Drug & supplement interaction

Cowhage + Esketamine

Esketamine brand name: Spravato.

Moderate Interaction
The bottom line Moderate

Cowhage has a moderate interaction with Esketamine. Theoretically, use of TCAs might reduce the levels and clinical effects of cowhage.

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

Cowhage and Esketamine

Here is the interaction we found between these two, with the evidence behind it.

Moderate

TRICYCLIC ANTIDEPRESSANTS (TCAs)

Why this applies to Esketamine

Esketamine falls under TRICYCLIC ANTIDEPRESSANTS (TCAs) — the group Cowhage interacts with.

Theoretically, use of TCAs might reduce the levels and clinical effects of cowhage.
Cowhage contains levodopa. Use of TCAs might reduce the absorption of levodopa. Some case reports describe patients that developed hypertension and dyskinesia when taking both levodopa and TCAs.
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 honest picture for esketamine (Spravato). The interaction we have on file was built around tricyclic antidepressants, and esketamine isn't a tricyclic at all, it's an NMDA receptor blocker given as a nasal spray. So this warning fits esketamine loosely at best, and the evidence behind it is only theoretical, based on how these drugs work rather than real cases.

The bigger thing I'd watch for is blood pressure. Esketamine can raise blood pressure on its own right after a dose, and cowhage's L-dopa can also nudge blood pressure around, so stacking them could add up. Both can affect mood and alertness too. Since cowhage is a potent, unpredictable source of L-dopa, please run it by your doctor or pharmacist before combining anything with your Spravato treatment.

References
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. HP-200 in Parkinson's Disease study group. An alternative medicine treatment for Parkinson's disease: Results of a multicenter clinical trial. J Alt Comp Med 1995;1:249-55. DOI
  3. Vadivel V, Janardhanan K. Nutritional and anti-nutritional composition of velvet bean: an under-utilized food legume in south India. Int J Food Sci Nutr 2000;51:279-87. PubMed
  4. Prakash, D., Niranjan, A., and Tewari, S. K. Some nutritional properties of the seeds of three Mucuna species. Int.J.Food Sci.Nutr. 2001;52(1):79-82.
  5. Vadivel, V. and Janardhanan, K. Nutritional and antinutritional characteristics of seven South Indian wild legumes. Plant Foods Hum.Nutr 2005;60(2):69-75. PubMed
  6. Creapure (Creatine Monohydrate). Toxicological Datasheet. Degussa BioActives. Available at: https://www.fda.gov/ohrms/DOCKETS/.../95s-0316-rpt0154-54-Ref-50-vol112.pdf.
  7. Pulikkalpura H, Kurup R, Mathew PJ, Baby S. Levodopa in Mucuna pruriens and its degradation. Sci Rep 2015;5:11078. 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

Cowhage Also Interacts With Other Medications

Cowhage has 17 major, 175 moderate known drug interactions in our database — the Esketamine one above is one of them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Cowhage

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

Everything else you take

See Every Supplement That Interacts With Esketamine

This page covers Cowhage 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), Dhea (moderate), Griffonia Simplicifolia (moderate), Indian Snakeroot (moderate) and Rauvolfia Vomitoria (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 Cowhage as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,218 real supplement products containing Cowhage, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Cowhage. Your product may carry other ingredients that interact with Esketamine too, on top of Cowhage — 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 Cowhage 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 Cowhage
Top 10%

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

29 days ago today
Medication Esketamine
Steady interest

#2,229 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 Cowhage

What is Cowhage?

  • Parkinson's disease symptoms
  • Male fertility and libido
  • Mood and stress support
  • Traditional aphrodisiac
  • General energy and vitality

Cowhage (Mucuna pruriens) is a tropical legume best known as a natural source of L-dopa, the compound the body turns into dopamine. It is most studied for Parkinson's disease symptoms and male fertility, but evidence is still limited and the L-dopa content makes it potentially powerful and risky—talk to your doctor or pharmacist before using it.

Read the full Cowhage monograph & all interactions
Medication

About Esketamine Nasal Spray

What Is Esketamine Nasal Spray Used For?

Brand name: Spravato

Spravato (esketamine) 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.

Important limitations: Spravato has not been shown to prevent suicide or reduce suicidal thoughts or behavior directly. Even if you feel better after an early dose, hospitalization may still be needed if your doctor determines it's necessary. Spravato is not approved for use in children or as an anesthetic.

See full Esketamine Nasal Spray drug information
Keep checking

Other Drugs & Cowhage

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

17Major
175Moderate
0Minor
2,637No known interaction
Major

17 interactions

Moderate

175 interactions

Showing 60 of 175 moderate interactions — see all 175 on the Cowhage page.

No interaction 2,637 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 Cowhage and Esketamine Together: Common Questions

Can you take Cowhage with Esketamine?
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.
How serious is the Cowhage and Esketamine 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.