Table of Contents
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 natural acetylcholinesterase inhibitor (AChE). Which means it prevents the breakdown down of acetylcholine (ACh). Boosting short-term memory and long-term brain health. But will stop its action on acetylcholine as soon as you stop using it.
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 and induced oxidative injury. And boosting brain cell longevity.
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 (a natural Chinese Herbal Medicine called Chinese Club Moss). Huperzine-A is a standardized compound found in this naturally occurring plant.
Note that Huperzine-A and Huperzia serrata are NOT the same supplement.
Some nootropic supplement stacks substitute genuine Huperzine-A with Huperzia serrata. All the research I’ve seen uses Huperzine-A in their clinical trials. Not Huperzia serrata.
Look for a supplement with genuine Huperzine-A on the label. And avoid stacks or supplements that use 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 inhibitor. Acetylcholinesterase (AChE) is an enzyme that breaks down the important neurotransmitter acetylcholine once it’s used in your system. So Hup-A helps prevent this breakdown. Allowing more acetylcholine to be available which improves learning and memory.
Scientists at the Weizmann Institute in Israel uncovered how Huperzine-A works to block this novel acetylcholinesterase inhibitor. 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 from being eliminated.
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 function 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 ion channel 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 Trials and 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 can cause cognitive deficits like a decline in memory. And are implicated in several neurodegenerative diseases including Alzheimer disease, 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 toxicity.
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.
In one of the randomized clinical trials done in Shanghai, researchers worked with 200 patients who met the criteria for having Alzheimer Disease therapy. 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 assisting participants with vascular dementia.[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 for the treatment of Alzheimer’s disease. 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 to Enhance Cognitive Function
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 one of your dietary supplements.
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.
Join The Discussion - 193 comments
Jin
November 3, 2022
Hi David,
is taking racetams necessary when taking CDP-choline?
or can I just take 300mg of CDP-choline daily and Hup-A 200mcg every other day to see improvement in focus and learning ability?
David Tomen
November 3, 2022
Jin, you can use CDP-Choline n its own to increase acetylcholine. But keep in mind the half-life of CDP-Choline is something like 7 – 89 hours. So if you use it only every second day you will only experience its benefits less than half the time.
Huperzine-A however must be used ever 2nd day because its half-life is around 12 hours.
Jin
November 3, 2022
thanks for your response!
I have read a few other questions in which you answered that if an individual experiences sleepiness when taking CDP-choline and racetams together, one should rest from taking racetams.
and in another comment, you answered that an individual who experiences headaches from taking CDP-choline alone should take racetams.
do you recommend taking CDP-choline by itself to check for results before taking racetams?
sorry, I might have double replied to your response.
David Tomen
November 3, 2022
Jin, the racetams potentiate the use of acetylcholine in your brain. Which is the reason why I always recommend using a supplement to increase acetylcholine.
People have different reasons for using any of the racetams. It could be to boost cognition or improve mood. The ONLY reason I would have recommended a racetam otherwise is if someone thought they had too much acetylcholine in their brain. The best way that I know of to reduce acetylcholine levels is to use a racetam.
CDP-Choline increases acetylcholine among other benefits and the reason why it is used. What are you trying to do? I think you are confused about the benefits of each and why each nootropic is used.
Chet
October 20, 2022
David,
I love your site but that’s besides the point. I’ve been a nutraceutical and nootropics student for years (I’m a 64 YO) and have recently embarked on methylene blue usage for a number of reasons. I’ve read what you said about cycling Huperzine-A regarding toxicity and half-life, and your comments about the dangers of it being in a “stack” product.
Well I recently purchased one such stack product called SonoVive for tinnitis which is a stack of Ginko B, St. Johns Wort, Bacopa Monnieri, Vinpocetine, and Huperzine-A. I haven’t received it yet, but I’d like to hear your thoughts, please.
BTW, I also take other nootropics regularly such as Mind Lab Pro, ashwagandha, CDP-choline, DHEA, Ginseng, glycine, magnesium, NAC, glutathione, cacao, quercetin, maca, and resveratrol; with no interactions or complications.
David Tomen
October 22, 2022
Chet, the danger of supplementing with Huperzine-A every day is it will build up in your system. I don’t think it is worth the risk. But if you are going to try it just keep in mind that the symptoms of acute toxicity are similar to those of other cholinergic inhibitors. And can include muscle tremors, drooling, tears, bronchial mucous and incontinence.
Ben
August 30, 2022
Hi,
I am 47 and a male. Would taking huperzine for 4 days on and 4 days off be ok, and can I use a choline supplement on the 4 days off?
Would adding a dopamine supplement help, as I am doing a foreign language course, and I want to improve my recall and focus?
David Tomen
August 31, 2022
Ben I suppose a 4 day holiday would work but CDP-Choline needs to be used twice per and every day if you want its full benefit.
See this article for filling out the rest of your stack: https://nootropicsexpert.com/best-memory-supplements-to-buy/
chris
August 1, 2022
Question, I read on a couple sites about Huperzine A should not be taken longer than 6 months. Haven’t seen why or seen clarification. Can you explain??
David Tomen
August 2, 2022
Chris, the thing with Huperzine-A is it’s 10-12 hour half life. Which is why you should not use it every day. But there is no evidence of how “long” you can use a supplement like Huperzine-A. Because no one wants to pay the multiple millions is would cost to conduct such a study.
If anyone says Huperzine-A should not be used any longer than 6 months I suggest asking them for clinical peer-reviewed proof backing up that claim.
Exceller
July 6, 2022
Hello David —
Though everyday dosing may lead to adverse events, periodic dosing has the same potential. The best way to mitigate risk and maximize utility is through steady blood levels. Stepping on the gas every two to three days with a strong neuroactive compound seems like chaos. In fact, I believe this chronic “missed dose” use pattern could lead to cholinergic desensitization. This insidiously occurs in the serotonergic system (Harvey et al., 2003).
The compound has a short elimination half-life (~5 hrs.), necessitating multiple daily doses to maintain smooth plasma concentration (Qian et al. 1995). The duration of acetylcholinesterase inhibition in animal models isn’t much longer than this (Tang et al. 1989). This has pushed the medical community to devise transdermal delivery systems for demented patients (Yan et al., 2020).
Concerning periodic dosing for long half-life medications: Donezipil, an acetylcholinesterase inhibitor, much like Huperzine A, has an 80-hour half-life. Alzheimer’s patients are started and maintained on a lower than (initially) efficacious dose for four to six weeks. This occurs because it takes five elimination half-lives to reach a steady-state (~17 days), then several weeks of observation at this strength. Had the patients started a dose that would reach that level their first day, it would have been disastrous to continue. This, I believe, is what you are trying to prevent. But just like Donezipil: low, slow, and steady works for some of the sickest patients.
Huperzine A does not induce a tolerance from consistent, non-periodic use (Laganiere et al., 1991) (Wang et al, 1998). These anecdotal claims may stem from a “missed dose” use pattern of desensitization.
[Always taper long-use psychoactive compounds.]
Thank you — Exceller
David Tomen
July 8, 2022
Exceller, the only problem with your analysis is comparing acetylcholinesterase inhibitor that have an elimination half life of 5 hr. with one like Huperzine-A which has a half-life of 10- 12 hrs.
Joel
June 13, 2022
Last night I was not able to sleep after taking 400 mcg of Huperzine-A for two mornings in a row. I did a Google search for Huperzine-A and insomnia and found your site. I’m very glad about that! Before taking this large dose recently, I had been taking an unspecified dose of Huperzine-A included in a Nootropic product called Piratall for about three months. I knew nothing about half-life and cycling, so I was taking it every day. Recently I switched to pure Huperzine-A in 200 mcg. doses and decided to double the amount, with the effect I already mentioned. After reading your warnings about overdosing, I’m a little concerned. How long do I need to abstain from taking Hup-A before resuming it at the recommended dose and at appropriate intervals?
David Tomen
June 13, 2022
Joel, because of the long half-life of this supplement I’d give yourself a week without using it to make sure it’s flushed out of your system. That’s likely overdoing it but you’ve been overdosing for so long that the result is unknown.
Whenever I see a pre-made stack that includes Huperzine-A I immediately put it back on the ‘shelf’ because clearly the designer of that stack didn’t know what they were doing.
Joel
June 14, 2022
Thanks a lot, David. I will follow your advice and not take Huperzine-A for a week, and then take 200 mcg every 2 or 3 days. In the meantime I can study your wonderful website
Why does the inclusion of Huperzine-A in a pre-made stack immediately suggest to you that the designer of the stack doesn’t know what he’s doing?
David Tomen
June 15, 2022
Joel, because the designer of that stack should know how long Huperzine-A lasts in your system. And using it in a stack meant for daily use could cause problems for someone using it daily because of the dangerous build-up of a strong acetylcholinesterase inhibitor.
Joel
June 17, 2022
Thank you, that’s clear. The producer also gave no indication of the amount of Huperzine-A in each dose..
Todd Beal
May 25, 2022
David, thanks to your recommendation on this website, Mind Lab Pro helped me greatly reduce sluggish thinking and improve memory recall post COVID-19. However, is the included 250mg CDP Choline dosage safe while taking Huperzine-A 200mcg 2x/3x per week, Vinpocetine 10mg 3 times per day, and Phenylpiracetam 100mg once per day?
By the way, Phenylpiracetam 100mg once per day – thanks to your Phenylpiracetam article on this website – is doing wonders for my Mom’s post COVID-19 brain fog and severe memory problems (I noticed an almost immediate difference – wow!). Thank you!
David Tomen
May 26, 2022
Todd, not only is the CDP-Choline safe to use with your stack it’s necessary. Especially when using Phenylpiracetam.
If you use Mind Lab Pro in the morning you may want to take an extra dose of CDP-Choline at noon as well.
Todd Beal
May 26, 2022
Wow! Okay, glad I asked. Thank you.
Jason Shim
February 11, 2022
Hi David, I started taking Huperzine A 200mcg daily for 3 days straight. I feel my focus, logic, memory, composition, comprehension skill improved a lot.
Some website say it’s ok to take Huperzine A daily, they said it’s half life is about 10 hours.
I will watch out for any symptoms of acetylcholine overdose.
David Tomen
February 11, 2022
Jason, looks like my info is old. The latest shows Huperzine-A half-life of 10 – 14 hours. https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0308078.htm
Jason Shim
February 11, 2022
Oh thanks for the update, another positive effect I feel is Im less distracted by my negative thoughts and also surrounding noises which is huge benefit to me.
chuck stanley
February 21, 2022
Half life doesnt mean that is how long it takes to clear the compound. It takes 4-5 half lives to clear completely from your system. Until it is cleared you are adding to this day’s dose what is still in your system from before.