipation.

    5 sources cited
    1. 31612. Zegarra, L., Vaisberg, A., Loza, C., Aguirre, R. L., Campos, M., Fernandez, I., Talla, O., and Villegas, L. Double-blind randomized placebo-controlled study of Bixa orellana in patients with lower urinary tract symptoms associated to benign prostatic hyp
    2. 31619. Ebo, D. G., Ingelbrecht, S., Bridts, C. H., and Stevens, W. J. Allergy for cheese: evidence for an IgE-mediated reaction from the natural dye annatto. Allergy 2009;64(10):1558-1560. PubMed
    3. 31621. Nish, W. A., Whisman, B. A., Goetz, D. W., and Ramirez, D. A. Anaphylaxis to annatto dye: a case report. Ann.Allergy 1991;66(2):129-131.
    4. 95158. Koc E, Arca E, Surucu B, Kurumlu Z. An open, randomized, controlled, comparative study of the combined effect of intralesional triamcinolone acetonide and onion extract gel and intralesional triamcinolone acetonide alone in the treatment of hypertrophic s
    5. 95157. Raddatz-Mota D, Pérez-Flores LJ, Carrari F, et al. Achiote (Bixa orellana L.): a natural source of pigment and vitamin E. J Food Sci Technol 2017;54(6):1729-1741. PubMed

    “When used as a food coloring, annatto causes rare cases of allergic reactions in children and adults. Reactions have occurred after consumption of cereal, cheese, ice cream, and other foods containing annatto food coloring, and use of cosmetics containing annatto. Symptoms include urticaria, angioedema, severe hypotension, and anaphylaxis (31619,31621,95157.109549).”

    Annatto · Natural Medicines adverse-effect record, reported in hypotension.

    2 sources cited
    1. 109549. Sadowska B, Sztormowska M, Chelminska M. Annatto hypersensitivity after oral ingestion confirmed by placebo-controlled oral challenge. Ann Allergy Asthma Immunol. 2021 Oct;127(4):510-511. PubMed
    2. 95157. Raddatz-Mota D, Pérez-Flores LJ, Carrari F, et al. Achiote (Bixa orellana L.): a natural source of pigment and vitamin E. J Food Sci Technol 2017;54(6):1729-1741. PubMed
  • Hives Worth acting on Additional detail

    Recorded for Annatto in the same Natural Medicines adverse-effect record shown under A severe allergic reaction / An allergic reaction above.

  • Bloating or gas / Stomach pain / Diarrhea Additional detail

    “Orally, annatto leaf powder has been reported to cause constipation. Annatto food coloring has been associated with an increase in symptoms of irritable bowel syndrome (IBS) in one case report. A woman with frequent symptoms of diarrhea, bloating, and abdominal pain experienced an improvement in all symptoms upon elimination of annatto-containing products;”

    Annatto · Natural Medicines adverse-effect record, reported in constipation.

    2 sources cited
    1. 31612. Zegarra, L., Vaisberg, A., Loza, C., Aguirre, R. L., Campos, M., Fernandez, I., Talla, O., and Villegas, L. Double-blind randomized placebo-controlled study of Bixa orellana in patients with lower urinary tract symptoms associated to benign prostatic hyp
    2. 95142. Stein HL. Annatto and IBS. J Clin Gastroenterol 2009;43(10):1014-5.
  • Low blood pressure Additional detail

    Recorded for Annatto in the same Natural Medicines adverse-effect record shown under A severe allergic reaction / An allergic reaction above.

  • Constipation Additional detail

    Recorded for Annatto in the same Natural Medicines adverse-effect record shown under A severe allergic reaction / An allergic reaction above.

Everything above comes from the Natural Medicines adverse-effect record for Annatto — expand a row for the licensed statement it rests on. We read the ADVERSE REACTIONS section of Esketamine’s FDA label too, and the two lists don’t meaningfully overlap — which is why no Esketamine column appears here.

Everything else you take

See Every Supplement That Interacts With Esketamine

This page covers Annatto only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Esketamine page lists 11 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Scopolia (major), Cowhage (moderate), Dhea (moderate), Griffonia Simplicifolia (moderate) and Indian Snakeroot (moderate).

By severity: 1 major · 6 moderate · 4 minor.

From our pharmacist’s overview on the Esketamine page

“Esketamine (Spravato) is the nasal spray for depression that hasn't responded to standard treatment, and its supplement list deserves genuine respect. Scopolia carries the only major rating and is the entry to understand before any other; pairing it with the medication can raise the risk of anticholinergic effects, meaning dry mouth, b…”

Reviewed by 2 · Jul 18, 2026

Open the Esketamine interaction page

One more smart check

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

We hold 304 real supplement products containing Annatto, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Annatto. Even though Annatto itself has no known interaction with Esketamine, another ingredient on your label might. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Annatto and Esketamine 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 Annatto
Top half

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

29 days ago today
Medication Esketamine
Steady interest

#2,708 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.

Where does our data come from?
  • Source: the Natural Medicines (TRC Healthcare) clinical database — the evidence-graded professional reference for herb & supplement interactions.
  • Citation library: 103,510 references behind our interaction content, 65,311 of them resolved to verified PubMed/DOI sources. See every Annatto reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 20, 2026. The Annatto and Esketamine records this page draws on were last updated July 10, 2026.
  • What “no known interaction” means: no documented interaction in the sources above — not a guarantee of safety. Supplements are studied far less than prescription drugs, so we say exactly what the evidence supports, and nothing more.
Data structure & sourcing designed and verified by .
Supplement

About Annatto

What is Annatto?

Annatto
  • Natural food and cosmetic coloring
  • Source of antioxidants
  • Antimicrobial/anti-infective (traditional use)
  • Athletic performance and muscle soreness
  • Skin and bad-breath remedies (traditional use)

Annatto is a plant-based coloring made from the seeds of the achiote tree and is widely used as a safe food dye. While it has a long history in traditional medicine and contains antioxidant compounds, there is little high-quality human research supporting its use as a supplement. It can trigger allergic reactions in some people, so use caution and talk with your pharmacist or doctor.

Bixa orellana · Bixaceae · Seeds (and the colored coating around them); leaves are sometimes used · Food coloring, powder, seed extract, capsules, oil-based extracts

An interaction check asks whether these two react with each other — it does not ask whether Annatto is a good idea for someone in your situation. Here is what our Annatto record says about it on its own.

Annatto: dosing

There is no established standard dose for annatto as a supplement. The amounts used to color foods are very small, and research has not defined a safe or effective dose for health purposes.If you use an annatto supplement, follow the directions on the product label and do not exceed the recommended amount.

From our Annatto monograph — the full record covers uses, side effects and every documented interaction.

Read the full Annatto monograph & all interactions
Medication

About Esketamine Nasal Spray

What Is Esketamine Nasal Spray Used For?

Brand name: Spravato

Spravato nasal spray is approved for two uses in adults. First, it treats treatment-resistant depression (TRD) — depression that has not responded to other antidepressants — either on its own or alongside an oral antidepressant. Second, it treats depressive symptoms in adults with major depressive disorder (MDD) who have acute suicidal ideation or behavior, always used together with an oral antidepressant in this case.

Important limits: Spravato has not been shown to prevent suicide or reduce suicidal thoughts or behavior on its own. It is not a replacement for hospitalization if that is clinically needed, and it is not approved as an anesthetic.

Most-Reported Side Effects for Esketamine

From FAERS, the FDA’s public side-effect reporting system (17,728 reports, all brands). Reports are voluntary and are not proof the drug caused the effect.

Dissociation 3,733 reports
Sedation 2,706 reports
Suicidal ideation 1,351 reports
Nausea 957 reports
Depression 873 reports
See full Esketamine Nasal Spray drug information
Keep checking

Other Drugs & Annatto

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

0Major
86Moderate
0Minor
2,743No known interaction
86 Moderate 2,743 No interaction
Moderate

86 interactions

Showing 60 of 86 moderate interactions — see all 86 on the Annatto page.

No interaction 2,743 drugs checked — show the list

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

Showing the 60 most looked-up of 2,743 medications checked with no known interaction — see the full Annatto list.

See the full Annatto interactions page
See every supplement checked against Esketamine, ranked by severity
Evidence & sources

Annatto References

The 15 references that drive our Annatto monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

  1. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
  2. Fernandes, A. C., Almeida, C. A., Albano, F., Laranja, G. A., Felzenszwalb, I., Lage, C. L., de Sa, C. C., Moura, A. S., and Kovary, K. Norbixin ingestion did not induce any detectable DNA breakage in liver and kidney but caused a considerable impairment
  3. Russell, K. R., Morrison, E. Y., and Ragoobirsingh, D. The effect of annatto on insulin binding properties in the dog. Phytother Res 2005;19(5):433-436. PubMed
  4. Morrison, E. Y., Thompson, H., Pascoe, K., West, M., and Fletcher, C. Extraction of an hyperglycaemic principle from the annatto (Bixa orellana), a medicinal plant in the West Indies. Trop.Geogr.Med 1991;43(1-2):184-188.
  5. Zegarra, L., Vaisberg, A., Loza, C., Aguirre, R. L., Campos, M., Fernandez, I., Talla, O., and Villegas, L. Double-blind randomized placebo-controlled study of Bixa orellana in patients with lower urinary tract symptoms associated to benign prostatic hyp
  6. Russell, K. R., Omoruyi, F. O., Pascoe, K. O., and Morrison, E. Y. Hypoglycaemic activity of Bixa orellana extract in the dog. Methods Find.Exp.Clin.Pharmacol. 2008;30(4):301-305.
  7. Ebo, D. G., Ingelbrecht, S., Bridts, C. H., and Stevens, W. J. Allergy for cheese: evidence for an IgE-mediated reaction from the natural dye annatto. Allergy 2009;64(10):1558-1560. PubMed
  8. Nish, W. A., Whisman, B. A., Goetz, D. W., and Ramirez, D. A. Anaphylaxis to annatto dye: a case report. Ann.Allergy 1991;66(2):129-131.
  9. Stein HL. Annatto and IBS. J Clin Gastroenterol 2009;43(10):1014-5.
  10. Raddatz-Mota D, Pérez-Flores LJ, Carrari F, et al. Achiote (Bixa orellana L.): a natural source of pigment and vitamin E. J Food Sci Technol 2017;54(6):1729-1741. PubMed
  11. Koc E, Arca E, Surucu B, Kurumlu Z. An open, randomized, controlled, comparative study of the combined effect of intralesional triamcinolone acetonide and onion extract gel and intralesional triamcinolone acetonide alone in the treatment of hypertrophic s
  12. Gonçalves MLL, da Mota ACC, Deana AM, et al. Antimicrobial photodynamic therapy with Bixa orellana extract and blue LED in the reduction of halitosis-A randomized, controlled clinical trial. Photodiagnosis Photodyn Ther. 2020 Jun;30:101751. PubMed
  13. Dominguez-Balmaseda D, Diez-Vega I, Larrosa M, et al. Effect of a blend of Zingiber officinale Roscoe and Bixa orellana L. herbal supplement on the recovery of delayed-onset muscle soreness induced by unaccustomed eccentric resistance training: A randomiz
  14. González-Gross M, Quesada-González C, Rueda J, et al. Analysis of effectiveness of a supplement combining Harpagophytum procumbens, Zingiber officinale and Bixa orellana in healthy recreational runners with self-reported knee pain: a pilot, randomized, tr
  15. Sadowska B, Sztormowska M, Chelminska M. Annatto hypersensitivity after oral ingestion confirmed by placebo-controlled oral challenge. Ann Allergy Asthma Immunol. 2021 Oct;127(4):510-511. PubMed

Medication overviews come from MedlinePlus (NIH); supplement label data from the NIH Dietary Supplement Label Database. Content is written and reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

Pharmacist Counseling Corner

Taking Annatto and Esketamine Together: Common Questions

Is it safe to take Annatto with Esketamine?
We do not list a known interaction between Annatto and Esketamine. That does not guarantee the combination is risk-free, so confirm with your pharmacist or doctor — especially if you take other medications or have a health condition.
How was the Annatto and Esketamine combination checked?
Interactions in our licensed database are recorded against drug classes. Esketamine is filed under 2 classifications, and Annatto has documented interactions with 1 drug class — none of Esketamine's classifications are among them. A medication can belong to classes beyond those recorded in our dataset, so this describes how the check was run rather than guaranteeing safety.
Does Annatto interact with any other medications?
Yes. Annatto has 86 documented drug interactions in our database — Esketamine is simply not one of them. If you take anything else, it is worth checking each one; they are all listed on this page.
Does Esketamine interact with any supplements?
Yes. Esketamine has documented interactions with 11 supplements in our database — Annatto is not one of them. The Esketamine interaction page linked on this page lists every one, ranked by severity.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Where next

Keep Exploring

Annatto monograph Uses, safety profile, and every drug interaction in one place Esketamine Nasal Spray drug information The full plain-English guide to this medication Esketamine supplement interactions Every supplement checked against Esketamine, 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 References The 15 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Esketamine and Annatto?

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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.