Smart Drugs (“nootropics”) are pharmaceutical drugs (i.e. Piracetam, Hydergine, Vasopressin), that are either available by prescription in the United States, or by overseas mail-order from off-shore companies. By law, American citizens are legally allowed to purchase, for their own personal use, up to a three month supply of many smart drugs from overseas distributors. The data on Smart Drugs is provided for informational purposes only.
Aniracetam, another chemical cousin of piracetam, is also known as Draganon, Ro 13-5057, and Sarpul. It is considered even more powerful, and is used to treat more conditions. Aniracetam has much the same effect as piracetam without problems of toxicity or side effects. Its use as a smart drug is less common. The U.S. patent holder, Hoffman-LaRoche, has had problems gaining FDA approval for treating Alzheimer’s disease. So far the drug has not been officially approved in any country. Though it has great potential, aniracetam is primarily used in research, and is not yet widely available as a smart drug.
One of the most venerable of the anti-aging compounds, centrophenoxine is a combination of dimethylaminoethanol (DMAE), a natural substance found in the human body, and auxin, a plant growth hormone. Although new research on centrophenoxine is limited, many experts feel that its potential anti-aging benefits may stem from its proven ability to combat free radicals, highly reactive molecules that damage cells and that many experts regard as a central feature of aging. Centrophenoxine has also been shown in some studies to boost memory and mental acuity in humans, and to combat cellular aging and increase life span in lab animals.
An experiment by Kalidas Nandy, Ph.D., of the Boston University School of Medicine found that centrophenoxine reduced buildup of lipofuscin, a pigment that accumulates in aging cells and can interfere with their functioning. Other research indicates that centrophenoxine can shore up cell membranes and increase cellular manufacture of RNA and certain proteins, which tend to decline with age. But the real eye-opener is a study by Imre Zs.-Nagy, M.D., of the Hungarian-Italian Verzar Laboratory for Experimental Gerontology, in which centrophenoxine extended life span in lab rats by as much as 33 percent.
Among the most promising of the human trials of centrophenoxine is a 1989 study in which the drug improved memory and learning in 50 elderly demented patients by as much as 48 percent.
Although centrophenoxine has not been shown to be toxic in animal tests, it should not be used by nursing mothers, or by people with high blood pressure, convulsions or involuntary musculoskeletal movements caused by such conditions as Parkinson’s disease.
A strong indication of the potency of centrophenoxine comes from Europe, where it is used in hospitals to revive patients in alcoholic or post-traumatic coma. Some European doctors routinely prescribe it to treat memory disorders or dementia. Although not marketed in the US, it is obtainable by mail order, and is among the most reliable-and certainly the most praised-of the “smart drugs” that are taken by people seeking to boost mental performance.
Excerpted from BRAIN BOOSTERS: Foods & Drugs That Make You Smarter
Commonly known by its trade name, Lucidril, centrophenoxine rejuvenates brain cells and reverses the aging process by getting rid of lipofuscin deposits, which are cellular garbage created by the buildup of toxic waste by-products of cellular metabolism. You might think of centrophenoxine as the “garbage man of the brain.” Lipofuscin deposits in the skin are the brown age spots or liver spots commonly seen in older people. Lipofuscin deposits build up in brain cells, causing neurons to die, which results in a decline in mental functioning.
Animal studies indicate an inverse relationship between lipofuscin deposits and learning. That is, the greater the lipofuscin in the brain cells, the less the learning ability; the less lipofuscin, the greater the learning ability. After taking centrophenoxine people report greater alertness and increased feelings of stimulation. Animal studies show improvements in learning.
The rejuvenating effects in humans is believed to be produced by regeneration of parts of the neurons. Centrophenoxine breaks down into dimethylaminoethanol (DMAE) in the blood stream. DMAE is normally found in small quantities in the brain. It is a free-radical scavenger, and has a variety of beneficial brain-boosting effects, including improving mood, intelligence, memory, and learning ability.
Centrophenoxine stimulates energy production. The uptake of glucose or sugar, which is essential for energy production, is increased by centrophenoxine. In the process of producing energy, oxygen is consumed and carbon dioxide created as a by-product. Both oxygen consumption and CO2 production are increased by centrophenoxine. The side effects are similar to those experienced by people taking too much of the nutrient choline. These symptoms are eliminated by reducing the dosage. People on an anti-cholinergic diet should not use centrophenoxine. Centrophenoxine is not currently available in the U.S. It is sold in Europe, however.
Scientific evidence from laboratories around the world suggests that deprenyl, also known as selegiline, may have broad anti-aging benefits, both mental and physical. Among other things, this compound inhibits monoamine oxidase-B, a natural substance which at increased levels has been associated with brain aging, senescence and Alzheimer’s disease. Long known as an antidepressant (although its role in alleviating depression is controversial), deprenyl has recently come into its own as an adjunct to L-dopa treatment for Parkinson’s disease. There are even impressive hints from animal studies that deprenyl lengthens life.
In 1988 Joseph Knoll, M.D., of Semmelweis University of Medicine in Budapest found that the average life span of rats treated with deprenyl was 34 percent longer than that of untreated rats. He also noted that while untreated rats lost their sexual vitality with age, 64 of 66 of the deprenyl-treated animals retained sexual vigor. More recently, in 1991, a team from the Israeli Institute for Biological Research in Ness-Ziona, reported that deprenyl significantly improved learning and memory in elderly rats.
Although deprenyl’s effectiveness as an antidepressant remains controversial, a 1988 study by J. John Mann, M.D., of the University of Pittsburgh Medical School, reported in our earlier article, concluded that deprenyl was three times better than placebo in alleviating depression. In a number of preliminary tests of deprenyl as a treatment for Alzheimer’s disease, patients showed some improvement in mental functioning, especially memory, verbal communication and daily-living skills.
The consensus among experts is that deprenyl is relatively free of adverse side effects. However, it can induce mild overstimulation similar to that from caffeine.
Because deprenyl is approved by the FDA for treatment of Parkinson’s disease (it is widely used for that purpose in both Europe and the US), it can be obtained with a doctor’s prescription and is thus among the more readily available of the anti-aging drugs. It may be well worth discussing with your doctor as a potential sexual invigorator or even as a general antiaging therapy.
DEPRENYL PROTECTS AGAINST DEATH OF NEURONS
Researchers have written a great about the benefits of deprenyl over the past few years, presenting evidence that deprenyl, in doses ranging from .5 mg every other day to 1.O mg per day, reverses the age-related increase in the enzyme monoamine oxidase B (MAO-B), which degrades the neurotransmitter dopamine, the loss of which dampens our mood, throttles our sex drive, and unhinges our coordination. It’s also been reported evidence that deprenyl combats the free radical mediated damage to neurons that plays an important role in pathologies associated with brain aging. But, perhaps, the most impressive evidence of deprenyl’s ability to fight brain aging is its ability to rescue dying neurons in tissue culture. This finding suggests that deprenyl can prevent the most critical event in brain aging-the death of irreplaceable neurons.
EFFECTS OF DEPRENYL ON BRAIN MICROANATOMY
A variety of degenerative changes occur in the brain’s microanatomy both in normal aging and senile dementia. A recent study at the University of La Sapienza in Rome, Italy (Mech Of Aging & Devel, 73:113126:1994) was designed to determine the effects of long-term administration of deprenyl on microanatomical changes in the aging rat brain, especially in areas of the brain involved in cognition, such and the frontal cortex and hippocampus, as well as the cerebellar cortex.
The Italian scientists used male Sprague-Dawley rats of 11 and 19 months of age. Twenty 1 9-month-old rats were randomly allotted to two groups of 10 animals each, which were injected with either 0.25 mg/kg of deprenyl or saline every other day. Another group of 11-month-old untreated rats was used to compare the effects of deprenyl in aging animals to healthy normal adult animals. Both the experimental and control groups were sacrificed at 24 months of age and their brains examined for age dependent changes.
DEPRENYL SLOWS MICROANATOMICAL BRAIN CHANGES
The scientists found that deprenyl was able to counteract, to some degree, all four of the age-dependent microanatomical changes in the rat brain examined in the study. The first is density of nerve cell profiles-a measure of the ability of the nervous system to receive, analyze, and store information-which is reduced progressively with advancing age in the rat brain. Less of a reduction in the density of nerve cell profiles was found in the rats given deprenyl, but this change was not statistically significant, except for the Purkinje neurons in the cerebellum.
The second parameter studied was the density of Nissl’s staining in the cytoplasm of pyramidal and Purkinje neurons, which is believed to be a measure of the ribonucleic acid content of nerve cells. Treatment with deprenyl restored the intensity of Nissl’s staining in nerve cell populations of the hippocampus and the cerebellar cortex in aged rats.
Third was age-dependent lipofuscin accumulation, which is believed to be a by-product of the peroxidative action of free radicals on membrane lipids. It was found that deprenyl decreased lipofuscin (aging pigment) accumulation in neurons, suggesting that it may have reduced oxidative stress on these cells.
Last was sulphide-silver staining within the hippocampus, which is related to the density of zinc-containing synaptic junctions, which are critical in learning, memory, and information processing within the brain. The administration of deprenyl countered, in part, the reduction of sulphide silver staining, which the scientists believe may be related to the improvement of cognitive function produced by deprenyl treatment in aged rats. (Pharmacol Biochem Behav, 39:297304:1 991).
These findings showing that deprenyl can slow important microanatomical changes in the aging rat brain provide further evidence to explain the ability of the drug to improve cognitive and behavioral function in both normally aging and demented humans by preventing the premature death of brain cells.
NEW STUDIES ON DEPRENYL
Every month, we see new studies on deprenyl showing it to be even more effective for aging than previously thought. Some of these new studies have duplicated the successful research conducted in Japan showing that one mechanism by which deprenyl extends lifespan is by boosting antioxidant enzyme levels of superoxide dismutase (SOD) and catalase. A new study has shown that oral doses of deprenyl given to dogs for only three weeks produced a dose-dependent increase of both SOD and catalase in the striatum, but not the hippocampus region of the brain (Life Sciences 54:201994). These results are in accordance with previously published results in rats. Endogenous antioxidant enzymes are more effective in preventing free radical damage than supplemental antioxidants.
Deprenyl is well known to boost brain levels of dopamine by inhibiting monoamine oxidase-B (MAO-B). Dopamine elevation conferred life extension benefits in an early study and is known to boost cognitive function and improve sexual performance. Raising base levels of SOD and catalase helps explain further the underlying mechanisms of deprenyl’s antiaging effects. In a study in the Feb 1994 issue of Mechanisms of Aging and Development, long term treatment with deprenyl was investigated on age dependent changes in the rat brain. Deprenyl treated rats (they were given the drug in their drinking water) were shown to have decreased levels of lipofuscin (aging pigment) in certain brain regions. Increased brain levels of lipofuscin have been linked to senile dementia in humans. The loss of density of certain neuronal fibers (especially in the hippocampus region of the brain) was reduced in animals receiving deprenyl (compared to the placebo group), which helps to explain deprenyl’s ability to improve memory in Alzheimer’s patients. Loss of neuronal fibers also occurs in “normal” aging.
Based upon recent studies suggesting the benefits of higher oral doses of deprenyl, the following are commonly used doses for deprenyl:
* Age 40-50: 5 mg of Deprenyl three to four times a week; * Age 50-60: 5 mg of Deprenyl four to six times a week; * Age 60-70: 5 mg of Deprenyl daily; * Over 70: 5 to 10 mg of Deprenyl daily.
Every decade over age 40-45 results in the death of 13% of the dopamine producing neurons in humans. If you suffer from an accelerated decline in your dopamine producing neurons, you are said to have Parkinson’s disease. Deprenyl protects against the death of dopamine producing neurons and for this reason alone, should be part of your life extension program if you are over 40 years of age.
Dilantin is a remarkable multipurpose drug that has been the subject of more than 8,000 published papers. It is the most common treatment for epilepsy, and is prescribed under the generic name phenytoin and its trade name, Dilantin. It normalizes and improves mental functioning in general and improves concentration, learning, and thinking in particular.
Discovered in 1938, Dilantin was used as an anticonvulsant and is still heralded as the most effective drug for this purpose ever discovered. Although scientists are just beginning to understand the electrical nature of humans and other animals, most people know that our nerves are electrical in nature. Thinking, memory, and pain are all electrically generated. Dilantin stabilizes the electrical activity in the body at the level of the cell membrane. Dilantin stops convulsions, which are electrical in nature. When cells show too much or too little electrical activity, phenytoin brings them back into balance. In addition, when the brain cells are functioning normally, the drug can calm the individual and increase energy levels. So phenytoin acts as a kind of medical equivalent to meditation, promoting calm and harmony.
Because Dilantin influences electric currents, it can affect thinking and recall. Scientists don’t really understand how phenytoin works; however, they postulate that it influences electromagnetic fields, which polarize the electrically charged elements in the cells. This results in a more effective organizational structure, so that cell and brain functioning is improved.
One of the major advantages of Dilantin is it stabilizes and normalizes the nervous system without acting as either a stimulant or a depressant. The result is that one can concentrate, learn, and remember better. Prolonged concentration can be exhausting. One effect of Dilantin is that it delays the onset of fatigue and thereby reduces errors that accompany fatigue. In this regard, phenytoin’s effect is similar to that of stimulants, but it is not a stimulant and has none of the side effects common to stimulants.
Generally Dilantin’s effectiveness for a wide variety of disorders is unknown to most doctors. Most doctors think it is useful only in maintaining epilepsy, and are not knowledgeable about its tremendous impact on general cognitive functioning, mood moderation, and concentration.
Dilantin does have some significant but infrequent side effects when taken in regular dosages. Some people report tremors, insomnia, headaches. dizziness, nausea, and vomiting. Dr. Pelton indicates that phenytoin can occasionally cause liver toxicity during the first few weeks of use. Some people, mostly children with epilepsy, report gum problems.
A major consideration for most people using Dilantin is that it can disturb absorption of vitamin D and folic acid, which are essential for health. Dr. Pelton recommends that people on phenytoin therapy take supplements of vitamin D, calcium, and folic acid.
Dilantin is available, by prescription, in capsule, tablet, and liquid forms. The original patent has expired, so it is available under its generic name, phenytoin, as well as under its trade name Dilantin in the United States, and Epanutin, Epamin, Eplin, Idantoin, and Aleviatan in other countries.
So far, little is known about the effects of this cognitive enhancer, which is also known by the names Attentil, BP 662, and Vigilor. Whereas most nootropics improve both learning and recall, fipexide helps learning but not recall. Nootropics in the pyrrolidone family work by affecting the parts of the nervous system that use acetylcholine as a neurotransmitter. Fipexide works by slightly increasing the amount of the neurotransmitter dopamine in the brain. With more dopamine, there is better motor coordination, an improved immune system, more motivation to act, and a better emotional balance, all of which might contribute to the kind of mental fine tuning that promotes learning.
Dr. Ana Aslan, director of the Institute of Geriatrics in Romania, developed Gerovital (GH-3) in the early 1950s. GH-3 has been hailed as a miraculous youth formula that combats the ravages of aging and makes people feel more energetic and youthful. It is claimed to reverse the aging process, and to improve thinking and memory by providing the nutrients needed to repair damaged cells and membranes.
Procaine hydrochloride can pass through the damaged membranes of diseased cells. It increases the cell’s consumption of oxygen, and provides nutrients that help the damaged cells repair or renew membranes.
Chemically, GH-3, which is an injectable treatment, is made of procaine hydrochloride mixed with potassium metabisulfate, disodium phosphate, and benzoic acid. Procaine breaks down in the body into PABA (paraminobenzoic acid), a B vitamin, and DEAE (diethylaminoethanol), which is chemically similar to DMAE and is converted in the cells into choline.
PABA aids the body in blood-cell formation, protein metabolism, and skin functions. A deficiency of PABA can cause constipation, depression, digestive disorders, stress, infertility, fatigue, gray hair, headaches, and irritability. PABA stimulates the intestinal bacterial system to produce the B vitamins folic acid, pantothenic, and biotin, and vitamin K. PABA is rapidly disposed of by the liver, so ingesting it alone can get disappointing results. However, when combined with the procaine hydrochloride molecule, PABA is more effective.
DEAE has an antidepressant effect. DEAE comprises choline and acetylcholine, which make up important neurotransmitters that facilitate brain functioning.
Ana Aslan experimented with the rejuvenative effects of procaine through the late 1940s and well into the 1950s. Out of this research she developed an improved formula, in which she buffered and stabilized the basic procaine hydrochloride, which she called Gerovital H-3 or GH-3. Dr. Aslan presented her results from treatment of more than 2,500 people using GH-3 to the Karlsruhe Therapy Congress. She claimed GH-3 relieved depression, arthritis, angina pectoris, and hypertension, produced muscular vigor, and had a rejuvenative effect at the cellular level. Her results were confirmed in the l970’s on 15,000 people aged 40 to 62.
People taking GH-3 claim relief from a host of ailments and pains. They say it is an antidepressant and brain tonic that makes people more alert and cheerful. It is reported to arrest aging symptoms, hair loss, graying, wrinkling, and hardened skin.
Depression in the elderly was researched by an NIMH team, who concluded that it was c caused by a buildup of the enzyme monoamine oxidase (MA0) in the brain. Typically this process begins around age 45 and continues with age.
Dr. Alfred Sapse, who had interned under Ana Aslan, showed that GH-3 is an MA0 inhibitor that gave rapid improvement in depression and insomnia patients. They also reported a general improved sense of well-being. Patients with high cholesterol showed reduced serum cholesterol after four weeks’ treatment. Sapse’s results were replicated at UCLA and Duke University.
Even though numerous impressive studies were conducted in the United States, Sapse was frustrated in his many attempts to gain FDA approval to market GH-3 in the United States as a treatment for depression and aging.
The Dr. Ana Aslan Institute in Miami, Florida, provides treatment using Aslan’s original formula. The treatment consists of Gerovital administered by injection three times a week for four weeks, followed by a ten-day rest period and another four-week treatment period. GH-3 also comes in tablet form. The dose is one tablet a day for twenty-five days, then no GH-3 for a five-day rest period.
Of all the substances with potential anti-aging properties, none has aroused such widespread excitement or generated such widespread controversy as Human Growth Hormone. Secreted by the pituitary gland, human growth hormone (also known as hGH or somatotropin) was shown in a widely reported 1990 study by Daniel Rudman, M.D., and his colleagues at the Medical College of Wisconsin to trim fat, build muscle and improve skin tone in a dozen elderly men. In the wake of Rudman’s report, headlines around the country trumpeted hGH as a rejuvenator and age-reverser. Since then, medical journals around the world have bulged with new reports of hGH’s many potential benefits, including the possibility that it may help the body fight off infectious diseases and cancer.
Of the many animal experiments using hGH, perhaps the most exciting has been a 1991 study by Michael Torosian, M.D., and Robert Donoway, M.D., of the University of Pennsylvania School of Medicine in Philadelphia, in which hGH significantly slowed the spread of lung cancer in rats. The researchers now hope to apply for permission to do human tests.
In addition to hGH’s ability to trim fat and increase muscle mass, newer studies are beginning to show that it may play an important role in combating age-related diseases. In 1991, a team led by Christian Wiedermann of the University of Innsbruck Medical School in Austria reported that hGH had stimulated the functioning of polymorphonuclear neutrophils, immune-system cells that fight off bacterial infections. (Age-related declines in the activity of these cells leave older people more vulnerable to infectious diseases.) In 1992, Fran Kaiser, M.D., of the St. Louis University School of Medicine reported that injections of synthetic growth hormone stimulated appetite, induced weight gain and increased muscle mass in five elderly patients who were suffering from chronic malnutrition. Since other studies have shown that up to 65 percent of older people in hospitals and nursing homes may be malnourished, Kaiser suggests that hGH be further considered and tested as a possible treatment for age-related malnutrition.
Taking large doses of hGH may result in acromegaly, a condition in which the bones of the face are grotesquely enlarged, and which has been associated with high blood pressure and cardiovascular disease. Some experts fear that hGH may stimulate tumor growth in people with cancer, although this has not been scientifically established.
Human growth hormone is approved by the FDA for the physician-supervised treatment of unusually short children, meaning that it is available by doctor’s prescription. Because of its muscle-building propensities, hGH is in considerable demand among athletes, many of whom consider it a legal and relatively safe alternative to anabolic steroids.
The granddaddy of the so-called smart drugs, hydergine has a long history as a mental de-ager. An extract of ergot, a fungus that grows on rye, hydergine (also known as dihydroergotoxine) was developed in the 1940s as a treatment for hypertension. Since then, hydergine has undergone scores of tests in patients with varying forms of dementia, including Alzheimer’s disease. Although the results have been equivocal, the Physicians’ Desk Reference lists hydergine as offering “some” relief for age-related declines in mental acuity.
In old rats, hydergine has been shown to increase metabolism and uptake of glucose in the brain. It also helps rejuvenate connections between brain cells, protect the brain against damage due to oxygen starvation and improve learning capabilities.
Although a 1990 study at Jefferson Medical College in Philadelphia concluded that hydergine was ineffective as a treatment for Alzheimer’s disease, Longevity reported in 1991 that exhaustive testing in a number of laboratories in the US of more than 1,000 patients with various kinds of senile disorders indicates that those treated with hydergine had consistently higher scores in such cognitive functions as mental alertness, clarity and mood.
Hydergine is nontoxic and relatively safe. Its potential side effects include mild nausea and gastric disturbance. It should not be taken by people with psychosis, or those with low blood pressure or abnormally slow heartbeat.
One of the most exciting things about hydergine is its availability. It has FDA approval as a treatment for Alzheimer’s disease, but some doctors may prescribe it to combat brain aging in healthy people.
Excerpt from BRAIN BOOSTERS: Foods & Drugs That Make You Smarter
Hydergine is considered by some to be an all-purpose brain booster . It increases mental abilities, prevents brain cells from being damaged by free radicals or by too little oxygen (hypoxia), and reverses brain-dell damage. Hydergine increases learning, memory, and recall in several ways. It speeds up the level of metabolism in the brain cells and increases the amount of blood and oxygen getting to the brain. Hydergine reduces brain damage when oxygen is insufficient, as during a stroke. Hydergine slows down lipofuscin deposits associated with brain-cell aging, and acts as a prophylactic against damage from free radicals.
The only FDA-approved uses of hydergine are senility and cerehrovascular insufficiency, which is caused by poor blood circulation to the brain. Hydergine’s effectiveness in reducing symptoms of senility have been well-established. Hydergine increases the oxygen supply in the brain, which keeps production of free radicals in check. When oxygen is in short supply because of smoking, cerebral insufficiency, strokes, or heart attacks, free radicals are rapidly produced, resulting in brain-cell damage.
In Europe, hydergine is regularly given in hospital emergency rooms to victims of strokes, heart attacks, hemorrhage, drug overdoses, drowning, and electrocution. Because brain damage can occur from emergencies during surgery where oxygen and blood can be cut off, European hospitals routinely administer hydergine pre-surgery as an extra measure of caution. In spite of the volumes of research demonstrating the effectiveness of hydergine in these cases, use with accident victims or as a preventive measure is not approved in the United States by the FDA.
Hydergine has been studied extensively, with more than 3,000 research papers published on it to date, making it one of the most widely studied and prescribed drugs. Hydergine was originally produced and distributed by Sandoz Pharmaceuticals, and later by Dorsey Pharmaceuticals, a division of Sandoz. Because the original patent has expired, numerous generic versions are now available in various strengths through prescription. According to FDA guidelines, prescription is permitted for anti-senility only. However, in practice it is often used for improving intelligence and combating aging, and is prescribed for higher doses than those usually approved in the U.S.
Hydergine is available in the U.S. by prescription only. Hydergine may have even better effects when used in conjunction with piracetam; researchers suggest taking smaller doses of both to get the best effect.
Another procaine formulation similar to Gerivital is KH3, which is a gelatin capsule containing procaine and hematoporphyrin. Hematoporphyrin boosts the procaine action. It is claimed to help alertness, concentration, and recall as well as improve a number of health problems. The benefits are attributed to improved circulation to the brain. The only state where KH3 is sold legally is Nevada. It is also available over the counter in Europe.
Two of the most common denizens of aging are atherosclerosis, a clogging of the arteries that can lead to life-shortening heart disease, and a declining immune system, which can mean decreased resistance to infectious diseases and even cancer. Metformin, a drug used for years in Europe to treat adult-onset diabetes, may also have some anti-aging properties-lowering cholesterol, for example, and boosting the immune system. New evidence from the University of Milan suggests that metformin may also help treat atherosclerosis.
Over the past 25 years, tests in rats and rabbits have shown that metformin reduces the ability of very low density lipoprotein, a form of “bad” cholesterol, to bind to blood vessel walls, while making blood platelets less likely to coagulate and form dangerous clots.
There’s exciting recent news concerning what may turn out to be one of metformin’s most important anti-aging properties: its ability to treat patients whose blood vessels are constricted by atherosclerosis. In 1992, a research team led by C.R. Sirtori of the Institute of Pharmacological Sciences at the University of Milan tested metformin on 11 patients with peripheral vascular disease. Their blood vessels were so clogged that they could not walk normally for more than about 550 yards. After treatment with metformin, however, the patients’ blood flow increased by 30 percent, and their exercise capacity increased by anywhere from 53 percent to 105 percent.
At the low doses (two 500 mg doses per day) used in the Italian study, no side effects were noted. Higher doses can produce lactic acidosis, a condition in which the blood becomes acidic, and which can lead to nausea and vomiting.
Because it helps normalize the metabolism of glucose, metformin is widely used in western Europe to treat adult-onset diabetes.
Chemically, oxiracetam is similar to piracetam, though stronger in effect. It is one of the more commonly used smart drugs, and known by a number of names, including CT-848, hydroxypiracetam, ISF-2522, Neuractiv, and Neuromet.
Oxiracetam has had the most widespread use in Italy, where it was developed in 1988 by ICF, an Italian drug company. In the U.S., use has not been approved by the FDA. Smith Kline Beckman Corporation is trying to get the drug approved for treating Alzheimer’s disease.
Some research indicates that the effects of oxiracetam may be greater than those of piracetam in improving elderly subjects ability to remember things. Oxiracetam has been shown to be nontoxic, like other nootropics, as well as safe in dosages that far exceed what the average person takes.
Piracetam, also called nootropil, is the most commonly taken nootropic. It helps boost intelligence without being toxic or addictive. Piracetam is very similar in chemical structure to the amino acid pyroglutamate, present in meat, vegetables, fruits, and dairy products. Piracetam stimulates the cerebral cortex and increases the rate of metabolism and energy level of brain cells. It does not have the side effects associated with other stimulants. The primary clinical use is to protect the brain from damage caused by hypoxia, which is oxygen starvation, and to help recover from it. Brain cells can be starved for oxygen by drinking too much alcohol, for example. Another clinical use is stemming memory loss caused by physical injury and chemical poisoning.
Piracetam seems to help step up the flow of messages between the two hemispheres or halves of the brain, which is sometimes called the interhemispheric flow of information. Dean and Morgenthaler speculate that the increased communication between right and left brains is associated with flashes of creativity. They believe that piracetam may actually have a regenerative effect on the nervous system. Piracetam may improve learning by increasing the brain’s ability to synthesize new proteins. The specific chain of events is complicated and beyond the scope of this book, but the upshot of the research is that piracetam is a powerful nootropic that seems to contribute to improved memory and learning through several different types of chemical changes that it triggers in the brain.
Research shows significant improvements in memory and mental performance. Piracetam has a synergistic effect, such as helping the individual remember things better, when taken with DMAE, centrophenoxine, choline, Deaner, lecithin, or hydergine. Reports show it works three to four times better when acetylcholine-enhancing nutrients or drugs are used. Studies suggest that when taken in combination, Piracetam and choline are much more effective both in improving memory and in preventing the mental decline that comes with aging than when either substance is used by itself.
The research indicates that either by itself or with choline, piracetam is one of the most effective nootropic drugs in its impact on memory and learning. Piracetam is most easily obtained over the counter in Mexico and in various European countries. Up until recently it could be obtained through the mail from an off-shore pharmacy.
Phenytoin is a remarkable multipurpose drug that has been the subject of more than 8,000 published papers. It is the most common treatment for epilepsy, and is prescribed under the generic name phenytoin and its trade name, Phenytoin. It normalizes and improves mental functioning in general and improves concentration, learning, and thinking in particular.
Discovered in 1938, Phenytoin was used as an anticonvulsant and is still heralded as the most effective drug for this purpose ever discovered. Although scientists are just beginning to understand the electrical nature of humans and other animals, most people know that our nerves are electrical in nature. Thinking, memory, and pain are all electrically generated. Phenytoin stabilizes the electrical activity in the body at the level of the cell membrane. Phenytoin stops convulsions, which are electrical in nature. When cells show too much or too little electrical activity, phenytoin brings them back into balance. In addition, when the brain cells are functioning normally, the drug can calm the individual and increase energy levels. So phenytoin acts as a kind of medical equivalent to meditation, promoting calm and harmony.
Because Phenytoin influences electric currents, it can affect thinking and recall. Scientists don’t really understand how phenytoin works; however, they postulate that it influences electromagnetic fields, which polarize the electrically charged elements in the cells. This results in a more effective organizational structure, so that cell and brain functioning is improved.
One of the major advantages of Phenytoin is it stabilizes and normalizes the nervous system without acting as either a stimulant or a depressant. The result is that one can concentrate, learn, and remember better. Prolonged concentration can be exhausting. One effect of Phenytoin is that it delays the onset of fatigue and thereby reduces errors that accompany fatigue. In this regard, phenytoin’s effect is similar to that of stimulants, but it is not a stimulant and has none of the side effects common to stimulants.
Generally Phenytoin’s effectiveness for a wide variety of disorders is unknown to most doctors. Most doctors think it is useful only in maintaining epilepsy, and are not knowledgeable about its tremendous impact on general cognitive functioning, mood moderation, and concentration.
Phenytoin does have some significant but infrequent side effects when taken in regular dosages. Some people report tremors, insomnia, headaches. dizziness, nausea, and vomiting. Dr. Pelton indicates that phenytoin can occasionally cause liver toxicity during the first few weeks of use. Some people, mostly children with epilepsy, report gum problems.
A major consideration for most people using Phenytoin is that it can disturb absorption of vitamin D and folic acid, which are essential for health. Dr. Pelton recommends that people on phenytoin therapy take supplements of vitamin D, calcium, and folic acid.
Phenytoin is available, by prescription, in capsule, tablet, and liquid forms. The original patent has expired, so it is available under its generic name, phenytoin, as well as under its trade name Phenytoin in the United States, and Epanutin, Epamin, Eplin, Idantoin, and Aleviatan in other countries.
Pramiracetam, also known as CI-879, is another chemical relative to piracetam, and has a similar effect in improving the operations of the neurotransmitter acetylcholine. Like oxiracetam, pramiracetam appears to be more potent than piracetam. Although pramiracetam seems to be more potent and effective, it is less common than piracetam. Pramiracetam is newer, less tested, and less available.
Parke Davis is working through the maze of FDA approval of pramiracetam to treat Alzheimer’s disease. If pramiracetam becomes legally available, it will probably be used not only for Alzheimer’s disease but for cognitive enhancement as well.
Tacrine or THA (tetrahydroaminoacridine) has been demonstrated in research by Dr. Mohs and by Dr. Summers to consistently improve memory in Alzheimer’s patients.
Dr. Summers has had very hopeful results treating Alzheimer’s with a combination of deprenyl and THA plus the nutrient lecithin. Deprenyl increases availability of the neurotransmitters dopamine, norepinephrine, and phenylethylamine, which play a critical role in motor, behavior, and cognitive functions. THA helps to preserve acetylcholine in the brain, and lecithin is a nutrient from which the body manufactures acetylcholine. Although deprenyl and THA plus lecithin work according to different mechanisms, it is believed the combination of the two is more effective in improving memory in Alzheimer’s patients.
Summers used THA plus lecithin extensively with patients with good success until July 1990, when the FDA forced him to stop his project. Unfortunately, THA is hard to obtain, and deprenyl has been approved only for treating Parkinson’s disease. As a result, research into improving this treatment is slow, and approval doesn’t look likely, which has lead to an outcry by Summers and the families of Alzheimer’s sufferers. In 1991, they filed a class-action suit against the FDA. Under pressure from the lawsuit, the FDA decided to allow “expanded access” to THA under its “treatment IND program.” However, Saul Kent, publisher of Life Extension Report, points out that the promised access is, in fact, limited by many restrictions. As an alternative, Summers’s group established an Alzheimer’s Buyer’s Club in Costa Rica.
Vasopressin has memory-enhancing effects and is widely known as the prescription drug manufactured by Sandoz Pharmaceutical Company under the trade name Diapid. Vasopressin is a brain hormone produced in the pituitary gland, and acts to imprint new information into the brain’s memory centers. Without vasopressin you can’t learn or acquire new information. Similarly, it helps in memory retrieval by drawing information into conscious thought.
Earliest research was conducted in the Netherlands in the mid-’60s by Dr. de Wied, who found that vasopressin acts directly on brain cells and the central nervous system to improve the imprinting system by which electric impulses with information became encoded into longterm memories. During this process new proteins are synthesized and deposited into the memory centers of the brain. Research on humans using vasopressin revealed similar memory enhancing results. Patients with memory problems showed improved attention span, concentration, recall, and ability to learn.
Stimulants like LSD, cocaine, amphetamines, Ritalin, and Cylert cause the pituitary to release vasopressin. Frequent use of these drugs can lead to sluggish mental performance and depression resulting from vasopressin depletion. On the other hand, marijuana and alcohol, which are depressants, inhibit the release of vasopressin This explains why regular users, especially of marijuana, often complain of memory loss. These problems can be reversed, almost immediately, by inhaling Diapid, because it is absorbed through the mucous membranes in the nose and goes quickly to the brain results are often evident in less than a minute.
Diapid, which is a nasal spray manufactured by Sandoz, has been approved by the FDA only to treat the frequent urination associated with diabetes insipidus and bedwetting in children. The FDA has not approved its use in healthy people for memory and learning enhancement. Diapid is considered to be very safe, with no major side effects. However, some people experience mild symptoms such as nose irritation, headaches, abdominal cramps, and an increased desire to move the bowels. Pregnant women should avoid it, since safety during pregnancy has not been established.
Vasopressin can be obtained in the United States by prescription. It is available over the counter in Mexico.
Sometimes called Cavinton, Vinpocetine is derived from vincamine, which is an extract of the periwinkle plant. It has a very powerful stimulating effect on memory. Vinpocetine ups the metabolism in the brain in four ways. It pumps up the blood flow, increases the rate at which brain cells produce ATP (which is a cell molecule that creates energy), and speeds up the use of glucose and oxygen in the brain. The result is that the cells of the brain can better retain information; so the individual can remember more. Because of its stimulating effect on blood flow, venpocetine has been used to treat circulatory problems in the brain and memory problems due to low circulation.
Gedeon Richter, a Hungarian company that markets vinpocetine in Europe, has funded more than a hundred studies to show it’s effectiveness and safety. Many of these studies have shown the drug’s powerful effect on memory improvement. Vinpocetine is not toxic and is considered safe. It takes about a year of daily use to achieve maximum effect.