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Huperzine A

Plant Part Used

Isolated from Chinese club moss.

Active Constituents

alkaloid N-oxides [huperzine J (1), huperzine K (2) and huperzine L (3)], (-)- huperzine A.(1),(2)

[span class=alert]This section is a list of chemical entities identified in this dietary supplement to possess pharmacological activity. This list does not imply that other, yet unidentified, constituents do not influence the pharmacological activity of this dietary supplement nor does it imply that any one constituent possesses greater influence on the overall pharmacological effect of this dietary supplement.[/span]


Huperzine A is extracted from the Chinese club moss (Huperzia serrata). Chinese club moss has been used for centuries in Chinese folk medicine for conditions such as blood loss, fever, as a diuretic, and for irregular menstruation.(3) Modern science, especially in China, has focused on huperzine’s potential benefit in memory and learning, along with treating patients with Alzheimer's disease and dementia.(4) Huperzine A has been reported to act as an acetylcholinesterase inhibitor similar to and as effective as pharmaceutical agents such as tacrine.(5),(6),(7)

HupA has been marketed in China as a new drug for Alzheimer's disease treatment and a derivative, ZT-1, is being developed as Alzheimer therapy candidate both in China and in Europe.(27)

The American Association for Geriatric Psychiatry made a statement in 2006 regarding the use of huperzine A for dementia – “Huperzine-A, an over-the-counter "nutraceutical," has been shown to have cholinesterase activity and may have efficacy as a treatment of the cognitive symptoms of AD in some clinical trials. However, Huperzine-A has not been adequately tested for this purpose and, given the alternative agents, is not high on the list of possible treatments.”(28)

Interactions and Depletions


Dosage Info

Dosage Range

50-800mcg, daily.

Most Common Dosage

400mcg daily.


[span class=doc]Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.[/span]

Not applicable.


Frequently Reported Uses

  • Alzheimer's Disease
  • Dementia
  • Memory Enhancement

Other Reported Uses

  • Organophosphate poisoning

Toxicities & Precautions


Huperzine A has been reported safe in recommended dosages.

Side Effects

Transient side effects such as dizziness may occur.(5)


The action of huperzine A has been attributed to its ability to strongly inhibit acetylcholinesterase, the enzyme that breaks down acetylcholine in the synaptic cleft.(8),(9) The inhibition is reversible, selective, and with a long duration of action.(10) One study measured the pharmacokinetics of huperzine A in six patients, reporting rapid absorption, wide distribution in the body, and elimination at a moderate rate.(11)

Acetylcholine is involved in memory and learning, and by inhibiting the enzyme that breaks it down, more acetylcholine becomes available to stimulate neurons. With this pharmacology, huperzine A is a potential agent in treating Alzheimer's disease, a condition where there is a relative shortage of acetylcholine.(10),(12) Huperzine A also has been reported in laboratory studies to regulate beta-amyloid presursor protein (APP) metabolism, protect against Abeta-mediated oxidative stress, apoptosis and mitochondrial dysfunction as well as anti-inflammatory effects.(29) Huperzine A may also aid in regulation of the expression and secretion of nerve growth factor (NGF) and NGF signaling.(30) The effects of huperzine A on amyloid beta-peptide (Abeta)-induced cell lesion, level of lipid peroxidation, antioxidant enzyme activities were investigated in vitro.(13),(14),(15) Preincubation of the cells with huperzine A prior to Abeta exposure elevated the cell survival and glutathione peroxidase and catalase activities, and decreased the level of malondialdehyde and superoxide dismutase activity. The authors concluded that huperzine A has protective effects against Abeta-induced cell toxicity, which might be beneficial for the treatment of Alzheimer's disease.

Huperzine A has exhibited memory-enhancing activities in a range of animal cognitive models with effects similar to and potentially even more effective than the pharmaceutical acetylcholinesterase inhibitors such as tacrine.(16),(17) Data indicates that huperzine A binds to the enzyme acylation site in the active site gorge, but interferes slightly with the binding of peripheral site ligands.(18) Laboratory animal studies have reported improvement in impaired learning and memory.(19),(20) Several human studies have been performed using huperzine A, both in China and the United States.(21),(22),(23),(31) A 2008 Cochrane Database System Review found that Huperzine A seems to have some beneficial effects on improvement of general cognitive function, global clinical status, behavioral disturbance and functional performance, with no obvious serious adverse events.(32) Larger, more rigorous trials are needed.

A small human study in China found that pre-treatment of patients before surgery with huperzine A produced a positive benefit on cerebral cholinergic system during recovery.(33)

As stated, huperzine A pharmacologically is an acetylcholinesterase inhibitor, with a potential for reversing organophosphate poisoning and decreasing the seizures seen with this type of poisoning.(24),(25) Huperzine A may be beneficial in treating the seizures associated with organophosphate poisoning in part due to a protective effect of both peripheral and central acetylcholine stores.(25) Another study reported neuroprotective effects of huperzine A, not only where cholinergic neurons are impaired, but also under conditions in which glutamatergic functions are compromised.(26)

A study was performed to compare the effectiveness of huperzine A in tablet and capsule form.(21) A multi-center, prospective, double-blind, double-mimic, parallel, randomized and positive controlled study of 60 patients with Alzheimer’s Disease reported that there is equal efficacy and safety between huperzine A in capsule and tablet form for treating patients with Alzheimer’s Disease.


  1. View Abstract: Raves ML, et al. Structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-huperzine A. Nat Struct Biol. Jan1997;4(1):57-63.
  2. View Abstract: Gao W, Li Y, Jiang S, Zhu D. Three lycopodium alkaloid N-oxides from Huperzia serrata. Planta Med. Oct2000;66(7):664-7.
  3. Pepping J. Huperzine A. Am J Health Syst Pharm. Mar2000;57(6):530, 533-4.
  4. Liu MY, et al. Intelligence promoting Chinese materia medica.Chung Kuo Chung Hsi I Chieh Ho Tsa Chih. Jan1995;15(1):59-61.
  5. Skolnick AA. Old Chinese herbal medicine used for fever yields possible new Alzheimer disease therapy. JAMA. Mar1997;277(10):776.
  6. View Abstract: Cheng DH, et al. Huperzine A, a novel promising acetylcholinesterase inhibitor. Neuroreport. Dec1996;8(1):97-101.
  7. View Abstract: Zhang RW, et al. Drug evaluation of huperzine A in the treatment of senile memory disorders. Chung Kuo Yao Li Hsueh Pao. May1991;12(3):250-2.
  8. View Abstract: Liu J, et al. Inhibitory effects of huperzine B on cholinesterase activity in mice. Chung Kuo Yao Li Hsueh Pao. Feb1999;20(2):141-5.
  9. View Abstract: Carlier PR, et al. Potent, easily synthesized huperzine A-tacrine hybrid acetylcholinesterase inhibitors. Bioorg Med Chem Lett. Aug1999;9(16):2335-8.
  10. View Abstract: Bai DL, et al. Huperzine A, a potential therapeutic agent for treatment of Alzheimer's disease. Curr Med Chem. Mar2000;7(3):355-74.
  11. View Abstract: Qian BC, et al. Pharmacokinetics of tablet huperzine A in six volunteers. Chung Kuo Yao Li Hsueh Pao. Sep1995;16(5):396-8.
  12. View Abstract: Tang XC. Huperzine A (shuangyiping): a promising drug for Alzheimer's disease. Chung Kuo Yao Li Hsueh Pao. Nov1996;17(6):481-4.
  13. View Abstract: Xiao XQ, Wang R, Han YF, Tang XC. Protective Effects of Huperzine A on Beta-amyloid(25-35) Induced Oxidative Injury in Rat Pheochromocytoma Cells. Neurosci Lett. Jun2000;286(3):155-8.
  14. View Abstract: Xiao XQ, Wang R, Tang XC. Huperzine A and Tacrine Attenuate Beta-amyloid Peptide-induced Oxidative Injury. J Neurosci Res. Sep2000;61(5):564-569.
  15. View Abstract: Xiao XQ, Zhang HY, Tang XC. Huperzine A attenuates amyloid beta-peptide fragment 25-35-induced apoptosis in rat cortical neurons via inhibiting reactive oxygen species formation and caspase-3 activation. J Neurosci Res. Jan2002;67(1):30-6.
  16. View Abstract: Barril X, et al. Predicting relative binding free energies of tacrine-huperzine A hybrids as inhibitors of acetylcholinesterase. J Med Chem. Dec1999;42(25):5110-9.
  17. View Abstract: Carlier PR, et al. Potent, easily synthesized huperzine A-tacrine hybrid acetylcholinesterase inhibitors. Bioorg Med Chem Lett. Aug1999;9(16):2335-8.
  18. View Abstract: Camps P, et al. Huprine X is a novel high-affinity inhibitor of acetylcholinesterase that is of interest for treatment of Alzheimer's disease. Mol Pharmacol. Feb2000;57(2):409-17.
  19. Zhu XD, et al. Improvement of impaired memory in mice by huperzine A and huperzine B. Chung Kuo Yao Li Hsueh Pao. Nov1988;9(6):492-7.
  20. Lu WH, et al. Improving effect of huperzine A on discrimination performance in aged rats and adult rats with experimental cognitive impairment. Chung Kuo Yao Li Hsueh Pao. Jan1988;9(1):11-5.
  21. View Abstract: Xu SS, et al. Huperzine-A in capsules and tablets for treating patients with Alzheimer disease. Chung Kuo Yao Li Hsueh Pao. Jun1999;20(6):486-90.
  22. View Abstract: Pilotaz F, et al. Huperzine a: an acetylcholinesterase inhibitor with high pharmacological potential. Ann Pharm Fr. Sep1999;57(5):363-73.
  23. Mazurek AA. Treatment of Alzheimer's disease. N Engl J Med. Mar2000;342(11):821.
  24. View Abstract: Lallement G. Pretreatment of organophosphate poisoning: potential interests of huperzine A. Ann Pharm Fr. Jan2000;58(1):13-7.
  25. View Abstract: Lallement G, et al. Efficacy of huperzine in preventing soman-induced seizures, neuropathological changes and lethality. Fundam Clin Pharmacol. 1997;11(5):387-94.
  26. View Abstract: Ved HS, et al. Huperzine A, a potential therapeutic agent for dementia, reduces neuronal cell death caused by glutamate. Neuroreport. Mar1997;8(4):963-8.
  27. Ma X, Tan C, Zhu D, Gang DR, Xiao P. Huperzine A from Huperzia species--an ethnopharmacolgical review. J Ethnopharmacol. 15 Aug 2007;113(1):15-34. Epub  2007 Jun 2. Review.
  28. Lyketsos CG, Colenda CC, Beck C, Blank K, Doraiswamy MP, Kalunian DA, Yaffe K; Task Force of American Association for Geriatric Psychiatry. Position statement of the American Association for Geriatric Psychiatry regarding principles of care for patients with dementia resulting from Alzheimer disease. Am J Geriatr Psychiatry. Jul 2006;14(7):561-572. No abstract available. Erratum in: Am J Geriatr Psychiatry. Sep 2006;14(9):808.
  29. Zhang HY, Zheng CY, Yan H, Wang ZF, Tang LL, Gao X, Tang XC. Potential therapeutic targets of huperzine A for Alzheimer's disease and vascular dementia. Chem Biol Interact. 25 Sep 2008;175(1-3):396-402. Epub 2008 May13. Review.
  30. Zhang HY, Tang XC. Neuroprotective effects of huperzine A: new therapeutic targets for neurodegenerative disease. Trends Pharmacol Sci. Dec 2006;27(12):619-625. Epub 2006 Oct 23.
  31. Desilets AR, Gickas JJ, Dunican KC. Role of huperzine a in the treatment of Alzheimer's disease. Ann. Pharmacother. 2009;43(3):514-518.
  32. Li J, Wu HM, Zhou RL, et al. Huperzine A for Alzheimer's disease. Cochrane Database Syst Rev. 16 Apr 2008;(2):CD005592.
  33. Wang G, Zhang SQ, Zhan H. [Effect of huperzine A on cerebral cholinesterase and acetylcholine in elderly patients during recovery from general anesthesia] Nan Fang Yi Ke Da Xue Xue Bao. Nov 2006;26(11):1660-1662. Chinese.

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