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COGNITION-ENHANCEMENT DRUGS AND PEAK PERFORMANCE PILLS Potential Brain-Food and Mind-Machine Interactions by Michael Hutchison and John Morganthaler Picture this: You have a business meeting tomorrow with your Japanese distributor. This meeting requires that you be in top form for some critical negotiations. You have several reports to go over, many facts to memorize, and above all you have to get some rest. Your first step? A trip to the drug store, of course. A meeting like this is much too important to take on without fine-tuning your biochemistry. You must create the optimal neurochemical conditions for learning and creativity. You ask the druggist, who then points you towards the shelf of cognitive enhancement compounds. You load up your basket with bottles of piracetam, vasopressin, hydergine, choline, DMAE, and maybe a little centrophenoxine. After arriving home, and taking the appropriate doses of each of these you go into your study to slip on your cranial electric stimulator along with your light and sound device. You know from your experience and that of many pioneers in the consciousness revolution that this particular combination of chemicals and brain machines have a synergistic effect that will create the optimal psycho-biological state for the tasks that lie ahead. You can be sure that your Japanese counterparts are engaged in a similar manner. After an hour in your study you feel very different. You are relaxed, yet alert and creative. Your brainwave activity has altered, and an EEG would show that it has become more regular and has increased in amplitude in certain frequencies, causing you to feel simultaneously profoundly relaxed yet in a state of intense concentration, loose and creative as well as mentally quick and alert. A brain-mapping device would show that the two hemispheres of your brain were in a state of "superconnection," with an enormous increase in the amount of information flowing between hemispheres. At the same time, the rate of metabolism and the energy level of your brain cells has sharply increased. You are now in the optimal state to imprint new memories, to plan new and more creative strategies, to visually rehearse every detail of your upcoming meeting. Sound far-fetched? Well, both the brain machines and the cognitive enhancement compounds already exist. Megabrain described a variety of devices that show evidence of enhancing cognition (for a summary of several recent studies suggesting that CES devices can have clear cognition-boosting effects see the "Research Update" elsewhere in this issue); and the book also mentioned the cognition-enhancing effects of such neurochemicals as vasopressin and MSH-ACTH 4-10. Since then other mind-magnifying drugs have emerged as well as even more astonishing evidence of their ability to amplify learning, memory and thinking. What we don't know is how to best use them together, or even whether they should be used together. That's what we want to find out. The problem, as many of you are aware, is that it is extremely difficult for those interested in performing research into the effects of brain machines to obtain the necessary funding and support. Mainstream science, particularly those elements in control of doling out grants and funds to support research, and many of the universities and institutions engaged in research, seem to have little interest in investigating these machines. What research is done usually involves the therapeutic applications of the devices rather than the induction of peak performance brain states. On the other hand, huge amounts of money are being spent for research into cognition enhancing drugs. But much of the research is being done by the big pharmaceutical companies, who are racing with each other to develop patentable memory-enhancement drugs and to obtain FDA approval for these compounds. Since the FDA is primarily oriented toward treating diseases in a medical context, and has not shown much interest in giving its approval to drugs that simply improve people's memories or boost intelligence, the pharmaceutical companies are directing their efforts toward gaining approval for their cognition-enhancement drugs as treatments for medical problems such as Alzheimer's disease, multiple-infarct dementia and senility. Since financial analysts estimate that such cognitive drugs could quickly produce sales of well over a billion dollars a year in the U.S. alone, and ultimately outsell antibiotics and tranquilizers, the competition is fierce, and these companies are in no mood to investigate ways their substances might work synergistically or in combination with other substances or other mechanisms such as mind machines. Also, since their efforts are directed toward drugs that are patentable, these companies have little interest in exploring the cognition enhancement properties of substances that cannot be patented. Vitamin C is a good example: in a controlled study in which healthy individuals were tested both for levels of vitamin C and IQ, those with higher levels of the vitamin averaged 5 points higher in IQ; when those with the lower levels of the vitamin were given vitamin C supplements, their IQ scores increased by over 3.5 points. In some way, Vitamin C is a cognition-enhancing substance. But, of course no one can patent vitamin C, which is cheap and readily available. In another example, one widely available and unpatentable substance (DHEA) is rumored to have demonstrated in a recent study some success in, among other things, treating AIDS, as well as cognition enhancement; however, the drug company involved in the experiments is now apparently trying to conceal the discoveries about DHEA until it can develop some variant that is patentable (i.e. has commercial value), and has obtained a court order forbidding the scientist in charge of the study to even speak with anyone about the matter. WE HAVE MET THE GUINEA PIG AND IT IS US And so. Megabrain Report has concluded that if we really want more research into mind-machine mind-food interactions we'd better start doing it ourselves. Thus we ask you to join us in a series of surveys, tests and assessments designed to explore the interactions between brain machines and cognitive enhancement compounds. This is not to say we are advising you to take any of the cognition-enhancement substances we describe. No! We do not advise you to take these compounds, just as we do not advise you to use mind machines or do anything to enhance your mental functioning. High level mental functioning can be exceedingly dangerous and have frightening and unpredictable side effects, as individuals from Socrates to Jesus to Galileo have discovered. However, we do have reason to believe that many of you are by nature curious, given to exploration and even experimentation-- that, in fact, many of you are already making use of some of cognition-boosting nutrients. This being so, it seems clear to us that you have information that would be of interest and value to the rest of us. It's also clear that if there are hundreds or even thousands of you with such information, then by gathering it together, we can synthesize it, analyze it, begin to search for trends, tendencies, proclivities, and perhaps even make some important connections. The first part of the survey is intended to be an open-ended exploration rather than a rigorous scientific study or an attempt to confirm an existing hypotheses. We hope not for solid conclusions or hard data, but rather to discover and delineate some interesting avenues for future research. In a later issue, we will report on the early survey results. It's possible--though we cannot guarantee it--that in investigating then subjective responses we hope to receive from Megabrain Report readers we will discover some trends. We can use this information to guide us in designing a more focused study for part two of the survey. For example, we might receive many reports that the effects of piracetam are amplified when used with the light and sound devices. Then we could plan to focus more deeply on this particular machine/compound interaction, investigating the interactive effects over differing periods of time, using different sound and light frequencies and modes, and in various areas, such as memory, reaction speed, creativity and so on. In this issue, we will introduce some of the more interesting compounds for cognitive enhancement, provide information about how to obtain each of them, present some methods for assessing and evaluating your own brain state and tracing your progress, and present a simple questionnaire. These self-assessment methods and our intial survey appear at the end of this article. First we will describe a few of the most promising cognition enhancing substances. NOOTROPIC DRUGS PIRACETAM "Last year a friend took me to hear Sun Ra and his Intergalactic Arkestra as a birthday present. I had just received a bottle of 800 mg tablets of Piracetam. My friend and I each took nine of the tablets (an "attack dose" they call it in the literature) before entering the hall. The music began 30 minutes later. I found myself able to concentrate as never before. I was completely lucid with absolutely no sense of intoxication. For the first time in my life I could hear each individual horn's timbre (Sun Ra has about 10 horn players, often all playing massed harmonies.) My friend has worked as a professional saxophone player. He, too, reported extraordinary hearing and concentration abilities. My ears felt as though they were being stimulated from all directions at once, but the feeling was entirely pleasant. I was enthralled." Piracetam has been the subject of intensive research for over 15 years, and has not only proven to be a powerful intelligence booster and cerebral stimulant, but also, even in massive acute and chronic dosages, appears to be nontoxic and to produce no side effects (it's so nontoxic one FDA employee reportedly claimed that since even huge doses produce no toxic effects, it can't possibly have any pharmacological effects and must be physiologically inert). It is so remarkable in its effects and safety that its discovery by UCB Laboratories in Belgium sent virtually every other major pharmaceutical company scrambling to develop its own cerebral stimulant. This "smart pill race" has resulted in the creation of a new drug category called the nootropics, from the Greek words noos (mind) and tropein (turn), meaning "acting on the mind". Some of the nootropic drugs being tested now on humans include vinpocetine (being developed by Ayerst Laboratories), which speeds up learning, improves memory and recall and seems to block the action of substances that disrupt memory; aniracetam (Hoffman-La Roche), which appears to be about ten times more potent in improving and protecting memory than piracetam, pramiracetam (Warner-Lambert/Parke Davis), which seems to improve learning and memory by enhancing the firing of neurons in the hippocampus (a key to the formation of long-term memories), and oxiracetam (Ciba- Geigy), apparently two to three times as powerful as piracetam (intriguingly, research shows that when oxiracetam is given to pregnant rats their offspring proved more intelligent than control groups--similar findings have been reported for the offspring of pregnant rats kept in "enriched environments," as described in the "Research Update" elsewhere in this issue). All of these substances seem remarkably nontoxic and free of side effects. As yet, there is no nootropic drug that is approved by the FDA for sale in the US, but, keenly aware of the multi-billion dollar potential of nootropics, the drug companies are pouring big bucks into research that will satisfy FDA requirements by proving how they work (still not well understood), and by proving their effectiveness in treating medical problems such as Alzheimer's disease and senility. In this article we will focus on the most extensively tested and widely available nootropic compound, piracetam. Piracetam has been proven to boost learning and memory in normal subjects as well as those who suffer cognitive deficits, and is also a cognitive enhancer under conditions of hypoxia, or too little oxygen (recent expeditions to climb Mt. Everest have included piracetam as an "essential" medication to treat frostbite and memory lapses caused by altitude). A variety of clinical studies with human subjects, including studies of young healthy volunteers, healthy middle-aged subjects with some memory decline, elderly subjects, elderly subjects with senility, and alcoholics, have proven that piracetam enhances cortical vigilance, improves integration of information processing, improves attention span and concentration, and can produce dramatic improvements in both direct and delayed recall of verbal learning. It's effective in the treatment of dyslexia, stroke, alcoholism, vertigo, senile dementia, sickle-cell anemia, and many other conditions, enhances the brain's resistance to various injuries and boosts its ability to recover from injuries, protects the brain against chemicals such as barbiturates and cyanides, and is widely used throughout Europe and Latin America (where it is sold over the counter). The subjective effect described by a lot of people is that it "wakes up your brain". In fact, it selectively stimulates the anterior or frontal part of the forebrain--that part of the brain that has evolved most recently, rapidly and remarkably in the course of our evolution from ape to human, and which is the seat of our "higher functions." Piracetam works in a number of ways to increase energy within the brain. First, it steps up the production of adenosine triphosphate (ATP), the energy storage and energy generating molecules within our cells. It also boosts cerebral metabolism by improving cerebral microcirculation (blood flow), increasing the brain's use of glucose, and increasing the brain's oxygen utilization. It also seems to enhance protein synthesis in the brain (it's been proven that protein synthesis is an essential step in laying down long-term memories). SUPERCONNECTING THE BRAIN. Perhaps the most intriguing aspect of piracetam is that it has been proven to increase the flow of information between the right and left hemispheres of the brain. As a result of experiments with human subjects one researcher concluded that piracetam causes the hemispheres to become "superconnected." Since there's increasing evidence that high level brain states--brilliance, insight, creativity, flow, peak performance, being "in the zone"--are a product of the integrated and synergistic functioning of both hemispheres simultaneously, we might suspect that piracetam enhances not only simple learning and memory but creative or synthesis thinking. Piracetam's capacity to superconnect the hemispheres becomes even more intriguing in light of the evidence indicating that many of the most widely used mind machines and techniques for brain enhancement (such as binaural beat frequencies and the sound and light machines) function in part by facilitating integrated hemispheric functioning. This raises the possibility that since both the machines and piracetam seem to facilitate interhemispheric communication, there might be a potentiating or synergistic effect when such mind machines are used in combination with piracetam, resulting in a quantum leap in brain-enhancement effects. PRECAUTIONS: Piracetam may increase the effects of certain drugs, such as amphetamines and psychotropics. Adverse effects are rare but include insomnia, psychomotor agitation, nausea, headaches and gastrointestinal distress. DOSAGE: Piracetam is supplied in 400mg or 800mg tablets. The usual dose is 2400-4800 mg per day in three divided doses. Some literature recommends that the first two days a high "attack" dose should be taken. We have noticed that when some people first take piracetam they do not notice any effect until they take a high dose. Thereafter, they may notice that a lower dosage is sufficient. The drug takes effect in 30 to 60 minutes. SOURCES: Piracetam is not sold in the US. It can be purchased over the counter in Mexico or by mail order from the address below. OTHER COGNITION ENHANCING SUBSTANCES Nootropics are exciting and fascinating, partly because of their lack of toxicity, but they are not the only substances that increase intelligence. There are over 30 chemicals that have been demonstrated to improve animal and/or human intelligence (including xanthinol nicotinate, idebenone, ginkgo biloba, acetyl-l-carnitine, DMAE, pyroglutamate, RNA [ribonucleic acid], isoprinosine, phenylalanine, amphetamines, pemoline, ritalin, vitamin B-12, ACTH 4-10, L-prolyl L-leucyl glycine amide, caffeine, niacin, vitamin C, ginseng, GH3 [Gerovital], PRL-8-53, R-58-735, ISF-2522, and THA). We will describe several we find most interesting. CENTROPHENOXINE (LUCIDRIL) Centrophenoxine, more commonly known by its trade name Lucidril, is an intelligence booster and also an effective anti-aging therapy. It has been shown to produce a 30% increase in the life span of laboratory animals. Perhaps the most obvious sign of aging is the appearance of brown "age spots" or "liver spots" on the skin. This pigmented material is known as lipofuscin, from the Greek lipo (fat) and the Latin fuscin (dusky), and it is the result of the progressive buildup of toxic waste by-products of cellular metabolism, or "cellular garbage." It accumulates with age not only on the skin but also in the muscle and nerve cells. The buildup of lipofuscin in brain cells is accompanied by a decline in mental functioning, and can ultimately lead to the death of the affected neurons. Centrophenoxine removes lipofuscin deposits from brain cells (as well as from skin). That is, it actually seems to reverse the aging process and have a rejuvenating effect on brain cells. It also reduces the rate of lipofuscin accumulation in young brain cells and rejuvenates the synaptic structure--the area where the actual transfer of information takes place between nerve cells. This suggests that the clinical rejuvenation effects of centrophenoxine in humans may be produced by the actual regeneration of parts of the neuron. It is used widely throughout Europe for its anti-aging properties, but studies of both animal and human subjects show that it produces improvements in alertness, learning and memory as well. PRECAUTIONS: Centrophenoxine should not be used by persons who are easily excitable, people with severe arterial hypertension, or those subject to convulsions or involuntary musculoskeletal movements. The drug also should not be used by nursing mothers. Adverse effects are rare but include hyperexcitability, insomnia, tremors, motion sickness, paradoxical drowsiness and depression. In therapeutic doses it has proven to be nontoxic. The dosage in clinical trials ranges from about 3000 to 8000 mg. per day based on body weight, but many self-experimenters take 1000 to 3000 mg per day. Centrophenoxine takes effect very quickly, producing an increase in alertness and a slight stimulating quality. SOURCES: Centrophenoxine is not sold in the US. It can be purchased over the counter in Mexico or by mail order from the address below. CHOLINE/LECITHIN "When I take a choline compound, I am more awake when I am awake, more sound asleep when I am asleep. Not only does my memory improve, but I have an easier time day dreaming when I want to, and concentrating on real world tasks when I want to." As these words suggest, choline seems to optimize mental functioning in a global way. An explanation is that choline is the nutrient that is used by the brain to manufacture acetylcholine, which is a principal component of brain cells and the major neurochemical messenger responsible for the processing, storage, and retrieval of information. Acetylcholine must be in abundant supply throughout the brain, and when acetylcholine levels drop (as happens as a result of poor nutrition, alcoholism and aging) the result is memory loss and a decline in thinking ability. Since choline passes through the blood-brain barrier into the brain and is transformed into acetylcholine, consuming choline directly increases levels of acetylcholine in the brain, and has been proven to prevent memory loss associated with aging and improve memory in young, healthy adults. There is also evidence that choline can improve mental functioning by actually strengthening neurons in the brain's memory centers and slowing down the age-related loss of dendrites of those neurons. Choline can be found in several forms including choline bitartrate, choline chloride, or phosphatidyl choline. Phosphatidyl choline (PC) is the active ingredient of lecithin. All of these forms of choline will produce memory boosting effects. DOSAGE: The studies that used dietary choline to improve memeory in young, healthy adults used at least 3 grams of choline per day in three or four divided doses (doses every 4 to 6 hours insure that blood levels of choline will remain in the effective range). Those taking lecithin may need to take more than three grams because only part of the lecithin is choline. Often the label will provide information on the quantity of choline per tablespoon. All forms of choline should be taken with one gram per day of pantothenic acid (vitamin B-5), which is essential for the conversion of choline into acetylcholine. SOURCES: Choline and lecithin are considered nutritional supplements and can be found at health food or drug stores. Commercial lecithin usually contains other oils and phosphatides besides phosphatidyl choline. Look at the label before you buy and make sure the product contains more than 30% phosphatidyl choline. Also, you should taste your lecithin and make sure it does not taste bitter (this indicates rancidity). PRECAUTIONS: Any compound that acts as a precursor to acetylcholine such as choline, PC, or DMAE should not be used by manic depressives, since it can deepen the depressive phase. Choline bitartrate and choline chloride can sometimes cause a fishy odor or diarrhea. Lecithin and PC, however, are metabolized differently and do not produce these effects. CHOLINE AND PIRACETAM Researchers have discovered that the combination of choline and piracetam has a synergistic effect that produces a greater improvement in memory and learning than the sum of each when taken alone. In one study of learning, animals receiving both substances scored four times higher than the control groups and those taking choline alone, and three times higher than those taking piracetam alone. Clinical studies of humans given piracetam and choline alone and in combination have shown similar extraordinary synergistic effects. One of the researchers, Dr. Raymond Bartus of Lederle Laboratories, suggests that in many cases (such as aging) brain metabolism is too low for optimal conversion of choline to acetylcholine; adding piracetam, which is known to boost brain metabolism, could thus produce dramatic increases in acetycholine levels in the brain. Individuals taking piracetam may want to supplement it with choline in any case as a safeguard, since there is some evidence that piracetam causes acetlycholine to be used up more quickly, and could deplete levels of choline inside the brain cells. We know of one person who claims she feels slightly agitated and depressed if she takes piracetam for more than a week without a choline supplement. This feeling is alleviated for her with a single dose of choline. DHEA "I started taking DHEA in order to build up my muscle mass and to decrease my weight. I found that within two months I was able to lift 70 pound weights during weight training--twice the amount I'd been able to lift previously. I lost the extra ten pounds I'd been working to take off for the past year. I like the increased feeling of strength and energy when weight lifting. As a woman, I had found it was difficult to do much more than just light muscle toning, so I was pleased by such obvious results." Dehydroepiandrosterone (DHEA), a steroid hormone produced in the adrenal gland and related to the male hormone testosterone, is the most abundant steroid in the human bloodstream. It seems to trigger the release of growth hormone and is a powerful booster of immune function. Research has found it to have significant anti-obesity, anti-tumor, anti-aging, and anti-cancer (particularly anti-breast cancer) effects. DHEA production naturally drops by as much as 95 percent as people age (the average drop is from about 30 mg per day at age 20 to less than 6 mg per day at age 80). According to Dr. William Regelson of the Medical College of Virginia, DHEA is "one of the best bio-chemical biomarkers for chronologic age," and there's good reason to think that taking a DHEA supplement may extend your life and make you more youthful while you're alive. In animal studies, it's extended lifespans up to 50 percent. In a 12 year study of hundreds of aging humans, researchers found that DHEA levels were inversely correlated with mortality: The lower the levels, the higher the probability of death, from any cause. Additionally, DHEA may be an important player in cognitive enhancement. It plays a key role in protecting brain cells from age-related degenerative conditions like Alzheimer's disease. Not only does neuronal degeneration occur most frequently when DHEA levels are lowest, but brain tissue contains more DHEA than is found in the bloodstream. In a recent experiment with brain cell tissue cultures, Dr. Eugene Roberts has discovered that even very low concentrations of DHEA will "increase the number of neurons, their ability to establish contacts, and their differentiation." He concludes that DHEA plays "a significant role in normal function of neuronal cells" and that supplementation with it "may prevent neuronal loss and/or damage." DHEA also enhanced long-term memory in mice, and raised the learning and memory of middle-aged and old mice to the high levels found in young mice. Perhaps it plays a similar role in human brain function. DOSAGE: Dosage of DHEA ranges from 50 mg to 2000 mg per day. There is no solid information indicating optimal dosage for humans but, those serious about self-experimentation can have their DHEA levels tested every few months (for about $65), each time raising the dosage of DHEA until reaching an optimal level--what is normal for a 20 year old human. Some women have reported a slight increase in the hair on their faces or bodies with the use of DHEA. Little is known about this effect, so caution should be execised by women considering using DHEA. Since it's a steroid with testesterone-like effects, it probably has the same risks as testesterone. SOURCES: DHEA is now being used by many people with AIDS because of its immune enhancement and antiviral effects. AIDS buyers groups sell DHEA to their members. Among the buyers groups selling DHEA are: Alliance 7, 619-281-5360, in San Diego, and Healing Alternatives Foundation, 415-626-2316, in San Francisco. DILANTIN This extraordinary prescription drug, also known by its generic names, phenytoin and diphenylhydantoin (DPH), was discovered in 1938 and has long been used for the treatment of epilepsy. But it's clear that it is much more than just a simple anticonvulsant. There are literally thousands of scientific studies documenting its effectiveness in treating a multitude of medical problems, including, Parkinson's disease, angina, headache, high blood pressure, hypoglycemia, asthma, diabetes, ulcers, alcohol and drug withdrawal, pain, cardiac arrhythmias and much more. More interestingly for our purposes, Dilantin has proven to be extremely effective in treating nervous disorders involving emotions and behavior: depression, moodiness, compulsive eating, violent behavior, chronic anger, irritability, fear, impulsiveness, hostility, insomnia, impatience, agitation, worry, anxiety, pessimism. And, even more interesting, the drug has proven to have remarkable cognition-enhancing effects. It can dramatically improve concentration abilities, boost long-term memory and comprehension, and produce sharp increases in IQ scores. What's more, DPH increases the regeneration of tissue and speeds up the healing of wounds by promoting the growth of collagen (the most abundant protein in the body, which acts as connective tissue to hold our bodies together), and has even shown evidence of extending life-span (in one study of laboratory mice DPH prolonged their mean life-span by 25 percent). The secret of DPH's wide range of beneficial effects seems to be that it functions by stabilizing and optimizing electrical activity throughout the body and brain. Among the ways it does this is to regulate the activity of the sodium, potassium and calcium ions, which produce bioelectric activity; to regulate the neurotransmitters that mediate bioelectric activity; and to influence the hormones (such as vasopressin, insulin and cortisol) that function in response to bioelectrical impulses. Epileptic seizures are a product of electrical disruptions--a sudden "kindling" or firing of masses of neurons which spreads through the brain--which DPH counteracts by normalizing the brain's electrical activity. But what this implies is that all the other disorders mentioned above, including such things as mood and behavioral problems such as compulsive eating, moodiness, anxiety and so on- -are somehow linked to bioelectrical activity. The idea that virtually all our capacities and functions from healing to cognition are dependent on the activity of a bioelectrical control system--a still little-understood semiconducting DC analog communication system that links and regulates every cell in the human body, functioning independently of the more obvious and well-understood digital, nerve-impulse operated "central" nervous system--is one that is being advanced by increasing numbers of scientists, in large part as a result of the groundbreaking research and thinking of Robert O. Becker (interviewed elsewhere in this issue). The extraordinary range of beneficial effects of DPH are perhaps a product of its capacity to normalize or optimize the functioning of this whole body bioelectrical system--the "body electric." PRECAUTIONS: Epileptics have been taking DPH for nearly 50 years with few problems. Side effects, which are fairly infrequent, can include nausea, headache, dizziness, insomnia, tremor, and a reduction in the body's absorption of Vitamin D and folic acid. DOSAGE: Epileptics generally take between 200 and 600 mg per day, but those using DPH for cognition-enhancement or life- extension purposes use from 100 to 300 mg a day, taken in two or three divided doses. SOURCES: DPH is available in the USA with a doctor's prescription, and approved by the FDA as an anticonvulsant--your doctor may not be familiar with the uses we discuss. It can also be purchased by mail order from overseas. (see below) HYDERGINE "I first tried Hydergine six years ago during a visit to see my Dad at Christmas. He and I started taking 9 mg per day. The results were apparent to us both within two days. He was in his 40's, and began to remember events from when he was in his 20's as clearly as if they'd happened yesterday. What was interesting was that the events were nothing outstanding--just ordinary times. In other words, the everyday events had been stored away all these years, it just took some chemical prodding to jog them loose into the conscious mind. I was in my early 20's and had similar memories going back to my childhood years. A unique opportunity had been presented to us to sit down and really share in the joys that our life had brought us. What a gift!" A wealth of research going back over 20 years suggests that Hydergine may be what psychologist-pharmacist Ross Pelton calls "the ultimate smart pill." The substance, whose generic name is ergoloid mesylates, is made from a natural, organic source: the ergot fungus of rye plants (it was discovered at Sandoz laboratories by the visionary chemist Dr. Albert Hofmann, also known for his discovery of another ergot derivative, LSD 25). It increases mental abilities, prevents damage to brain cells, and may even be able to reverse existing damage to brain cells. Hydergine acts in several ways to enhance mental capabilities and to slow down or reverse the aging processes in the brain. A few of the huge number of beneficial effects scientists have attributed to Hydergine include: increased protein synthesis in the brain; reduced accumulation of lipofuscin in the brain; increased quantities of blood and oxygen delivered to the brain; improvement of memory, learning and intelligence; beneficial improvements in brainwave activity; increased metabolism in brain cells; normalization of blood pressure; and increased production of such neurotransmitters as dopamine and norepinephrine (neurochemical messengers essential to the formation of memory, and also associated with arousal, alertness, elation and pleasure). Hydergine also functions as a powerful antioxidant and thus protects the brain against the damage caused by those infamous rascally free radicals (unstable and extremely reactive molecules produced by normal metabolism, which cause damage associated with aging, cancer and cardiovascular disease). One way that Hydergine may enhance brain functioning is by mimicking the effect of a substance called nerve growth factor (NGF). NGF is an essential component of protein synthesis in the brain, which we have noted is a key to the formation of long term memory. NGF promotes the growth of dendrites--the long branching fibers by which neurons receive information from other neurons. Scientists studying the effects of learning on the brain have found it is directly related to dendritic growth. Hydergine seems to work by the same neurochemical pathway as NGF to produce neural growth. While Hydergine is widely used for the treatment of senility, scientists have also studied its effects, both short term and long term, in normal healthy humans; these studies noted significant improvements in a variety of cognitive functions, including alertness, memory, reaction time, abstract reasoning and cognitive processing ability. PRECAUTIONS: If too large a dose is used when first taking Hydergine, it may cause slight nausea, gastric disturbance, or headache. Overall, Hydergine does not produce any serious side effects, it is non-toxic even at very large doses and it is contraindicated only for individuals who have chronic or acute psychosis. DOSAGE: The US recommended dosage is 3 mg per day, however, the European recommended dosage is 9 mg per day taken in three divided doses. Most of the research has been done at levels of 9 to 12 mg per day or higher, and there is some evidence that 3 mg per day is simply insufficient for significant cognition- enhancement effects. It may take several weeks or even months before Hydergine produces noticeable effects. Hydergine (though not its generic counterpart) is available in a sublingual form, and there's evidence that sublingual doses reach the brain in greater quantity. SOURCES: Hydergine is available in the USA with a doctor's prescription, and approved by the FDA for the treatment of senile dementia and insufficient blood circulation to the brain--your doctor may not be familiar with the uses discussed. It can also be purchased over the counter in Mexico or by mail order from overseas. (see below) In many cases these mail order companies sell the generic form, Ergoloid Mesylates. The FDA has rated the generic as biologically equivalent to the Sandoz product. More testing needs to be done on this question. SULBUTIAMINE Sulbutiamine, also known as Arcalion, is a new compound that has been described as being like Hydergine, only better. It has been shown to facilitate wakefulness, improve long-term memory, decrease reaction time, reduce fatigue, decrease anxiety, and increase overall resistance to stress. DOSAGE: Those who use this substance to combat fatigue generally take two 200 mg tablets per day, with breakfast or an A.M. meal, for a period of 20 days. They warn users not to exceed three tablets per day, as this very powerful substance may cause severe headaches. SOURCES: Sulbutiamine is not sold in the US. It can be purchased by mail order from the address below. VASOPRESSIN "The most immediate result I get from using vasopressin is increased clarity and alertness. I can be logical without the usual speediness associated with caffeine use. After five minutes I've noticed that I'm busily accomplishing tasks that I'd been putting off for a week. The duration is about two hours for the energetic feelings. Overall, I feel my short-term memory recall improving over the past two weeks of using vasopressin. It seems that the longer I use it, the more I can rely on my mind to be a portable note pad." "I have smoked pot on a more or less (usually more) daily basis for 20 years. When I read that vasopressin is inhibited by pot, I found a source for buying some. Now I notice I that when I use vasopressin with marijuana I still get stoned, but I have little or none of the 'dummying down' effect of the pot. And what a surprise to find that vasopressin intensifies orgasms!" Vasopressin, called "the memory hormone," is a natural brain peptide, stimulated by acetylcholine and released in the pituitary. It actually helps create, imprint, and store memories, and is essential to remembering. Apparently vasopressin is involved in picking out and chunking together related bits of information from the stream of consciousness, integrating these chunks into coherent structures, and then "imprinting" these images or concepts into long-term memory by transforming electrical impulses into complex proteins that contain memories and are stored away in the brain. The act of remembering the stored information is also mediated by vasopressin. Over 20 years ago scientists discovered that vasopressin had extraordinary effects on the memory of laboratory animals-- preventing chemically and electrically induced amnesia, actually reversing amnesia, and dramatically boosting the memory and intelligence of normal animals. These findings spurred much research into the cognition-enhancement effect of vasopressin on humans. Among the key findings are that small doses of the hormone can have striking success in quickly reversing traumatic amnesia (amnesia caused by injuries such as car crashes), can reverse age- related memory loss and actually restore lost memories, and can produce sharp improvements in learning and memory using measures such as abstract and verbal memory, organizational capacities, recall, attention, concentration, focus, short-term memory, optical memory, and long-term memory. It also boosts performance in such areas as reaction speed, visual discrimination, and coordination. Vasopressin pours out during moments of trauma or extreme arousal, which may explain why those times seem to be so deeply imprinted in our brains, and are remembered with such clarity. Vasopressin is also released by cocaine, LSD, amphetamines, Ritalin, and Pemoline (Cylert). Those who make frequent use of these drugs deplete their brain's vasopressin supply. The result is depression, and a decline in cognitive function. The frequent user's response to this depression is to take more of the drug, thus trying to wring more vasopressin out of their depleted brain: ultimately the well runs dry. Vasopressin, however, is not a drug but the actual brain hormone that has been depleted, so it can produce dramatic and virtually instantaneous improvements in mood and mental functioning. Unlike stimulants, alcohol and marijuana do not deplete but actually suppress the release of vasopressin, which could account for the loss of memory many have noticed when drunk or stoned, or when trying to remember events that occurred while they were high. Vasopressin can reduce the harmful effects of these drugs and enhance alertness, reaction speed and concentration. Anecdotal evidence suggests that vasopressin can produce a state of euphoria accompanied by self-confidence, energy, assertiveness, and a sensation of extreme mental clarity. Many believe it is ideal for situations in which lots of new information needs to be processed and remembered--such as studying for an exam, learning a language, ploughing through difficult or complex works. Some use it for more mundane purposes, such as when they have to drive late at night and want to remain alert. PRECAUTIONS: Vasopressin can occasionally produce the following side effects; runny nose, nasal congestion, irritation of the nasal passages, headache, abdominal cramps, and increased bowel movements. Angina pectoris sufferers should not use vasopressin, since it can trigger angina pains. Vasopressin has not been proven to be safe for use during pregnancy. DOSAGE: Vasopressin usually comes in a nasal spray bottle. Most studies showing memory improvement have been done with a dose of 12 to 16 USP per day, which is one whiff in each nostril three to four times per day. Vasopressin produces a noticeable effect within seconds. SOURCES: Vasopressin (known as Diapid and produced by Sandoz) is available in the USA with a doctor's prescription, but keep in mind that your doctor may not be familiar with the uses we have discussed (it is approved by the FDA for treatment of diabetes insipidus). It can also be purchased over the counter in Mexico or by mail order from overseas (see below). POTENTIAL MIND-MACHINE BRAIN-FOOD INTERACTIONS I0 took four 800 mg tablets of piracetam at a recent holistic health expo. After an hour, I sat down at a booth and donned the MC2 glasses and headset and put on a tape of space sounds. Within minutes, I was in theta state and out there in outer space, oblivious to the crowd. I found myself on an incredible cosmic amusement ride, flying in vast circles around the solar system. I imagined the sounds and dolphins and alien super-intelligences. I had to hold back to keep from screaming with delight. Ideas for inventions and solutions to problems poured into my brain effortlessly. After 20 minutes the program ended and I leaped up, refreshed. I'd been exhausted but now I had boundless energy. A previously boring expo became a magical discovery experience." Writer/networker Wes Thomas has provided us with a good description of one type of brain-machine cognitive-drug interaction. It makes sense that if these substances heighten our senses by turning up the volume control knob in our brains (making us more alert, heightening our perceptions), then our perceptions of the sensory stimuli and sensual experiences provided by the mind machines will be made even more intense (and therefore more memorable) by the drugs. But Thomas mentions another level of potential interaction that could be even more significant: dramatically enhanced creativity and problem-solving capacities. As we've noted, there's evidence that some of the cognition-enhancment substances influence brain activity in ways that are similar or parallel to the mind- machines, or selectively stimulate specific areas of the brain that are also stimulated by brain machines. Piracetam, for example, produces what has been called "superconnectivity," facilitating the flow of information between hemispheres, and there's increasing evidence such hemispheric integration can facilitate creativity, problem solving, and original thinking. Some of the brain machines also seem to enhance hemispheric connectivity, for example some of the sound and light machines, and the binaural or "Hemi Sync" signal generators. Is it possible that the combination of piracetam and such brain tools could be potentiating, and facilitate even greater hemispheric connectivity and greater creativity? Vasopressin's intriguing ability to eliminate post-traumatic amnesia becomes even more intriguing when we consider recent research using cranial electrostimulation (CES) devices to treat post-traumatic amnesia (such as the work of Dr. Allan Childs, mentioned in the "Research Update" elsewhere in this issue). The success of vasopressin (also Hydergine) in reversing memory loss associated with aging is also interesting in light of evidence that CES devices can have similar effects. Is it possible that CES is interacting with vasopressin or with those parts of the brain--the hypothalamus, pituitary, hippocampus--that are also affected by vasopressin or Hydergine? Could vasopressin or Hydergine enhance the effects of CES and vice versa, possibly leading to far more effective treatments for memory loss and the decline with age of other cognitive functions? Hydergine, Dilantin and other cognition-enhancement substances alter or optimize electrical activity in the brain. There is also evidence that many of the brain machines, including sound and light devices, CES, vestibular stimulation machines, ganzfelds, and binaural beat frequencies, alter the brain's electrical activity. Again, could there be potential synergistic effects, leading to more rapid and powerful alterations in bioelectrical patterns? Dilantin's ability to regulate electrical activity makes it extremely useful for treating epilepsy--is it possible that a combination of Dilantin and, say, sound and light at selected frequencies, could be an effective way to "train" the brain to avoid epileptic seizures? If so it would constitute a significant medical breakthrough. We are interested in learning more about such brain-machine cognitive-drug interactions. Perhaps you are interested too. If you are, we hope you will complete the questionnaire that we have included with this issue of the newsletter. HOW TO OBTAIN COGNITION-ENHANCEMENT SUBSTANCES BY MAIL ORDER While some of the substances described above are not available in the U.S., or are available only by prescription, it is easy and quite legal to obtain these substances by mail order. One reason some of these substances are not available in the U.S. is that they have not yet gone through the extraordinarily expensive and lengthy process required to obtain FDA approval. This does not mean however that it is not quite legal to use these substances. And some of the substances have been approved by the FDA for limited medical applications. This does not mean that it is not quite proper to use these substances for "unapproved" purposes. In the April, 1982 issue of the FDA Drug Bulletin, the agency included a policy statement clarifying the question of "unapproved" uses for drugs, clearly stating that "'unapproved' uses may be appropriate and rational in certain circumstances, and may, in fact, reflect approaches to drug therapy that have been extensively reported in medical literature. . . . Valid new uses for drugs already on the market are often first discovered through serendipitous observations and therapeutic innovations." In sum, the FDA clearly approves of the "unapproved" uses as an important means for innovation and discovery. Also, though it is not widely known, a July, 1989 FDA ruling now makes it quite legal to import effective drugs used elsewhere but not available in the U.S. The FDA now allows the importation and mail shipment of a three month supply of drugs, for personal use, as long as they are regarded as safe in other countries. The new ruling, FDA pilot guidelines chapter 971, was made as a result of heavy pressure from AIDS political action groups, which insisted AIDS sufferers were denied access to potentially life-saving substances that were widely used abroad but were still unapproved for use in the U.S. FOR FURTHER INFORMATION: An excellent compendium of information about cognition- enhancement drugs is Mind Food & Smart Pills, by Ross Pelton, R.Ph., Ph.D., with Taffy Clarke Pelton, Doubleday (1989). Life Extension: A Practical Scientific Approach by Durk Pearson and Sandy Shaw, Warner (1983) is a rich source. For more detailed information, consult the books and scientific papers below. BIBLIOGRAPHY Ammassari-Teule, M., et al. "Avoidance Facilitation in Adult Mice by Prenatal Administration of the Nootropic Drug Oxiracetam." Pharmacological Research Communications. 1986, Vol. 18, No. 12, pp. 1169-78. Bartus, Raymond T., et al. "Profound Effects of Combining Choline and Piracetam on Memory Enhancement and Cholinergic Function in Aged Rats." Neurobiology of Aging. 1981, Vol. 2, pp. 105-11. Benton, David, and Gwilym Roberts. "Effect of Vitamin and Mineral Supplementation on Intelligence of a Sample of School Children. The Lancet, January23, 1988, pp. 140-43. Bologa, L., J. Sharma, and E. 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Anti-Aging News. 1984, No. 4, pp. 13-21. Dreyfus, Jack. A Remarkable Medicine Has Been Overlooked, Pocket Books, 1981. Emmenegger, H., and W. Meier-Ruge. "The Actions of Hydergine on the Brain." Pharmacology. 1968, Vol. 1, pp. 65-78. Exton-Smith, A. N., et al. "Clinical Experience with Ergot Alkaloids." Aging. New York: Raven Press, 1983, Vol. 23, p. 323. Fanchamps, Albert. "Dihydroergotoxine in Senile Cerebral Insufficiency." Aging. New York: Raven Press, 1983, Vol. 23, pp. 311-22. Ferrero, Enrico. "Controlled Clinical Trial of Oxiracetam in the Treatment of Chronic Cerebrovascular Insufficiency in the elderly. Current Therapeutic Research. August 1984, Vol. 36, No. 2, pp. 298-308. Ferris, S.H., et al. "Combination of Choline/Piracetam in the Treatment of Senile Dementia." Psychopharmacology Bulletin. 1982, Vol. 18, pp. 94-98. Flood, James and Eugene Roberts, "Dehydroepiandrosterone sulfate improves memory in aging mice," Brain Research 448, 178-181 (1988) Friedman, E., et al. "Clinical Response to Choline Plus Piracetam in Senile Dementia: Relation to Red-Cell Choline Levels." The New England Journal of Medicine. 1981, 304, No. 24, pp. 1490-91. Giuli, D., et al. "Morphometric Studies on Synapses of the Cerebellar Glomerulus: The Effect of Centrophenoxine Treatment in Old Rats." Mechanisms of Aging and Development. 1980, Vol. 14, pp. 265-71. Giurgea, C.E. "A Drug for the Mind." Chemtech. June 1980, pp. 360-65. ____________. "The 'Nootropic' Approach to the Pharmacology of the Integrative Activity of the Brain." Conditional Reflex. 1973, Vol 8, No. 2, pp. 108-15. _____________, and M. Salama. "Nootropic Drugs." Progress in Neuropsychopharmacology. 1977, Vol. 1, pp. 235-47. Gold, Philip W., et al. "Effects of 1-Desamo-8-Arginine Vasopressin on Behavior and Cognition in Primary Affective Disorders." The Lancet. November 10, 1979, pp. 992-94. Haward, L.R. C. "Effects of Sodium Diphenylhydanoinate and Pemoline Upon Concentration: A Comparative Study." Drugs and Cerebral Function. 103-120 (1970) Hindmarch, I., et al. "The Effects of an Ergot Alkaloid Derivative (Hydergine) on Aspects of Psychomotor Performance, Arousal, and Cognitive Processing Ability." The Journal of Clinical Pharmacology. November-December 1979, pp. 726-31. Hochschild, R. "Effect of Diethylaminoethanol p-Chlorophenoxy-acetate on the Life Span of Male Swiss Webster Albino Mice." Experimental Gerontology. 1973, Vol. 8, pp. 177177- 83. Hughes, Rohn R., et al. "An Ergot Alkaloid Preparation (Hydergine) in the Treatment of Dementia: A Critical Review of the Clinical Literature." Journal of the American Geriatrics Society. 1976, Vol. 24, pp. 490-97. Itil, R.M., et al. "CNS Pharmacology and Clinical Therapeutic Effects of Oxiracetam." Clinical Neuropharmacology. 1986, Vol. 9, Supp. 3. New York: Raven Press, pp. S70-S78. Kent, Saul. "Piracetam Increases Brain Energy." Anti-Aging News. 1981, Vol. 2, No. 10, pp. 65-69. __________. Your Personal Life-Extension Program, William Morrow, 1985. Legros, J.J., et al. "Influence of Vasopressin on Learning and Memory." The Lancet. January 7, 1978, pp. 41-42 Marcer, D., and S.M. Hopkins. "The Differential Effects of Meclofenoxate on Memory Loss in the Elderly." Age and Aging. 1977, Vol. 6, pp. 123-31. Mindus, P., et al. "Piracetam-Induced Improvement of Mental Performance: A Controlled Study on Normally Aging Individuals." ACTA Psychiatrica Scandinavia. 1976, Vol. 54, pp. 150-60. Mondadori, C., et al. "Effects of Oxiracetam on Learning and Memory in Animals: Comparison with Piracetam." Clinical Neuropharmacology. 1986, Vol. 9, Supp. 13. New York: Raven Press, pp. S27-S37. Murphree, H.B., et al. "The Stimulant Effect of 2-Diethylaminoethanol (Deanol) in Human Volunteer Subjects." Clinical Pharmacology and Therapeutics. 1960, Vol. 1, pp. 303-10. Nandy, K., and F.H. Schneider. "Effects of Dihydroergotoxine Mesylate on Aging Neurons in vitro." Gerontology, 1978, Vol. 24, pp. 66-70. Nandy, K. "Aging Neurons and Pharmacological Agents." Aging. New York: Raven Press, 1983, Vol. 21, pp. 401-15. Nandy, K., "Lipofuscinogenesis in Mice Early Treated with Centrophenoxine." Mechanisms of Aging and Development. 1978, Vol. 8, pp. 131-38. Nandy, K. and G.H. Bourne. "Effect of Centrophenoxine on the Lipofuscin Pigments of the Neurons of Senile Guinea Pigs." Nature. 1966, Vol. 210, pp. 313-14. Nickerson, V.J., and O.L. Wolthuis. "Effect of the Acquisition Enhancing Drug Piracetam on Rat Cerebral Energy Metabolism Comparison with Naftidrofuryl and Methamphetamine." Biochemical Pharmacology. 1976, Vol. 35, pp. 2241-44. Oettinger, Leon. "The Use of Deanol in the Treatment of Disorders of Behavior in Children." The Journal of Pediatrics. 1958, Vol. 3, pp. 671-75. Oliveros, J.C., et al. "Vasopressin in Amnesia." The Lancet. January 7, 1978, p. 42. Osvaldo, Rey. 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Pfeiffer, Carl C., et al. "Stimulant Effect of 2-Dimethyl-1-aminoethanol: Possible Precursor of Brain Acetylcholine." Science. 1957, Vol. 126, pp. 610-611. Poschel, B.P.H. "New Pharmacologic Perspectives on Nootropic Drugs." Handbook of Psychopharmacology. 1988, pp. 11-18. Rao, Dodda B., and John R. Norris. "A Double-Blind Investigation of Hydergine in the Treatment of Cerebrovascular Insufficiency in the Elderly." Johns Hopkins Medical Journal. 1971, Vol. 130, pp. 317-23. Reznick, O. "The Psychoactive Properties of Diphenylhydantoin: Experiences with Prisoners and Juvenile Delinquents." International Journal of Neuropsychiatry. 3:30-48 (1967) Riga, S., and D. Riga. "Effects of Centrophenoxine on the Lipofuscin Pigments of the Nervous System of Old Rats." Brain Research. 1974, Vol. 72, pp. 265-75. Sitaram, N., and H. Weingartner. "Human Serial Learning: Enhancement with Arecholine and Choline and Impairment with Scopolamine." Science. 1978, 201, pp. 275-76. Smith, W.L. and J.B. Lowrey. "The Effects of Diphenylhydantoin on Cognitive Functions in Man." Drugs, Development, and Cerebral Function. 344-351 (1972). __________________________. "Effects of Diphenylhydantoin on Mental Abilities in the Elderly." Journal of the American Geriatrics Society. 23, 5: 207-211 (1975). Spiegel, Rene, et al., "A Controlled Long-Term Study with Ergoloid Mesylates (Hydergine) in Healthy, Elderly Volunteers: Results After Three Years." Journal of the Geriatrics Society. 1983, Vol. 31, No. 9, pp. 549-55. Stegink, A.J. "The Clinical Use of Piracetam, a New Nootropic Drug." Arzneimittelgorschung. 1972, Vol. 22, No. 6, pp. 975-77. Subhan, Z., and I. Hindmarch. "Psychopharmacological Effects of Vinpocetine in Normal Healthy Volunteers." European Journal of Clinical Pharmacology. 1985, Vol. 28, pp. 567-71. U.B.C. Laboratories, Pharmaceutical Division. "Basic Scientific and Clinical Data of Nootropil." Brussels, Belgium: U.B.C. Laboratories, 1977. Vincent, George, et al. "The Effects of Aniracetam (Ro-13-5057) on the Enhancement and Protection of Memory." Annals of the New York Academy of Sciences. 1985, Vol. 244, pp. 489-91. Weil, C., ed. "Pharmacology and Clinical Pharmacology of Hydergine." Handbook of Experimental Pharmacology. New York: Springer-Verlag, 1978. Wilsher, Colin R., et al. "Piracetam and Dyslexia: Effects on Reading Tests." Journal of Clinical Psychopharmacology. 1987, Vol. 7, No. 4, pp. 230-37. Wurtman, R.J., et al., "Piracetam Diminishes Hippocampal Acetylcholine Levels in Rats." Life Science. 1981, Vol. 28, pp. 1091-93. Yesavage, Jerome A., et al. "Dihydroergotoxine: 6-Mg versus 3-Mg Dosage in the Treatment of Senile Dementia. Preliminary Report." Journal of the American Geriatrics Society. 1979, Vol. 27, No. 2, pp. 80-82. Yoshikawa, Masami, et al. "A Dose-Response Study with Dihydroergotoxine Mesylate in Cerebrovascular Disturbances." Journal of the American Geriatrics Society. 1983, Vol. 31, No. 1, pp. 1-7. John Morgenthaler has BA degrees in psychology and computer science and has worked in the field of artificial intelligence. He is the founder of the Cognitive Enhancement Research Institute (CERI) and the president of INTREND Incorporated, a marketing firm. He is the author of the forthcoming book, Brain Food. If you would like to receive a publication announcement please write to: CERI, POB 483, Santa Cruz, CA 96061. --------------------------------------------------------------- TO BE ENCLOSED IN SHADED BOX WITH THICK BORDER: -------------------------------------------------------- --------------------------------------------------------- DISCLAIMER/WARNING This article is not intended to provide medical advice. It is intended to be educational and informational only. Please consult with a health professional for medical advice. The authors and Megabrain Report are not recommending that anyone use any of the substances described, but rather are presenting and seeking information. We emphasize that adequate studies of both long and short term effects of some of these substances have not been performed, that some of them can have adverse side effects, and that all humans have different biochemical natures and sensitivities, so that safe dosages of some of these substances may vary enormously from individual to individual. Also, some of these substances may be dangerous for individuals not in sound mental and physical health. As a result, we strongly recommend that anyone interested in experimenting with these substances do so with caution and under the supervision of a medical professional. We strongly recommend that children and pregnant or lactating women should not experiment with these substances under any circumstances. Megabrain Report does not have any financial interest in any of the drugs or nutrients or suppliers of such substances mentioned in this article.