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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 the club moss (Huperzia serrata).

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

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].

An 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, R].

Huperzine A results in a more prolonged increase in acetylcholine in the whole brain than tacrine, physostigmine, and metrifonate [R, R, R].

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

No tolerance for 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 the 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

1-5) Huperzine A is Neuroprotective

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].

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].

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].

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-acetylcysteine, and alpha lipoic acid), multivitamin and fish oil, seems 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].

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.

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].

How Huperzine A Helps with Alzheimer's, source:

Figure (1): How Huperzine A Helps 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 for 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].

Health Tools I Wish I Had When I Was Sick

At SelfHacked, it’s our goal to offer our readers all the tools possible to get optimally healthy. When I was struggling with chronic health issues I felt stuck because I didn’t have any tools to help me get better. I had to spend literally thousands of hours trying to read through studies on pubmed to figure out how the body worked and how to fix it.

That’s why I decided to create tools that will help others cut down the guesswork:

  • Lab Test Analyzer – a software tool that will analyze your labs and tell you what the optimal values are for each marker — as well as provide you with actionable tips and personalized health and lifestyle recommendations to help you get there.
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  • SelfHacked Secrets – an ebook where we examine and explain the biggest overlooked environmental factors that cause disease. This ebook is a great place to start your journey if you want to learn the essential steps to optimizing your health.
  • SelfHacked Elimination Diet course – a video course that will help you figure out which diet works best for you
  • Selfhacked Inflammation course – a video course on inflammation and how to bring it down
  • Biohacking insomnia – an ebook on how to get great sleep
  • Lectin Avoidance Cookbook – an e-cookbook for people with food sensitivities
  • BrainGauge – a device that detects subtle brain changes and allows you to test what’s working for you
  • SelfHacked VIP – an area where you can ask me (Joe) questions about health topics

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1 Star2 Stars3 Stars4 Stars5 Stars (28 votes, average: 4.18 out of 5)


  • Fern Heloiza

    Hi there Walter Foster.
    I’m very interested in hearing more details about your experience with the MG herbal mix from South Africa. Were you taking any meds for your MG at the time like the huperzine A or mestinon? Any interactions with the mix?
    What were the ingredients?
    Any healing reactions?

  • Rose Price

    Hi, I have been taking a product for a while now that contains Huperzine A (300mcg). The product has replaced all my meds for depression, anxiety, and and I am very satisfied. This product has changed my life! But I am now pregnant. I cant find anything on risks or safety for the Huperzine A. All other ingredients I feel are safe so I would like to keep taking this product. I am afraid if I don’t I will end up back on a lot of pharmaceuticals w a lot of side effects.
    Is there anyone who knows how this drug works that can tell me a more clear answer of safety or risk. I keep reading about it and it sounds good but since it crosses the placenta and blood brain barrier I just need to know more.
    Thank you!! Please someone w any info let me know!

  • Concerned

    I have been taking a product that contains huperzine a (300mcg) and it has really improved my life. I have been able to completely stop taking pharmaceutical drugs for depression, anxiety and also adhd. Recently I have found out I am pregnant. I cant find anything that tells me if this is still safe to take or not. I’ve scoured the internet. If I quit taking it I am afraid ill end up back on all sorts of pharmaceuticals w side effects. Is this safe while pregnant? I know it crosses the placenta and the blood brain barrier but I can’t find anything I can see as being a bad thing for the baby. But I am also super scared to take it as I cant find anything on pregnancy and breastfeeding while taking this. Does anyone who truly understands how this substance works have any idea if it should be safe or if not why not?
    Thank you!!!!
    All other ingredients in this product I have researched and deemed safe but I just cannot make my mind up on this one.

  • Walter foster

    I am a female patient with Myasthenia Gravis for 30 years and I have suffered tremendously because of this disorder. I had a thymectomy twenty five years ago and still have symptoms of MG. I came across Best Health Herbal Centre website after so many years researched through the internet. I was so desperate to find a way to treat this disorder naturally. Thank God for leading me to Best Health Herbal Centre. I started using Best Health Herbal Centre MG herbal formula this year. After 10 weeks of usage, my MG was totally reversed, symptoms like muscle weakness, difficulty swallowing, double vision, fatigue, impaired voice, or shortness of breath disappeared completely..Am now 67 years old living MG free.

  • Robert

    I am starting to take this for simple memory loss. Early dementia?? Not sure. Wasn’t diagnosed. Just want to sharpen up the grey matter somewhat. Hoping this will enhance my life. I’ll report back in a month or so. The Hup-A that I bought is 300 mcg. I plan to start with 1 pill a day.

  • Shane


    I plan on taking this for another reason, but is there any evidence as this article suggests that this may help with the positive symptoms of schizophrenia??

  • Susan F Goryan

    Been on it for 5 years, shortly after diagnosis and a thymectomy. It works great, no side effects in all these years and I don’t have to take any other treatment. However, I supplement my diet with vitamin D3 and make sure to eat a good diet, get plenty of rest, make sure if I am having some weakness that I have a glass of milk or a protein bar, banana or even a bottle of Boost and slow down! I am usually doing way too much as I feel so well on just huperzine. It doesn’t work for every mg patient but has been such a wonderful alternative to what the doctor wanted to treat me with, which needed constant dosage increases!

  • Susan F Goryan

    Correction: I mean 100 mcg 2-4 times a day in milder months, NOT 2-4 mcg’s.

  • Susan F Goryan

    I have myasthenia gravis and am so, so lucky to have found huperzine-A within 6 months of my diagnosis and subsequent thymectomy. I take 100 mcg 4-6 times a day in summer months when heat can really slow me down and 2-4 mcg’s the rest of the year. It has gotten me off of the usual prescription drug and keeps me stable from the weakness and usual necessity of other treatments.
    My neurologist would have me on constant RX drugs and plasma transfusions and I dropped him when he said NOT to take huperzine. Most doctors have no clue that their patients would rather use holistic and natural methods to live better lives, so doctors don’t know much about these alternate methods or seem afraid of them. Been on huperzine-only for more than 5 years and with a good diet and enough rest and listening to my body when I’m over doing something, I live a better life and am pretty active on huperzine….while I’m not in remission or cured, I am stable and without huperzine, I’d be on more & more drugs & treatments as the disease only has drastic treatments that only help for short periods…with huperzine, there are NO other treatments needed in my case!

  • Zhang Jian

    Yes, Lu CZ was the most famous neurologist in CHINA. Sang GW is the academician of China National Engineering Resarch Institute. The research is reliable.

  • 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).

    1. Nattha Wannissorn

      Oh yes. Great catch. Thanks. Corrected.

  • Ahmad Awadallah

    Since HuperzineA breaks down Acetylcholine does this mean one should also supplement with Acetylcholine?

    1. Natcha M

      Nope. It prevents or slow down break down of acetylcholine. You can’t really supplement with acetylcholine but you can increase production or decrease breakdown.

      1. Ahmad Awadallah

        Thank you.

  • Lauri

    It is effective treatment for Myasthenia Gravis too.

    1. 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

      1. Milka

        I have mg and I just started yesterday so far it seems that is working fine

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