Research

Huperzine A

26 peer-reviewed studies curated from PubMed and Semantic Scholar.

6
Meta-analyses
3
Systematic reviews
15
RCTs
2
Other studies
Meta-analyses (23%)
Systematic reviews (12%)
RCTs (58%)

Studies

Sorted by quality and recency

2016·Human psychopharmacology·Wei Zheng, Ying-Qiang Xiang, Xian-Bin Li, et al

Adjunctive huperzine A for cognitive deficits in schizophrenia: a systematic review and meta-analysis.

Meta-analysisn = 1,117Brain Health

Systematic review and meta-analysis of 12 RCTs (n=1117) examining huperzine A (HupA) as an adjunctive treatment for cognitive deficits in schizophrenia. HupA outperformed comparators on cognitive measures such as the Wechsler Memory Scale and Wisconsin Card Sorting Test, suggesting it is effective for improving cognitive function in schizophrenia spectrum disorders.

PubMedRead on PubMed
2014·Evidence-based Complementary and Alternative Medicine : eCAM·Shu-huai Xing, Chun-xiao Zhu, Rui Zhang, et al

Huperzine A in the Treatment of Alzheimer's Disease and Vascular Dementia: A Meta-Analysis

Meta-analysisn = 825Brain Health

Meta-analysis of placebo-controlled RCTs assessing Huperzine A on Alzheimer's disease and vascular dementia patients. Huperzine A significantly improved cognitive function as measured by MMSE and ADL scores, with longer durations showing better efficacy in Alzheimer's patients. Adverse effects were generally mild to moderate.

Semantic ScholarRead on Semantic Scholar
2013·PloS one·Guoyan Yang, Yuyi Wang, Jinzhou Tian, et al

Huperzine A for Alzheimer's disease: a systematic review and meta-analysis of randomized clinical trials.

Meta-analysisn = 1,823Brain Health

Systematic review and meta-analysis of 20 RCTs with 1823 participants evaluating Huperzine A for Alzheimer's disease. Huperzine A showed significant beneficial effects on cognitive function, daily living activities, and global clinical assessment, though findings should be interpreted with caution due to high risk of bias in included trials.

PubMedRead on PubMed
2008·The Cochrane database of systematic reviews·J Li, H M Wu, R L Zhou, et al

Huperzine A for Alzheimer's disease.

Meta-analysisn = 454Brain Health

Meta-analysis of six trials with 454 patients assessing Huperzine A for Alzheimer's disease. Huperzine A showed beneficial effects on general cognitive function, global clinical status, behavioral disturbance, and functional performance, but not on specific cognitive functions. Adverse events were mild, but evidence quality was generally low.

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2019·Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica·Po Huang, Bo Li, Yu-Hong Guo, et al

[Efficacy and safety of huperzine A in treating patients with mild cognitive impairment: a systematic review and Meta-analysis].

Meta-analysisBrain Health

Systematic review and meta-analysis of nine RCTs evaluating huperzine A for mild cognitive impairment. Huperzine A significantly increased memory quotient and mini-mental state examination scores compared to placebo, with mild side effects. More high-quality studies are needed to confirm efficacy.

PubMedRead on PubMed
2018·Clinical interventions in aging·Jinghong Liang, Jiayu Li, Ruixia Jia, et al

Identification of the optimal cognitive drugs among Alzheimer's disease: a Bayesian meta-analytic review.

Systematic reviewBrain Health

Bayesian meta-analysis comparing the effectiveness of six drugs, including huperzine-A, in improving cognitive function in Alzheimer's disease patients. Memantine showed the most significant efficacy, followed by galantamine, huperzine-A, rivastigmine, tacrine, and donepezil.

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2012·The Cochrane database of systematic reviews·Jirong Yue, Bi Rong Dong, Xiufang Lin, et al

Huperzine A for mild cognitive impairment.

Systematic review

Systematic review assessing the clinical efficacy and safety of huperzine A for the treatment of mild cognitive impairment (MCI). No eligible randomised placebo-controlled trials were identified, and the evidence is insufficient to assess huperzine A's potential for MCI treatment.

PubMedRead on PubMed
2011·Neurology·M S Rafii, S Walsh, J T Little, et al

A phase II trial of huperzine A in mild to moderate Alzheimer disease.

RCTn = 210Brain Health

Phase II trial assessing safety, tolerability, and efficacy of huperzine A in mild to moderate Alzheimer's disease. Huperzine A 200 µg BID showed no cognitive benefit, while 400 µg BID showed some improvement in ADAS-Cog scores at 11 weeks but not at 16 weeks.

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2009·Journal of neural transmission (Vienna, Austria : 1996)·Bai-Song Wang, Hao Wang, Zhao-Hui Wei, et al

Efficacy and safety of natural acetylcholinesterase inhibitor huperzine A in the treatment of Alzheimer's disease: an updated meta-analysis.

Meta-analysisBrain Health

Updated meta-analysis of huperzine A efficacy and safety in Alzheimer's disease. Analyzed data from four RCTs showing significant improvements in mini-mental state examination and activities of daily living with oral HupA administration for 8-24 weeks. Most adverse events were cholinergic, with no serious adverse events reported.

PubMedRead on PubMed
2019·Journal of the Chinese Medical Association : JCMA·Amara Gul, Jehan Bakht, Farah Mehmood

Huperzine-A response to cognitive impairment and task switching deficits in patients with Alzheimer's disease.

RCTn = 100Brain Health Mental Clarity

Double-blind study with 50 AD patients and 50 healthy individuals assessing Huperzine-A's effect on cognition and task switching. AD patients showed significant improvement in cognition and task switching abilities post eight weeks of Huperzine-A treatment.

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2019·Brain injury·Ross D Zafonte, Felipe Fregni, Michael J G Bergin, et al

Huperzine A for the treatment of cognitive, mood, and functional deficits after moderate and severe TBI (HUP-TBI): results of a Phase II randomized controlled pilot study: implications for understanding the placebo effect.

RCTBrain Health -Mood

Phase II randomized controlled trial investigating the effect of Huperzine A on memory and learning in individuals with moderate-severe traumatic brain injury. No difference was found between Huperzine A and placebo groups in memory performance after 12 weeks, but both groups showed clinically important improvements in depression.

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2017·Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban·San-Lan Wu, Jun Gan, Jing Rao, et al

Pharmacokinetics and tolerability of oral dosage forms of huperzine a in healthy Chinese male volunteers: a randomized, single dose, three-period, six-sequence crossover study.

RCT

This study compared the pharmacokinetics, tolerability, and bioavailability of two formulations of huperzine A with a reference formulation in healthy Chinese male volunteers. It was a randomized, single-dose, 3-period, 6-sequence crossover study. The formulations met regulatory criteria for bioequivalence and were well tolerated with no adverse events reported.

PubMedRead on PubMed
2012·Cell biochemistry and biophysics·Zhi-Qiang Xu, Xiao-Min Liang, Juan-Wu, et al

Treatment with Huperzine A improves cognition in vascular dementia patients.

RCTn = 78Brain Health

Randomized, double-blinded, placebo-controlled study with 78 patients with mild to moderate vascular dementia. Participants received either Huperzine A or placebo for 12 weeks. The Huperzine A group showed significant improvements in MMSE, CDR, and ADL scores, indicating improved cognitive function.

PubMedRead on PubMed
2009·The Cochrane database of systematic reviews·Zilong Hao, Ming Liu, Zhiqin Liu, et al

Huperzine A for vascular dementia.

Systematic reviewn = 14Brain Health -

Systematic review assessing the efficacy and safety of Huperzine A in patients with vascular dementia. Only one small trial with 14 participants was included, showing no significant beneficial effect on cognitive function. The confidence intervals were wide, suggesting the need for further research.

PubMedRead on PubMed
2016·Acta pharmacologica Sinica·Lei Sheng, Yi Qu, Jing Yan, et al

Population pharmacokinetic modeling and simulation of huperzine A in elderly Chinese subjects.

RCTn = 49

Population pharmacokinetic modeling of huperzine A in elderly Chinese subjects was conducted using data from 49 participants across two clinical trials. The study identified age as a significant covariate affecting huperzine A clearance, and developed a PPK model to predict pharmacokinetic parameters for optimal administration in elderly AD patients.

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2015·The international journal of neuropsychopharmacology·Richard De La Garza, Christopher D Verrico, Thomas F Newton, et al

Safety and Preliminary Efficacy of the Acetylcholinesterase Inhibitor Huperzine A as a Treatment for Cocaine Use Disorder.

RCTn = 31

Double-blind, placebo-controlled study with participants randomized to huperzine A or placebo, receiving cocaine infusions. Huperzine A was safe and well-tolerated, and 0.4 mg significantly attenuated cocaine-induced increases in subjective effects like 'Any Drug Effect' and 'High'.

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2013·Acta pharmacologica Sinica·Jing-ying Jia, Qian-hua Zhao, Yun Liu, et al

Phase I study on the pharmacokinetics and tolerance of ZT-1, a prodrug of huperzine A, for the treatment of Alzheimer's disease.

RCTn = 40

This study evaluated the pharmacokinetics and tolerance of ZT-1, a prodrug of huperzine A, in healthy Chinese subjects. ZT-1 was rapidly absorbed and converted into huperzine A, with dose-proportional increases in AUC and Cmax. No serious adverse events were observed, indicating good tolerance.

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2008·Chemico-biological interactions·Julian R Haigh, Scott R Johnston, Adam Peppernay, et al

Protection of red blood cell acetylcholinesterase by oral huperzine A against ex vivo soman exposure: next generation prophylaxis and sequestering of acetylcholinesterase over butyrylcholinesterase.

RCTn = 12

Phase Ib clinical trial assessing the tolerability and safety of huperzine A in 12 healthy elderly individuals with escalating doses. Significant inhibition of red blood cell acetylcholinesterase was observed, with gradual recovery post-dose. Huperzine A showed potential for improved prophylaxis against organophosphate poisoning compared to pyridostigmine bromide.

PubMedRead on PubMed
2007·European journal of drug metabolism and pharmacokinetics·Y X Li, R Q Zhang, C R Li, et al

Pharmacokinetics of huperzine A following oral administration to human volunteers.

RCTn = 12

Pharmacokinetic study of huperzine A in 12 healthy human volunteers. Huperzine A was administered in tablet form at a single dose of 0.4 mg, showing a biphasic profile with rapid distribution followed by a slower elimination rate.

PubMedRead on PubMed
2007·Schizophrenia research·Zhang-Jin Zhang, Yao Tong, Xue-Yi Wang, et al

Huperzine A as add-on therapy in patients with treatment-resistant schizophrenia: an open-labeled trial.

RCT

The study investigates the use of Huperzine A as an add-on therapy in patients with treatment-resistant schizophrenia in an open-labeled trial.

PubMedRead on PubMed
1999·Zhongguo yao li xue bao = Acta pharmacologica Sinica·Q Q Sun, S S Xu, J L Pan, et al

Huperzine-A capsules enhance memory and learning performance in 34 pairs of matched adolescent students.

RCTn = 68Mental Clarity

Double-blind RCT with 34 pairs of junior middle school students to assess the efficacy of huperzine-A capsules on memory and learning performance. The Hup group showed significantly higher memory quotient and improved Chinese language lesson scores compared to placebo.

PubMedRead on PubMed
1999·Zhongguo yao li xue bao = Acta pharmacologica Sinica·S S Xu, Z Y Cai, Z W Qu, et al

Huperzine-A in capsules and tablets for treating patients with Alzheimer disease.

RCTn = 60Brain Health

RCT comparing the efficacy and safety of huperzine-A in capsules versus tablets for treating Alzheimer disease in 60 patients. Both forms showed significant improvements in psychological evaluations and reduced oxygen free radicals, with no severe side effects.

PubMedRead on PubMed
1995·Zhongguo yao li xue bao = Acta pharmacologica Sinica·S S Xu, Z X Gao, Z Weng, et al

Efficacy of tablet huperzine-A on memory, cognition, and behavior in Alzheimer's disease.

RCTn = 103Brain Health Mental Clarity

RCT evaluating the efficacy and safety of huperzine-A in 103 Alzheimer's patients. 58% of patients treated with huperzine-A showed improvements in memory, cognition, and behavior compared to 36% in the placebo group. No severe side effects were found.

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1991·Zhongguo yao li xue bao = Acta pharmacologica Sinica·R W Zhang, X C Tang, Y Y Han, et al

[Drug evaluation of huperzine A in the treatment of senile memory disorders].

RCTn = 160Brain Health

RCT studying the effects of huperzine A on 56 patients with multi-infarct dementia or senile dementia and 104 patients with senile and presenile simple memory disorders. Huperzine A showed significant curative effects as evaluated by the Wechsler memory scale, with only slight dizziness reported by a few patients.

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2014·Frontiers in Aging Neuroscience·Z. Qian, Y. Ke

Huperzine A: Is it an Effective Disease-Modifying Drug for Alzheimer’s Disease?

ReviewBrain Health

Narrative review discussing the potential of Huperzine A as a disease-modifying agent for Alzheimer's disease. Huperzine A is noted for its cognitive-enhancing effects via acetylcholinesterase inhibition and protective effects against amyloid beta-induced oxidative injury and mitochondrial dysfunction.

Semantic ScholarRead on Semantic Scholar
2012·Hai-Yan Zhang

New insights into huperzine A for the treatment of Alzheimer's disease

ReviewBrain Health

The paper discusses huperzine A, a Lycopodium alkaloid used in China for Alzheimer's disease treatment. It highlights huperzine A's acetylcholinesterase inhibitory effect and its multifaceted neuroprotective mechanisms, including activation of the cholinergic system and mitochondrial action. Efforts to optimize its drug delivery system are also reviewed.

Semantic ScholarRead on Semantic Scholar