Huperzine-A dosage

Huperzine-A

David Tomen
Author:
David Tomen
11 minute read
Huperzine-A improves cognition, memory, learning, recall, is an antioxidant, helps neuroplasticity, and protects against glutamate-toxicity.

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.

Overview

Huperzine-A (Hup-A) is a water-soluble natural plant alkaloid nootropic that easily crosses the blood-brain barrier.

Huperzine-A
Huperzine-A

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?

Cognitive scienceHuperzine-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 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.

Huperzine-A-boosts-acetylcholine

How does Huperzine-A Work in the Brain?

Huperzine-A boosts brain health and function in several ways. But two in particular stand out.

  1. Huperzine-A acts as an acetylcholinesterase (AChE) inhibitor. 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 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 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]

  1. 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 boosts cognition

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 is an antioxidant and neuroprotectant

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 dosageHuperzine-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

Nootropics Expert Tested and ApprovedI 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.

As an Amazon Associate I earn from qualifying purchases. This post may also contain other affiliate links and I will be compensated if you make a purchase after clicking on my links.

[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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Join The Discussion - 179 comments

Kevin
June 13, 2021

Hi David,

Is it OK to stack Huperzine-A with Bacopa or would that be too much ACh?

thank you,

    David Tomen
    June 13, 2021

    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.

Wong
May 3, 2021

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.

    David Tomen
    May 4, 2021

    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.

      MattD
      November 9, 2021

      Well he said he took it at 11pm… Probably don’t want to take this anywhere near the evening right? This would probably be best taken right when you wake up, would you agree Dave?

        David Tomen
        November 12, 2021

        Matt, I agree that Huperzine-A is best used earlier in the day. It boosts acetylcholine which is used primarily during the day.

      Volodymyr
      September 16, 2022

      I have pretty much the same side effect from Huperzine A.
      The first day I took 20 mg (I use Huperzine A 1% Powder from Nootropics Depot), three hours later I felt a sudden weakness, a tremor, and spent the rest of the day lying down.
      The next day I took 100 mg in the morning and went for a run. When I came back from jogging, I decided to lie down for a while, after which I felt strange muscle twitching in different parts of the body. Then weakness and vomiting, which lasted until evening. Since then I decided not to repeat the game.
      My current stack: Lion’s mane, Lecithine, L-Tyrosine, Ashwagandha, Vitamin E, Omega 3, Vitamin C, ALA.

        David Tomen
        September 17, 2022

        20 mg Huperzine-A is overdosing this supplement. More is never better with nootropics.

        Stay with the recommended adult dosage with any supplement. If it does not work or you get negative side effects then it’s the wrong supplement for you.

        Volodymyr
        September 18, 2022

        Hi David,

        thanks for your reply.
        Please note – as I said, I’m using Huperzine A 1% Powder, which means that the actual content of the substance in the powder is 100 times less than in pure form, i.e. just exactly 20/100 = 0,2 mg of pure Huperzine A.

        David Tomen
        September 20, 2022

        The symptoms you describe are some of the symptoms of excess acetylcholine. Which would happen from using too much Huperzine-A. But if that’s not you then I am not sure what is going on.

Min
April 28, 2021

Is there tolerance of Huperzine A?

    David Tomen
    April 30, 2021

    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.

      Min
      May 8, 2021

      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?

        David Tomen
        May 8, 2021

        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.

        Min
        May 9, 2021

        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?

        David Tomen
        May 10, 2021

        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.

Lee
March 3, 2021

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.

    David Tomen
    March 3, 2021

    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.

      RONNIE
      May 28, 2021

      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

        David Tomen
        May 28, 2021

        Great suggestion Ronnie. Thanks.

Elena
January 20, 2021

Hi David, I am taking anti cholinergic drugs, would it be good to take Huperzine A?

    David Tomen
    January 21, 2021

    Elena, it depends on the anticholinergic drug you are using. Huperzine-A will amplify the effects of some of these drugs. And reduce the effects of other drugs. So it depends on what you are taking.

Matteo Giovanni
December 24, 2020

Hello David, for an optimal increase of Acethylcholine, can I cycle between Huperzine A and Phosphatidylcholine during the week? For instance taking every 3 days Huperzine A 50-100 mcg and the rest of the days taking Phosphatidylcholine standard dose?

    David Tomen
    December 26, 2020

    Matteo, Huperzine-A is not going to “increase” acetylcholine. It just makes more the existing acetylcholine in your brain available.

    And supplements like Alpha GPC and CDP-Choline are more effective for direct increases in acetylcholine levels in your brain than PC.

    The method you are suggesting is not the most efficient “for an optimal increase of Acetylcholine” in my opinion based on what I know of how those two supplements work. You can certainly try it and see if it provides the benefits you’re looking for.

Rob L.
September 14, 2020

Hi David, are you aware of blood pressure issues due to using Huperzine A? Last night, I took 200mcg of Huperzine A along with some Krill Oil, 150mg of Magnesium Orotate, & Ashwaganda. About 90min later, my blood pressure was 169/90 where is normally is 120/80. Additionally, resting my heart rate was elevated and bounced around between 65 and 78. My normal resting heart rate is in in the mid-40’s as I am an athlete. I went the ER and my blood and EKG came back fine so they sent me home. This morning at 9am (12 hours after), my blood pressure was still a bit elevated so I am waiting until 9pm tonight to check it again. I’m a bit disappointed as I noticed a huge benefit while I am on it. That was the first time I taken it in several days after taking it 3 times last week along with my racetam stack. Please note that I had taken no nootropics since Friday so 2+ days without anything. Please let me know your thoughts. Thanks.

    David Tomen
    September 15, 2020

    Rob, take a look at the Side Effects section above and you’ll quickly recognize the symptoms you describe. 200 mcg is the absolute maximum dose for Huperzine-A and is a lot especially if you’ve never used this nootropic before.

    Give it a 3 or 4 days so you clear it from your system and you should be back to normal.

    If you want to try it again please use only 50 mcg and see how you feel. You don’t need much of this potent nootropic to get its benefits. And use it only every 2nd or 3rd day. Because it has a 24 hour half life.

Matheus
August 4, 2020

Should one avoid taking in the morning Vyvanse (lisdexanphetamine) + 200 mg of Huperazine A? Didnt found any drug interactions between them in Uptodate or in Pubmed. Also, considering the phisio-pharmacology of them, maybe one can prevent the colaterals of the other (something like Caffeine + L-Theanine). What do you think?

Best regards, Matheus

    David Tomen
    August 6, 2020

    Mattheus, look up the “mechanism of action” or “pharmacology” for each to understand why they’re not contraindicated.

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