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 benefits
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 of 10 – 14 hours. 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 2 or 3-times per week.
Huperzine-A Clinical 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]
Huperzine-A Recommended Dosage
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 10 – 14 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.
Huperzine-A 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.
Types of Huperzine-A to Buy
Huperzine-A is sold in tablet or capsule form. Tablets and capsules are usually 50 – 200 mcg each.
Be careful with pre-made nootropic stacks containing Huperzine-A where the manufacturer recommends daily use. Because Huperzine-A should only be used every 2nd or 3rd day because of its 10 – 14 hr. half-life.
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
I recommend using Huperzine-A as a nootropic supplement with caution.
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 10 – 14 hr. half-life so you should 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)
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Antagonism of nmda receptors will not reduce the production of GABA?
Nope. Everything you wanted to know about NMDA receptors can be found here: https://www.ncbi.nlm.nih.gov/books/NBK519495/. And producing GABA, or anything to do with GABA is not one of them.
It seems to me that in the long run it may work the opposite of what is expected…
There is much evidence that strong NMDA receptor antagonists impair memory.
NMDA receptor antagonists do impair memory. That is why you follow dosage recommendations including only using it every 2nd or 3rd day.
Can i stack Huperzine-A if i’m already on 10g of sunflower lecithin and 300mg Alpha GPC per day?
Alex, 10 grams of lecithin is a LOT of lecithin. I suggest revisiting that one. Of ditch it altogether and use sunflower lecithin-based phosphatidylserine instead.
Huperzine-A will potentiate that way a choline supplement works because it is a potent acetylcholinesterase inhibitor. And it is possible to have too much acetylcholine. But only you can figure this out for you and your system. And keep in mind that you should only use Huperzine-A every 2nd or 3rd day because of its 12 – 14 hour half-life.
Thanks for the reply
The Main reason i take the lecithin is because it helps me reach my daily choline intake. I don’t eat eggs so stuggle to get enough and this gives me an extra 330mg. I’ll give the phosphatidylserine a try.
After it I feel anxious and very sleepy.
Huperzine-A is a very powerful acetylcholinesterase inhibitor. So, unless you need to reuse the acetylcholine already in your system for some reason it’s not a good idea to use Huperzine-A as a supplement.
David, what is your opinion on Noocube using Huperzine serrata 0.5% Hup A
20mg in that stack? Is that safe to take daily?
Also, what does that mean 0.5% Hup A in 20mg?
Will that mean only 5mg of Hup A is there?
If this is, is this amount still needs to be recycled?
Marcie, I’d need to look up the label on that pre-made stack to understand the exact amount of Huperzine-A. But they did as me to become an affiliate and recommend their product and I turned them down. Because I refuse to recommend any supplement that is meant to be use daily if it contains any amount of Huperzine-A. There are far better choices on the market than that stack.
Hi David, is it necessary to take a choline supplement with Huperzine?
Thank you
Kenneth, it is not necessary to use a choline supplement with Huperzine-A. The biggest concern with this nootropic is its long half life which is why it should be used only every 2nd or 3rd day. And NOT every day.
Please say “Huperzine A
(from toothed clubmoss [Huperzia serrata] whole plant Extract)” is it Huperzine A or a plant?
Loki, scroll back up and read this section “Huperzine-A vs. Huperzia serrata: What’s the Difference?”
Isn’t it dangerous to take it with cdf-choline, pc and any other choline? the half-life is a maximum of 14 hours, why take such a break and take it every 2 days, isn’t it better every other day?
Or can its effects last for more than a day? I did not find such information.
Daniel use Huperzine-A every 2nd day to prevent it building up in your system. It will potentiate the way other sources of choline work in your system so be careful about how much you use. If you are using CDP-Choline it is not necessary to also use Phosphatidylcholine (PC).
Do you mean every 48 hours?
Yes, every 48 hours.
Forgive my last question…I didn’t realize you had an entire website with more information. I had landed on this particular page during a search for Hup A.
After looking through your personal supplement list, it appears you do not take Hup A. Is there a contraindication with Hup A and citicoline? I am interested in the Mindlab Pro stack supplement and Hup A. Would this be too much considering there is Citicoline in the other supplement?
Thanks again!
Mia, this is the Huperzine-A supplement I recommend: https://geni.us/QQVBk (Amazon). But keep in mind you should only use this supplement every 2nd day or it will build up in your system. Possibly to unsafe levels.
Using Huperzine-A will potentiate the way Citicoline works. So Mind Lab Pro may work a little better for you using them together. I suggest trying Mind Lab Pro on its own for a week or two. Then add Huperzine-A and see how it feels.
Hi thank you so much for the information you have researched and shared here on your site.
Do you have a particular brand you have researched for Hup A? A quick look online and I’m already overwhelmed. Would like to know if you use a reputable and trustworthy brand.
Many Thanks!
Hi David,
So I started on citicholine (cdp choline) two days ago. I experienced little heavy headedness the first day but my focus was much better and very less internal monologue. I use it for studying.
But on the 3rd day I did not experience the same benefits. Is it because I’m missing ALCAR? I do take a multivitamin with bio available b complex.
Thanks.
Jatin, you need ALCAR as a cofactor to make acetylcholine along with Vitamins B1 & B5. Citicoline can not do it on its own.
acting as an NMDA receptor antagonist, how much does it reduce the action of glutamate? Glutamate is also important for the brain
Daniel, scroll back up and read the 2 paragraphs right above the sub-head “Huperzine-A vs. Huperzia serrata: What’s the Difference?“
Hi David,
I’ve received my Huperzine A today and toke the first pill. I’m also taking Ashwagandha combined with either caffeine or Guaranà.
Is it ok to combined them together? I’m also taking Magnesium and planning to combine Alpha GPC
Marcello, there are no known contraindications so you should be safe. Just make sure you only use Huperzine-A every 2nd or 3rd day because of its long half-life.
I have been taking Huperzine , 200 mcg, daily for years. Over past 6 months, I have developed frequent premature ventricular contractions requiring to take beta blockers. Do you think there is a connections with Huperzine usage?
Jerry, that is one of the very rare side effects from using Huperzine-A.
Greetings David,
Can I take HUP-A together with lion’s mane? Also, what time of the day should I take HUP-A? Is it a good idea taking it before going to bed? Thanks in advance.
Histor there is no problem taking both of those supplements together. But not sure why you would want to take Huperzine-A before bed. Your brain using acetylcholine primarily during the day.