A Review of the Highlights

Remember Galantamine?
(How Could You Forget?)

Why galantamine is the best available agent for restoring memory and cognitive function when age begins to take its toll
By Will Block

alantamine Improves Both Alzheimer's and Dementia." That was the title of the most recent of 15 previous articles on galantamine published in Life Enhancement (see list), and it summarizes better than any of the others the principal virtue of this remarkable substance. Even the subtitle was the best: "Dual mode of action of this natural supplement accounts for its exceptional ability to restore and maintain acetylcholine function." Between them, they gave the gist, the whole gist, and nothing but the gist of the galantamine story.

Our Previous Galantamine Articles

Then why have article number 16? Well, this one summarizes some of the highlights of the others, for those who wish to have a quick overview or who are new to the subject. Besides, there's a new wrinkle on galantamine: see the sidebar on schizophrenia.

Can Galantamine Help in Schizophrenia?

Medical case histories of patients being treated for some disease have little inherent scientific value, but they can be illuminating and helpful to other physicians, and they sometimes suggest avenues of research that might be promising.

In Durham, North Carolina, two psychiatrists believe that galantamine may be beneficial in schizophrenia, judging by the case histories of two of their patients.1 One was a 28-year-old man suffering from auditory hallucinations and paranoid delusions of persecution. The other was a 53-year-old man with profoundly disorganized thoughts and bizarre behavior, such as wearing multiple layers of clothing inside out and backward. Both were doing poorly on the antipsychotic drug risperidone.

When the psychiatrists added galantamine to their drug regimen, both men improved significantly (the second patient even began dressing normally) and were able to function in society with less difficulty than before. The psychiatrists cite literature suggesting that the pathophysiology of schizophrenia may involve abnormal neurotransmission at nicotinic receptors in the brain. These are the receptors whose function galantamine is known to improve. So, connecting the dots . . . .

The psychiatrists report that controlled, double-blind trials of galantamine as an adjunctive treatment for schizophrenia are currently underway. Only clinical trials of this kind can provide scientifically credible information regarding the efficacy of a treatment, and it will be interesting to see the results when they become available.

  1. Allen TB, McEvoy JP. Galantamine for treatment-resistant schizophrenia (letter). Am J Psychiatry 2002 July;159(7):1244-5.

Galantamine Comes from Flowers

Galantamine is an alkaloid found in certain flowers, notably the common snowdrop, the daffodil, and the spider lily. Most of the galantamine used commercially today is extracted from daffodils or is synthesized in the laboratory. Galantamine's history as an herbal supplement dates back to the time of Homer, when it was used to restore memory - and that is its primary use to this day. In the United States, galantamine can be obtained without prescription as a nutritional supplement.

Galantamine Restores Memory

Galantamine is used primarily in counteracting memory loss and other symptoms of age-related cognitive impairment, an insidious condition that eventually affects everyone to some degree. In some cases, this condition evolves into full-blown dementia, a serious, progressive loss of memory accompanied by significant impairment in other areas of mental function or behavior, including the simple activities of daily living, such as bathing, dressing, and eating.

The most common form of dementia is Alzheimer's disease, whose cause is unknown. The symptoms generally include reduced levels of the neurotransmitter acetylcholine in certain parts of the brain, a substantial loss of neurons (brain cells), and the development of pathological changes in the brain called plaques and tangles. As the disease progresses, there is a relentless decline in cognitive function, accompanied by increasing behavioral disturbances. Memory problems, at first ambiguous, become undeniable and ultimately debilitating.

Vascular dementia is the second most common form of dementia, accounting for most of the remaining cases. As the name implies, it's related to impaired function in the blood vessels of the brain. Typically it is the result of damage to parts of the brain caused by a stroke (or a succession of "mini-strokes") or by the effects of such diseases as atherosclerosis, hypertension, and diabetes.

Galantamine's star shines
brightest in preventing and
alleviating the symptoms of
Alzheimer’s disease and age-
related memory loss.

It is often difficult to distinguish between Alzheimer's disease and vascular dementia - all the more so because they often occur together to varying degrees and share most of the same outward symptoms. And, although their origins are different, the distinction between them is not as clear as was previously thought - they have some factors in common, such as certain pathological changes in the brain. This may make it harder to tell one from the other, but it also makes it easier for an agent such as galantamine to counteract not just one form of dementia, but both.

Dementia Is a Disease of Aging

Age is the single greatest risk factor for dementia, and women are affected more than men, probably because women live longer than men. The prevalence of dementia at age 65 is 1%, but by age 85 it's 30-50%, and the incidence of new cases thereafter is 5-10% per year.1

Other risk factors include all those for heart disease: lack of exercise, high cholesterol, high blood pressure, obesity, smoking, and diabetes. Low income, low educational level, and low intellect are also factors, as are prior head injuries severe enough to have caused loss of consciousness. Finally, there is a gene that apparently predisposes one to Alzheimer's disease, although having this gene will not necessarily lead to the disease, nor will lacking the gene provide protection from it.

Galantamine Shines in Alzheimer's Disease

At any age and in any state of health, one can argue that it is always beneficial to enhance cognitive function, including memory. The benefits become more apparent, of course, the greater the degree of cognitive deficit to begin with, such as that caused by age-related cognitive impairment or, in the worst case, dementia.

With healthy blood vessels, there can be no vascular dementia. This disease can thus be relatively easily prevented, and sometimes even reversed to some degree. All it takes is a good diet and regular exercise, both of which are essential to preserve the health of our blood vessels and, therefore, the organs they supply with life-giving nutrients. There are also nutritional supplements that can help with prevention, through a variety of mechanisms. Although galantamine is not one of those, it does help to alleviate the symptoms of existing vascular dementia.2

Galantamine appears to retain
its efficacy indefinitely -- 
a major advantage.

Where galantamine's star shines brightest, however, is in preventing and alleviating the symptoms of the number one dementia, Alzheimer's disease, as well as the age-related memory loss that eventually affects us all.3 Because normal brain function depends critically on acetylcholine, which is deficient in Alzheimer's disease - and, to some degree, in vascular dementia as well - the primary goal of all Alzheimer's therapy is to restore normal levels of acetylcholine (ACh). Galantamine contributes to this goal in two ways:4

Galantamine's Edge Is Its Dual Function

1. Inhibition of acetylcholinesterase. This is an enzyme that destroys ACh. By inhibiting its action, therefore, galantamine effectively boosts ACh levels. Donepezil and rivastigmine, the two prescription drugs most commonly used in Alzheimer's disease, do the same thing - but that's all they do. By contrast, galantamine has another, entirely different mode of action - its ace in the hole - against Alzheimer's. It is:

2. Modulation of nicotinic receptors. These are the most important category of ACh receptors in the brain, occurring in large numbers at the synaptic junctions between nerve endings. By modulating nicotinic receptors so as to make them more receptive to ACh - and by protecting them from age-related deterioration in both function and numbers - galantamine effectively boosts the efficiency of neurotransmission via ACh.

With drugs such as donepezil and rivastigmine, this protective action on nicotinic receptors is absent. In fact, there is a gradual desensitization of these receptors to the drugs, resulting in drug tolerance, an increasing resistance to the drugs' efficacy. The symptoms of Alzheimer's disease thus gradually become worse. It takes the prescription drugs about a year to begin losing their efficacy as acetylcholinesterase inhibitors, whereas galantamine appears to retain its efficacy indefinitely - a major advantage.

Galantamine Has Minimal Side Effects

Since galantamine is a plant-based nutrient, it does not bring with it the usual baggage of unpleasant side effects that accompany synthetic drugs such as donepezil and rivastigmine. Actually, galantamine's adverse effects are almost nonexistent, the worst being mild gastrointestinal upset, such as nausea.5 (For a list of the common side effects of donepezil and rivastigmine, see this sidebar.)

Galantamine's Advantages Over Prescription Drugs

It is apparent from the scientific literature on the treatment of dementias with acetylcholinesterase inhibitors that galantamine is the safest and most effective of these agents. Following are the main advantages of galantamine over prescription drugs.

  • Galantamine modulates the nicotinic receptors in the brain's cholinergic system, enhancing cholinergic function in this way. Donepezil and rivastigmine do not.
  • Galantamine is not subject to drug tolerance and therefore retains its efficacy indefinitely. Donepezil and rivastigmine are effective for about one year.
  • Galantamine has few and mild side effects, whereas the common side effects of donepezil and rivastigmine include nausea, vomiting, diarrhea, headache, dizziness, drowsiness, fatigue, insomnia, flushing, hot flashes, skin rash, and tremor.
  • Galantamine is available without prescription, whereas donepezil and rivastigmine are available only by prescription and are more costly.

Galantamine Can Extend Life

Because galantamine's efficacy is not limited by drug tolerance, it may retard the progress of dementia, in which case it may well extend the life of the patient. Research published recently in the New England Journal of Medicine indicates that life expectancy in people suffering from dementia is much shorter than had previously been believed: 3.3 years after onset of the disease, rather than the previous estimate of 5 to 9.3 years.6 The study, using sophisticated statistical methods of analysis, was done on 821 elderly Canadian dementia patients with an average age of 84.

Galantamine may retard the
progress of dementia, in which
case it may well extend the
life of the patient.

The American authors of an accompanying editorial paint a grim picture of dementia, projecting that in the next half-century, the prevalence of Alzheimer's disease in the United States will nearly quadruple. This means that one in every 45 Americans will be afflicted (the rate among the elderly will, of course, be much higher than that, because the disease rarely affects young people).7 They go on to say, "In the new study, the prognosis for patients with dementia was similar to that for patients with some of the most malignant diseases, including many forms of cancer and heart disease."

Galantamine's ability to slow the progress of dementia can have important financial as well as health consequences. According to a study conducted by the independent consulting firm Caro Research, galantamine treatment could save $3000 annually per patient compared to those receiving no treatment, owing to the diminished need for paid help.8 As a bonus, the patient's improved condition (relatively speaking) would surely lighten the physical and emotional burden on caregivers.

Galantamine Helps Muscles Too

In ancient times, and to this day in Eastern Europe, where it is best known, galantamine was used not just to enhance memory but also to soothe aching muscles. In fact, much of the evidence for the folkloric use of galantamine pertains not to the improvement of cognitive function but to the alleviation of neuromuscular ailments such as neuritis and neuralgia.9 Galantamine is also known to be a muscle stimulant (it counteracts the effects of the muscle relaxant curare, for example), and there is some evidence that it may be beneficial for combating jet lag,10 fatigue syndromes,11 and even, perhaps, impotence.12

The connection with muscular function is not surprising, because acetylcholine is the primary neurotransmitter of the peripheral nervous system, for both skeletal muscles and smooth muscles (which are found in the walls of most internal organs). Here the ACh molecules provide direct stimulation of the muscle cells at the neuromuscular junction - the body's equivalent of a neural synapse within the brain. ACh also serves our exocrine glands, such as salivary and sweat glands, which secrete directly to the outside via ducts.

Collectively, all the nerve cells that utilize ACh as their primary neurotransmitter - in both the peripheral nervous system and the central nervous system - constitute the body's cholinergic nervous system. (Cholinergic means "activated by, or capable of liberating, or having physiological effects similar to, acetylcholine.") The actions mediated by ACh are collectively called cholinergic function.

As we age, cholinergic function slowly declines: our brain's ability to use its ACh is impaired, in part because the nicotinic receptors tend to deteriorate and decrease in number.13 The deficit in cholinergic function in certain parts of the brain is an early and consistent neurological feature of Alzheimer's disease, manifesting itself in slowly declining memory and cognitive function. The role of galantamine is to halt that decline and even, to some extent, reverse it.

Galantamine - Gift from the Gods

The modern rediscovery of galantamine about 50 years ago in Bulgaria led eventually to a startling hypothesis regarding the Odyssey, Homer's epic celebration of heroic memory. Our current knowledge of pharmacology and ethnobotany suggests that the medicinal plant that Hermes, the messenger of the gods, gave to King Odysseus of Ithaca to enable him to rescue his crew of sailors from the seductive spell cast upon them by the beautiful sorceress Circe was probably the snowdrop (Galanthus nivalis), which contains galantamine! Circe's spell, in Homer's description of it, bore the earmarks of amnesia and hallucinatory delusions such as those caused by atropine, which is found in jimsonweed (Datura stramonium), a plant also known to the ancient Greeks.14

Atropine is an anticholinergic, a substance that disrupts the brain's acetylcholine-mediated messaging system, resulting in cognitive dysfunction and memory impairment. The ideal antidote to such a drug would be an acetylcholinesterase inhibitor, and Homer's description of Hermes' gift from the gods - small white flowers - points to the snowdrop, and thus galantamine, which was well suited to this purpose. (The snowdrop was known to the ancient Greeks as moly.)

How uplifting it is to think that Homer's imperishable words could convey to us, over the three millennia since he composed them, the hidden messages that have allowed modern scientists to deduce some of the pharmacological knowledge of the ancients. Looking back on them, we think, "They still had so much to learn." But then, so do we.

Next month: A review of the literature supporting galantamine's benefits in Alzheimer's disease and vascular dementia.


  1. Goodwin L. Underwriting dementia and memory loss. The Messenger (Transamerica Reinsurance Risk Management newsletter), June 2000, pp 1-12.
  2. Erkinjuntti T, Kurz A, Gauthier S, Bullock R, Lilienfeld S, Damaraju CV. Efficacy of galantamine in probable vascular dementia and Alzheimer's disease combined with cerebrovascular disease: a randomised trial. Lancet 2002 Apr 13;359:1283-90.
  3. Olin J, Schneider L. Galantamine for Alzheimer's disease (Cochrane review). In The Cochrane Library, Issue 2, 2001. Oxford: Update Software.
  4. Woodruff-Pak DS, Vogel RW, Wenk GL. Galantamine: effect on nicotinic receptor binding, acetylcholinesterase inhibition, and learning. Proc Natl Acad Sci USA 2001 Feb 13;98(4):2089-94.
  5. Farlow MR. Pharmacokinetic profiles of current therapies for Alzheimer's disease: implications for switching to galantamine. Clin Ther 2001; 23 Suppl A:A13-24.
  6. Wolfson C, Wolfson DB, Asgharian M, M'Lan CE, Østbye T, Rockwood K, Hogan DB. A reevaluation of the duration of survival after the onset of dementia. N Engl J Med 2001 Apr 12;344(15):1111-6.
  7. Kawas CH, Brookmeyer R. Aging and the public health effects of dementia. N Engl J Med 2001 Apr 12;344(15):1160-1.
  8. Woodman R. Shire's Reminyl shows further promise in vascular dementia. Reuters Health, June 19, 2001.
  9. Venturi VM, Piccinin GL, Taddei I. Pharmacognostic study of self-sown Galanthus nivalis (var. gracilis) in Italy. Boll Soc Ital Biol Sper 1965 Jun 15;41(11):593-7.
  10. Davis BM. Method for alleviating jet lag. US Patent 5,585,375, issued Dec. 17, 1996.
  11. Snorrason E. Treatment of fatigue syndrome. US Patent 5,312,817, issued May 17, 1994.
  12. Katz R. Method of treating physiologic male erectile impotence. US Patent 5,177,070, issued Jan. 5, 1993.
  13. Ji D, Lape R, Dani JA. Timing and location of nicotinic activity enhances or depresses hippocampal synaptic plasticity. Neuron 2001;31(1):131-41.
  14. Plaitakis A, Duvoisin RC. Homer's moly identified as Galanthus nivalis L.: physiologic antidote to stramonium poisoning. Clin Neuropharmacol 1983 Mar;6(1):1-5.

Will Block is the publisher and editorial director of Life Enhancement magazine.

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