Ingredient Type: Botanical, Extract
Also Known As: Selagine, Huperzia serrata extract, Toothed clubmoss extract, Chinese clubmoss extract, Lycopodium serrata extract, Qian Ceng Ta extract
Nootropics, known as ‘smart drugs’ or cognition enhancers, are drugs or supplements which are used to improve memory, attention, reasoning ability and other cognitive functions. Huperzia serrata, or toothed club moss, is a nootropic plant that belongs to the Huperziaceae family and indigenous to China (1,2,3).
The plant’s nootropic properties are known to come from the alkaloid, huperzine A, which was first isolated from Huperzia serrata by a group of Chinese scientists in 1986 (4). Later, a study done in China in 2005, showed that the plant Phlegmariurus carinatus also of the Huperziaceae family, has the highest content of hyperzine A, even higher than Huperzia serrata (5).
The first total artificial synthesis of huperzine A in the laboratory was reported in 1989, both by a group of researchers in China and a group of researchers in the United States (6,7).
Qian Ceng Ta, a traditional Chinese medicine produced from the whole plant of the club moss Huperzia serrata, has been used for over 1,000 years in China for treatment of several ailments including fever, inflammation (8), contusions, strains, swellings, schizophrenia, and myasthenia gravis (9). Tea brewed from the leaves of Huperzia serrata was given to elderly people to alleviate their memory problems (10).
The earliest record of medicinal usage of Qian Ceng Ta can be traced back to an ancient Chinese pharmacopeia “Ben Cao Shi Yi”, which was written by Zangqi Chen in 739 A.D. during the Tang Dynasty. The herb was named Shi Song in this book, and it was prescribed for relieving rheumatism, colds, relax muscles and tendons, and to promote blood circulation. The same herb, with different names but similar usage prescriptions, can be found in “Ben Cao Gang Mu” by Shizhen Li in 1578 during the Ming Dynasty and “Zhi Wu Ming Shi Tu Kao” by Qijun Wu in 1848 during the Qing Dynasty. Later known as Qian Ceng Ta, this herb was most commonly used in southern China (9).
WHAT DOES SCIENCE TELL US?
Huperzine A Probably Helps Enhance Memory and Cognition:
Several clinical trials have been conducted to investigate the effect of huperzine on memory and cognitive function of patients suffering from Alzheimer’s disease (AD). Most of these studies have been conducted in China and an estimated 100,000 patients have been treated with huperzine A (9). These studies indicate that huperzine A significantly improves memory, cognition and the activities of daily living in AD patients.
A group of researchers in China conducted a randomized, double-blind, placebo-controlled study (11) on a small group of 28 patients suffering from AD. They reported the beneficial effect of huperzine A tablets given at a dose of 200 µg, twice a day for 60 days. Huperzine A treatment caused a 71.4% improvement in the cognitive evaluation (using WMS scale) as compared to 25.5% with the placebo (p <0.005). No significant side effects were reported.
A large and comprehensive clinical study was conducted across 39 mental hospitals in China, where 819 patients who met the AD criteria of National Institute for Communicative Disorders and Stroke-AD and Related Disorders Association (NINCDS-ADRDA) and Diagnostic and Statistical Manual of Mental Disorders-Third Edition-Revised (DSM-III-R) were enrolled. After treatment with huperzine A at a dose of 30 – 400 µg/day, the patients showed improvement in their memory, cognitive skills, and daily life activities. No severe side effects were found (12).
Another randomized, double-blinded, placebo-controlled trial (13) tested the efficacy and safety of huperzine A in 78 patients with mild to moderate vascular dementia. The participants were randomized and 39 received vitamin C (100 mg, twice a day) as a placebo; while the other 39 received huperzine A (0.1 mg, twice a day) for 12 consecutive weeks. The cognition assessments were made prior to treatment, and 4, 8, and 12 weeks of the treatment. After 12 weeks of treatment, the MMSE, clinical dementia rating (CDR), and ADL scores significantly improved in the huperzine A group (P < 0.01 for all comparisons), whereas the placebo group did not show any such improvement (P > 0.05 for all comparisons). No serious adverse events were recorded during the treatment.
A study done by Xu et al. reported that huperzine A could be a safe and effective treatment for benign senescent forgetfulness (14). They conducted a 4 week long multicenter, prospective, double-blind, parallel, placebo-controlled and randomized study. Oral huperzine A was administered to 50 patients, at a dose of 150 µg (3 tablets) twice a day for the study duration. Another group of 50 patients was given placebo orally at 3 tablets twice a day for 4 weeks. In the huperzine A group, 37 out of 50 patients (74%) showed improvements in their memory (p 0.01) and cognitive functions (p 0.01). The efficacy of huperzine A was 40% better than placebo (p 0.05). No severe cholinergic side effect was noted.
A recent meta-analysis (15) was performed on 12 randomized controlled trials from China, with the objective of assessing the efficacy of huperzine A as an adjunct therapy for the treatment of cognitive deficits in schizophrenia spectrum disorders. Twelve RCTs with a total of 1,117 patients, lasted 11.7 ± 6.0 weeks. The observations revealed that huperzine A outperformed comparators on the cognitive performance outcome measures like the Wechsler Memory Scale-Revised including memory quotient (p < 0.0001), Wechsler Adult Intelligence Scale-Revised including verbal intelligence quotient (IQ), performance IQ, and full IQ (p = 0.01 to 0.00001) and the Wisconsin Card Sorting Test (p = 0.03 to 0.003). The authors concluded that adjunctive huperzine A is an effective choice for improving cognitive function for patients with schizophrenia spectrum disorders.
An open-labeled trial (16) tested the nootropic effect of huperzine A in 17 patients diagnosed with treatment-resistant schizophrenia and having significant cognitive impairments (baseline MMSE scores ≤ 26). While patients continued the antipsychotic treatment, oral huperzine A at a dose of 300 µg/ day was given for 12 weeks. The addition of huperzine A resulted in significant cognitive improvement. There was an approximately 15% increase in mean MMSE score from baseline to endpoint (p<0.001) and 76% (13/17) of patients displayed at least a 3-point improvement. There were no patients who experienced serious adverse events during the 12-week treatment with huperzine A.
Huperzine A Might Help Support Brain Health:
In an open-label study done on 30 former NFL players with traumatic brain injury and cognitive impairment, huperzine A was administered among a cocktail of other supplements like fish oil, gingko, vinpocetine and other vitamins. The trial average was 6 months and the results showed statistically significant increases in scores of attention, memory, reasoning, information processing speed, and cognition (17).
An in-vitro study reported in 2008, demonstrated for the first time that huperzine A has the ability to protect a motor neuron-like cell line and motor neurons in spinal cord organotypic cultures against toxins (18).
Other studies conducted on animals demonstrate the neuroprotective potential of huperzine A (19,20). It has been shown to interfere with the formation of a neurotoxic protein called Amyloid β (which is also implicated in AD pathology). Amyloid β also plays a role in apoptosis or cell death and huperzine A has been shown to possess protective effects against apoptosis models. Huperzine A has also shown a protective effect against oxidative stress by increasing the antioxidant enzymes (21) and decreasing lipid peroxidation products (22). This might be beneficial in neurodegenerative diseases where oxidative stress is an important pathological factor (23).
Huperzine A Possibly Helps Stabilize Brain Function:
Huperzine A, along with being an effective acetylcholinesterase inhibitor, has also been shown to possess anti-convulsant potential in preclinical studies (24). To date, there is no available published data outlining the efficacy and safety of huperzine A in patients with epilepsy. Further studies in humans need to be done to establish whether huperzine A can have a realistic role as an anticonvulsant (25).
The general dosage regimens at which huperzine A has been tested clinically are 0.2 – 0.4 mg given twice a day. It has been well tolerated up to 24 weeks, even in subjects unable to take other cholinesterase inhibitors (26). Further, there is no scientific evidence to support the safety of huperzine A in pregnant and breastfeeding women.
There are no reported interactions of huperzine A with other drugs/supplements. This might be due to insufficient clinical studies with a focus on its interaction spectrum.
- Only mild to moderate side effects have been observed which are mainly cholinergic in nature. Due to the inhibition of acetylcholinesterase, huperzine A can also cause acetylcholine concentration to increase at the neuromuscular junctions, causing cholinergic side effects like nausea, vomiting, and diarrhea (27,28).
Larger samples and long-term follow up studies would be required to detect the adverse effects with any reliability.
- Plants Profile for Huperzia serrata (toothed clubmoss)|USDA PLANTS. https://plants.usda.gov/core/profile?symbol=HUSE2. Accessed February 28, 2018.
- Kozikowski AP, Tückmantel W. Chemistry, Pharmacology, and Clinical Efficacy of the Chinese Nootropic Agent Huperzine A. Acc Chem Res. 1999;32(8):641-650. doi:10.1021/AR9800892
- Ferreira A, Rodrigues M, Fortuna A, Falcão A, Alves G. Huperzine A from Huperzia serrata: a review of its sources, chemistry, pharmacology and toxicology. Phytochem Rev. 2016;15(1):51-85. doi:10.1007/s11101-014-9384-y
- Liu J-S, Zhu Y-L, Yu C-M, et al. The structures of huperzine A and B, two new alkaloids exhibiting marked anticholinesterase activity. Can J Chem. 1986;64(4):837-839. doi:10.1139/v86-137
- Ma X, Tan C, Zhu D, Gang DR. Is There a Better Source of Huperzine A than Huperzia serrata ? Huperzine A Content of Huperziaceae Species in China. J Agric Food Chem. 2005;53(5):1393-1398. doi:10.1021/jf048193n
- Xia Y, Kozikowski AP. A practical synthesis of the Chinese "nootropic" agent huperzine A: a possible lead in the treatment of Alzheimer’s disease. J Am Chem Soc. 1989;111(11):4116-4117. doi:10.1021/ja00193a062
- Qian L, Ji R. A total synthesis of (±)-huperzine A. Tetrahedron Lett. 1989;30(16):2089-2090. doi:10.1016/S0040-4039(01)93719-0
- Patocka J. Huperzine A–an interesting anticholinesterase compound from the Chinese herbal medicine. Acta medica (Hradec Kral.) 1998;41(4):155-157.
- Ma X, Tan C, Zhu D, Gang DR, Xiao P. Huperzine A from Huperzia species—An ethnopharmacolgical review. J Ethnopharmacol. 2007;113(1):15-34. doi:10.1016/J.JEP.2007.05.030
- Bai D. Traditional Chinese medicines and new drug development. Pure Appl Chem. 1993;65(6):1103-1112. doi:10.1351/pac199365061103
- Liu F, Fang Y, Gao Z, Zhuo J, Su M. Double-blind control treatment of huperzine-A and placebo in 28 patients with Alzheimer disease. Chinese J Pharmacoepidemiol. 1995;4(4):196-198.
- Wang R, Yan H, Tang X. Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine. Acta Pharmacol Sin. 2006;27(1):1-26.
- Xu Z-Q, Liang X-M, Juan-Wu, Zhang Y-F, Zhu C-X, Jiang X-J. Treatment with Huperzine A Improves Cognition in Vascular Dementia Patients. Cell Biochem Biophys. 2012;62(1):55-58. doi:10.1007/s12013-011-9258-5
- Xu S, Xie H, Du Z, et al. Efficacy of tablet huperzine－A on memory and cognition in patients with benign senescent forgetfulness. Chinese J Clin Pharmacol Ther. 1997;2:1-4.
- Zheng W, Xiang Y-Q, Li X-B, et al. Adjunctive huperzine A for cognitive deficits in schizophrenia: a systematic review and meta-analysis. Hum Psychopharmacol Clin Exp. 2016;31(4):286-295. doi:10.1002/hup.2537
- Zhang Z-J, Tong Y, Wang X-Y, Yao S-M, Jin G-X, Wang X-P. Huperzine A as add-on therapy in patients with treatment-resistant schizophrenia: an open-labeled trial. Schizophr Res. 2007;92(1-3):273-275. doi:10.1016/j.schres.2007.02.005
- Amen DG, Wu JC, Taylor D, Willeumier K. Reversing Brain Damage in Former NFL Players: Implications for Traumatic Brain Injury and Substance Abuse Rehabilitation. J Psychoactive Drugs. 2011;43(1):1-5. doi:10.1080/02791072.2011.566489
- Hemendinger RA, Armstrong EJ, Persinski R, et al. Huperzine A provides neuroprotection against several cell death inducers using in vitro model systems of motor neuron cell death. Neurotox Res. 2008;13(1):49-61.
- Lu H, Jiang M, Lu L, Zheng G, Dong Q. Ultrastructural mitochondria changes in perihematomal brain and neuroprotective effects of Huperzine A after acute intracerebral hemorrhage. Neuropsychiatr Dis Treat. 2015;11:2649-2657. doi:10.2147/NDT.S92158
- Antar V, Baran O, Yuceli S, et al. Assessment of the neuroprotective effects of the acetylcholinesterase inhibitor Huperzine A in an experimental spinal cord trauma model. J Neurosurg Sci. October 2015. http://www.ncbi.nlm.nih.gov/pubmed/26472141. Accessed March 5, 2018.
- Wang LM, Han YF, Tang XC. Huperzine A improves cognitive deficits caused by chronic cerebral hypoperfusion in rats. Eur J Pharmacol. 2000;398(1):65-72. doi:10.1016/S0014-2999(00)00291-0
- Shang YZ, Ye JW, Tang XC. Improving effects of huperzine A on abnormal lipid peroxidation and superoxide dismutase in aged rats. Acta Pharmacol Sin. 1999;20(9):824-828.
- Zhang HY, Tang XC. Neuroprotective effects of huperzine A: new therapeutic targets for neurodegenerative disease. Trends Pharmacol Sci. 2006;27(12):619-625. doi:10.1016/J.TIPS.2006.10.004
- Schachter SC. TREATMENTS (NON-ANTIEPILEPTIC DRUGS) | Herbal Therapies for Epilepsy. In: Encyclopedia of Basic Epilepsy Research. Elsevier; 2009:1450-1454.
- Damar U, Gersner R, Johnstone JT, Schachter S, Rotenberg A. Huperzine A: A promising anticonvulsant, disease modifying, and memory enhancing treatment option in Alzheimer’s disease. Med Hypotheses. 2017;99:57-62. doi:10.1016/j.mehy.2016.12.006
- Rafii MS, Walsh S, Little JT, et al. A phase II trial of huperzine A in mild to moderate Alzheimer disease. Neurology. 2011;76(16):1389-1394. doi:10.1212/WNL.0b013e318216eb7b
- Birks JS. Cholinesterase inhibitors for Alzheimer’s disease. In: Birks JS, ed. Cochrane Database of Systematic Reviews. Chichester, UK: John Wiley & Sons, Ltd; 2006:CD005593. doi:10.1002/14651858.CD005593
- Wang BS, Wang H, Wei ZH, Song YY, Zhang L, Chen HZ. Efficacy and safety of natural acetylcholinesterase inhibitor huperzine A in the treatment of Alzheimer’s disease: an updated meta-analysis. J Neural Transm. 2009;116:457-465. doi:10.1007/s00702-009-0189-x
See this Mayo Clinic article on huperzine A for Alzheimer’s, the Examine.com entry for huperzine A, the WebMD entry for huperzine A, the Michigan Medicine Health Library entry for Huperzia, or the RXList entry for huperzine A for more information.