Huperzine A has been used for centuries in Chinese folk medicine. Its action has been attributed to its ability to strongly inhibit acetylcholinesterase, the enzyme that breaks down acetylcholine in the synapse. Acetylcholine is involved in memory and learning. By inhibiting the enzyme that breaks down acetylcholine, more acetylcholine becomes available to stimulate neurons. Alzheimer's disease is a condition where there's a relative shortage of acetylcholine. Several studies have been done over the past few years with huperzine A, both in China and the United States. These studies found that Huperzine A is many times more effective and selective than tacrine (a cholinesterase-inhibiting pharmaceutical drug) in inhibiting cholinesterase (Cheng 1996). Huperzine A has also been found to be beneficial in patients with Alzheimer's disease. Scientists at Zhejiang Medical University, in Hangzhou, China administered 0.2 mg of huperzine A to fifty patients with Alzheimer's disease for a period of eight weeks and compared the results to a group who received placebo pills (Xu 1995). The study was done in a double blind, placebo controlled and randomized manner. The results showed 58 percent of the patients treated with huperzine A had improvements in memory, cognition, and behavioral functions whereas only 36 percent of those on placebo improved. No severe side effects were found. Blood pressure, heart rate, electrocardiogram,electroencephalogram, liver and urine tests did not show any major abnormalities. The researchers say, "Huperzine A is a promising drug for symptomatic treatment of Alzheimer's disease." This club moss extract may also benefit older individuals with dementia. A study was conducted with fifty-six patients suffering from multi-infarct dementia (multiple small strokes) and one hundred patients with senile memory disorders (Zhang 1991). The dose used for multi-infarct dementia was 0.05 mg twice a day for four weeks, whereas that for senile memory disorders was 0.03 mg twice a day for two weeks. Most patients had an improvement in memory. A few reported slight dizziness, but this did not affect the therapeutic effects.

Traditional Chinese Herbal Medicine Looks Promising
A traditional Chinese herbal treatment for fever and inflammation may one day help treat Alzheimer's disease. The herb (which shows little benefit for fever and inflammation) is the moss Huperzia serrata, known in Chinese medicine as Qian Ceng Ta. This medicine contains a compound, huperzine A (HupA), which is a powerful and highly selective acetylcholinesterase inhibitor, meaning that it has similar action to the four drugs currently approved to treat Alzheimer's disease--tacrine (Cognex), donepezil (Aricept), rivastigmine (Exelon) and galantamine (Reminyl). According to researchers at the Weizmann Institute of Sciences in Rehovot, Israel, and at Georgetown University in Washington, D.C., HupA appears to inhibit acetylcholinesterase more effectively than either tacrine or donepezil. Reports from China, where an estimated 100,000 people have used the compound, suggest that it is at least as safe as the approved Alzheimer's drugs. HupA is still a long way from pharmacy shelves, but researchers express cautious optimism about its potential as an Alzheimer's treatment in the future.
Source: Journal of the American Medical Association, 3/12/97

Chinese researchers:

Efficacy of tablet huperzine-A on memory, cognition, and behavior in Alzheimer's disease. Xu SS, Gao ZX, Weng Z, Du ZM, Xu WA, Yang JS, Zhang ML, Tong ZH, Fang YS, Chai XS, et al. Zhongguo Yao Li Xue Bao 1995 Sep;16(5):391-5

Using multicenter, prospective, double-blind, parallel, placebo controlled and randomized method, 50 patients were administered orally 0.2 mg (4 tablets) Hup and 53 patients were given po 4 tablets of placebo bid for 8 wk. All patients were evaluated with Wechsler memory scale, Hasegawa dementia scale, mini-mental state examination scale, activity of daily living scale, treatment emergency symptom scale, and measured with BP, HR, ECG, EEG, ALT, AKP, BUN, Cr, Hb, WBC, and urine routine.
RESULTS: About 58% (29/50) of patients treated with Hup showed improvements in their memory (P < 0.01), cognitive (P < 0.01), and behavioral (P < 0.01 functions. The efficacy of Hup was better than placebo (36%, 19/53) (P < 0.05). No severe side effect was found.
CONCLUSION: Hup-A is a promising agent for symptomatic treatment of Alzheimer's disease.

2002 Update: Some animal research doesn't look too promising:
Effects of chronic administration of huperzine A on memory in guinea pigs. Filliat P, Foquin A, Lallement G. Drug Chem Toxicol 2002 Feb;25(1):9-24.
Effects of subchronic administration of huperzine A, a cholinesterase inhibitor, on spatial memory were studied in guinea pig. Spatial memory was assessed by the Morris water maze test. At a dose of 0.25 microgram/h, inhibiting 36% of blood AChE and 14-20% of central AChE, no effect on spatial learning was found. At a dose of 1 microgram/h, inhibiting 20% of blood AChE and 14-20% of central AChE, no memory impairment was found, on the other hand, a memory enhancing effect, limited to the first day was shown. It thus appears that subchronic administration of huperzine A did not induce deleterious effects on spatial memory.

2003 Update: Progress in clinical, pharmacological, chemical and structural biological studies of huperzine A: a drug of traditional chinese medicine origin for the treatment of Alzheimer's disease. Curr Med Chem. 2003 Nov;10(21):2231-52 (a comprehensive documentation of the progress in the studies on HupA during the period of 1999-2002).

2004 Update: Zhang HY, Yan H, Tang XC. Huperzine A enhances the level of secretory amyloid precursor protein and protein kinase C-alpha in intracerebroventricular beta-amyloid-(1-40) infused rats and human embryonic kidney 293 Swedish mutant cells. Neurosci Lett. 2004 Apr 22; 360(1-2):21-4.

2005 Update: Hup A is available mixed with vitamins in an over-the-counter supplement made by the Natrol company or mixed with soy products by the Acenta company. As with many other supplements, the hype vastly exceeds the research. However, Hup A is being taken very seriously. It is now in rigorous Phase 2 clinical trials.