Skip to main content

Huperzine A

Scientific Name(s): Huperzia serrata (Thunb.) Trev., Lycopodium serratum (Thunb.).
Common Name(s): Brainmax, Chien Tseng Ta, Club moss, Jin Bu Buan, Memorzine, Neuroflow, Qian Ceng Ta, She Zu Cao, Shi Song

Medically reviewed by Last updated on Aug 23, 2021.

Clinical Overview


Historically, club moss has been used for the treatment of bruises, strains, swelling, rheumatism, and colds, to relax muscles and tendons, and to improve blood circulation. Because of its anticholinesterase activity, huperzine A, a constituent of the whole plant, has been studied for potential use in treating Alzheimer disease and other CNS disorders; however, there is still insufficient evidence to support its routine use.


Huperzine A has been studied at oral dosages of 0.2 to 0.4 mg/day for Alzheimer disease.


Contraindications have not been identified.


Information regarding safety and efficacy in pregnancy and lactation is lacking.


None well documented.

Adverse Reactions

In clinical trials, cholinergic adverse reactions have been noted, including hyperactivity, nasal obstruction, nausea, vomiting, diarrhea, insomnia, anxiety, dizziness, thirst, and constipation. One trial reported abnormalities in electrocardiogram (ECG) patterns (cardiac ischemia and arrhythmia).


Symptoms of acute toxicity are similar to those of other cholinergic inhibitors and include muscular tremor, drooling, tears, increased bronchial secretions, and incontinence. No mutagenicity or teratogenicity were found in rodent studies.

Scientific Family

  • Lycopodiaceae (club moss)


Huperzine A is isolated from the club moss Huperzia serrata, also known as Lycopodium serratum Thunb. Distributed worldwide, club moss is found in subtropical zones of the United States and in southern China. It has been extensively cultivated and may be threatened in the wild in China.

Club mosses are primitive, vascular plants that differ from true mosses by having specialized fluid-conducting tissues, but, like mosses, they reproduce by means of spores, which are either clustered into small cones or born in the axils of the small, scale-like leaves. Plants older than 15 years may only grow to 10 cm in height. Some species of Lycopodium are called ground pine or creeping cedar, especially those that resemble miniature hemlocks, with flattened fan-shaped branches often used for Christmas decorations.1, 2 A synonym is Lycopodium serratum Thunb.


The use of club moss can be traced back to the Chinese pharmacopoeias of the Tang dynasty as Shi Song, used for the treatment of rheumatism and colds, to relax muscles and tendons, and to improve blood circulation. As Qian Ceng Ta, it has been used for the treatment of bruises, strains, and swelling, and, more recently, for organophosphate poisoning, myasthenia gravis, and schizophrenia. The study of the chemistry and pharmacology of the plant and its alkaloids gained momentum in the 1980s from Chinese scientists.3, 4, 5, 6


A review of the chemical composition of club moss has been published. The plant contains mainly alkaloids, triterpenes, flavones, and phenolic acids. Four major structural classes of Lycopodium alkaloids have been described, including lycopodine, lycodine (to which huperzine A belongs), fawcettimines, and others.4 The yield of huperzine A from H. serrata is reported to be approximately 0.1% on a dry weight basis.7

Huperzine analogs have been synthesized to improve binding and pharmacological actions. More detailed analyses of huperzine B and the enantiomer of natural huperzine A have also been made.8, 9, 10, 11, 12, 13, 14, 15, 16

Uses and Pharmacology

Huperzine A is approved for use as a drug for the treatment of Alzheimer disease in China; however, it is regulated as an herbal supplement in the United States.17 Several firms (Solgar, Pharmavite, GNC, Kingchem, and NOW Foods) filed the required premarket notifications with the Food and Drug Administration between 1997 and 2000 for huperzine A products manufactured in China from natural sources.18

Alzheimer disease

A Cochrane review of the effect of huperzine A in Alzheimer disease has been published, as well as other reviews.19, 20, 21 All reviews note the lack of quality long-term clinical trials to support definitive statements about a place in therapy for huperzine A, despite the numerous clinical studies being undertaken.19, 20, 22

Animal data

Animal and in vitro experiments have been conducted, and the mechanism of action for huperzine appears to be a combination of anticholinesterase activity and antiglutamate, antioxidant, and neuroprotective effects.6, 9, 19, 21, 22, 23, 24, 25, 26 Huperzine A crosses the blood-brain barrier more effectively than tacrine or donepezil and acts with greater potency than tacrine, physostigmine, or galanthamine.22, 27 Huperzine A is selective for brain acetyl cholinesterase over plasma butyryl cholinesterase, which may account for its reported lower adverse effect profile in clinical studies.22, 28

Clinical data

Based on limited data, some beneficial effects are attributed to huperzine A in Alzheimer disease, including an increase in general cognitive function, global clinical status, behavioral disturbances, and physical performance. Not all measurement scales found positive effects for huperzine A over placebo.19 The results of a US multicenter, phase 2 clinical trial (now closed), in which huperzine A was evaluated at 2 different doses versus placebo, are awaited.22, 29 A systematic review and meta-analysis evaluating the effect of huperzine A for treatment of Alzheimer disease identified 20 randomized clinical trials that included over 1,800 participants; the quality of most trials had a high risk of bias. Regardless of disease course, disease severity, treatment preparation, dose, or duration, results showed favorable and sometimes significant effects on cognitive function and favorable effects on activities of daily living for huperzine A compared with placebo.43 The American Psychiatric Association (APA) guideline watch for the treatment of patients with Alzheimer disease and other dementias (2014) did not find enough definitive new evidence to change the 2007 guideline recommendations for alternative agents, including huperizine A.44

Other CNS effects


High quality clinical trials are lacking; however, 1 review of 4 clinical trials found improvement against memory, dementia, and Alzheimer scales,30 while a Cochrane review found only 1 clinical trial meeting inclusion criteria in which no difference compared with placebo was found for vascular dementia.31


Anticonvulsant activity of huperzine A has been demonstrated in mice, and a pilot clinical study is being undertaken.32

Organophosphate antidote

Huperzine A's potent inhibition of cholinesterase has also made it a candidate for prevention of poisoning by the nerve agent soman and other organophosphates. In contrast to pyridostigmine, huperzine A crosses the blood-brain barrier and, therefore, may be effective in preventing seizures and other neuropathology caused by soman.6, 33 Animal experiments have demonstrated activity against soman-induced seizures and mortality; however, clinical studies are lacking.9, 33, 34, 35, 36, 37

Parkinson disease

Protective effects have been demonstrated in mice models, but clinical trials are lacking.38


A small (N = 19), open-label clinical study found improved cognitive effects for huperzine A over 12 weeks.39 Clinical trials on the use of huperzine in schizophrenia in the United States are being prepared for recruitment.40, 41


Huperzine A in pure form has been studied at oral dosages of 0.2 to 0.4 mg/day for Alzheimer disease. It has also been administered intramuscularly at 0.06 to 0.4 mg/day in dementia studies.9, 19, 20, 21, 22, 30

In an open-label study among patients with schizophrenia, 0.3 mg/day for 12 weeks was used.39

The pharmacokinetics of huperzine A have been studied in healthy adult volunteers. A half-life of 288 minutes was reported, comparable with that of donepezil, while no tolerance was noted with multiple dosing.22 Transdermal patches have been tested in beagles.6

Pregnancy / Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.


Concomitant use of huperzine A with cholinesterase inhibitors could lead to potentiation of adverse reactions, although case reports are lacking.21

In vitro studies suggest potentiation of huperzine A by the green tea polyphenol epigallocatechin-3-gallate.42

Adverse Reactions

In clinical trials, cholinergic side effects were noted, including hyperactivity, nasal obstruction, nausea, vomiting, diarrhea, insomnia, anxiety, dizziness, thirst, and constipation. One trial reported abnormalities in ECG patterns (cardiac ischemia and arrhythmia).19


Symptoms of acute toxicity are similar to those of other cholinergic inhibitors and include muscular tremor, drooling, tears, increased bronchial secretions, and incontinence.22

The acute oral median lethal dose of huperzine A in rats has been reported as 4.6 mg/kg and as an intravenous dose of 0.63 mg.4 One toxicological study reported increases in serum aminotransferases.6 No pathological changes were found in histological studies of the liver, kidney, heart, lungs, or brain after 180 days of administration, and no mutagenicity or teratogenicity were found in rodent studies.4

Index Terms

  • Lycopodium serratum Thunb.
  • Club Moss
  • Creeping Cedar
  • Ground Pine


1. USDA, NRCS. 2009. The PLANTS Database (, December 2009). National Plant Data Center, Baton Rouge, LA 70874-4490 USA.
2. Ma X, Tan C, Zhu D, Gang DR. A survey of potential huperzine A natural resources in China: the Huperziaceae. J Ethnopharmacol. 2006;104(1-2):54-67.16203116
3. Tang XC, He XC, Bai DL. Huperzine A: a novel acetylcholinesterase inhibitor. Drugs Future. 1999;24(6):647-663.
4. Ma X, Tan C, Zhu D, Gang DR, Xiao P. Huperzine A from Huperzia species—an ethnopharmacolgical review. J Ethnopharmacol. 2007;113(1):15-34.17644292
5. Zhu XZ, Li XY, Liu J. Recent pharmacological studies on natural products in China. Eur J Pharmacol. 2004;500(1-3):221-230.15464035
6. Wang R, Yan H, Tang XC. Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine. Acta Pharmacol Sin. 2006;27(1):1-26.16364207
7. Yu CM, Tang XC, Liu JS, Han YY, inventors. Huperzines and analogs. US Patent 5,177,082. January 5, 1993.
8. Darrouzain F, André C, Ismaili L, Matoga M, Guillaume YC. Huperzine A—human serum albumin association: chromatographic and thermodynamic approach. J Chromatogr B Analyt Technol Biomed Life Sci. 2005;820(2):283-288.15899379
9. Jiang H, Luo X, Bai D. Progress in clinical, pharmacological, chemical and structural biological studies of huperzine A: a drug of traditional Chinese medicine origin for the treatment of Alzheimer's disease. Curr Med Chem. 2003;10(21):2231-2252.14529340
10. Foricher Y, Mann J. A convergent approach to huperzine A and analogues. Tetrahedron Lett. 2000;41(12):2007-2009.
11. Carlier PR, Du DM, Han YF, et al. Dimerization of an inactive fragment of huperzine A produces a drug with twice the potency of the natural product. Angew Chem Int Ed Engl. 2000;39(10):1775-1777.10934357
12. Dvir H, Jiang HL, Wong DM, et al. X-ray structures of Torpedo californica acetylcholinesterase complexed with (+)-huperzine A and (-)-huperzine B: structural evidence for an active site rearrangement. Biochemistry. 2002;41(35):10810-10818.12196020
13. Kozikowski AP, Miller CP, Yamada F, et al. Delineating the pharmacophoric elements of huperzine A: importance of the unsaturated three-carbon bridge to its AChE inhibitory activity. J Med Chem. 1991;34(12):3399-3402.1766006
14. Wong DM, Greenblatt HM, Dvir H, et al. Acetylcholinesterase complexed with bivalent ligands related to huperzine A: experimental evidence for species-dependent protein-ligand complementarity. J Am Chem Soc. 2003;125(2):363-373.12517147
15. Rajendran V, Saxena A, Doctor BP, Kozikowski AP. Synthesis of more potent analogues of the acetylcholinesterase inhibitor, huperzine B. Bioorg Med Chem Lett. 2002;12(11):1521-1523.12031333
16. McKinney M, Miller JH, Yamada F, Tuckmantel W, Lozikowski AP. Potencies and stereoselectivities of enantiomers of huperzine A for inhibition of rat cortical acetylcholinesterase. Eur J Pharmacol. 1991;203(2):303-305.1800123
17. Alzheimer Research Forum. Drugs in clinical trials. Huperzine A. Updated December 14, 2009. Accessed June 8, 2010.
18. 75-day premarket notification for new dietary ingredients. Dockets Management. Food and Drug Administration Web site. Published October 29, 1997. Accessed June 8, 2010.
19. Li J, Wu HM, Zhou RL, Liu GJ, Dong BR. Huperzine A for Alzheimer's disease. Cochrane Database Syst Rev. 2008;(2):CD005592.
20. Desilets AR, Gickas JJ, Dunican KC. Role of huperzine A in the treatment of Alzheimer's disease. Ann Pharmacother. 2009;43(3):514-518.19240260
21. Kelley BJ, Knopman DS. Alternative medicine and Alzheimer disease. Neurologist. 2008;14(5):299-306.18784599
22. Little JT, Walsh S, Aisen PS. An update on huperzine A as a treatment for Alzheimer's disease. Expert Opin Investig Drugs. 2008;17(2):209-215.18230054
23. Peng Y, Jiang L, Lee DY, Schachter SC, Ma Z, Lemere CA. Effects of huperzine A on amyloid precursor protein processing and beta-amyloid generation in human embryonic kidney 293 APP Swedish mutant cells. J Neurosci Res. 2006;84(4):903-911.16862548
24. Patil KD, Buerki RA, Patil PN. Potentiation of acetylcholine action by huperzine-A and physostigmine on some vertebrate effectors, including human iris sphincter muscle. J Ocul Pharmacol Ther. 2003;19(2):135-143.12804058
25. Tang LL, Wang R, Tang XC. Huperzine A protects SHSY5Y neuroblastoma cells against oxidative stress damage via nerve growth factor production. Eur J Pharmacol. 2005;519(1-2):9-15.16111675
26. Zhang HY, Yan H, Tang XC. Non-cholinergic effects of huperzine A: beyond inhibition of acetylcholinesterase. Cell Mol Neurobiol. 2008;28(2):173-183.17657601
27. Lallement G, Baille V, Baubichon D, et al. Review of the value of huperzine as pretreatment of organophosphate poisoning. Neurotoxicology. 2002;23(1):1-5. 12164543
28. Cheng DH, Tang XC. Comparative studies of huperzine A, E2020, and tacrine on behavior and cholinesterase activities. Pharmacol Biochem Behav. 1998;60(2):377-386.9632220
29. Aisen PS. Huperzine A in Alzheimer's disease (NCT00083590). Web site. Published May 26, 2004. Updated February 19, 2008. Accessed December 10, 2009.
30. Diamond B, Johnson S, Torsney K, et al. Complementary and alternative medicines in the treatment of dementia: an evidence-based review. Drugs Aging. 2003;20(13):981-998.14561102
31. Hao Z, Liu M, Liu Z, Lv D. Huperzine A for vascular dementia. Cochrane Database Syst Rev. 2009;(2):CD007365.19370686
32. Bialer M, Johannessen SI, Kupferberg HJ, Levy RH, Perucca E, Tomson T. Progress report on new antiepileptic drugs: a summary of the Eigth Eilat Conference (EILAT VIII). Epilepsy Res. 2007;73(1):1-52.17158031
33. Grunwald J, Raveh L, Doctor BP, Ashani Y. Huperzine A as a pretreatment candidate drug against nerve agent toxicity. Life Sci. 1994;54(14):991-997.8139389
34. Tonduli LS, Testylier G, Masqueliez, Lallement G, Monmaur P. Effects of Huperzine used as pre-treatment against soman-induced seizures. Neurotoxicology. 2001;22(1):29-37.11307848
35. Eckert S, Eyer P, Worek F. Reversible inhibition of acetylcholinesterase by carbamates or huperzine A increases residual activity of the enzyme upon soman challenge. Toxicology. 2007;233(1-3):180-186.17097792
36. Gordon RK, Haigh JR, Garcia GE, et al. Oral administration of pyridostigmine bromide and huperzine A protects human whole blood cholinesterases from ex vivo exposure to soman. Chem Biol Interact. 2005;157-158:239-246.16256090
37. Bajgar J, Fusek J, Kassa J, Kuca K, Jun D. Chemical aspects of pharmacological prophylaxis against nerve agent poisoning. Curr Med Chem. 2009;16(23):2977-2986.19689278
38. Chen LW, Wang YQ, Wei LC, Shi M, Chan YS. Chinese herbs and herbal extracts for neuroprotection of dopaminergic neurons and potential therapeutic treatment of Parkinson's disease. CNS Neurol Disord Drug Targets. 2007;6(4):273-281.17691984
39. Zhang ZJ, Tong Y, Wang XY, Yao SM, Jin GX, Wang XP. Huperzine A as add-on therapy in patients with treatment-resistant schizophrenia: an open-labeled trial. Schizophr Res. 2007;92(1-3):273-275.17383858
40. Woods SW. Huperzine for cognitive and functional impairment in schizophrenia (NCT00963846). Web site. Published August 10, 2009. Updated March 19, 2010. Accessed December 10, 2009.
41. Padala PR. Huperzine-A to help with mental problems and the inability to care for oneself in patients with schizophrenia (NCT01012830). Web site. Published November 12, 2009. Accessed December 10, 2009.
42. Zhang L, Cao H, Wen J, Xu M. Green tea polyphenol (-)-epigallocatechin-3-gallate enhances the inhibitory effect of huperzine A on acetylcholinesterase by increasing the affinity with serum albumin. Nutr Neurosci. 2009;12(4):142-148.19622237
43. Yang G, Wang Y, Tian J, Liu JP. Huperzine A for alzheimer’s disease: a systematic review and meta-analysis of randomized clinical trials. PLoSONE 2013;8(9):e74916.24086396
44. Rabins PV, Rovner BW, Rummans T, Schneider LS, Tariot PN. Guideline watch (October 2014): practice guideline for the treatment of patients with Alzheimer’s disease and other dementias. Accessed July 22, 2017.


This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

More about huperzine a

Related treatment guides

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.