Everything You Should Know About Huperzine A

Huperzine A’s Status As A Nootropic Is Well Established, But Is It Right For You?

Although Huperzine A is a common ingredient in modern nootropic supplements, it’s actually very poorly understood.

Many natural nootropic stacks contain Huperzine A, but few manufacturers actually understand precisely how it works, and fewer regular users know why it does what it does. 

One thing is clear though, this stuff has been used as a nootropic for quite a long time, and countless users swear by it. 

As usual, the only question probably going through your mind at this point is: how does it help me? 

How does Huperzine A work?

Does it improve memory, focus, or mood? Does it affect all three?

What are the dangers of using this stuff long-term?

Should I add it to my existing stack? 

Let’s take a closer look at Huperzine A, the evidence behind its efficacy, and its mechanism of action to see whether this stuff is the right choice for you as you build your own natural nootropic stack. If you have any concerns at the end of the article, please post them in the comments section below and we’ll do our best to answer them right away. 

What Is Huperzine A? 

Huperzine A is an extract taken from Huperzia Serrata, which is sometimes known as firm moss, Chinese club moss, and a lot of other names depending on who you ask. 

It is native to certain parts of India and much of South East Asia, hence the diversity in nomenclature.

It has been used in traditional medicine for a long time, and it is still sold in many parts of China as an OTC treatment for a range of ailments, including cognitive decline. 

Many supplement manufacturers confuse Huperzine A with the plant from which is is derived. This is quite a big problem; Huperzine A should never be taken in amounts of similar size to the Huperzia Serrata usually used for cognitive benefits. The concentration of Huperzine A in Huperzia Serrata is very small (usually somewhere around 0.1% of dried weight), and the side effects of taking too much Huperzine A can be quite pronounced. 

It is therefore important to make sure that you understand the difference between the two substances, and to get in touch with the manufacturer if there is any uncertainty about dosage.

Now that that’s cleared up, on to Huperzine A itself.

Huperzine A is technically a sesquiterpene alkaloid. 

The word sesquiterpene refers to its structure; it is formed of three isoprene molecules. Isoprene is simply an organic compound with the formula  CH₂=C(CH₃)−CH=CH_2.

Sesquiterpene alkaloid compounds are commonly found in plants and certain insects. These organisms typically use them as part of a defensive or breeding mechanism. 

But enough of the biochemistry. 

This is all probably quite boring to any of you who just want to know how Huperzine A can help you improve your cognitive function. With that in mind, let’s discuss how it work. 

How Does Huperzine A Work?

Huperzine A is an acetylcholinesterase inhibitor. 

This means that it inhibits the formation of the enzyme acetylcholinesterase. 

Acetylcholinesterase inhibitors are often referred to in the literature as AChEI. As such, this is the abbreviation we will give it from now on. 

Not all AChEI work in precisely the same way. They each seem to prevent the synthesis of different forms of the enzyme.

Huperzine A seems to work by inhibiting the synthesis of the G4 form of acetylcholinesterase; tetrameric acetylcholinesterase (reference). 

There are several naturally occurring acetylcholinesterase inhibitors. Scientists are now studying how these alternative sources compare to Huperzia Serrata in terms of efficiency and concentration. 

However, for the time being, Huperzine A is the best known, most reliable, and probably the most cost-effective acetylcholinesterase inhibitor we have. 

So why is inhibiting this enzyme good? How does it help cognitive function?

Why is acetylcholinesterase important?

Acetylcholinesterase is the enzyme which breaks down the neurotransmitter acetylcholine. 

Acetylcholine is often referred to as the “learning neurotransmitter”.

It is involved in a wide array of brain functions, including muscle contraction and, crucially, memory formation.

Acetylcholine is also the neurotransmitter which acts on the areas of the brain responsible for attention, focus, and motivation. 

In effect, therefore, much of your brain function is limited by acetylcholine availability.

Since acetylcholine is the neurotransmitter used in the parts of the brain associated with attention, learning, memory and focus, a dearth of this neurotransmitter means that the brain cells in these areas will not be able to communicate with one another as efficiently as possible.

As a result, your cognitive faculties will be hindered. They may not be negatively affected, per se, but they will be far from reaching their potential. 

To put it another way, acetylcholine is involved in almost every aspect of your cognitive function. If you are interested in maximizing your mental performance, it is not a variable you can afford to ignore. 

So, one tactic often used by nootrpics enthusiasts is to raise acetylcholine availability. 

This is usually done in one of two ways.

One way is that the person in question uses a cholinergic compound to raise acetylcholine availability in the brain. A cholinergic is a compound, usually an analogue of choline, which physically confers choline to the brain. It either contains choline itself in a more readily absorbed and transportable form, or it contains other precursors which can be used to synthesize acetylcholine. 

The other way is to preserve your current acetylcholine levels; this is how Huperzine A works. 

It prevents the breakdown of acetylcholine by stopping the formation of the enzyme responsible for breaking the neurotransmitter down. This means that you keep acetylcholine levels high without actually increasing the production rate.

So your body keeps synthesizing acetylcholine at the rate it usually does, but it can no longer get rid of the old stuff. Acetylcholine availability in the brain will therefore start to steadily climb (at exactly the rate your brain synthesizes acetylcholine). 

We hope that’s covered how Huperzine A works in theory. But this is all very reminiscent of the kind of sales spiel we get from manufacturers. 

Sure, a substance might be thought to do X or Y in theory, but whether or not it works for people in the real world is always a different matter. 

Studies can be easily manipulated, and the real world effects of certain physiological processes can be exaggerated at will. 

Let’s look at some studies looking at Huperzine A’s effect on cognitive function in real, human subjects. 

Does it really work in the real world?

We’re going to dive right in and start linking to some studies proving the efficacy of Huperzine A as a nootropic. 

For starters, that Huperzine A inhibits acetylcholinesterase formation is a well established fact. This has been proven in humans as well as mice.

It is always worth making sure that a substance actually does the fundamental thing that everybody claims it does!

Now, does Huperzine A enhance cognitive function in humans? Indeed, several scientific studies have shown that it does. 

For instance, take a look at this study, published in Zhongguo Yao Li Xue Bao (China Pharmacology News in English – one of our reviewers speaks Chinese) in 1999. Here, researchers looked at Huperzine A’s effects on young students in relation to their memory quotient (MQ). The researchers found that “Hup capsules enhance the memory and learning performance of adolescent students.”

The researchers noted that the students treated with Huperzine A returned better MQ results, as well as scoring better in their Chinese language tests compared to placebo. 

Another robust study attesting to the power of Huperzine A was published in the Journal of Neural Transmission in 2009. 

The researchers conducting this study were looking to “provide an updated meta-analysis of the efficacy and safety of huperzine A (HupA) in Alzheimer’s disease (AD).” To that end, they looked for trials comparing Huperzine A with placebo in the treatment of Alzheimer’s Disease. The conclusion of this meta-analysis was pretty resounding in favor of the compound:

“The results of meta-regression showed that the estimated effect size of MMSE and ADL was increased over the treatment time. Most adverse events were cholinergic in nature and no serious adverse events occurred. Huperzine A is a well-tolerated drug that could significantly improve cognitive performance and ADL in patients with AD.”

Other studies have observed the same phenomenon again and again. 

One, published in China Pharmacology News, concluded that “Hup is a promising drug for symptomatic treatment of Alzheimer’s disease.”

Another, published in the Journal of Pharmacology and Experimental Therapeutics in 1999, concluded that “huperzine A may be a promising agent for clinical therapy of cognitive impairments in patients with Alzheimer’s disease.”

We could go on quoting research which seems to support the fact that Huperzine A promotes memory, focus and learning, but we think this will suffice for this article. If you wish to learn more about Huperzine A, then we strongly encourage you to go on digging through the available scientific research. If you are keenly interested in the detail, it would also be worth your time getting in touch with some experts in the compound, as well as looking at various pharmacology forums.

Is Huperzine A Safe? 

For many of you, this is undoubtedly the most important section of this article. It may even be that most of you ended up here looking for a straight answer to the question: “is Huperzine A safe?”

The answer to that question is, however, far from simple. Whether or not Huperzine A is safe, and whether or not Huperzine A is likely to cause side effects, is entirely dependent on both dosage and how it is used. 

The fact of the matter is, Huperzine A presents a lot more risk than most other natural nootropic substances. When compared to the cholinergics which are commonly used to boost acetylcholine levels, Huperzine A requires far more care and attention. 

The reason for this is that Huperzine A does not boost acetylcholine production. Rather, it disables the brain’s acetylcholine regulation system. 

When you use cholinergics such as CDP-Choline, you do run the risk of raising acetylcholine levels too high. However, if you do, your brain can regulate these levels. It will produce more acetylcholinesterase, thereby bringing acetylchyoline levels back to within normal, healthy limits. 

If you take too much Huperzine A, your acetylcholine levels will very quickly get too high. But you will have effectively disabled the brain’s ability to bring acetylcholine levels back down. 

To make this problem even more pronounced, Huperzine A has quite a long half-life. By this we mean that it stays in the blood for a long period of time, and it continues to have an effect for the entire time it is in the blood. 

Most estimates put the half-life of Huperzine A at just over 24 hours. 

That does not mean, however, that 24 hours is sufficient for your acetylcholine levels to return to normal. 

If you have been taking Huperzine A for more than 4 weeks, your acetylcholine levels will by that point quite high. 

So imagine then you stop using Huperzine A for 24 hours. This is only long enough for the last few molecules of Huperzine A to leave your system. It is only then that your body can begin producing acetylcholinesterase again.

It is not an ‘on-off’ switch mechanism. 

Once the body begins producing this enzyme again, it will take some time for it to break down the extra acetylcholine you have accumulated. 

If you begin taking Huperzine A again the very next day, having only taken a 24 hours break, your acetylcholine levels will have hardly changed at all. You would then be beginning the process again with acetylcholine levels that are potentially already too high. 

This is why we often speak of the concept of Huperzine A cycling.

Huperzine A Cycling – Is It Necessary

For the reasons explained above, Huperzine A cycling is absolutely necessary. 

If you fail to take a break in usage of at least 24 hours, then your acetylcholine levels will continue to rise, and your brain will have no self-regulatory mechanism for keeping things within healthy limits, not to mention limits that are conducive to cognitive function (more on this later).

Unfortunately, this is currently a very poorly understood practice. 

Most sensible, cautious users of nootropics will run cycles of Huperzine A for about 2-4 weeks, before taking a break of about 5-7 days.

While this seems to be effective for most users, the ideal length of a cycle or a break has not been established.

Unsurprisingly, this is because the ideal length of cycle and break depends on the dose being used, the quality of the extract, and the person in question – their goals, their physiology, their tolerance. 

If you’re considering using Huperzine A to enhance your memory function or your learning capacity, we strongly advise you to practice caution on your first cycle. 

Start with a dosage that will most probably be too low: perhaps 50mcg. Note we said micrograms, not milligrams! 

Use this for 2-4 weeks, take a break of at least 7 days, and try to gauge how you have reacted.

It is crucial not to expect too much here; Huperzine A isn’t going to turn you into Rain Man overnight – no nootropics will do that.

So just because you weren’t suddenly a new person doesn’t mean that you need to up the dosage drastically next time. 

If you didn’t experience any adverse side effects, try 75mcg next cycle, but keep the cycle length to under 4 weeks and increase the break length.

Gradually experiment like this, tempering rising doses with longer break lengths or shorter cycles, and you should minimize your chances of experiencing any serious side effects.

If you do experience any side effects, or you feel like your cognitive function is not improving, either cut the dosage, take a prolonged break of at least 4 weeks, or cease use altogether. Huperzine A is not necessarily going to work well for everyone. Experimenting with nootropics is about finding what works for you. 

We keep talking of side effects. What are these side effects likely to be exactly?

Side Effects Of High Acetylcholine Levels

If you experience any side effects from taking Huperzine A, they will no doubt be caused by excessively high acetylcholine levels. 

After all, that is how Huperzine A works as a nootropic; it boost acetylcholine levels by stopping the brain from getting rid of any. 

So what are the side effects of having too much acetylcholine?

First of all, when acetylcholine levels get too high, cognitive function actually begins to waver. This wont be surprising to any of you with knowledge of drug interactions; many depressants are powerful stimulants when taken in tiny doses, and vice versa. 

So as your acetylcholine levels climb beyond what we would deem the ‘optimal level’, you will encounter:

• Decreased motivation
• ‘Brain fog’
• Lack of focus
• Poor memory function

Eventually, as your acetylcholine levels continue to rise, these side effects become more pronounced. As this happens, more psychical side effects will also begin to set in. These will include:

• Headaches
• Drowsiness
• Insomnia
• Nausea
• Anxiety

Of course, the severity of these symptoms will vary according to your circumstances. They are linked to dose, length of usage, and your own sensitivities. 

If you manage to avoid all of these symptoms, but your acetylcholine levels continue to increase, then you will eventually run into some quite severe negative effects. These will effectively be extreme forms of the side effects listed above. 

We are sure that none of you want to get to that point, so please exercise caution when using Huperzine A. If you feel mild side effects, even if you aren’t sure they are caused by Huperzine A use, discontinue use until you are sure of the origin of the problem. 

Is Huperzine A Right For You?

Whether or not you should use Huperzine A depends on your specifric goals. 

Over time, we have become convinced that it should not really be used as part of a broader nootropic stack. 

This is for the simple reason that most of the best nootropics (CDP-Choline, Lion’s Mane Mushroom, Bacopa Monnieri, and so on) all work best when taken for long periods of time without interruption. 

Huperzine A demands that you take a break of about a week every 28 days. This will really limit the effectiveness of the other substances found in high quality natural nootropics these days. 

If you’re looking for something to use on its own, then Huperzine A may indeed be the right choice for you. 

This is particularly true if you have tried cholinergics before (e.g Alpha GPC), and you’ve found that you are highly sensitive or allergic to them.

That said, if you are looking for an individual supplement to help boost memory and focus, we think a straight cholinergic would be a preferable choice to Huperzine A.

Huperzine A is effective, and it has been studied thoroughly enough for us to conclude that it is safe when used properly. 

However, there is the added nussance of cycling to consider, as well as the uncertainty about ideal dosage, cycle length, or break duration. 

As such, we think someone looking to boost their focus or memory shoudl opt for a cholinergic such as choline bitartrate or Citicoline, as these substances are well tolerated, reliable, effective, and side effects are rare. What is more, than can and indeed should be taken continuously for periods of 12 weeks or more.