Drug & supplement interaction

Methylsynephrine + 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 Methylsynephrine 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

Methylsynephrine 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 Methylsynephrine 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.

Methylsynephrine safety at a glance

Methylsynephrine overall Avoid It is a stimulant drug not approved as a supplement and has been tied to serious cardiovascular events.
Pregnancy Avoid Stimulant with unknown safety; should not be used during pregnancy.
Breastfeeding Avoid No safety data; avoid while breastfeeding.

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

Still wondering about combining Esketamine and Methylsynephrine? 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. Methylsynephrine has documented interactions with 2 drug classes — the most serious being beta-adrenergic agonists (moderate) and stimulant 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

Methylsynephrine Does Interact With Other Medications

Methylsynephrine has 191 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 191 No known interaction 2,639 (incl. Esketamine)
Taking anything else?

Check Another of Your Medications Against Methylsynephrine

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

What to actually watch for

No Interaction Found — But Data Suggests Methylsynephrine 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

    Methylsynephrine

    “There is currently a limited amount of information available about the adverse effects of methylsynephrine. Orally, it has been reported to cause increased blood pressure, palpitations, and arrhythmia.”

    Methylsynephrine · Natural Medicines adverse-effect record, reported in arrhythmia.

    2 sources cited
    1. 94386. Pawar RS, Grundel E. Overview of regulation of dietary supplements in the USA and issues of adulteration with phenethylamines (PEAs). Drug Test Anal 2017;9:500-517. PubMed
    2. 99910. Cohen PA, Avula B, Venhuis B, Travis JC, Wang YH, Khan IA. Pharmaceutical doses of the banned stimulant oxilofrine found in dietary supplements sold in the USA. Drug Test Anal. 2017;9(1):135-142. PubMed

    “Orally, methylsynephrine has been reported to cause increased blood pressure, palpitations, and arrhythmias.

    In the Netherlands, the supplement dexaprine was removed from the market because of reported cases of tachycardia, palpitations, chest pain, and a single report of cardiac arrest. As little as half a tablet was associated with these adverse effects, which occurred within one hour of ingestion.”

    Methylsynephrine · Natural Medicines adverse-effect record, reported in arrhythmia.

    3 sources cited
    1. 94386. Pawar RS, Grundel E. Overview of regulation of dietary supplements in the USA and issues of adulteration with phenethylamines (PEAs). Drug Test Anal 2017;9:500-517. PubMed
    2. 99910. Cohen PA, Avula B, Venhuis B, Travis JC, Wang YH, Khan IA. Pharmaceutical doses of the banned stimulant oxilofrine found in dietary supplements sold in the USA. Drug Test Anal. 2017;9(1):135-142. PubMed
    3. 99913. Venhuis B, Keizers P, van Riel A, de Kaste D. A cocktail of synthetic stimulants found in a dietary supplement associated with serious adverse events. Drug Test Anal. 2014;6(6):578-81. 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 ›

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

    Methylsynephrine

    “In the Netherlands, the supplement dexaprine was removed from the market following reported cases of nausea and vomiting. As little as half a tablet was associated with these adverse effects, which occurred within one hour of ingestion. Dexaprine was found to contain methylsynephrine, synephrine, deterenol, yohimbine, caffeine, theophylline, and possibly beta-methyl-beta-phenylethylamines.”

    Methylsynephrine · Natural Medicines adverse-effect record, reported in nausea and vomiting.

    1 source cited
    1. 99913. Venhuis B, Keizers P, van Riel A, de Kaste D. A cocktail of synthetic stimulants found in a dietary supplement associated with serious adverse events. Drug Test Anal. 2014;6(6):578-81. 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 ›

Reported for Methylsynephrine but not commonly for Esketamine: a fast or pounding heartbeat, an irregular heartbeat and chest pain.

Effects for Esketamine come from the ADVERSE REACTIONS section of its FDA label; effects for Methylsynephrine 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.

Everything else you take

See Every Supplement That Interacts With Esketamine

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

We hold 55 real supplement products containing Methylsynephrine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Methylsynephrine. Even though Methylsynephrine 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 Methylsynephrine 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 Methylsynephrine
Top half

#666 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 Methylsynephrine reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 20, 2026. The Methylsynephrine 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 Methylsynephrine

What is Methylsynephrine?

  • Weight loss and fat burning
  • Boosting energy
  • Athletic and workout performance
  • Appetite control

Methylsynephrine (also called oxilofrine) is a synthetic stimulant sometimes added to weight-loss and pre-workout products, but it is not a legal or approved dietary ingredient in the United States. It has been linked to serious heart and blood pressure problems, and there is no good evidence it is safe or effective for these uses, so it is best avoided.

Synthetic compound (also reported in some Citrus species) · Capsules, tablets, powders (mostly in weight-loss and pre-workout supplements)

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

Methylsynephrine: dosing

There is no established safe or approved dose of methylsynephrine for use as a dietary supplement, and we will not suggest one. It is not a legal supplement ingredient in the United States.Supplement labels may list it under different names (such as oxilofrine or methylsynephrine) and amounts can be inconsistent or unreliable. The safest choice is to avoid products that contain it.

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

Read the full Methylsynephrine 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 & Methylsynephrine

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

0Major
191Moderate
0Minor
2,638No known interaction
191 Moderate 2,638 No interaction
Moderate

191 interactions

Showing 60 of 191 moderate interactions — see all 191 on the Methylsynephrine page.

No interaction 2,638 drugs checked — show the list

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

Showing the 60 most looked-up of 2,638 medications checked with no known interaction — see the full Methylsynephrine list.

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

Methylsynephrine References

The 3 references that drive our Methylsynephrine 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. Pawar RS, Grundel E. Overview of regulation of dietary supplements in the USA and issues of adulteration with phenethylamines (PEAs). Drug Test Anal 2017;9:500-517. PubMed
  2. Cohen PA, Avula B, Venhuis B, Travis JC, Wang YH, Khan IA. Pharmaceutical doses of the banned stimulant oxilofrine found in dietary supplements sold in the USA. Drug Test Anal. 2017;9(1):135-142. PubMed
  3. Venhuis B, Keizers P, van Riel A, de Kaste D. A cocktail of synthetic stimulants found in a dietary supplement associated with serious adverse events. Drug Test Anal. 2014;6(6):578-81. 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 Methylsynephrine and Esketamine Together: Common Questions

Is it safe to take Methylsynephrine with Esketamine?
We do not list a known interaction between Methylsynephrine 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 Methylsynephrine 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.
How was the Methylsynephrine and Esketamine combination checked?
Interactions in our licensed database are recorded against drug classes. Esketamine is filed under 2 classifications, and Methylsynephrine has documented interactions with 2 drug classes — 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 Methylsynephrine interact with any other medications?
Yes. Methylsynephrine has 191 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 — Methylsynephrine 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

Methylsynephrine 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 3 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Esketamine and Methylsynephrine?

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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.