Drug & supplement interaction

Palmitoylethanolamide (pea) + 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 Palmitoylethanolamide (pea) 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

Palmitoylethanolamide (pea) 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 Palmitoylethanolamide (pea) 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 Palmitoylethanolamide (pea) 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.

Palmitoylethanolamide (pea) safety at a glance

Palmitoylethanolam... overall Use caution Generally well tolerated in studies, but long-term safety data are limited.
Pregnancy Avoid Not enough safety information, so avoid use during pregnancy.
Breastfeeding Avoid Not enough safety information, so avoid use while breastfeeding.

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

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

No Interaction Found — But Data Suggests Palmitoylethanolamide (pea) and Esketamine May Share a Side Effect

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.

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

    Palmitoylethanolamide (pea)

    “Orally, PEA has been rarely reported to cause mild and transient gastrointestinal symptoms, such as nausea.”

    Palmitoylethanolamide (pea) · Natural Medicines adverse-effect record, reported in nausea and vomiting.

    3 sources cited
    1. 93325. Indraccolo U, Barbieri F. Effect of palmitoylethanolamide-polydatin combination on chronic pelvic pain associated with endometriosis: preliminary observations. Eur J Obstet Gynecol Reprod Biol. 2010 May;150(1):76-9. PubMed
    2. 93327. Murina F, Graziottin A, Felice R, Radici G, Tognocchi C. Vestibulodynia: synergy between palmitoylethanolamide + transpolydatin and transcutaneous electrical nerve stimulation. J Low Genit Tract Dis. 2013 Apr;17(2):111-6.
    3. 106266. Papetti L, Sforza G, Tullo G, et al. Tolerability of palmitoylethanolamide in a pediatric population suffering from migraine: A pilot study. Pain Res Manag 2020;2020:3938640. 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 Palmitoylethanolamide (pea) but not commonly for Esketamine: itching and dry skin.

Effects for Esketamine come from the ADVERSE REACTIONS section of its FDA label; effects for Palmitoylethanolamide (pea) 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.

Overlapping uses

What Esketamine Is Prescribed For, and What Palmitoylethanolamide (pea) Has Been Studied For

These two come up together because they touch the same health topic — not because they do the same job. Esketamine is a prescription medicine with approved uses on its FDA label. Palmitoylethanolamide (pea) is a supplement: what follows is what researchers have looked at it for, and how strong that evidence is.

Esketamine is prescribed for: 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.

Read the rest of what Esketamine is prescribed for

It is not a replacement for hospitalization if that is clinically needed, and it is not approved as an anesthetic.

Palmitoylethanolamide (pea) has been studied for:

  • Depression studied, not established Palmitoylethanolamide (pea) has been studied for this. Natural Medicines rates the evidence: Insufficient Reliable Evidence To Rate Read what the research shows

    Palmitoylethanolamide (pea) for depression

    It is unclear if oral PEA is beneficial for depression when used in combination with citalopram.

Effectiveness ratings and the research summaries above are the verbatim record from the Natural Medicines database, which grades evidence from “Effective” down to “Insufficient Reliable Evidence To Rate”. A rating below the top of that scale means researchers have looked at it — not that it works, and never that it can stand in for a prescribed medicine. Do not stop or replace Esketamine on your own; if you are taking Palmitoylethanolamide (pea) for the same health topic, tell your prescriber, especially if the medicine is being adjusted to a target.

Everything else you take

See Every Supplement That Interacts With Esketamine

This page covers Palmitoylethanolamide (pea) 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 Palmitoylethanolamide (pea) as Part of a Dietary Supplement Product? Check It for Interactions

We hold 97 real supplement products containing Palmitoylethanolamide (pea), each one broken down to its full ingredient list — and combination products often carry several ingredients besides Palmitoylethanolamide (pea). Even though Palmitoylethanolamide (pea) 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 Palmitoylethanolamide (pea) 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 Palmitoylethanolamide (pea)
Steady interest

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

What is Palmitoylethanolamide (pea)?

  • Chronic pain
  • Nerve (neuropathic) pain
  • Inflammation
  • Low back and sciatica pain
  • General immune and recovery support

Palmitoylethanolamide (PEA) is a fat-like molecule made naturally in the body and studied mainly for pain and inflammation. Some research suggests it may help certain types of chronic and nerve pain, but the overall evidence is still limited and more high-quality studies are needed. It appears generally well tolerated, but talk with your pharmacist or doctor before starting it.

Not a plant; a fatty acid compound made in the body and found in some foods · Capsules, tablets, sublingual tablets, powders, and 'micronized' or 'ultramicronized' formulations

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

Palmitoylethanolamide (pea): dosing

There is no official, standardized dose of PEA. Studies have used a range of amounts and different formulations, including micronized and ultramicronized versions, which can affect how the body absorbs it.Because of this, the best approach is to follow the directions on the product label and start with the lowest suggested amount.

From our Palmitoylethanolamide (pea) monograph — the full record covers uses, side effects and every documented interaction.

Read the full Palmitoylethanolamide (pea) 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 & Palmitoylethanolamide (pea)

Browse every other medication we’ve checked against Palmitoylethanolamide (pea) — 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 Palmitoylethanolamide (pea) 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 Palmitoylethanolamide (pea) list.

See the full Palmitoylethanolamide (pea) interactions page
See every supplement checked against Esketamine, ranked by severity
Evidence & sources

Palmitoylethanolamide (pea) References

The 4 references that drive our Palmitoylethanolamide (pea) 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. Indraccolo U, Barbieri F. Effect of palmitoylethanolamide-polydatin combination on chronic pelvic pain associated with endometriosis: preliminary observations. Eur J Obstet Gynecol Reprod Biol. 2010 May;150(1):76-9. PubMed
  2. Murina F, Graziottin A, Felice R, Radici G, Tognocchi C. Vestibulodynia: synergy between palmitoylethanolamide + transpolydatin and transcutaneous electrical nerve stimulation. J Low Genit Tract Dis. 2013 Apr;17(2):111-6.
  3. Papetti L, Sforza G, Tullo G, et al. Tolerability of palmitoylethanolamide in a pediatric population suffering from migraine: A pilot study. Pain Res Manag 2020;2020:3938640. PubMed
  4. Visse K, Blome C, Phan NQ, Augustin M, Ständer S. Efficacy of body lotion containing N-palmitoylethanolamine in subjects with chronic pruritus due to dry skin: A dermatocosmetic study. Acta Derm Venereol. 2017;97(5):639-641. 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 Palmitoylethanolamide (pea) and Esketamine Together: Common Questions

Is it safe to take Palmitoylethanolamide (pea) with Esketamine?
We do not list a known interaction between Palmitoylethanolamide (pea) 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 Palmitoylethanolamide (pea) and Esketamine have any of the same side effects?
Yes — our sources link each of them separately to one 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.
Are Palmitoylethanolamide (pea) and Esketamine used for the same thing?
They overlap in purpose, which usually means the real question is whether you need both rather than whether they are safe together. This page lists the shared uses and how strong the evidence is for Palmitoylethanolamide (pea) in each. That is a conversation for your prescriber, especially if Esketamine is being adjusted to a target.
Does Esketamine interact with any supplements?
Yes. Esketamine has documented interactions with 11 supplements in our database — Palmitoylethanolamide (pea) 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

Palmitoylethanolamide (pea) 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 4 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Esketamine and Palmitoylethanolamide (pea)?

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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.