Huperzine A

While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy.

Related Terms

  • 8-Deoxyserratinine, acetylcholinesterase inhibitors, Cerebra®, Chien Tseng At, Chinese club moss, club moss, dimethylhuperzine A (DMHA), hup, Hup, HupA, huperzia, huperzine, (–)-huperzine A, (+-)-huperzine A, huperzine A, huperzine B, huperzine J, huperzine K, huperzine L, huperzine P, huperzine S, huperzine T, huperzine U, huprine X, huprine Y, lycodine, lycopodium alkaloids, Lycopodium selago, Lycopodium serrata, Memorall®, N-methylhuperzine B, phlegmariurine B, qian ceng ta, qian chen ta, selago, serratane-type triterpenoids, shezushishan, shuangyiping, thump, toothed club moss.

  • Select combination products: Huprine X (huperzine A plus tacrine; not commercially available).

Background

  • Huperzine A is a chemical compound known as an alkaloid. It is derived from the club moss Huperzia serrata, which is a member of the Lycopodium genus. It was first isolated in the 1940s.

  • In China, huperzine A is popular for its role in maintaining and enhancing memory. In traditional health practices, it has been brewed into teas and used for the treatment of fevers, inflammation, swelling, and various mental disorders, such as schizophrenia.

  • Currently, huperzine A is available in China as a prescription drug for Alzheimer’s disease. In the West, huperzine A has not been widely developed as a drug due to its declining natural sources and legal property protection by Chinese scientists. In the United States and Europe, huperzine A is marketed as a nonprescription diet supplement to aid memory.

  • Early research in humans has shown promising results for the use of huperzine A for Alzheimer’s disease. In China, human research is currently being conducted in this area. Further research in humans is being funded by the National Institute of Health in the United States.

  • Limited research also suggests that huperzine A may play a role in protecting neurons against vascular injury and organophosphate nerve gas. However, further research is needed in these areas.

Scientific Evidence

Uses

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Alzheimer’s disease

Early research suggests that huperzine A may be effective in the treatment of dementia (gradually declining mental ability) and dementia-related conditions, such as Alzheimer’s disease. However, further research is needed to compare its usefulness to that of other current treatments.

Cognitive disorders

Initial research suggests that huperzine A may be effective in improving memory in people with mild cognitive impairment (MCI). Further research is needed in this area.

Dementia

Huperzine A has been promoted as a potential treatment for dementia (gradually declining mental ability) in the United States and Europe. However, results in this area are conflicting, and firm conclusions cannot be made at present. This is likely due in part to the vague clinical definition and presentation of dementia itself. More robust research in this area is needed.

Memory

Huperzine A is theoretically believed to have positive effects on memory and learning. However, scientific evidence in this area is limited. Well-designed research in humans is needed before any firm conclusions may be made.

Myasthenia gravis

Huperzine A has been proposed as a possible alternative treatment for myasthenia gravis (autoimmune muscle weakness). Myasthenia gravis is a condition in which the body’s immune system attacks acetylcholine (ACh) receptors. As a result, muscles do not adequately receive signals from ACh to contract, and muscle weakness ensues. Theoretically, huperzine A may help increase available ACh. Compared to standard treatments, huperzine A may be an attractive alternative due to its minimal side effects. Further high-caliber research in this area is needed.

Neuroprotective

According to traditional practices and theoretical models, huperzine A may exert nerve-protecting effects. Although huperzine A has not been well studied in humans, early research suggests that huperzine A may prevent or reverse neuronal cell loss and memory deficits. It has therefore been proposed as a possible therapy for blood- and oxygen-deficient brain injuries. However, research in this area is currently very limited. Research in humans is needed before any firm conclusions may be made.

Organophosphate poisoning (pretreatment)

Huperzine A has been proposed as a potential nerve gas pretreatment agent due to its biological and chemical properties. Theoretically, it may be useful during times of war or terrorist attacks. Human research in this area is currently lacking.

Recovering from anesthesia

Limited research suggests that huperzine A may increase levels of acetylcholinesterase (AChE) in elderly patients after surgery. AChE is an enzyme that breaks ACh and makes it more available to the body. Theoretically, increased ACh may aid anesthesia recovery. Though current research is promising, more research is needed in this area.

Schizophrenia

Early research has been done to examine the effects of huperzine A in people with schizophrenia. Current findings remain unclear. Further high-caliber research in this area is needed.

Thyroid conditions

Limited research suggests a possible relationship between Alzheimer’s disease and thyroid function. By increasing ACh, huperzine A is thought to also stimulate the thyroid and increase thyroid hormone levels. More high-quality research in this area is needed before any conclusions may be drawn.

*Key to grades:

Tradition

The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious and should be evaluated by a qualified health care professional.

  • Alertness, anticonvulsant (reducing spasms), anti-inflammatory, antioxidant, bleeding, blood disorders, cancer, cardiac function, cerebral ischemia (impaired blood flow to the brain), diuretic (increasing urine flow), enhancing recovery from surgery or illness, fever, glaucoma (increased pressure within the eye), menstrual irregularities, sprains, swelling.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)

  • Much of the research on huperzine A has used an injectable form, which is available in Asian countries, but is not common in the United States. Huperzine A is marketed in a number of oral dosage forms (i.e., capsules, liquid, and tablets).

  • For Alzheimer’s disease, the following doses of huperzine A have been taken by mouth: 100 micrograms (or 0.1 milligram) three times daily for either 60 days, 16 weeks, or three months; 200 micrograms (four 50-microgram capsules each) twice daily for 60 days; 0.15 milligrams (three 0.05-milligram tablets each) twice daily for eight weeks; 0.2 milligrams (four 0.05-milligram tablets each) twice daily for eight weeks; 400 micrograms daily for 12 weeks; or an average of 0.50 ± 0.20 milligrams daily for an unclear amount of time. Although this dose has not been well studied, 50 micrograms of huperzine A twice daily with meals has been suggested.

  • In people with mild cognitive impairment, 0.2 milligrams of huperzine A has been taken by mouth for 12 weeks.

  • For dementia, 150 micrograms of huperzine A (three 50-microgram tablets each) has been taken by mouth twice daily for 30 days. In people with multisite dementia, 0.05 milligrams has been injected into muscle twice daily for four weeks. In people with age-related memory disorders, 0.03 milligrams twice daily for two weeks has also been injected into muscle.

  • Although this dose has not been well studied, 50 micrograms of huperzine A once daily in the morning with breakfast, or one 200-microgram tablet (Source Naturals) 1-2 times daily has been suggested in people with memory loss.

  • For thyroid function in people with Alzheimer’s disease, 0.1 milligrams of huperzine A taken by mouth twice daily for six months showed no obvious treatment benefit.

  • For anesthesia recovery, 0.3 milligrams of huperzine A per two milliliters has been injected into veins 30 minutes before the end of the operation.

Children (under 18 years old)

  • For memory and learning, two 50-microgram capsules of huperzine A have been taken by mouth twice daily for four weeks.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

  • Avoid in people with a known allergy or sensitivity to huperzine A.

Side Effects and Warnings

  • Huperzine A may cause ankle swelling, anorexia, blurred vision, bradycardia (slow heartbeat), cramps, diarrhea, dizziness, excitability, excess activity, fainting, indigestion, insomnia, nasal obstruction, nausea, slurred speech, sweating, temporary dizziness, or vomiting. According to personal reports, huperzine A may also cause breathing problems, chest pain, itchy or swollen skin, rash, skin hives, or tightness in the throat or chest.

  • Huperzine A is likely safe when used at doses up to 400 micrograms daily. Use with caution at higher-than-normal treatment doses.

  • Use cautiously in people with liver disease, asthma, or vertigo (feeling dizzy and off balance).

  • Use cautiously when combined with other acetylcholinesterase (AChE) inhibitors, due to possible additive side effects.

  • Use cautiously in children, due to a lack of safety information.

  • Avoid in people with kidney disease.

  • Avoid in pregnant or lactating women, due to a lack of safety information.

  • Avoid with known allergy or sensitivity to huperzine A.

Pregnancy and Breastfeeding

  • There is currently a lack of scientific evidence on the use of huperzine A during pregnancy or lactation.

Interactions

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Drugs

  • Huperzine A may interfere with the way the body processes certain drugs using the liver’s cytochrome P450 enzyme system. As a result, the levels of these drugs may be altered in the blood and may change the intended effects or cause potentially serious adverse reactions. People taking any medications should check the package insert and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.

  • Huperzine A may also interact with agents that affect gamma-aminobutyric acid (GABA), agents that affect the heart and blood vessels, agents that decrease the force and rate of heart contractions (known as beta-blockers), agents that inhibit acetylcholinesterase (AChE), agents that inhibit N-methyl-D-aspartic acid (NMDA), pain relievers, scopolamine, or seizure-reducing agents.

Interactions with Herbs and Dietary Supplements

  • Huperzine A may interfere with the way the body processes certain herbs or supplements using the liver’s cytochrome P450 enzyme system. As a result, the levels of other herbs or supplements may be altered in the blood. It may also alter the effects that other herbs or supplements possibly have on the P450 system.

  • Huperzine A may also interact with antioxidants, Ginkgo biloba, herbs or supplements that affect the heart and blood vessels, herbs or supplements that inhibit acetylcholinesterase (AChE), herbs or supplements that inhibit N-methyl-D-aspartic acid (NMDA), pain relievers, scopolamine, or seizure-reducing agents.

Author Information

  • This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

References

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

  1. Chow TW. Review: insufficient evidence on huperzine A for Alzheimer’s. Evid Based Ment Health 2008;11(4):112. View Abstract
  2. Diamond B, Johnson S, Torsney K, et al. Complementary and alternative medicines in the treatment of dementia: an evidence-based review. Drugs Aging 2003;20(13):981-998. View Abstract
  3. Hao Z, Liu M, Liu Z, et al. Huperzine A for vascular dementia. Cochrane Database Syst Rev 2009;(2):CD007365. View Abstract
  4. Lallement G, Baille V, Baubichon D, et al. Review of the value of huperzine as pretreatment of organophosphate poisoning. Neurotoxicology 2002;23(1):1-5. View Abstract
  5. Li J, Wu HM, Zhou RL, et al. Huperzine A for Alzheimer’s disease. Cochrane Database Syst Rev 2008;(2):CD005592. View Abstract
  6. Little JT, Walsh S, Aisen PS. An update on huperzine A as a treatment for Alzheimer’s disease. Expert Opin Investig Drugs 2008;17(2):209-215. View Abstract
  7. Sun QQ, Xu SS, Pan JL, et al. Huperzine-A capsules enhance memory and learning performance in 34 pairs of matched adolescent students. Zhongguo Yao Li Xue Bao 1999;20(7):601-603. View Abstract
  8. Wang G, Zhang SQ, Zhan H. [Effect of huperzine A on cerebral cholinesterase and acetylcholine in elderly patients during recovery from general anesthesia]. Nan Fang Yi Ke Da Xue Xue Bao 2006;26(11):1660-1662. View Abstract
  9. Wang R, Tang XC. Neuroprotective effects of huperzine A. A natural cholinesterase inhibitor for the treatment of Alzheimer’s disease. Neurosignals 2005;14(1-2):71-82. View Abstract
  10. Wang R, Yan H, Tang XC. Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine. Acta Pharmacol Sin 2006;27(1):1-26. View Abstract
  11. Ye JW, Shang YZ, Wang ZM, et al. Huperzine A ameliorates the impaired memory of aged rat in the Morris water maze performance. Acta Pharmacol Sin 2000;21(1):65-69. View Abstract
  12. Zhang HY, Tang XC. Neuroprotective effects of huperzine A: new therapeutic targets for neurodegenerative disease. Trends Pharmacol Sci 2006;27(12):619-625. View Abstract
  13. Zhang HY, Yan H, Tang XC. Non-cholinergic effects of huperzine A: beyond inhibition of acetylcholinesterase. Cell Mol Neurobiol 2008;28(2):173-183. View Abstract
  14. Zhang ZJ, Tong Y, Wang XY, et al. Huperzine A as add-on therapy in patients with treatment-resistant schizophrenia: an open-labeled trial. Schizophr Res 2007;92(1-3):273-275. View Abstract
  15. Zhang Z, Wang X, Chen Q, et al. [Clinical efficacy and safety of huperzine alpha in treatment of mild to moderate Alzheimer disease, a placebo-controlled, double-blind, randomized trial]. Zhonghua Yi Xue Za Zhi 2002;82(14):941-944. View Abstract

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.