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. 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.
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 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.
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 24 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 24 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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David – You said on one of your pages – Hup A should be cycled -I saw a formula they rated# 1 for many reasons incl it has too 3 nootropics / the nutropics – besides the nutrients were in a proprietary blend – 617 mg. HUP A in there – is it a problem taking that daily for a while cause you said Hup A should be cycled -? Did you say that because it could build up ? What is side effect from build up – if there is one ? I get these barriers so often . I just want to know if a reason I should not take daily for a while- because of what you said about Hup A and 24 hours .
Steve, I avoid those types of pre-formulated nootropic supplement like the plague if they contain Huperzine-A. Hup-A is an acetylcholinesterase inhibitor with a 24 hour half-life. That means that if you take it every day it’ll build up in your system and bad things will happen.
Consider that acetylcholinesterase inhibitors are used in biological warfare for exactly that reason.
Hello David, i am planning on using Huperzine-A and cdp-choline. Can i combine both or should i rather alternate between the two? Using either Huperzine or cdp-choline as i want to avoid ach levels that are too high.
Regards,
Edgar, it depends on the dosage for each. If you keep both low you may be OK. But keep in mind you can only safely use Huperzine-A every 2nd or 3rd day.
Hi David,
Is it OK to stack Huperzine-A with Bacopa or would that be too much ACh?
thank you,
Kevin, it may be too much if you combine the two because both are acetylcholinesterase inhibitors.
And keep in mind the half-life of Huperzine-A is about 24 hours. So you should only use it every 2nd or 3rd day.
Hi david
I tried huperzine A the first time 200mcg around 11pm and I had side effects of nausea and vomiting. After that my eyes start to itch .
I could not sleep. It was the first time I was so wide awake. I manage to slept at 4am but it wasn’t deep sleep and I had lucid dream and was drooling all over my pillow. The next day I was not tired and my mental energy last through the next 18 hours.
I had tried quite few nootropics but never had such a effect with huperzine A.
Was the itch a boost in NGF and I truly believe it’s half life of 24 hours.
Wong, that is an impressive reaction to Huperzine-A. Haven’t had anyone mention it before although I did include it in the side effects section of the review above.
It sounds like a choline-overload of epic proportions.
Is there tolerance of Huperzine A?
Min, developing tolerance with Huperzine-A is not the problem. Overdosing it is because Huperzine-A has a 24 hour half-life. Which means you should not use it anymore often than every 2nd or 3rd day. Otherwise it builds in your system to toxic levels and can result in some pretty nasty consequences.
Thank you for your reply.
I’ve been taking several types of Nootropics.
Among them, Huperzine-A is the best for me.
Can Long-Term Use of Huperzine-A Cause Tolerance?
I am afraid that I eventually reach tolerance and diminished effect.
I tried 50mg, 100mg. 150mg of Huperzine-A at bedtime.
100 mg was good.
150 mg interfered with sleep. and I had a mild headache the next day.
So I found out that more than 100 mg of Huperzine-A is too much for me.
Now, I take 50 mg of Huperzine-A on Mondays and Tuesdays in the morning and not on Wednesdays.
And I take 50mg of Huperzine-A on Thursdays and Fridays in the morning and not on Saturdays and Sundays.
Even if I take it for more than 1 year like this, won’t I develop a tolerance to Huperzine-A?
Min, if you are going to grow tolerant to Huperzine-A you’ll know within the first month of usage.
But your dosing regimen is not likely spaced out enough to clear Huperzine-A from your system. Better to use it every second day because it has a 24 hr. half-life.
Thank you so much for the quick reply.
Do you mean Huperzine-A has no tolerance issues?
It is okay for me to take up to 100 mcg of Huperzine-A.
So now I’m taking 50 mcg of Huperzine-A on Monday, Tuesday, Thursday and Friday.
Do you recommend me taking 100 mcg of Huperzine-A on Monday, Wednesday, Friday?
Do you recommend that I take Huperzine-A in the morning or at bedtime?
Min, you are safe up to 200 mcg of Huperzine-A per day but only if you use it every second or third day. So yes, I mean taking Hup-A Mon., Wed., and Fri. with breaks in between.
It is likely best to Huperzine-A in the morning because it increases acetylcholine which is your main signaling neurotransmitter. You use acetylcholine throughout your day.
Hi David, I’m trying to quit vaping badly. Would Huperzine-A help with that? Or anything else you can recommend? I know NAC is used mostly to help with a lot of drug addictions.
Lee, I don’t see how Huperzine-A would help. NAC is the only thing I know of that reduces the cravings for tobacco. Don’t know if it would help with vaping.
Full spectrum CBD oil (dark stuff with CBG & CBN & a tiny bit THC) helps the most of anything with quitting smoking or vaping. I like NAC at night for it (isn’t NAC a godsend?) and just enough CBD in the day to where im not stoned or tired from it. usually 40mg is enough
Great suggestion Ronnie. Thanks.