Drug & supplement interaction

Podophyllum + 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 Podophyllum 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. Additionally, although there is no interaction, the two are separately associated with some of the same side effects, which would make a new symptom harder to attribute to one or the other.

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Interaction report

Podophyllum 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 Podophyllum 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.

Worth understanding: our licensed dataset holds no drug-interaction record for Podophyllum at all — not against Esketamine, and not against any other medication we track. This verdict therefore rests on the absence of any recorded data, not on research that looked at this combination and found nothing. We cannot rule an interaction out.

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.

Podophyllum safety at a glance

Podophyllum overall Avoid The plant and its crude resin are toxic; only standardized prescription topical products should be used under supervision.
Pregnancy Likely Unsafe When used orally or topically for self-medication; avoid using. Podophyllum is potentially embryotoxic and teratogenic. Oral and topical use can result in birth... Read the full pregnancy detail
Breastfeeding Likely Unsafe When used orally or topically for self-medication; avoid using. Read the full breastfeeding detail

Pregnancy & breastfeeding ratings are from Natural Medicines (Therapeutic Research Center) — the full detail is in the Special populations card below. Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Esketamine and Podophyllum? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
What to actually watch for

No Interaction Found — But Data Suggests Podophyllum and Esketamine May Share Several of the Same Side Effects

This is not an interaction. Neither one changes how your body handles the other, and nothing here says they react together. What our sources do show is that each has separately been linked to the effects below — so taking both can make those effects more likely to turn up, and harder to pin on one or the other if they do. One of them is worth acting on rather than waiting out — marked below.

  • Raised blood pressure Worth acting on reported in 4.8% of FDA reports for Esketamine Additional detail

    Podophyllum

    “Orally and topically, podophyllum resin can cause tachycardia, hypertension or hypotension, and cardiotoxicity.”

    Podophyllum · Natural Medicines adverse-effect record, reported in hypertension.

    3 sources cited
    1. 5617. Cassidy DE, Drewry J, Fanning JP. Podophyllum toxicity: a report of a fatal case and a review of the literature. J Toxicol Clin Toxicol 1982;19:35-44. PubMed
    2. 12898. Frasca T, Brett AS, Yoo SD. Mandrake toxicity. A case of mistaken identity. Arch Intern Med 1997;157:2007-9.
    3. 12900. Mack RB. Living mortals run mad. Mandrake (podophyllum) poisoning. N C Med J 1992;53:98-9.

    Esketamine

    Listed in the ADVERSE REACTIONS section of the FDA label for Esketamine, and in voluntary FDA adverse-event reports. Read the label on DailyMed ›

  • Nausea reported in 5.4% of FDA reports for Esketamine Additional detail

    Podophyllum

    “Orally and topically, podophyllum resin can cause nausea, severe vomiting, diarrhea, abdominal pain, and ileus.

    Topically, podophyllum resin applied to the tongue or oral mucosa can cause transient loss of taste and local irritation.”

    Podophyllum · Natural Medicines adverse-effect record, reported in diarrhea.

    6 sources cited
    1. 5617. Cassidy DE, Drewry J, Fanning JP. Podophyllum toxicity: a report of a fatal case and a review of the literature. J Toxicol Clin Toxicol 1982;19:35-44. PubMed
    2. 12898. Frasca T, Brett AS, Yoo SD. Mandrake toxicity. A case of mistaken identity. Arch Intern Med 1997;157:2007-9.
    3. 12900. Mack RB. Living mortals run mad. Mandrake (podophyllum) poisoning. N C Med J 1992;53:98-9.
    4. 12897. Lozada-Nur F, Costa C. Retrospective findings of the clinical benefits of podophyllum resin 25% sol on hairy leukoplakia. Clinical results in nine patients. Oral Surg Oral Med Oral Pathol 1992;73:555-8. PubMed
    5. 68895. Moura, M. D., Guimaraes, T. R., Fonseca, L. M., de, Almeida Pordeus, I, and Mesquita, R. A. A random clinical trial study to assess the efficiency of topical applications of podophyllin resin (25%) versus podophyllin resin (25%) together with acyclovir c
    6. 68942. Gowdey, G., Lee, R. K., and Carpenter, W. M. Treatment of HIV-related hairy leukoplakia with podophyllum resin 25% solution. Oral Surg.Oral Med.Oral Pathol.Oral Radiol.Endod. 1995;79(1):64-67. PubMed

    Esketamine

    Listed in the ADVERSE REACTIONS section of the FDA label for Esketamine, and in voluntary FDA adverse-event reports. Read the label on DailyMed ›

  • Vomiting Additional detail

    Podophyllum

    Recorded for Podophyllum in the same Natural Medicines adverse-effect record shown under Raised blood pressure above.

    Esketamine

    Listed in the ADVERSE REACTIONS section of the FDA label for Esketamine. Read the label on DailyMed ›

Reported for Podophyllum but not commonly for Esketamine: stomach pain, hallucinations, liver problems and kidney problems.

Effects for Esketamine come from the ADVERSE REACTIONS section of its FDA label; effects for Podophyllum come from the Natural Medicines adverse-effect record, quoted above. Where a percentage is shown, it is the share of 17,728 voluntary FDA FAERS reports for Esketamine that mention that effect — a reporting proportion, not an incidence rate and not evidence the drug caused it. Wording is matched across sources by our own clinical vocabulary, so treat this as a prompt to pay attention, not a diagnosis.

Special populations

Podophyllum in Pregnancy & Breastfeeding

Pregnancy Likely Unsafe

When used orally or topically for self-medication; avoid using. Podophyllum is potentially embryotoxic and teratogenic. Oral and topical use can result in birth defects and fetal death.

Lactation Likely Unsafe

When used orally or topically for self-medication; avoid using.

DISCLAIMER: This tool is intended for informational purposes only, and should not be interpreted as specific medical advice. Patients should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.© 2026 Therapeutic Research Center

Everything else you take

See Every Supplement That Interacts With Esketamine

This page covers Podophyllum 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 Podophyllum as Part of a Dietary Supplement Product? Check It for Interactions

We hold 9 real supplement products containing Podophyllum, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Podophyllum. Even though Podophyllum 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 Podophyllum 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 Podophyllum
Steady interest

#997 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 Podophyllum reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 20, 2026. The Podophyllum and Esketamine records this page draws on were last updated July 11, 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 Podophyllum

What is Podophyllum?

  • Genital and skin warts (topical)
  • Constipation (historical/traditional laxative)
  • Digestive complaints (homeopathic)
  • Watery diarrhea (homeopathic)
  • Liver and gallbladder remedies (traditional)

Podophyllum (American mayapple) is a toxic plant whose resin contains podophyllotoxin, used in prescription topical products to treat warts. The raw plant and crude resin are poisonous if taken by mouth and should never be self-used. Only use FDA-approved wart products exactly as directed and under medical guidance.

Podophyllum peltatum · Berberidaceae · Dried root and rhizome (and the resin extracted from it, called podophyllin) · Topical resin/solution (prescription podophyllin and podofilox), homeopathic preparations; historically a crude purgative

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

Podophyllum: dosing

There is no safe self-care oral dose for podophyllum, and the whole plant should not be taken by mouth. For warts, dosing is determined entirely by the strength of the prescription product and your clinician's instructions.If you are prescribed a topical podophyllin or podofilox product, use only the amount directed, apply it only to the warts, and follow the schedule and wash-off instructions exactly. Never increase the amount or frequency on your own.

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

Read the full Podophyllum 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 & Podophyllum

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

0Major
0Moderate
0Minor
2,829No known interaction
2,829 No interaction
No interaction 2,829 drugs checked — show the list

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

Showing the 60 most looked-up of 2,829 medications checked with no known interaction — see the full Podophyllum list.

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

Podophyllum References

The 13 references that drive our Podophyllum 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. Cassidy DE, Drewry J, Fanning JP. Podophyllum toxicity: a report of a fatal case and a review of the literature. J Toxicol Clin Toxicol 1982;19:35-44. PubMed
  2. Rosenstein G, Rosenstein H, Freeman M, Weston N. Podophyllum-a dangerous laxative. Pediatrics 1976;57:419-21. DOI
  3. Lozada-Nur F, Costa C. Retrospective findings of the clinical benefits of podophyllum resin 25% sol on hairy leukoplakia. Clinical results in nine patients. Oral Surg Oral Med Oral Pathol 1992;73:555-8. PubMed
  4. Frasca T, Brett AS, Yoo SD. Mandrake toxicity. A case of mistaken identity. Arch Intern Med 1997;157:2007-9.
  5. Schwartz J, Norton SA. Useful plants of dermatology. VI. The mayapple (Podophyllum). J Am Acad Dermatol 2002;47:774-5. PubMed
  6. Mack RB. Living mortals run mad. Mandrake (podophyllum) poisoning. N C Med J 1992;53:98-9.
  7. Longstaff E, von Krogh G. Condyloma eradication: self-therapy with 0.15-0.5% podophyllotoxin versus 20-25% podophyllin preparations--an integrated safety assessment. Regul Toxicol Pharmacol 2001;33:117-37. PubMed
  8. Wiley DJ, Douglas J, Beutner K, et al. External genital warts: diagnosis, treatment, and prevention. Clin Infect Dis 2002;35:S210-24. PubMed
  9. Moura, M. D., Guimaraes, T. R., Fonseca, L. M., de, Almeida Pordeus, I, and Mesquita, R. A. A random clinical trial study to assess the efficiency of topical applications of podophyllin resin (25%) versus podophyllin resin (25%) together with acyclovir c
  10. Martin, L. K., Rubin, A. I., Theocharous, C., and Murrell, D. F. Podophyllin reaction mimicking Bowen's disease in a patient with delusions of verrucosis. Clin Exp.Dermatol 2008;33(4):443-445. PubMed
  11. Chamberlain, M. J., Reynolds, A. L., and Yeoman, W. B. Medical memoranda. Toxic effect of podophyllum application in pregnancy. Br.Med.J. 8-12-1972;3(823):391-392. PubMed
  12. Karol, M. D., Conner, C. S., Watanabe, A. S., and Murphrey, K. J. Podophyllum: suspected teratogenicity from topical application. Clin.Toxicol. 1980;16(3):283-286. PubMed
  13. Gowdey, G., Lee, R. K., and Carpenter, W. M. Treatment of HIV-related hairy leukoplakia with podophyllum resin 25% solution. Oral Surg.Oral Med.Oral Pathol.Oral Radiol.Endod. 1995;79(1):64-67. 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 Podophyllum and Esketamine Together: Common Questions

Is it safe to take Podophyllum with Esketamine?
We do not list a known interaction between Podophyllum 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.
Do Podophyllum and Esketamine have any of the same side effects?
Yes — our sources link each of them separately to 3 of the same effects. That is not an interaction: neither changes how your body handles the other. It does mean that if one of those effects turns up, it can be harder to tell which one is behind it. They are listed on this page with the source behind each.
Does Esketamine interact with any supplements?
Yes. Esketamine has documented interactions with 11 supplements in our database — Podophyllum 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

Podophyllum 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 13 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Esketamine and Podophyllum?

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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.