Drug & supplement interaction

Sceletium + 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 Sceletium 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

Sceletium 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 Sceletium 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.

Sceletium safety at a glance

Sceletium overall Use caution It appears generally tolerable in small studies, but long-term safety is not well established.
Pregnancy Avoid There is not enough safety information, so it is best avoided during pregnancy.
Breastfeeding Avoid Safety data are lacking, 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 Sceletium? 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. Sceletium has documented interactions with 1 drug class — the most serious being cns depressants (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

Sceletium Does Interact With Other Medications

Sceletium has 248 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 248 No known interaction 2,582 (incl. Esketamine)
Taking anything else?

Check Another of Your Medications Against Sceletium

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

What to actually watch for

No Interaction Found — But Data Suggests Sceletium 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. 2 of them are worth acting on rather than waiting out — marked below.

  • Low mood Worth acting on reported in 4.9% of FDA reports for Esketamine Additional detail

    Sceletium

    “Orally, a sceletium extract has been reported to cause anxiety, headache, insomnia, and irritability. There are also anecdotal reports that chewing sceletium can cause headache, depression, and listlessness. Additionally, anecdotal reports suggest that sceletium can cause euphoric effects when inhaled or taken orally in high doses.”

    Sceletium · Natural Medicines adverse-effect record, reported in anxiety.

    3 sources cited
    1. 106745. Gericke J, Lekhooa M, Steyn SF, Viljoen AM, Harvey BH. An acute dose-ranging evaluation of the antidepressant properties of Sceletium tortuosum (Zembrin®) versus escitalopram in the Flinders Sensitive Line rat. J Ethnopharmacol. 2022 Feb 10;284:114550. do PubMed
    2. 17580. Smith MT, Crouch NR, Gericke N, Hirst M. Psychoactive constituents of the genus Sceletium N.E.Br. and other Mesembryanthemaceae: a review. J Ethnopharmacol 1996;50:119-30. PubMed
    3. 100649. Meyer GMJ, Wink CSD, Zapp J, Maurer HH. GC-MS, LC-MS(n), LC-high resolution-MS(n), and NMR studies on the metabolism and toxicological detection of mesembrine and mesembrenone, the main alkaloids of the legal high "Kanna" isolated from Sceletium tortuosum

    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 ›

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

    Sceletium

    “Orally, a sceletium extract has been reported to cause hypertension.”

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

    1 source cited
    1. 106745. Gericke J, Lekhooa M, Steyn SF, Viljoen AM, Harvey BH. An acute dose-ranging evaluation of the antidepressant properties of Sceletium tortuosum (Zembrin®) versus escitalopram in the Flinders Sensitive Line rat. J Ethnopharmacol. 2022 Feb 10;284:114550. do 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 ›

  • Anxiety or restlessness / Headache Additional detail

    Sceletium

    “There is currently a limited amount of information on the adverse effects of sceletium. A thorough evaluation of safety outcomes has not been conducted.

    Most Common Adverse Effects:

    Orally: Anxiety, headache, insomnia, irritability, and nausea.”

    Sceletium · Natural Medicines adverse-effect record, reported in anxiety.

    Esketamine

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

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

    Sceletium

    “Orally, a sceletium extract has been reported to cause nausea. There are anecdotal reports that chewing sceletium can cause loss of appetite.”

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

    2 sources cited
    1. 106745. Gericke J, Lekhooa M, Steyn SF, Viljoen AM, Harvey BH. An acute dose-ranging evaluation of the antidepressant properties of Sceletium tortuosum (Zembrin®) versus escitalopram in the Flinders Sensitive Line rat. J Ethnopharmacol. 2022 Feb 10;284:114550. do PubMed
    2. 17580. Smith MT, Crouch NR, Gericke N, Hirst M. Psychoactive constituents of the genus Sceletium N.E.Br. and other Mesembryanthemaceae: a review. J Ethnopharmacol 1996;50:119-30. 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 Sceletium but not commonly for Esketamine: reduced appetite, mood changes or irritability and trouble sleeping.

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

Sceletium has been studied for:

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

    Sceletium for depression

    Although there has been interest in using oral sceletium for depression, there is insufficient reliable information about the clinical effects of sceletium for this purpose.

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

We hold 132 real supplement products containing Sceletium, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Sceletium. Even though Sceletium 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 Sceletium 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 Sceletium
Top half

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

29 days ago today
Medication Esketamine
Steady interest

#2,247 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 Sceletium reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 20, 2026. The Sceletium 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 Sceletium

What is Sceletium?

  • Anxiety and stress
  • Low mood
  • Mental focus and cognition
  • Relaxation
  • Traditional use as a mood lifter

Sceletium (often sold as 'kanna') is a South African plant traditionally used to ease stress and lift mood. Early human studies are small and short, so its benefits are not well proven. Talk to your pharmacist or doctor before trying it, and avoid it during pregnancy and breastfeeding.

Sceletium tortuosum · Aizoaceae · Aerial parts (leaves, stems, and flowers), often fermented · Capsules, tablets, powders, tinctures, chewed plant material, and tea

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

Sceletium: dosing

There is no official, well-established dose for Sceletium. Products differ greatly in their strength and in how they are prepared and standardized.If you choose to use it, follow the directions on the product label and do not exceed the suggested amount.

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

Read the full Sceletium 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 & Sceletium

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

0Major
248Moderate
0Minor
2,581No known interaction
248 Moderate 2,581 No interaction
Moderate

248 interactions

Showing 60 of 248 moderate interactions — see all 248 on the Sceletium page.

No interaction 2,581 drugs checked — show the list

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

Showing the 60 most looked-up of 2,581 medications checked with no known interaction — see the full Sceletium list.

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

Sceletium References

The 3 references that drive our Sceletium 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. Smith MT, Crouch NR, Gericke N, Hirst M. Psychoactive constituents of the genus Sceletium N.E.Br. and other Mesembryanthemaceae: a review. J Ethnopharmacol 1996;50:119-30. PubMed
  2. Meyer GMJ, Wink CSD, Zapp J, Maurer HH. GC-MS, LC-MS(n), LC-high resolution-MS(n), and NMR studies on the metabolism and toxicological detection of mesembrine and mesembrenone, the main alkaloids of the legal high "Kanna" isolated from Sceletium tortuosum
  3. Gericke J, Lekhooa M, Steyn SF, Viljoen AM, Harvey BH. An acute dose-ranging evaluation of the antidepressant properties of Sceletium tortuosum (Zembrin®) versus escitalopram in the Flinders Sensitive Line rat. J Ethnopharmacol. 2022 Feb 10;284:114550. do 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 Sceletium and Esketamine Together: Common Questions

Is it safe to take Sceletium with Esketamine?
We do not list a known interaction between Sceletium 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 Sceletium and Esketamine have any of the same side effects?
Yes — our sources link each of them separately to 5 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 Sceletium 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 Sceletium in each. That is a conversation for your prescriber, especially if Esketamine is being adjusted to a target.
How was the Sceletium and Esketamine combination checked?
Interactions in our licensed database are recorded against drug classes. Esketamine is filed under 2 classifications, and Sceletium 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 Sceletium interact with any other medications?
Yes. Sceletium has 248 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 — Sceletium 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

Sceletium 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 Sceletium?

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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.