Huperzine-A is a cognitive enhancer that inhibits an enzyme that degrades the learning neurotransmitter, acetylcholine; due to this, a relative increase occurs. It belongs to the cholinergics class of molecules, and may be useful in fighting cognitive decline in the elderly. May need to be cycled.

This page features 21 unique references to scientific papers.

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All Essential Benefits/Effects/Facts & Information

In Progress

This page on Huperzine-A is currently marked as in-progress. We are still compiling research.

Huperzine-A is a compound extracted from the herbs of the Huperziceae family. It is known as an acetylcholinesterase inhibitor, which means that it stops an enzyme from breaking down acetylcholine which results in increases in acetylcholine.

Acetylcholine is known as the learning neurotransmitter, and is involved in muscle contraction as well. Increasing levels of acetylcholine is routinely used as a technique amongst weight-lifters and scholars.

Huperzine-A appears to be a relatively safe compound from animal studies of toxicity and studies in humans showing no side-effects at dosages routinely supplemented with. Huperzine-A is in preliminary trials for usage in fighting Alzheimer's Disease as well.

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Things to Know

Also Known As

(1R, 9S, 13E)-1-amino-13-ethylidene-11-methyl-6-azatricyclo- 2, 7 trideca-2(7), 3, 10-trien-5-on, Qian Ceng Ta (Huperzia Serrata)

Things to Note

  • Huperzine-A appears to be water-soluble, and taking with food is not needed

  • Although its initial spike is quick, it appears to have a long half-life; the pharmacokinetic profile might change when changing dosages though.

Is a Form Of

Goes Well With

Caution Notice

Consult your doctor before using if you are currently taking any anticholinergic drugs, acetylcholinesterase inhibitors, or cholinergic drugs. Medical Disclaimer

How to Take

Recommended dosage, active amounts, other details

Supplementation of huperzine-A tends to be in the range of 50-200mcg daily, and while this can be divided into multiple dosages throughout the day it tends to be taken at a single dose. Supplementation of huperzine-A does not require food to be coingested with it and can be taken in a fasted state.

Cycling of huperzine-A tends to be used since it can remain in the body for quite some time (half-life of 10-14 hours), and although a 'cycle' of huperzine-A tends to last 2-4 weeks followed by a break the optimal cycle length is not yet known.

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1Structure and Sources

1.1. Sources

Huperzine-A is a compound found in the plant families of Huperziaceae, Lycopodiaceae, and Selaginella.[1][2] It is normally extracted from the plants of the Huperziaceae family, but can be propogated in other cell lines for cheap mass production.[3] This synthetic Huperzine-A has bioequivlance to the natural version.

Its chemical structure is a pyridone moiety fused to a benzo{3,3,1}ring system with a ethylidene group attached to it. The (-)Huperzine stereoisomer is more bioactive than the (+)Huperzine Isomer.[2][4]

1.2. Isomers

Huperzine-B is a congener (like compound) to that of Huperzine-A with a similar pharmacodynamic profile. Huperzine-B is less potent acutely[5] but has a longer dissiciation and subsequently a greater potential safety index and therapeutic index.[6] It is also an NMDA antagonist[5] and neural anti-oxidant.[7] It is currently being chemically modified to increase potency without risking the longer dissociation.[8][9]


Orally administered tablets tend to appear in the blood in 15 minutes or less and peak at a variable time around 70 minutes post-ingestion.[10][11] It shows a biphasic response of a rapid serum increase followed by a slower excretion rate[10] and has an alpha and beta half-life of 21.13+/-7.28 and 716.25+/-130.18 min, respectively.[11] These half-lifes were noted to be different in another study though, in which Huperzine-A fitted a one-compartment model at 0.99mg.[10]

It appears in the cerebrospinal fluid and is easily able to cross the blood-brain barrier.[2]


3.1. Cholinergic Neurotransmission

Huperzine-A's most renowned action is that of an acetylcholinesterase inhibitor. Specifically, it can inhibit the G4 isoform of acetylcholinesterase which is highly prevalent in mammalian brains.[12] It is of greater or equal potency to other acetylcholinesterase inhibitors such as Tacrine or Rivastigmine.[12] It has a high affinity for acetylcholinesterase as an inhibitor, and a slow dissociation constant which enables a long active half-life.[13]

It may be preferable for usage as a cholinergic since it has been reported to have less cholinergic-related side-effects,[14] possibly through its high affinity for brain G4 acetylcholine resulting in less availability for systemic butrylcholine inhibition, which leads to various systemic effects which may be seen as side effects.[15][16]

3.2. Neuroprotection

In addition to acetylcholinesterase inhibition, it can also be seen as neuroprotective against glutamate,[17] beta-amyloid pigmentation,[18] and H2O2-induced toxicity.[19]

Huperzine-A can also block the NDMA receptor ion channel without psychomimetic side-effects.[20]

3.3. Neurogenesis

Huperzine-A is able to promote proliferation of hippocampal neural stem cells (NSCs) at a concentration of 1μM for 48 hours (which is more potent than 10-100μM) to 125% of control secondary to activating the ERK pathway,[21] and this neurogenesis was confimed in vivo with injections of 0.2mg/kg of huperzine-A for 4 weeks (about a 25% increase in BrdU stained cells, affecting both newborn and adult mice).[21]

Appears to promote neurogenesis in biologically relevant dosages

4Safety and Toxicity

A study in rats concluded that the LD50 (dose needed to acutely kill half a population of rats) was 2-4mg/kg bodyweight in females and >4mg/kg in males whereas others pinpoint the level at around 3mg/kg bodyweight over a longer period (180 days).[13] The NOAEL (No Observable Adverse Effects Limit) is postulated to be 1mg/kg for females rats, 3mg/kg for males rats, and 0.1mg/kg for canines. No toxicity data for humans currently exists.

Scientific Support & Reference Citations


  1. Howes MJ, Perry NS, Houghton PJ Plants with traditional uses and activities, relevant to the management of Alzheimer's disease and other cognitive disorders. Phytother Res. (2003)
  2. Ha GT, Wong RK, Zhang Y Huperzine a as potential treatment of Alzheimer's disease: an assessment on chemistry, pharmacology, and clinical studies. Chem Biodivers. (2011)
  3. Ma X, Gang DR In vitro production of huperzine A, a promising drug candidate for Alzheimer's disease. Phytochemistry. (2008)
  4. Total Synthesis of (−)-Huperzine A.
  5. Wang XD, et al. Comparison of the effects of cholinesterase inhibitors on {3H}MK-801 binding in rat cerebral cortex. Neurosci Lett. (1999)
  6. Rajendran V, et al. Synthesis of more potent analogues of the acetylcholinesterase inhibitor, huperzine B. Bioorg Med Chem Lett. (2002)
  7. Zhang HY, Tang XC Huperzine B, a novel acetylcholinesterase inhibitor, attenuates hydrogen peroxide induced injury in PC12 cells. Neurosci Lett. (2000)
  8. Feng S, et al. Bis-huperzine B: highly potent and selective acetylcholinesterase inhibitors. J Med Chem. (2005)
  9. He XC, et al. Study on dual-site inhibitors of acetylcholinesterase: Highly potent derivatives of bis- and bifunctional huperzine B. Bioorg Med Chem. (2007)
  10. Qian BC, et al. Pharmacokinetics of tablet huperzine A in six volunteers. Zhongguo Yao Li Xue Bao. (1995)
  11. Li YX, et al. Pharmacokinetics of huperzine A following oral administration to human volunteers. Eur J Drug Metab Pharmacokinet. (2007)
  12. Effects of huperzine A on acetylcholinesterase isoforms in vitro: comparison with tacrine, donepezil, rivastigmine and physostigmine.
  13. Chemistry, Pharmacology, and Clinical Efficacy of the Chinese Nootropic Agent Huperzine A.
  14. Development of huperzine A and B for treatment of Alzheimer’s disease.
  15. Boudinot E, et al. Effects of acetylcholinesterase and butyrylcholinesterase inhibition on breathing in mice adapted or not to reduced acetylcholinesterase. Pharmacol Biochem Behav. (2005)
  16. Lane RM, Potkin SG, Enz A Targeting acetylcholinesterase and butyrylcholinesterase in dementia. Int J Neuropsychopharmacol. (2006)
  17. Ved HS, et al. Huperzine A, a potential therapeutic agent for dementia, reduces neuronal cell death caused by glutamate. Neuroreport. (1997)
  18. Huperzine A regulates amyloid precursor protein processing via protein kinase C and mitogen-activated protein kinase pathways in neuroblastoma SK-N-SH cells over-expressing wild type human amyloid precursor protein 695.
  19. Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine.
  20. The NMDA receptor ion channel: a site for binding of Huperzine A.
  21. Ma T, et al. Huperzine A promotes hippocampal neurogenesis in vitro and in vivo. Brain Res. (2013)

(Common misspellings for Huperzine-A include Huperzine, huperizine, hooperzine, hooperzeen, huperzeen)