13 Health Benefits of Huperzine A

Huperzine A is an alkaloid extracted from a club moss called Huperzia serrata. Huperzine A has neuroprotective and nootropic properties and is suggested as a treatment for Alzheimer’s disease. Read this post to learn more about huperzine A and its health benefits.


Huperzine A (HupA) is an alkaloid extracted from club moss (Huperzia serrata).

Club moss (Qian Ceng Ta) was traditionally used in Chinese medicine for fever, inflammation, and schizophrenia (R, R2).

It has demonstrated both memory enhancement and neuroprotective effects in animal and clinical trials  (R).

There are two forms of huperzine A, (+) and (-). The (-) form is found naturally in the Huperzia moss and is more potent than the (+) form.

How Huperzine A Works

The impact of huperzine A can vary among people due to their genetic differences. Visit SelfDecode to learn how you can investigate your own genetic makeup to see how it affects the use of huperzine A.

Huperzine A Inhibits an Enzyme that Breaks Down Acetylcholine

Huperzine A is a potent, reversible, and specific inhibitor of the enzyme acetylcholine esterase (ACHE), which breaks down acetylcholine, although huperzine A also has other brain-supporting effects that do not involve ACHE (R).

Huperzine A binds to ACHE but its structure is not similar to that of acetylcholine.

Huperzine A works in similar ways to Alzheimer’s drugs, including donepezil, rivastigmine, tacrine, and galantamine, although with fewer side effects and somewhat more favorable pharmacokinetics (R).

Huperzine A helps with inflammation by reducing activities of NF-kB signaling, which may happen both through inhibition of acetylcholine esterase or in other ways (R).

Huperzine A Changes Neurotransmitter Levels

Huperzine A Increases Acetylcholine

Huperzine A increases acetylcholine levels in rat brain for up to 6 hours post administration (R).

Increase of acetylcholine seems to differ between different parts of the rat brain. Following administration, maximum levels are observed in the hippocampus after 30 min and in the frontal and prefrontal cortex after 60 min. This shows that it can influence the function of diseases that specifically affect these parts of the brain (R, R2).

Huperzine A results in a more prolonged increase in acetylcholine in the whole brain than tacrine, physostigmine, and metrifonate (R, R2, R3).

Huperzine A Increases Norepinephrine and Dopamine, but not Serotonin

Huperzine A increases levels of norepinephrine and dopamine, but not that of serotonin (R).

Pharmacokinetics of Huperzine A

Huperzine Crosses the Blood Brain Barrier

After injecting mice with 183 micrograms/kg Huperzine A, it was found throughout all regions of the brain, particularly in the cortex, hippocampus, and nucleus accumbens (R). Thus, huperzine A crossed the blood brain barrier and readily distributes throughout the brain.

Huperzine is Readily Absorbed and Turned Over

In humans, oral huperzine A is absorbed quickly, distributed widely and eliminated at a moderate rate (R).

In mice, huperzine A is highest in kidney and liver 15 minutes after injection. After 12 hours no trace of huperzine A is found anywhere in the body (R).

Huperzine A Crosses the Placenta

In pregnant mice a small amount of huperzine A is found in the fetus, suggesting huperzine A crosses the placenta (R).

Most Huperzine A in the Body is Eliminated in the Urine

In mice, 73% of huperzine A is excreted in urine 24 hours post-injection, and only 2.4% is found in feces (R).

Dosage Studies in Humans

At a very high dose of 0.99 mg, a peak serum concentration is reached at 79 minutes. Half of huperzine A is found (half-life) at 288 minutes, suggesting that it may be necessary to dose huperzine A multiple times a day to achieve continuous effects (R).

No notable side effects were observed at doses between 0.18 – 0.54 mg in humans (R).

No tolerance from continued use has been reported from repeated use (R).

Another study found that huperzine A appears in the blood at 5 – 10 minutes after subjects ingest 0.4 mg of huperzine A. Huperzine A in the blood reaches maximum concentration at around 58 minutes. After 10 hours 50% of it still present (half-life = 10 hours) and its mostly eliminated after 24 hours (R).

Health Benefits of Huperzine A

Neuroprotective Effects of Huperzine A

1) Huperzine A Protects Against Toxic Organophosphates

Nerve gasses and organophosphates are irreversible inhibitors of acetylcholine esterase. Huperzine A use can prevent seizures and nervous system dysfunctions caused by soman, an organophosphate (R, R2).

2) Huperzine A Protects Neurons Against Glutamate Toxicity

Glutamate is an amino acid neurotransmitter that can kill neuronal cells by overstimulating the NMDA receptors, especially in more mature neurons (R).

Huperzine A is an NMDA receptor antagonist, which means it can help prevent neurons from cell death due to glutamate toxicity (R).

3) Huperzine A Protects the Brain From Oxidative Damage

In addition to binding to NMDA receptors, huperzine A also alleviates oxidative damage from glutamate toxicity by activating BDNF-dependent and mTOR signaling pathways (R).

Huperzine A also protects against oxidative damage from iron overload (R).

4) Huperzine A Helps With Recovering from Traumatic Brain Injury and Spinal Cord Injury

Huperzine A, together with other brain-supporting substances (vinpocetine, acetyl-L-carnitine, n-acetyl cysteine, and alpha lipoic acid), multivitamin and fish oil, seem to help increase brain blood flow and improve cognitive functions in retired NFL football players with a history of concussions (R).

Huperzine A aids in recovery from brain bleeding by preventing damage to the mitochondria and postponing cell death (R).

Huperzine A decreases apoptosis and improved neurological symptoms in rats with spinal cord trauma (R).

5) Huperzine A Prevents and Treats Alzheimer’s Disease


In a systematic review of different interventions for Alzheimer’s, aggregate data from multiple studies show that huperzine A has a stronger (most statistically significant) effect in mitigating Alzheimer‘s and cognitive decline than other interventions. However, the quality of these studies is lower than the quality of studies of other interventions (R).

Many of such studies are poorly controlled or were not designed to rule out biases from the authors. In addition, most of the studies and clinical trials were from China.

Systematic comparison between various types of interventions for Alzheimer's disease. Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854009/

A systematic comparison between various types of interventions for Alzheimer‘s disease. Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854009/

By decreasing the inflammatory response triggered by amyloid beta huperzine A could stop apoptosis (R).

In some patients with Alzheimer’s Disease a clinical trial has shown that huperzine A improves mental ability and overall well-being (R).

Huperzine A significantly reduces the NF-kB pathway in immune cells in the brain, suggesting it reduces inflammation, which can help with Alzheimer’s (R).

6) Huperzine A Helps with Brain Damage from Severe Bacterial Infections (Sepsis)

In rats model of severe bacterial infection (sepsis), huperzine A protects the brain from damage by reducing inflammation and increasing functions of cholinergic neurons (R).

7) Huperzine A Helps with Cognitive Symptoms from Depression

As an add-on treatment for depression, huperzine A helped resolved some cognitive symptoms associated with depression but did not resolve depression itself (R).

8) Huperzine A Helps with Epileptic Seizures

In studies done on animals, Huperzine A was shown to protect brain cells from overexcitement and death associated with convulsions (R).

Huperzine A is an effective treatment of epilepsy in rats (R).

Huperzine A can make the tissue more resistant to seizures associated with various forms of epilepsy (R).

9) Huperzine Could be a Safe way to Treat Addiction


A study based on self-administration showed that huperzine A decreased the individual’s perception of the effects of cocaine and could be a safe way to treat addiction (R).

10) Huperzine A Promotes Liver Health


Huperzine A protects liver cells that receive oxygen after a prolonged period of deoxygenation.

Through its role as a controller of signaling pathways that govern oxidation and cell death, it can decrease the amount of damage caused to cells because of liver reoxygenation such as that which occurs during an organ transplant (R).

11) Huperzine A as a Nootropic

Huperzine A helps with memory in high school students when compared to a placebo (R).

Huperzine A helps with chemical-induced cognitive impairment in mice (R).

12) Huperzine A Promotes Growth of Neural Cells

Huperzine A can stimulate the growth of neuronal cells in the hippocampus of mice (R).

13) Huperzine A Helps with Myasthenia Gravis

Myasthenia gravis is an autoimmune disease where the immune system attacks acetylcholine receptors, and the treatments involve immunosuppressants and acetylcholine esterase inhibitors (R).

In one clinical study, involving 128 patients, huperzine A helped with muscle weakness in Myasthenia gravis patients (R).

Drug Interaction

Huperzine A is unlikely to interact with cytochrome P450.

Experiments using human liver cells have shown that it is not modified and excreted whole making it unable to react with other drugs that are metabolized by the cytochrome P450 system (R).


For Alzheimer’s patients, a dosage of 0.4 mg twice daily was required to produce clinically significant results, as 0.2 mg twice daily did not (R).

Dosages of huperzine A in clinical trials for Alzheimer’s range from 0.2 mg to 0.8 mg (R).

In high school students who struggle with memory, 0.1 mg was sufficient to improve memory (R).


Side Effects

Reported adverse effects are very rare, but are cholinergic symptoms, such as dizziness, nausea, digestive upsets, headache, and decreased heart rate (R).


  • HupA has a strong preference against tetrameric ACHE, and inhibits AchE by a non-covalent reversible interaction with the aromatic amino acids located in the catalytic gorge (R).
  • The neuroprotective effect of Huperzine A occurs concurrently with a decrease in ROS and an increase in ATP (R).
  • It is substantially excreted by kidney unchanged rather than metabolized by the human liver and is unlikely to cause clinically relevant drug-drug interaction (DDI) when co-administrated with drugs that are metabolized by CYP isoenzyme system (R).
  • Huperzine A significantly down-regulated p65 expression induced by Aβ in astrocytes (R).
  • Huperzine A can regulate NF-κB pathway to treat Alzheimer’s Disease (R).
  • It provides protection from excitotoxicity and neuronal death as well as an increase in GABAergic transmission associated with an anticonvulsant activity (R).
  • Huperzine A inhibits cell apoptosis through restraining microglia’s inflammatory response induced by Aβ1-42 (R).
  • HA treatment decreased mitochondrial injury and apoptosis, inhibited caspase-3 activation and cytochrome C translocation, and improved behavioral recovery (R).
  • Muscarinic and GABA receptors play a role in Huperzine A-mediated seizure protection (R).
  • Huperzine A might provide a novel therapeutic strategy for increasing seizure resistance in DS and GEFS+, and more broadly, in other forms of refractory epilepsy (R).
  • Huperzine A attenuates the HI/R injury of rats through its anti‑oxidative and anti‑apoptotic signaling pathways (R).
  • Huperzine A inhibits NF-kB activation, which attenuates nitric oxide synthase, cyclooxygenase -2 and nitric oxide over-expression by indirectly activating a type of acetylcholine receptors called α7nAChRs (R).
  • ZT-1 is a prodrug that is hydrolyzed into HupA.
  • Huperzine A stimulates nerve growth factor secretion and signaling (R).
How Huperzine A Helps with Alzheimer's, source: www.ncbi.nlm.nih.gov/pubmed/17056129

How Huperzine A Helps with Alzheimer’s, source: www.ncbi.nlm.nih.gov/pubmed/17056129
How Huperzine A Increases Acetylcholine levels in the brain

How Huperzine A Increases Acetylcholine levels in the brain, source: https://www.ncbi.nlm.nih.gov/pubmed/27086593


  1. Lee Ingram

    just letting you know I see what I think must be a typo – I think 100mg should be 100mcg? here –


    For Alzheimer’s patients, a dosage of 0.4 mg twice daily was required to produce clinically significant results, as 0.2 mg twice daily did not (R).

    Dosages of huperzine A in clinical trials for Alzheimer’s range from 0.2 mg to 0.8 mg (R).

    In high school students who struggle with memory, 100 mg was sufficient to improve memory (R).

    • Natcha M

      Hi Lauri, thanks for your comment.
      I looked into the studies and found that there’s one single paper about Huperzine A for MG patients. This paper is in Chinese, and I could not look further into the details to assess the quality of the study so I decided not to include this point at first. Because, in principle, Huperzine A could really help with MG as an AchE inhibitor, I decided to add it to the post. If you find any other references about this, please let me know. A translation of the original Chinese article: Cheng YS, Lu CZ, Ying ZL, Ni WY, Zhang CL, Sang GW. 128 Cases of
      myasthenia gravis treated with huperzine A. New Drugs Clin Remedies
      1986;5:197– 9 will be very welcomed as well. ~Team SelfHacked

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