How a Safe, Natural Supplement Can Enhance Our Memory and Physical Well-Being

What would you think of a small, white flower that contained an exotic but very safe - and obviously natural - substance that could enable you to experience improved memory and muscle function, to counteract jet lag, to combat fatigue, and even, perhaps, to overcome impotence?

Well, such a flower exists. It is the common snowdrop (Galanthus nivalis), and the molecular treasure it contains is galantamine. In this article we will look at the various benefits to be had from supplementing with galantamine (which is also extracted from other species of Galanthus, as well as from daffodils). But first, let us review a few key aspects of our nervous system, beginning with a surprising player: nicotine.

U.S. Postcard issued in honor of Galanthus nivalis, the snowdrop from which galantamine was originally derived.

Nicotine is an alkaloid that, in tiny amounts, is known to have a positive effect on cognitive functions such as learning and memory. (No, we are not recommending that you take up smoking - quite the contrary, as smoking is extremely destructive of good health.) Although you probably don't smoke, you do get nicotine in very small amounts from such foods as eggplant, potatoes, and tomatoes.1

Certain receptor sites in the brain are called nicotinic receptors because they are highly sensitive to nicotine, which gains entry to the brain by crossing the blood-brain barrier. A receptor site on a neuron (nerve cell) is a specific molecular structure that responds in a characteristic manner to the arrival of a neurotransmitter molecule from a neighboring neuron. This chemical messaging mechanism enables nerve impulses to be propagated across the synapse, the tiny gap between adjacent neurons.

Although nicotinic receptors are stimulated by nicotine, as well as by a number of other substances, their main function is to respond to acetylcholine, one of the body's principal neurotransmitters. Collectively, the neurons in which this process occurs constitute the body's cholinergic nervous system. (Cholinergic means "activated by or capable of liberating acetylcholine"; it also means "having physiological effects similar to those of acetylcholine.")

Disruption of the cholinergic system is believed to be largely responsible for the mental problems of old age, including Alzheimer's disease, which is primarily a condition of memory loss. A characteristic feature of this terrible disease is a complicated pattern of degenerative changes in the brain, including the atrophy or dysfunction of cholinergic cell groups that underlie the normal neural mechanisms associated with higher cognitive functions. There is also a progressive loss of nicotinic receptors in particular.

Among the other forms of age-related cognitive impairment are confusion, delirium, hallucinations, and dementia. An important piece of evidence for the belief that cholinergic dysfunction is at the root of these disorders is the fact that they can be mimicked by taking various drugs that interfere with cholinergic activity.1 Throughout history, in fact, it has been a common practice in many cultures to ingest such "cholinergic antagonists" (atropine and scopolamine, e.g.) for ritualistic or sacred purposes, including initiation rites and religious ecstasies.

The opposite of a cholinergic antagonist is a cholinergic agonist, a substance that stimulates cholinergic activity. Galantamine has been shown to be a cholinergic agonist, both by stimulating ACh receptors and by inhibiting the action of AChE (acetylcholinesterase), an enzyme that breaks down ACh.2 By interfering with the action of AChE, galantamine boosts the levels of ACh. (Think of it this way: ACh, good. AChE, bad. Inhibition of AChE, good.)

In performing its complementary roles, galantamine acts as a powerful cognitive enhancer, helping to prevent Alzheimer's-related memory loss. And, as a cholinergic agonist, it's an effective antidote to cholinergic antagonists. (For more information, including literature references, on these topics, see Fight Alzheimer's Disease – Oct. 2000 and Boost Memory and Keep It – Nov. 2000.)

In a recent study to determine the effects of galantamine and the prescription drug donepezil on memory in aged rats (22 months old), researchers found that both substances produced a striking improvement in long-term potentiation (LTP).2 This is a neural mechanism  that facilitates long-term memory. Compared with the control group, both galantamine and donepezil significantly reduced the decay time for LTP, i.e., induced memories were maintained for a longer time in the treated groups than in the control group.

The daily doses of galantamine and donepezil administered were those which were necessary to produce a 60% reduction in AChE activity in the rats' brains. This is the same level as that achieved in human Alzheimer's patients who are given therapeutic doses of AChE inhibitors.

The memory improvements noted were insufficient to produce measurable changes in the rats' behavior in standardized tests, but the researchers concluded that "Taken together, the electrophysiological, biochemical, and behavioral results of this study suggest that the 60% inhibition of AChE targeted in human patients with AD [Alzheimer's disease] may be very close to the threshold for producing a significant cognitive benefit."

Much of the evidence for the folkloric use of galantamine in Eastern Europe, where it is best known, pertains not to the improvement of cognitive function, but to the alleviation of neuromuscular ailments such as neuritis and neuralgia. Galantamine is also known to be a muscle stimulant (it counteracts the effects of the muscle relaxant curare, for example).

From the foregoing (and recall the list of benefits in the first paragraph of this article), one might conclude that the cholinergic nervous system is not confined to the brain or even the central nervous system as a whole - and one would be correct. Indeed, most cholinergic neurons are somatic - out in the body, where ACh acts as 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 somatic 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.

Wherever ACh is, or ought to be in greater amounts than it actually is, galantamine can be of help to increase its concentration and enhance its effects. Galantamine's cholinergic activity throughout the body is also notable for its lack of toxicity and side effects, something that cannot be said for the synthetic drugs - primarily tacrine and donepezil - that are most commonly prescribed as AChE inhibitors for Alzheimer's disease. Tacrine is notorious for its liver toxicity and gastrointestinal side effects, and donepezil can cause a variety of gastrointestinal disturbances as well as heart-rate irregularities and liver problems.

Part of galantamine's advantage may lie in the fact that it's about 50 times more effective in inhibiting AChE than a related enzyme called BChE (butyrylcholinesterase), which is apparently not involved in any cognitive function. By contrast, most other AChE inhibitors are also effective BChE inhibitors, and it is believed that this may contribute to their peripheral toxicity, for reasons beyond the scope of this article.2

It is known that ACh levels in the brain are lower in sleeping animals than in those that are awake, and that artificial depletion of ACh can disrupt the normal sleep-wake cycle. The implications of these facts for travelers who are prone to jet lag are obvious: the travelers may have to cope with the demands of daily activities, including stressful business meetings, while operating on a low, nighttime level of ACh.

In a recently issued United States patent, it is claimed that galantamine is effective in combating jet lag.3 To reset the body's biological clock, the recommended procedure is to take galantamine at a time early in the "day" (i.e., the period during which one wishes to be awake) in the time zone to which the person is going to travel, starting several days in advance and continuing for several days after the trip. The typical preferred dosage for this purpose is about 10­-35 mg per day, but the optimal dosage depends on the traveler's metabolism, the number of time zones to be crossed, and the time at which the galantamine is taken.

Another useful application of this ability to reset the body's biological clock is for shift workers who are switching from a day shift to a night shift, or vice versa. Not only can this make the transition easier to bear, but it can lessen the risk of on-the-job injuries caused by impaired alertness.

Fatigue syndromes have only recently come to be recognized by the medical community as real disorders and not just the complaints of neurotics and malingerers. The concept encompasses chronic fatigue syndrome, postinfectious fatigue syndromes, and fatigue syndromes associated with HIV infection or preeclampsia (a condition of hypertension occurring during pregnancy). The common thread in all these syndromes is that the primary symptom is a persistent and debilitating fatigue of uncertain cause.

To be regarded as a bona fide medical condition, the fatigue must be severe enough to cause the patient to complain of it. Furthermore, it should affect the patient's normal functioning and be disproportionate to exertion. It should represent a clear change from a previous state, and it should be present at least half the time.

Fatigue syndromes are generally reported as having two aspects: (1) physical fatigue, a feeling of lack of energy or strength, often felt in the muscles, and (2) mental fatigue, a subjective feeling characterized by lack of motivation and alertness. Beyond the fatigue itself, other symptoms may include:

  • Sleep disturbances, possibly related to a decrease in REM (rapid-eye-movement) sleep, the most restful kind.
  • Disability, in the sense of a restricted ability to perform an activity within the normal range.
  • Mood disturbances, such as depression, anxiety, or irritability.
  • Myalgia (pain or aching in the muscles) beyond what can be accounted for from normal causes.

A reasonable hypothesis to explain all this, described in detail in another United States patent, is that the cause is an ACh insufficiency in both the peripheral nervous system (where it diminishes muscular function) and the central nervous system (where it impairs mental function).4 The patent claims a method for treating fatigue syndromes with "pharmaceutically acceptable" (i.e., safe) AChE inhibitors, particularly galantamine and some of its chemical derivatives, but also several other compounds, including huperzine.

The author states that the "excellent and surprising" effect of galantamine can be attributed to its high degree of specificity for nicotinic receptors, among other factors. To combat fatigue syndromes, it is typically administered in doses of about 30­-40 mg per day for several months. He notes that in four decades of the use of galantamine as an anticurare agent in anesthesiology in Eastern bloc countries, there have been no reports of liver toxicity or serious side effects. When used in the recommended low therapeutic doses, the only side effects have been rare instances of nausea, vomiting, and slight headache.

Impotence - the inability to obtain or maintain an erection - may be due to either physiological or psychiatric factors. The condition may be secondary to some other disease state (typically a chronic disease), or it may be the result of a specific disorder of the urogenital or endocrine systems. It may also be secondary to the administration of drugs such as antihypertensives, antidepressants, or antipsychotics.

Distinguishing between physiological and psychogenic impotence is generally easy. From early childhood through at least the eighties, human males experience nocturnal erections for an average of about 100 minutes per night. They occur typically during periods of REM sleep (which is characterized by more vivid and bizarre dreams than in slow-wave sleep and is believed to be largely under the control of cholinergic neurons in a certain region of the brain stem). These nocturnal erections are undiminished in men with psychogenic impotence, but they do not occur in men whose problem is physiological. Therefore, merely observing what does or does not occur during sleep (there are simple devices for detecting this) is sufficient to make the distinction.

In yet another United States patent, the claim is made that galantamine is effective in treating physiologically caused impotence, without the side effects of other substances that have been used for this purpose.5 (The author pointed out that galantamine had previously been reported to be helpful in alleviating psychogenic impotence.6 He was not addressing this problem himself, however.) The preferred dosage for a 70-kg (154-lb) man is about 10­-20 mg of galantamine hydrobromide, taken three times per day.

Galantamine is a remarkable substance, some of whose benefits have been known and appreciated for thousands of years. How fortunate we are to have it still and to be able to explore further its uncanny ability to improve our mental function and our physical well-being, especially as we age.

But how many similarly wondrous chemical compounds have already been lost to us forever because of the ongoing, wanton extinction of plant species throughout the world? Let us hope that our stunning technological powers are someday matched by the wisdom to stop destroying the unimaginable medicinal riches that undoubtedly still lie undiscovered in obscure little plants growing in the forests and grasslands and deserts and marshes of the earth.


  1. Perry EK. Cholinergic phytochemicals: from magic to medicine. Aging & Mental Health 1997;1(1):23-32.
  2. Barnes CA, Meltzer J, Houston F, Orr G, McGann K, Wenk GL. Chronic treatment of old rats with donepezil or galantamine: effects on memory, hippocampal plasticity, and nicotinic receptors. Neurosci 2000;99(1):17-23.
  3. Davis BM. Method for alleviating jet lag. US Patent 5,585,375, issued Dec. 17, 1996.
  4. Snorrason E. Treatment of fatigue syndrome. US Patent 5,312,817, issued May 17, 1994.
  5. Katz R. Method of treating physiologic male erectile impotence. US Patent 5,177,070, issued Jan. 5, 1993.
  6. Paskov D, Traikov D. Treatment of psychogenic form of sexual astenia with nivalin. Suremenna Meditsina 1974;25(12):30-4.