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5 Benefits and Side Effects of Huperzine A (Please Be Aware of 7 Contraindications in Use)[Updated Feb/2023]

Huperzine A is an alkaloid derived from the traditional Chinese medicine plant Huperzia serrata, which is approved in some regions as an anti-Alzheimer’s disease drug ingredient.

There is a long history of using snakefoot liquor as a medicine in traditional medicine to treat ailments, including pain relief, detoxification, swelling, bruising, tension, swelling, rheumatism, schizophrenia, myasthenia gravis, and fever.

What are the benefits of using Huperzine A in empirical medicine? Are there any side effects or contraindications? See text analysis for details.

What is Huperzine A?

Huperzine A, a natural alkaloid isolated from Huperzia serrata, a plant of the Huperziaceae family, is a potent, highly specific, reversible inhibitor of acetylcholinesterase.

Compared with other acetylcholinesterase inhibitors, such as tacrine, physostigmine, donepezil, rivastigmine, etc., huperzine A is more effective in increasing corticotic acetylcholine levels, lasts longer, penetrates the blood-brain barrier more easily, and has a variety of pharmacological functions.

Other potential pharmacological functions include attenuating β-β amyloid toxicity, preventing glutamate-induced neurotoxicity, and anti-free radicals.

What are the benefits of Huperzine A?

  1. Huperzine A is beneficial for mild cognitive dysfunction

Mild cognitive impairment is a clinical stage in the continuous process of cognitive decline between “normal aging” and dementia.

The key criteria for distinguishing mild cognitive impairment from dementia are maintenance of functional independence without impairment in the cognitive domain, including memory, executive function, attention, language, or visuospatial skills, and lack of significant impairment in social or occupational functioning.

Related studies have shown that patients with mild cognitive impairment develop Alzheimer’s disease at a rate of 10% to 15% per year, and 80% of these patients transition to Alzheimer’s disease after about 6 years of follow-up.

A systematic literature review and meta-analysis (9 randomised controlled trials associated with mild cognitive impairment) found that Huperzine A improved memory quotient (MQ) and Mini-mental State Test (MMSE) scores compared with placebo. Note 1

*Conclusion: Huperzine A may provide positive help for mild cognitive impairment, but more high-quality trials are needed to support this due to the low quality of the available evidence

  1. Huperzine A is beneficial for depression

Major Depressive Disorder is a pervasive, chronic, disabling, multidimensional mental disorder. Cognitive dysfunction is a core diagnostic and symptomatic criterion for depression.

Cognitive dysfunction refers to deficits in attention, verbal and nonverbal learning, short-term and working memory, visual and auditory processing, problem solving, processing speed, and motor function.

A systematic review (3 randomised controlled trials, 238 people with depression) noted that the combination of Huperzine A and antidepressants did not lead to more significant improvement in depressive symptoms (compared with antidepressants alone). Note 3

However, the Huperzine A group did have greater improvements in cognitive function (as measured by the Wisconsin Card Classification Test and the Wechsler Memory Scale) and quality of life than in the antidepressant group alone.

*Conclusion: For patients receiving antidepressant therapy, the combination of Huperzine A may have a positive effect on cognitive function and quality of life, but more studies are needed to support it due to small sample sizes and low quality of evidence

  1. Huperzine A is beneficial for Alzheimer’s disease

Alzheimer’s disease is a degenerative disease of the central nervous system that occurs in early old age.

Clinical manifestations include memory impairment, aphasia, apraxia, agnosia, visuospatial disturbances, abstract thinking deficits, numeracy, and personality and behavioral disorders. These symptoms gradually worsen, eventually leading to a complete loss of motor function.

While there is no specific treatment to reverse or prevent Alzheimer’s disease, treatment strategies that provide early support and symptom relief can alleviate the rapid decline in a patient’s quality of daily life.

A systematic literature review and meta-analysis (20 randomized controlled trials involving 1823 Alzheimer’s patients) noted that Huperzine A improved cognitive function, activities of daily living, and global clinical assessment compared with placebo. Note 4

*Conclusion: Huperzine A may bring positive help to Alzheimer’s disease improvement, but due to the low quality of the available evidence, more rigorous experiments are needed to confirm its efficacy and safety in long-term use

  1. Huperzine A is beneficial for schizophrenia

Schizophrenia, also known as schizophrenia, is a complex, chronic mental health disorder characterized by a range of symptoms, including delusions, hallucinations, speech or behavior disturbances, and impaired cognitive abilities.

Impaired cognitive function is a core feature of schizophrenia, which includes moderate to severe deficits in working memory, attention, processing speed, vision, language learning, reasoning, planning, abstract thinking, and problem-solving.

A systematic literature review and meta-analysis (12 randomized controlled trials involving 1117 people with schizophrenia spectrum disorder) noted that Compared with antipsychotics alone, the combination of Huperzine A further improved memory quotient, verbal intelligence quotient, performance IQ, full IQ, response management errors, non-persistent errors, and total psychopathological symptom scores. Note 5

*Conclusion: For schizophrenia spectrum disorder, Huperzine A-adjuvant therapy can bring positive help to cognitive function and overall psychopathological improvement, but due to the heterogeneity, low quality and short duration of the available evidence, more precisely designed studies are needed to support it

  1. Huperzine A in the treatment of cocaine drug abuse

Cocaine, also known as cocaine, is considered one of the most dangerous drugs today, producing a strong physical addiction that has serious negative effects on the health, social relationships and economy of users.

Chronic cocaine use causes persistent changes in the vascular system, increasing the likelihood of myocardial infarction, hypertension, atherosclerosis, and stroke.

A randomized, double-blind, placebo-controlled study (10-day study of 47 participants receiving intravenous cocaine) noted that the use of Huperzine significantly reduced any drug effects, exaltation, exhilaration, willingness to pay, and adverse effects associated with cocaine compared with placebo. Note 6

*Conclusion: Huperzine A may be of positive help in the treatment of cocaine addiction, but due to the small sample size, more large trials are still needed for further validation

Are there any side effects of Huperzine A?

It has been found in the known literature that moderation with Huperzine A is safe in the short term (6 months).

However, possible side effects or adverse effects include: anxiety, nausea, diarrhea, vomiting, dry mouth, constipation, sweating, blurred vision, slurred speech, hyperactivity, nasal congestion, fainting, loss of appetite, convulsions, cramps, abnormal heart rhythm, increased saliva and urine, inability to control urination, high blood pressure, dizziness, insomnia (especially when used in high doses)

Safety precautions

  1. Do not use for pregnant women, breastfeeding women, and children (because the relevant safety is unknown)
  2. Patients with heart disease should use caution, because Huperzine A may lower heart rhythm, which may worsen related symptoms
  3. Patients with epilepsy should use caution, because Huperzine A may affect brain neurotransmitters and may worsen related symptoms
  4. Patients with gastrointestinal obstruction, urethra or reproductive system obstruction, peptic ulcer, asthma or emphysema should be used with caution, because Huperzine A increases the secretion of tissue mucus and fluid and may worsen symptoms.
  5. Do not use in combination with anticholinergic drugs, which may reduce the efficacy of the drug. The names of related drugs are: atropine, scopolamine (hyoscyamine), and some antihistamines and antidepressants
  6. Do not use in combination with Acetylcholinesterase inhibitors, which may increase the side effects of the drug. The related drug names are: Galantamine, donepezil, rivastigmine, tacrine
  7. Do not use in combination with Cholinergic drugs, which may increase the side effects of the drug. Related drug names are: pilocarpine, donepezil, tacrine
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