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Cognition-Enhancement Drugs This text has been excerpted from MEGABRAIN REPORT: THE PSYCHOTECHNOLOGY NEWSLETTER. Included here are dosages, precautions, and mail-order sources for three intelligence and memory enhancing substances. Please feel free to duplicate this excerpt and put it onto other bulletin boards or conference systems. For a copy of the full length article, including references, contact MEGABRAIN REPORT, POB 2744, Sausalito, CA 94965, Phone: (415) 332-8323, FAX: (415) 332-8327. The authors of this article are Michael Hutchison and John Morgenthaler. Michael Hutchison is the editor and publisher of MEGABRAIN REPORT and can be contacted there (see the address above). He is also the author of the books, MegaBrain: New Tools and Techniques For Brain Growth and Mind Expansion, The Book of Floating, and the recently published Anatomy of Sex and Power: An Investigation of Mind Body Politics. John Morgenthaler is the co-author with Ward Dean, MD, of a full length book on over thirty cognition enhancing compounds. The book includes an index, references, and sources of compounds. John can be contacted at POB 483 Santa Cruz, CA 95061, Phone: (800) 669-2030, MCI mail address: 3144541. A free copy of the book goes to anyone who posts this article to another bulletin board or conference system. COGNITION-ENHANCEMENT DRUGS by Michael Hutchison and John Morgenthaler 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 has a synergistic effect that will create the optimal psychobiological 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 the 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 that 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 these 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 that 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 the 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 the 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 initial 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 individuals 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 the 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 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 that 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 causes 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 syntheses 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 syntheses 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. . . . HYDERGINE "I first tried Hydergine six years ago during a visit to see my Dad at Christmas. He and I started taking 9mg and results were apparent to us both within two days. He was in his 40s, and began to remember events from when he was in his 20s 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 20s 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 syntheses 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 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 function, 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 and 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 3mg 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 is 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 the question. . . . 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 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 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). . . . 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 application. 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 innovation." 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. InHome Health Services, a mail order pharmacy in Switzerland, is one of a number of companies established in response to this new FDA ruling. InHome carries a wide variety of drugs for cognitive enhancement, life extension, and the treatment of AIDS which are not available in the US. All of the drugs discussed here can be purchased without a prescription. You can request a full price sheet by writing to: InHome Health Services, Dept. E, POB 3112, CH-2800 Delemont, Switzerland. Those who want to order some of the substances described above right away may send a personal check for the amount of the item(s) plus $13 for shipping. Some sample prices (in June, 1990) are: