Huperzine-A (Hup-A) is a water-soluble alkaloid nootropic derived from Chinese Club Moss (Huperzia serrata). This plant is native to southeast Asia. And has been used in traditional medicine for millennia to treat skin conditions, muscle problems and to boost blood circulation.
Huperzine-A is a reversible acetylcholinesterase (AChE) inhibitor. Which means it prevents the breakdown down of acetylcholine (ACh). Boosting short-term memory and long-term brain health.
Huperzine-A also seems to be a NMDA receptor antagonist. Which is beneficial in that it prevents an excess of glutamate from damaging brain cells.
Huperzine-A helps:
- Neurotransmitters: Huperzine-A prevents the enzyme AChE from breaking down acetylcholine. Improving cognition and memory.
- Brain Energy: Huperzine-A supports brain cell mitochondria. The primary energy sources fueling brain cells and brain cell function.
- Neuroprotectant: Huperzine-A works as an antioxidant and boosts the activity of other brain antioxidants. Preventing free radical damage in brain cells. And boosting brain cell longevity.
Table of Contents
Overview
Huperzine-A (Hup-A) is a water-soluble natural plant alkaloid nootropic that easily crosses the blood-brain barrier.
Hup-A is derived from Chinese Club Moss (Huperzia serrata). A plant native to southeast Asia where it’s been used in traditional medicine for thousands of years.
Huperzine-A has a strong inhibitory effect on acetylcholinesterase (AChE). This enzyme AChE, is responsible for degrading the neurotransmitter acetylcholine (ACh).
Boosting levels of acetylcholine (ACh) transmission in your brain improves memory and attention. And promotes greater neuroplasticity which is necessary for long-term memory formation and general brain cell health.
Huperzine-A is also a NMDA receptor antagonist. This glutamate receptor’s job is to control synaptic plasticity and memory function. Which is a positive thing. But blocking its function can also be effective at times. By preventing damage from too much glutamate. And blocking the toxicity from certain nerve agents.[i]
This combination of boosting acetylcholine and blocking NMDA receptors requires a fine balance. And could explain why it’s beneficial to cycle the use of Huperzine-A. To maintain the delicate balance of neurochemistry in the brain while realizing Huperzine-A’s benefits.
Huperzine-A vs. Huperzia serrata: What’s the Difference?
Huperzine-A (Hup-A) is produced in the lab from Huperzia serrata (Chinese Club Moss). Huperzine-A is a standardized compound found in this naturally occurring plant.
Note that Huperzine-A and Huperzine serrata are NOT the same supplement.
Some nootropic supplement stacks substitute genuine Huperzine-A with Huperzia serrata. All the research we’ve seen uses Huperzine-A in their trials. Not Huperzia serrata.
Look for nootropics stacks with genuine Huperzine-A on the label. Or sold as a stand-alone supplement. And avoid stacks or supplements called Huperzine serrata.
How does Huperzine-A Work in the Brain?
Huperzine-A boosts brain health and function in several ways. But two in particular stand out.
- Huperzine-A acts as an acetylcholinesterase (AChE) inhibitor. AChE is an enzyme that breaks down the important neurotransmitter acetylcholine. So Hup-A helps prevent this breakdown. Allowing more acetylcholine to be available which improves memory and learning.
Scientists at the Weizmann Institute in Israel uncovered how Huperzine-A works to block acetylcholinesterase (AChE). They made a 3-D image of the structure of the AChE molecule. And found a deep chasm, called the “active-site gorge”.
The scientists found the active-site gorge acts like a guide to funnel acetylcholine into the interior of the enzyme where it is cut apart prior to recycling. This is how AChE blocks acetylcholine.
The study revealed that Huperzine-A has the unique ability to fit into this active-site gorge. Like a key into a lock. And appears to bind more tightly and specifically to AChE than other AChE inhibitors.
This ability for Huperzine-A to take acetylcholine’s place within the AChE enzyme is how more acetylcholine is made available in the brain.
Professor Joel Sussman said, “It is as if this natural substance were ingeniously designed to fit into the exact spot in AChE where it will do the most good.”[ii]
- Huperzine-A also plays a neuroprotective role. Researchers discovered that Hup-A prevents glutamate-induced toxicity. Protecting the hippocampus and other cerebral neurons from cell death caused by the amino acid glutamate.[iii]
In addition to protecting from glutamate-induced toxicity, Huperzine-A also promotes new dendrite growth in neurons.[iv]
How things go bad:
As we get older, our brain chemistry and metabolism changes.
↓ Acetylcholine levels decline
↓ Concentration, attention and mental agility decline
↓ Nerve growth factor declines
↓ Free radicals damage brain cell mitochondria
All of these changes can happen at any age. And are a product of the food we eat, what we drink, lifestyle habits, the air we breathe and more.
So Huperzine-A can help for age-related cognitive decline, as well as a student looking to do better in school. By boosting the availability of acetylcholine in your brain.
Huperzine-A to the rescue
Huperzine-A boosts acetylcholine
Huperzine-A boosts levels of available acetylcholine in the brain by blocking the effect of the enzyme acetylcholinesterase (AChE).
Acetylcholine (ACh) is critical for encoding new memories, reasoning, concentration, cognition, and neuroplasticity. Not enough ACh can result in diseases like ADHD, Alzheimer’s and other neurodegenerative diseases.
Huperzine-A’s benefit as a nootropic can boost short-term mental performance like attention and memory. And even helping your brain for long-term brain health.
Huperzine-A is an antioxidant
Huperzine-A supports brain cell mitochondria. The main energy centers of each cell. It reduces free radical damage by acting as an antioxidant. Free radicals degrade mitochondria and their function. Studies have shown that Hup-A enhances the activities of other antioxidant enzymes as well.[v]
Huperzine-A resists beta-amyloid dysfunction
Huperzine-A boosts neuron resistance to beta-amyloid induced dysfunction that could lead to diseases like Alzheimer’s. Beta-amyloid affects ATP levels in mitochondria. Hup-A protects against this damage.[vi]
Huperzine-A prevents glutamate toxicity
Huperzine-A protects brain cells from glutamate toxicity. Too much of the neurotransmitter glutamate has been associated with brain cell degeneration. And other cognitive dysfunction and behavior. Hup-A seems to slow down this glutamate toxicity at least partly by acting as a NMDA receptor antagonist.[vii]
Huperzine-A increases nerve growth factor
Huperzine-A boosts nerve growth factor (NGF) in the brain. NGF is critical in brain cell development, maintenance and repair. Declines in NGF-levels in the brain are associated with Alzheimer’s and other neurodegenerative diseases. Studies show Hup-A not only prevents this drop in NGF from happening. It actually helps boost the production of NGF.[viii]
How does Huperzine-A feel?
Nootropics users report Huperzine-A provides a boost in mental energy. Without the side effects normally associated with a stimulant.
Improved cognition and clear thinking are common when using Hup-A. Many report a boost in short-term memory. Recall is better in the long-term.
And some with Alzheimer’s report the progression of the disease slows down. Instead of advancing.
You should be able to experience the effects of Huperzine-A soon after you take it. It’s water-soluble so it’s digested and enters your cells quickly.
One thing to note is; Huperzine-A has a long half-life. In other words, it does not leave your system nearly as quickly as most other nootropics. So many neurohackers restrict their use of Hup-A to a couple of times per week.
The Research
Huperzine-A is most known for boosting acetylcholine (ACh) in the brain. Efficient ACh neurotransmission is critical for learning, memory and attention.
Reduced levels of ACh are associated with declines in cognition and memory. And are implicated in several neurodegenerative diseases including Alzheimer’s, Parkinson’s, ALS and others.
Huperzine-A supplementation helps even in those with no sign of brain disease. It can enhance attention and memory in most looking to boost cognition.
Huperzine-A Provides Protection in Chemical Warfare
If you ever find yourself in a war-zone, you may want to stock up on Huperzine-A.
Researchers at the Walter Reed Army Institute of Research in Washington D.C. are investigating Huperzine-A’s potential as a pretreatment to protect soldiers against chemical warfare nerve agent poisoning.
One of the studies conducted at Walter Reed looked at Huperzine-A’s protective potential. Scientists found Hup-A to be twice as effective in protecting against the lethal effects of the nerve agent soman as the leading drug in that role called physostigmine. Huperzine-A’s effects lasted for six hours compared to only 90 minutes for the drug.[ix]
Huperzine-A Improves Learning & Memory
This study is verification of using Huperzine-A as a nootropic at any age. Researchers in China selected 68 students who complained of bad memory. And their learning performance was getting worse in school.
In this double-blind, placebo-controlled trial students were given either 100 mcg of Hup-A or a placebo for 4 weeks.
At the conclusion of the trial, researchers found that the students using Huperzine-A scored higher on memory testing than those who took the placebo.[x]
Huperzine-A Improves Cognition
Much of the research on Huperzine-A has been done in China. And many of the studies have been with patients suffering from neurodegenerative diseases like Alzheimer’s.
One study done in Shanghai worked with 200 patients who met the criteria for having Alzheimer’s Disease. Researchers gave one group of patients 300-500 mcg of Hup-A daily for 8 – 24 weeks. The other group got a placebo.
The results of the study showed that Huperzine-A’s effects increased over time. The patients that used Hup-A showed significant improvements in cognition, orientation, attention, memory, mood and behavior.[xi]
Dosage Notes
Recommended Huperzine-A dosage is 50 – 200 mcg every second or third day. Hup-A is water-soluble so you don’t need to take it with a meal, or healthy fat like some nootropics.
Huperzine-A is typically sold as 50, 100, or 200 mcg tablets or capsules. Several retail nootropic stacks often include Huperzine-A in their formula. So you should not supplement with more Hup-A while using these pre-made stacks.
Since Huperzine-A has at least a 24-hour half-life most neurohackers prefer cycling. This means using Hup-A every 2nd day, or even only twice per week.
Huperzine-A is also available as an injection for therapeutic use. Typically used to treat diseases like Alzheimer’s. Or the muscle weakness condition called myasthenia gravis.
Side Effects
Huperzine-A can be toxic if used in larger than recommended doses. Or if you already have too much acetylcholine(ACh) in your system. Remember, Hup-A boosts levels of ACh.
Side effects with Huperzine-A are rare but can include symptoms similar to choline-overload like nausea, vomiting, diarrhea, insomnia, anxiety, dizziness, thirst and constipation.
Very rarely will Huperzine-A cause cardiac arrhythmia.
Symptoms of acute toxicity are similar to those of other cholinergic inhibitors. And can include muscle tremors, drooling, tears, bronchial mucous and incontinence.
Do not use Huperzine-A if you’re dealing with epilepsy. And if you have heart disease, use Hup-a with caution. It can slow heart rate.
Huperzine-A may make asthma or emphysema worse. Because it can cause mucous in the lungs. The same goes for those dealing with urinary tract or reproductive system blockages. It can cause mucous buildup there as well.
An important note for Alzheimer’s patients: Huperzine-A can increase the effects of drugs you may already be taking. Talk to your doctor before trying Hup-A.
Available Forms
Huperzine-A is sold in tablet or capsule form. Tablets and capsules are usually 50 – 200 mcg each.
Some ready-made nootropic stacks include Huperzine-A in their formula.
Huperzia serrata is simply raw, powdered Chinese Club Moss and should be avoided. It’s not standardized so you don’t know how much you’re getting. And it’s NOT the same as Huperzine-A.
Nootropics Expert Recommendation
Huperzine-A 200 mcg every 2nd or 3rd day
We recommend using Huperzine-A as a nootropic supplement.
Your body does not make Huperzine-A on its own. So to get its benefits you must take it as a supplement.
Huperzine-A is especially helpful for those suffering from cognitive dysfunction caused by diseases like Alzheimer’s.
Huperzine-A is also particularly useful to students and executives who want to boost cognition, learning and memory.
Huperzine-A is a fast-acting nootropic that can also help prevent brain degeneration later in life.
Huperzine-A does have a long half-life so you may want to cycle it. Either take it every 2nd day, or even twice per week. The benefits are long-lasting and will stay with you.
[i] Coleman B.R., Ratcliffe R.H., Oguntayo S.A., Shi X., Doctor B.P., Gordon R.K., Nambiar M.P. “[+]-Huperzine A treatment protects against N-methyl-D-aspartate-induced seizure/status epilepticus in rats.” Chemico-Biological Interactions. 2008 Sep 25;175(1-3):387-95. (source)
[ii] Raves M.L., Harel M., Pang Y.P., Silman I., Kozikowski A.P., Sussman J.L. “Structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-huperzine A.” Nature Structural Biology. 1997 Jan;4(1):57-63. (source)
[iii] Gordon R.K., Nigam S.V., Weitz J.A., Dave J.R., Doctor B.P., Ved H.S. “The NMDA receptor ion channel: a site for binding of Huperzine A.” Journal of Applied Toxicology. 2001 Dec;21 Suppl 1:S47-51. (source)
[iv] Shen J.N., Wang D.S., Wang R. “The protection of acetylcholinesterase inhibitor on β-amyloid-induced injury of neurite outgrowth via regulating axon guidance related genes expression in neuronal cells” International Journal of Clinical and Experimental Pathology. 2012; 5(9): 900–913. (source)
[v] Xiao X.Q., Wang R., Han Y.F., Tang X.C. “Protective effects of huperzine A on beta-amyloid(25-35) induced oxidative injury in rat pheochromocytoma cells.” Neuroscience Letters. 2000 Jun 9;286(3):155-8. (source)
[vi] Gao X., Tang X.C. “Huperzine A attenuates mitochondrial dysfunction in beta-amyloid-treated PC12 cells by reducing oxygen free radicals accumulation and improving mitochondrial energy metabolism.”Journal of Neuroscience Research. 2006 May 1;83(6):1048-57. (source)
[vii] Hynd M.R., Scott H.L., Dodd P.R. “Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer’s disease.”Neurochemistry International. 2004 Oct;45(5):583-95. (source)
[viii] Tang L.L., Wang R., Tang X.C. “Effects of huperzine A on secretion of nerve growth factor in cultured rat cortical astrocytes and neurite outgrowth in rat PC12 cells.” Acta Pharmacologica Sinica. 2005 Jun;26(6):673-8. (source)
[ix] Saxena A., Qian N., Kovach I.M., Kozikowski A.P., Pang Y.P., Vellom D.C., Radić Z., Quinn D., Taylor P., Doctor B.P. “Identification of amino acid residues involved in the binding of Huperzine A to cholinesterases.” Protein Science. 1994 Oct;3(10):1770-8. (source)
[x] Sun Q., et. Al. “Huperzine-A capsules enhance memory and learning performance in 34 pairs of matched adolescent students” Acta Pharmacologica Sinica 1999; (7)：601—603 (source)
[xi] Wang B.S., Wang H., Wei Z.H., Song Y.Y., Zhang L., Chen H.Z. “Efficacy and safety of natural acetylcholinesterase inhibitor huperzine A in the treatment of Alzheimer’s disease: an updated meta-analysis.”Journal of Neural Transmission (Vienna). 2009 Apr;116(4):457-65. (source)
Hi David,
thanks for the great Huperzine-A article, I better understand how it works. However, within the half-life of Huperzine-A, multiple sources reports only 10-14 hours, not 24 as you indicate. Are you sure about that?
R.
Radek, I’ve checked this multiple times and based my findings on clinical studies. I caution you about what you read. Because often one blogger back in 1993 made some statement and everyone but me copies them without checking the accuracy of the information.
I can prove my source. Can they prove theirs?
Hello David,
What are good nootropics to stack with huperzine a and which ones are to be avoided when stacking with huperzine a?
Thanks
Lora
Lora, it’s impossible to answer your question about which nootropics should be stacked with Huperzine-A because it depends on what your goals are.
And please go back and learn the mechanism of action of this nootropic and how it “works in your brain”. All is explained in this review.
Huperzine-A is an acetylcholinesterase (AChE) inhibitor. Which means it prevents the breakdown down of acetylcholine (ACh). You need to be careful with any other nootropic that also increases acetylcholine. Because excess ACh produces side effects like fatigue.
David, i just found this article, and have seen that i shouldnt be taking this. im kind of worried, as for the past couple of months i have been takinga lot of choline type pills, am i in danger? should I take the Hup, or the Alpha/CDP/Uridine pills? which is better?
this is what i take every day
Huperzine-A 200mcg 2 times per day
Alpha GPC 300mg 1-2 times per day
CDP Choline 300mg 1-2 times per day
Uridine 300mg 1-2 times per day
Sulbutiamine 500mg 1 per day
Magnesium L-Threonate 2000mg 1 per day
in addition to:
5-HTP 400mg 1 per day
Lions Mane 2100mg 1 per day
Rhodiola Rosea 600mg 1 per day
KSM-66 1000mg 1 per day
Vitamins:
C 1000mg
MSM 3000mg
Evening Primrose Oil 1300mg
Omega 3 fish oil 1200MG EPA/900MG DHA
D3 800iu/calcium 600mg
Biotin 10,000MCG
10G Multi Collagen powder
Adam, it could be that your brain and body are starved for acetylcholine. Which may be the reason why you are not yet experiencing side effects from too much of this neurotransmitter.
But the thing is Huperzine-A has a half-life of 24 hours. Which means that if you use it every day it keeps building up in your system. And sooner or later this will backfire on you badly.
As long as this is working for you the only thing I’d strongly recommend is cutting back on your Huperzine-A dosage to once every 2 or 3 days.
I currently take adderall, and also take tyrosine, magnesium and citicoline. Would it be safe to add Hup A in the morning? What effects would it have on adderall?
Josh, Huperzine-A is an acetylcholinesterase (AChE) inhibitor. Which means it increases acetylcholine. Citicoline also increases acetylcholine.
I don’t see much benefit in your using it considering the rest of your stack. You can try it and see if it helps in any way.
There is no contraindication with Adderall that I’m am aware of. But keep in mind its half-life is 24 hours. So if you do decide to use Hup-A you should only use in every 2nd or 3rd day.
David
Whats the difference between 1% Huperzine A and 5% and 98% and 99%? Whats the heaviest concentration of these? 1 miligram of 1 % huperzine A is the equivalent of 100 mcg of huperzine A. So takeing 1/64th of a teaspoon of 1% huperzine A = 15 milgrams of huperzine A. This is extremely potent.
But. 99% huperzine A is being sold in 100mcg??? I dont under stand this math???
CY, I think you are mistaking Huperzia serrata for Huperzine-A. They are not the same thing. There is only one type of Huperzine-A which is a water-soluble alkaloid derived from Chinese Club Moss (Huperzia serrata).
I tried Huperzine-A for about a week recently and had a weird time with it. I just took a beginning dose. I noticed that I got progressively more tired and unmotivated as the week went on. By the end of the week, it took all the effort I had to pry myself out of bed. Once I stopped taking it, my energy and motivation climbed back to normal after maybe a couple days. I wasn’t taking any other nootropics or meds during that week. I don’t think I’ll be trying it again for a while, but I was wondering if you had any theory as to what this might tell me about my brain’s needs?
Thank you.
Kevin, if you were using it every day it was forcing the synthesis of more and more acetylcholine without giving your body a break. Too much acetylcholine is bad news.
Hello David,
Can we take Huperzine A with a meal?Does it absorb the same way as with empty stomach?
Thank you,
Rui
Rui, Huperzine-A is water soluble so you can take it with or without a meal. Works just as well on an empty stomach and taken with water.
ive watched the video of huperzine a what it does to boost acetycholine but some of the side effects that may occur is slow down the heart rate is in a rare occassion it may happen in order to boost acetycholine to you need other supplements like cdp choline , alpha gpc , bacopa monneri these increase acetycholine
Cihan, if your primary goal is to increase acetylcholine then CDP-Choline or Alpha GPC are much better choices.
but when it mentions for huperzine a will either block or reduce glutamate from toxicity from over exited cells will alpha gpc and cdp choline reduce glutamate the promblem with me is i do get overexited too quickly . if you reduce glutamate in the brain would’nt that mean you nerve cells won’t be as excited as much because the neurotransmitter gaba and glutamate does need to be balanced i probably also have way more glutamte and very low of gaba and same with serotonin
Cihan, Huperzine-A is a NMDA-receptor antagonist which means it prevents their over-excitation and modulates glutamate as a result. But this requires a fine balance and one of the reasons it’s wise to cycle this nootropic. And only use it every 2nd or 3rd day.
But it’s biggest claim to fame is as an acetylcholinesterase inhibitor. Which means it boosts acetylcholine.
This is not a nootropic to mess around with. If your neurotransmitters are out of whack as you suggest I would not suggest using Huperzine-A. Because it could throw things out of balance even more.
Hey David, i bought a premade stack that i bought primarily for the Lions mane, panax ginseng, bacopa monnierie and rhodiola rosea. However it also contains 50mcg of huperzine-a.
My question now is,
Since i already take cdp choline, ALCAR and uridine monophosphate 2-3 days a week , would it be ok to take the premade stack that contains huperzine-a 2-3 days a week when i don’t take the other supplements?
2-3 days cdp-choline, ALCAR, uridine monophosphate
and then
2-3 days of the premade stack that contains huperzine-a 50mcg
or should i remove one of those stacks completely to avoid boosting my acetylcholine levels too high?
Frank, the stack containing Huperzine-A needs to be taken every 2nd day. The rest of your supplements can be taken 2 – 3 times daily if you need them.
Everyone’s brain is different. Only you can know if you are getting too much acetylcholine (ACh). Look up the symptoms of excess ACh so you know what to watch out for.
Thank you a lot for your fast reply.
I have be taking Huperzine A, 200mcg pills, 4 times a day, a total of 800mcg for the last 5 years. I am 82 years old and on the border between MCI and dementia. I was not dreaming at night prior to the Huperzine A, which I do now, a little buzzing in my ears for a few minutes when I first wake up. It does not seem to help my memory but I think more clearly. I live by myself, still drive and can play video games. If I don’t see my friends for a couple of months, I forget their names. Energy level is fair and I sleep 8 to 10 hours. I was told my my Neurologist 5 years ago to take Huperzine A.
Herbert, that’s a lot of Huperzine-A to be using especially every day. It’s good that it works for you. But for most people that would be far too much and too often considering that its half-life in your body is 24 hours.
If I want to take Huperzine A and use it everyday without cycling, do you think it would be safe using a lower dose like 25 – 50 Micrograms daily?
Shauna, no because of it’s half-life. Dosing every day will have serious consequences on your acetylcholine levels. It’s just not worth it.
Hi David. I see that you don’t include Huperzine A in your own daily stack. I know you do take plenty of choline precursors, but is there another reason why you don’t include it in your daily stack? I noticed that the old mind lab pro formula use to include it but then changed the formula. You only kept taking the Vipocentine if I’m not mistaken. Thanks a bunch.
Derek, there simply isn’t any good reason for me to use Huperzine-A. It’s a hassle having to remember to cycle it because of its unusually long half-life. And you are right in that I’m using other acetylcholine precursors so don’t need to use Huperzine-A.
Mr. David , I can not find any form of genuine Huperzine-A , all I see online is Huperzia serrata. On every label where it list Ingredients, Made from
Huperzia serrata leaf standardized extract or it will say, A standardized mental tonic derived from the Chinese club moss Huperzia serrata. So if you know of a company who makes it without the Serrata, could you let me know. Maybe I miss understood ,maybe it was Huperzia serrata I am suppose to look for. Thanks for any feed back on this.
Tammy, Huperzine-A is a standardized extract of Huperzia serrata. I know that Double Wood Supplements and Source Naturals sell a Huperzine-A product. The label should say “Huperzine-A” or “Huperzine-A (Huperzia serrata leaf standardized extract)”.
Hey David, the one from source naturals says that it has Huperizien a (from Huperzia serrata whole plant extract). Is that okay?
Huperzia serrata is simply raw, powdered Chinese Club Moss and should be avoided. It’s not standardized so you don’t know how much you’re getting. And it’s NOT the same as Huperzine-A.
To clarify the Huperizien a from Source naturals not good and should be avoided? Thank you for the help.
Ish, I took a look at the label of the Source Naturals Hup-A I think you are referring to. It appears to be a standardized extract which is preferred.
Thank you for clarifying David.