Drug & supplement interaction

Huperzine A + 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 Huperzine A 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

Huperzine A 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 Huperzine A 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.

Huperzine A safety at a glance

Huperzine A overall Use caution It is a pharmacologically active compound that can cause real side effects, so use it with care and medical guidance.
Pregnancy Avoid There is not enough safety data, so it is best avoided during pregnancy.
Breastfeeding Avoid Safety while breastfeeding is unknown, so avoid it.

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

Still wondering about combining Esketamine and Huperzine A? 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. Huperzine A has documented interactions with 2 drug classes — the most serious being anticholinergic drugs (moderate) and cholinergic 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

Huperzine A Does Interact With Other Medications

Huperzine A has 219 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 219 No known interaction 2,611 (incl. Esketamine)
Taking anything else?

Check Another of Your Medications Against Huperzine A

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

What to actually watch for

No Interaction Found — But Data Suggests Huperzine A 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

    Huperzine A

    “Orally, huperzine A might cause decreased heart rate. There are two cases reported where consumption of a tea mistakenly brewed from Lycopodium selago, a source of huperzine A, has resulted in significant cholinergic toxicity, including hypertension.”

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

    3 sources cited
    1. 3138. Xu SS, Gao ZX, Weng Z, et al. Efficacy of tablet huperzine-A on memory, cognition, and behavior in Alzheimer's disease. Zhongguo Yao Li Xue Bao 1995;16:391-5.
    2. 93482. Yang G, Wang Y, Tian J, Liu JP. Huperzine A for Alzheimer's disease: a systematic review and meta-analysis of randomized clinical trials. PLoS One 2013;8(9):e74916. PubMed
    3. 13193. Felgenhauer N, Zilker T, Worek F, Eyer P. Intoxication with huperzine A, a potent anticholinesterase found in the fir club moss. J Toxicol Clin Toxicol 2000;38:803-8.. 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 ›

  • Dizziness Additional detail

    Huperzine A

    “Orally, huperzine A can cause cholinergic side effects such as dizziness and sweating. Huperzine A can also cause hyperactivity and insomnia. Fainting has also been reported. In two case reports, consumption of a tea mistakenly brewed from Lycopodium selago, a source of huperzine A, has resulted in significant cholinergic toxicity, including sweating and slurred speech.”

    Huperzine A · Natural Medicines adverse-effect record, reported in insomnia.

    6 sources cited
    1. 3140. Zhang RW, Tang XC, Han YY, et al. [Drug evaluation of huperzine A in the treatment of senile memory disorders]. Chung Kuo Yao Li Hsueh Pao 1991;12:250-2.
    2. 55613. Zhang, Z., Wang, X., Chen, Q., Shu, L., Wang, J., and Shan, G. [Clinical efficacy and safety of huperzine Alpha in treatment of mild to moderate Alzheimer disease, a placebo-controlled, double-blind, randomized trial]. Zhonghua Yi Xue Za Zhi 7-25-2002;82
    3. 93481. Xu ZQ, Liang XM, Juan-Wu, Zhang YF, Zhu CX, Jiang XJ. Treatment with Huperzine A improves cognition in vascular dementia patients. Cell Biochem Biophys 2012;62(1):55-8. PubMed
    4. 93482. Yang G, Wang Y, Tian J, Liu JP. Huperzine A for Alzheimer's disease: a systematic review and meta-analysis of randomized clinical trials. PLoS One 2013;8(9):e74916. PubMed
    5. 3138. Xu SS, Gao ZX, Weng Z, et al. Efficacy of tablet huperzine-A on memory, cognition, and behavior in Alzheimer's disease. Zhongguo Yao Li Xue Bao 1995;16:391-5.
    6. 4624. Xu SS, Cai ZY, Qu ZW, et al. Huperzine-A in capsules and tablets for treating patients with Alzheimer disease. Zhongguo Yao Li Xue Bao 1999;20:486-90.

    Esketamine

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

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

    Huperzine A

    “Orally, huperzine A can cause cholinergic side effects such as nausea, vomiting, diarrhea, and anorexia. Constipation and thirst have also been reported. In two case reports, consumption of a tea mistakenly brewed from Lycopodium selago, a source of huperzine A, has resulted in significant cholinergic toxicity, including vomiting and diarrhea.”

    Huperzine A · Natural Medicines adverse-effect record, reported in anorexia.

    5 sources cited
    1. 93480. Wang BS, Wang H, Wei ZH, Song YY, Zhang L, Chen HZ. Efficacy and safety of natural acetylcholinesterase inhibitor huperzine A in the treatment of Alzheimer's disease: an updated meta-analysis. J Neural Transm (Vienna) 2009;116(4):457-65. PubMed
    2. 93481. Xu ZQ, Liang XM, Juan-Wu, Zhang YF, Zhu CX, Jiang XJ. Treatment with Huperzine A improves cognition in vascular dementia patients. Cell Biochem Biophys 2012;62(1):55-8. PubMed
    3. 93482. Yang G, Wang Y, Tian J, Liu JP. Huperzine A for Alzheimer's disease: a systematic review and meta-analysis of randomized clinical trials. PLoS One 2013;8(9):e74916. PubMed
    4. 93483. Xing SH, Zhu CX, Zhang R, An L. Huperzine a in the treatment of Alzheimer's disease and vascular dementia: a meta-analysis. Evid Based Complement Alternat Med 2014;2014:363985. PubMed
    5. 13193. Felgenhauer N, Zilker T, Worek F, Eyer P. Intoxication with huperzine A, a potent anticholinesterase found in the fir club moss. J Toxicol Clin Toxicol 2000;38:803-8.. 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 Huperzine A but not commonly for Esketamine: a slow heartbeat, blurred vision, constipation and dry mouth.

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

Huperzine A has been studied for:

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

    Huperzine A for depression

    It is unclear if oral huperzine A is beneficial in patients with major depressive disorder.

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

We hold 86 real supplement products containing Huperzine A, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Huperzine A. Even though Huperzine A 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 Huperzine A 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 Huperzine A
Top half

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

29 days ago today
Medication Esketamine
Steady interest

#1,947 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 Huperzine A reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 20, 2026. The Huperzine A 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 Huperzine A

What is Huperzine A?

Huperzine A
  • Memory and cognitive support
  • Alzheimer's disease and dementia
  • Age-related memory decline
  • Focus and mental performance
  • Myasthenia gravis (traditional/older use)

Huperzine A is a purified compound from a Chinese clubmoss that acts like a mild cholinesterase inhibitor, similar in mechanism to some prescription Alzheimer's drugs. Some small studies suggest it may modestly help memory in people with dementia, but the evidence is limited and the quality is uncertain. Because it is biologically active and not well standardized, talk with a pharmacist or doctor before using it, and avoid it during pregnancy and breastfeeding.

Huperzia serrata · Lycopodiaceae · Whole plant (clubmoss), from which the compound huperzine A is extracted · Capsules, tablets, and as an ingredient in nootropic or 'brain health' supplement blends

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

Huperzine A: dosing

There is no official, well-established standard dose of huperzine A for supplement use. Studied amounts are very small and are usually measured in micrograms, not milligrams, which makes accurate dosing difficult with over-the-counter products.The safest approach is to follow the directions on the product label and not to exceed them.

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

Read the full Huperzine A 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 & Huperzine A

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

0Major
219Moderate
0Minor
2,610No known interaction
219 Moderate 2,610 No interaction
Moderate

219 interactions

Showing 60 of 219 moderate interactions — see all 219 on the Huperzine A page.

No interaction 2,610 drugs checked — show the list

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

Showing the 60 most looked-up of 2,610 medications checked with no known interaction — see the full Huperzine A list.

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

Huperzine A References

The 13 references that drive our Huperzine A 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. Skolnick AA. Old Chinese herbal medicine used for fever yields possible new Alzheimer Disease therapy. JAMA 1997;277:776. DOI
  2. Ye JW, Cai JX, Wang LM, Tang XC. Improving effects of huperzine A on spatial working memory in aged monkeys and young adult monkeys with experimental cognitive impairment. J Pharmacol Exp Ther 1999;288:814-9.. DOI
  3. Wang T, Tang XC. Reversal of scopolamine-induced deficits in radial maze performance by (-)-huperzine A: comparison with E2020 and tacrine. Eur J Pharmacol 1998;349:137-42. PubMed
  4. Xu SS, Gao ZX, Weng Z, et al. Efficacy of tablet huperzine-A on memory, cognition, and behavior in Alzheimer's disease. Zhongguo Yao Li Xue Bao 1995;16:391-5.
  5. Zhang RW, Tang XC, Han YY, et al. [Drug evaluation of huperzine A in the treatment of senile memory disorders]. Chung Kuo Yao Li Hsueh Pao 1991;12:250-2.
  6. Xu SS, Cai ZY, Qu ZW, et al. Huperzine-A in capsules and tablets for treating patients with Alzheimer disease. Zhongguo Yao Li Xue Bao 1999;20:486-90.
  7. Felgenhauer N, Zilker T, Worek F, Eyer P. Intoxication with huperzine A, a potent anticholinesterase found in the fir club moss. J Toxicol Clin Toxicol 2000;38:803-8.. PubMed
  8. Zhang, Z., Wang, X., Chen, Q., Shu, L., Wang, J., and Shan, G. [Clinical efficacy and safety of huperzine Alpha in treatment of mild to moderate Alzheimer disease, a placebo-controlled, double-blind, randomized trial]. Zhonghua Yi Xue Za Zhi 7-25-2002;82
  9. Cheng, D. H., Ren, H., and Tang, X. C. Huperzine A, a novel promising acetylcholinesterase inhibitor. Neuroreport 12-20-1996;8(1):97-101. PubMed
  10. Wang BS, Wang H, Wei ZH, Song YY, Zhang L, Chen HZ. Efficacy and safety of natural acetylcholinesterase inhibitor huperzine A in the treatment of Alzheimer's disease: an updated meta-analysis. J Neural Transm (Vienna) 2009;116(4):457-65. PubMed
  11. Xu ZQ, Liang XM, Juan-Wu, Zhang YF, Zhu CX, Jiang XJ. Treatment with Huperzine A improves cognition in vascular dementia patients. Cell Biochem Biophys 2012;62(1):55-8. PubMed
  12. Yang G, Wang Y, Tian J, Liu JP. Huperzine A for Alzheimer's disease: a systematic review and meta-analysis of randomized clinical trials. PLoS One 2013;8(9):e74916. PubMed
  13. Xing SH, Zhu CX, Zhang R, An L. Huperzine a in the treatment of Alzheimer's disease and vascular dementia: a meta-analysis. Evid Based Complement Alternat Med 2014;2014:363985. 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 Huperzine A and Esketamine Together: Common Questions

Is it safe to take Huperzine A with Esketamine?
We do not list a known interaction between Huperzine A 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 Huperzine A and Esketamine have any of the same side effects?
Yes — our sources link each of them separately to 4 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 Huperzine A 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 Huperzine A in each. That is a conversation for your prescriber, especially if Esketamine is being adjusted to a target.
How was the Huperzine A and Esketamine combination checked?
Interactions in our licensed database are recorded against drug classes. Esketamine is filed under 2 classifications, and Huperzine A 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 Huperzine A interact with any other medications?
Yes. Huperzine A has 219 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 — Huperzine A 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

Huperzine A 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 Huperzine A?

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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.