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Home My WebLink AboutCOM 0193.044 2006-2008 Zero-Out Green Harvest Restore Cannabis to its rightful place as a medicine Bc Michael T. H~ son, Ph.D. Puna. Ha~cai~i (alanetuuna(7n vahoo.com. www.ulanetnuna.com. www.ulanetpuna.comisirius) . Cannabis has been used and praised as a most useful medicine since long before it wTS.first listed in the phamacopeia of Chen Nung in China, 3000 BC. To name just a few of its , myriad advantages: ~ - The seeds aze a complete food, containing all essential amino acids The best vegetable source of essential fatty acids The leaf has high concentrations of eicosanoic acid, an oil usually found only in fish and seafood, and which is reyuired for our proper brain development. ...And smoking it slows lung cancer growth, inter alia. Yet this most useful plant on Earth was demonized for economic and political reasons. The so-called war against marijuana is and always has been based on fraud and lies pushed by government, timber and chemical interests starting in the 1930's. Current suppression of Cannabis is an obvious failure, a waste of money, and largely caused the current Ice problems, which was fully predicted by NIDA studies which found that Ice use increased proportional to the suppression of Cannabis. -the good agents will drive out the bad agents if left alone to do so Allowing the free use of Cannabis, which is our right since the founding of this nation, would eliminate the "Ice" problem altogether Liberty for Cannabis is OUR liberty too, and will change the face of the planet. For all our sakes, especially ow children -ZERO OUT GREEN HARVEST - Let us follow the advice of our country's founders: Hemp is the first necessity of a free nation -Thomas Jefferson Grow lots of hemp -George Washington Everyone in the world would be fed in 30 to 90 days from seed crops, eliminating world hunger. We can start here by easily feeding the hungry people on this island. Oil from the seeds can replace diesel fuel cost effectively, eliminating the need for foreign oil and serving as the source of at least 50,000 demonstrated products. ~ Comm. No. l9 a . ~ Ref. To: G Ref. Date Cannabis must be restored to its long-honored and traditional place in medicine and as a near perfect food. The anandamide mimic called THC and other alkaloids have been used as a calmative and medicine, including ONE THIRD of all our medicines before they were outlawed. Cannabis is the best way to ease the withdrawl from methamphetamine and also help with PTSD or trauma recovery for anyone. From Dr. Dreher's work, (attached) it is also clear that use of Cannabis teas in Jamaica help children have better concentration and performance in school, and thus we can eliminate Ritalin, Prozac and other agents now drugging our children, increasing their suicide rate and contributing to school shootings like Columbine and Virginia Tech. Therefore, the way out of the Ice problem is to employ Cannabis in a therapeutic way, help people with their withdrawl and healing, and we can actually be "the healing island". The above approaches offer us a better paradigm, a humane and compassionate approach, that above all, promises to be effective. I propose that such alternatives be offered and made available. We have qualified people ready to implement such approaches. For our sanity, to mend the rending of our social fabric, and to restore a world where whole children aze raised in love, let us start. I can provide more complete background and substantiation on request. in the spirit of Aloha, 7llichpel~~an,~.~? PO Box 1979 Pahoa, Hawaii 96778 michaelhyson(awahoo.com Profile at: www.alanetauna.com/hvson 2 Children, Drugs, the "Ice" Problem -and ways out- Michael T. Hyson, Ph.D -July 21, 2003 Children, Drugs, the "Ice" Problem -and ways out B~ Michael T. Hvson, Ph.D., Research Director, Sirius Institute. Puna. Ha~~ai~i (ulanetpuna(nwahoo.com, www.ulanetpuna.com, www.planetpuna.com/si.htm) This island, state, and nation have a serious "ice" and cocaine problem. It is reported that some 90% of local Child Protective Services cases involve "ice" or methamphetamines and related drugs. At the same time, the number of children being classed as AD, HD, ADHD and prescribed stimulants and other drugs is increasing. Some districts have put up to 25% of the children on drugs. These situations are linked. Ritalin (methylphenidate) binds to the same receptor in the brain as cocaine, and is, in fact, more effective than cocaine, and while chemically different, the effects of Ritalin and Cocaine aze the same. Another drug commonly used in these cases is Adderol which contains methamphetamine - "ice") This is considered accepted medical treatment and enforced on children and parents by the Child Protective Services and related agencies. Parents that wish to apply alternate treatments, as part of seeking the best for their children, may have their children taken by force. Now we see that part of the "ice", cocaine and crack use comes from adults, treated for years with Ritalin and Adderol ("ice" & "cocaine" equivalents), even starting at ages of 2-4. These drugs have yet to be tested or approved for children. Similar situations obtain in the use of Prozac, Paxil, and other drugs that are known to have severe side-effects in adults, and the cffccts in children are beyond our knowledge. Drugging of children predisposes them to drug abuse, hence the current and growing use of"ice", cocaine and other stimulant drugs. All this is happening with little data showing that these drugs "prescribed" for our children are even effective as treatments for ADHD and similar conditions. Further, many diagnoses are wrong because the diagnostic criteria for hyperactivity aze crude, arbitrary, and poorly quantified, requiring a large measare of judgement on the part of the diagnostician. It was once thought that valid rates of hyperactivity might be, at most, 2%, much lower than the rates now being claimed. A medical model proposed by Dr. Ivan Mefford and supported by the work of neurophysiologist Dr. John Pettigrew and others offers understanding - and a way out. According to Dr. Pettigrew, a group of nerve cells, the Locus Coeruleus, in the brain stem, can become hyperactive and flood the brain with norepinephrine, leading to ahyper-attentive state, just like that seen in hyperactive children and which is similaz to the normal state of rabbits. Locus Coeruleus hyperactivity occurs when adrenaline levels are too low. This can occur as a result of trauma and lead to traumatic stress disorders. A person overwhelmed by chronic stress will over-stress the adrenal glands and they will eventually shut down, leading to low adrenaline levels. Mefford proposes that this is occurring in children, so that many of the children presenting with hyperactivity syndromes may, in fact, be already suffering from Post Traumatic Stress Disorders (PTSD), even at the 1 Children, Drugs, the "Ice" Problem -and ways out- Michael T. Hyson, Ph.D -July 21, 2003 young ages they are first examined in schools, because of the traumas of birth and/or abuse and/or domestic violence. Key to this model is the fact that dosing a child with stimulant drugs like Ritalin will "replace" the low adrenaline levels and lead to the apparent paradox of a stimulant having a calming effect. According to this model, the stimulants cause inhibitory effects similar to adrenaline on the Locus Coeruleus, which then reduces its norephinephrine production and thereby, the child/adult becomes calmer. PTSD was called "shell shock" when encountered in soldiers in WWI & W WII. Such an individual has been pushed beyond their stress limits. They require treatment and therapy to recover. Adding stimulants to the mix is like putting a PTSD soldier back into battle. From what we have shown here, this is similar to our current standard medical approach. Fortunately for us all, there are better approaches. Drug use can deplete the brain of nutrients and neurotransmitters. For example, Serotonin (5-hydroxy-tryptryptamine) is often depleted. Supplementation with proper nutrients, nutraceulicals can help. In our example, 5-hydroxy- tryptophan, aprecursor of Serotonin, when provided as a supplement, helps the brain recover from depletion ofSerotonin stores. Based on such knowledge, mixes of nutrients have been devised to restore balanced brain function to those who have become depleted by use of various dnigs. For example, Recovery Essentials (www.recoveryessentials.com), founded by Dr. Richard Kaufman, offers several products of this type. They offer formulas to aid those affected by amphetamines, opiates, alcohol and tobacco, among others. Traumas leading to PTSD-like states also powerfully condition and imprint the individual. Part of drug use is self-medication to alleviate effects of trauma and abuse, especially childhood abuse. Therapy seeks to heal the trauma, freeing the person to make other choices, through love, acceptance, understanding. With the addition of proper nutrition and nutraceuticals designed by the best biochemists, we have a way to achieve a high rate of recovery both for our children, and the adults effected by the overuse of "ice" and other agents. One important part ofthis is the discovery and characterization ofAnandamide. Anandamide (from the Sanskrit "ananda" for "bliss") is a neurotransmitter involved in play, reward, creativity and is necessary for suckling. Anandamide is necessary for forgetting things. A major function of the anandamide system is to allow a traumatized person to selectively forget things, which releases and heals the trauma. Thus the action of anandamide is crucial for the resolution and forgetting of deep trauma. Anandamide binds to the same receptor site in the brain as tetrahydrocannabinol (THC), which is the main active ingredient in Cannabis, and has quite similar effects. For example, baby animals missing anandamide fail to suckle, and will therefore ordinarily die soon after birth. These babies suckle properly when THC is provided. Therefore Cannabis is a natural plant substance that mimics anandamide. It follows that proper medical use of Cannabis is one way to supplement Anandamide and help those damaged by trauma and drug use to recover and move on with their lives. This is the practical experience of communities that 2 Children, Drugs, the "Ice" Problem -and ways out • Michael T. Hyson, Ph.D -July 21, 2003 use Cannabis in sacramental ways. Therefore, use of Cannabis is one way to help people recover balance and is supported by available evidence. The alwve approaches offer us a better paradigm, a humane and compassionate approach, that above all, promises to be effective. I propose that such alternatives be offered and made available. Of course, trials would be wise to develop the finest approaches and take advantage of increasing knowledge. This approach has the benefit of being safe, since the necessary agents are nutrients and herbs with well known effects, some of which have been used safely for thousands of years in many cultures. We have qualified people ready to implement such approaches. For our sanity, to mend the rending of our social fabric, and to restore a world where whole children are raised in love, let us start. I can provide more complete background and substantiation on request. In the spirit of Aloha, 7ll~hael9'~v~ Research Director Sirius Institute PO Box 1645 Pahoa, Hawaii 967"78 michaelhvson(a vahoo.com Profile at: www.planetnuna.com/hvson 3 Dr. Melanie Dreher, reefer researcher Despite political pressure to have it otherwise, Dr. Dreher's research reveals that pot-smoking moms can have smart, healthy babies. by Pete Brady (Ol Nov, 1998) 9 i i 1 1 Dr Melanie Dreher When Dreher released solidly researched reports showing that children ofganja-using mothers were better adjusted than children born to non-using mothers, she encountered political and professional turbulence. Dr. Melanie Dreher is one of a handful of scientists who have reseazched mazijuana objectively and intelligently in the last three decades. Dr Dreher is Dean of the University of Iowa's College of Nursing, and also holds the post of Associate Director for the University's Department of Nursing and Patient Services. She's a perpetual overachiever who earned honours degrees in nursing, anthropology and philosophy before being awazded a PhD in anthropology from prestigious Columbia University in 1977. Although Dreher is amulti-faceted researcher and teacher whose expertise ranges from culture to child development to public health, she began early onto specialize in medical anthropology. After distinguishing herself as a field reseazcher in graduate school, Dreher was hand-picked by her professors to conduct a major study of marijuana use in Jamaica. Her doctoral dissertation was published as a book titled "Working Men and Gagja," which stands as one of the premier cross-cultural studies of chronic mazijuana use. Along with being awidely-published researcher, writer, and college administrator, Dreher is a professor or lecturer at several institutions, including the University of the West Indies. She recently served as president of the 120,000 member Sigma Theta Tau International Nursing Honour Society, has been an expert witness in a religious freedom case involving ganja use by the Ethiopian Zion Coptic Church, and is one of the most well-respected academicians in the world. Governmental and private organizations, including the US State Department, have funded Dreher's many reseazch projects, some of which focused on ganja's role in Jamaican culture, and the effects of ganja and cocaine on Jamaican women and children. Dreher has impeccable credentials and a wealth of proprietary information on ganja use, but when she released solidly-researched reports showing that children ofganja-using mothers were better adjusted than children born to mothers who did not use ganja, she encountered political and professional turbulence. Some observers accuse the government and anti-pot 1 groups of working to suppress her findings, but Dreher continues to speak openly about her research. When Dreher spoke to Cannabis Culture from her office at the University of Iowa, she was affable and intriguing, pleasantly but firmly defending her right to study ganja use and to publish valid scientific findings regardless of political pressure. How did you first become involved in studying ganja in Jamaica? Dr Dreher: I had already spent one summer in jamaica studying obeah, a kind of black magic, and my professor, Ur Lambros Comitas, felt that if I could study an illegal and undergound practice like obeah then [could probably get information on ganja use. This was in the 70's, when American pundits were saying that marijuana caused people to be lary and dysfunctional. We were especially interested in testing the notion that ganja caused an amotivational syndrome. My dissertation research studied various kinds of men's work, primarily agricultural work, and how ganja interacted with that. Jamaica was a great place to study because these men used ganja every day for eight to ten years, unencumbered by cocaine or other drugs, and just a little bit of tobacco or alcohol, so you could really measure how ganja affected them. After nearly two years of study in Jamaica, I'd found ganja was used to stimulate work. The amotivational syndrome, whatever it was, certainly didn't manifest itself in the people I studied. So you just walked up to Jamaican villagers and started asking them about ganja? Weren't you afraid they'd think you were a police agent? [t was an interesting experience! 1 had never smoked anything, not even a cigarette. I'm a white woman, a former cheerleader, about as 'American' as you could get. I didn't have an intermediary or liaison. I went into villages and politely introduced myself as an American student. I established trust by going to church and schools and living with these people, telling them 1 was there to study certain aspects of their culture, especially herbs and particularly marijuana, and people began to trust me. They gave me a few social tests to see if they could really trust me, and after I passed those tests pretty soon I was going into their fields and seeing where ganja was gown, dried, stored, processed and sold. There is a cultural division between men and women in this culture, but even though l was a woman, as a white American researcher I had more privilege and access to men's rituals than a Jamaican woman. I got to sit with the men surrounded by these big clouds of smoke, and as they smoked their chillums I asked questions about ganja use and took notes. So ganja use had its own cultural identity and rules? Yes. Ganja use is governed by customs, beliefs, and social rules. Ganja arrived in Jamaica through the Indian indentured labour; Indians brought with them this whole tradition of preparation of teas, tonics, hash, cooking ganja in food. The Jamaican ganja-users, except for the Rastas who tend to use more ganja than the people we studied, had strict cultural contexts in which to use marijuana. It isn't like in the US where people indiscriminately light up and walk around all day stoned. The Jamaicans prescribed certain situations and ways to use ganja. There were people prohibited from using it. When you smoked you had to act a certain way - serious, intelligent, reasonable. A man who used ganja and got silly or got the munchies or laughed too much or acted like afool -the other men stopped smoking with him because they felt the ganja 2 was a spiritual thing. It's to be taken seriously in a mature and responsible way. A whole set of cultural rules guided use and made sure it was positive. The set and setting and cultural traditions in Jamaica made ganja use a positive thing. It's useful to study ganja in a place where its use is notjust a recreational activity -its use is sacramental, medicinal and social, but it is designed to be a thoughtful activity -not like you stop at the store and get a six pack of beer to get drunk. Did ganja culture affect how men and women used ganja? It did. The men believed that ganja inhaled went to the brain and had a psychoactive effect, but that ganja consumed as tea or tonic went into the blood and had a health effect rather than intoxication. They only allowed men to smoke ganja because they didn't believe women had the right kind of brain for it. Now there are physiological differences between men and women, and it's also true that ganja eaten or ingested as tea follows a different route in the body than ganja smoked, but 1 am not expert enough in this to comment on whether the cultural tradition is supported by science. Women were allowed to control the medicinal use of ganja. I spent lots of time with rural women, who taught me how to make ganja tonics and teas. They were the administrators of ganja, open the producers and sellers of ganja. It gave them some power and income, like a cottage industry. They gave ganja to men and children as teas, and they knew how to titrate the strength of marijuana teas so anew baby would getjusl a teat's worth but men and boys got more, so they could go and work in the fields with enough strength to survive the hard days. So women never got to smoke ganja? When 1 first started research in Jamaica in 1970, women were the ganja medicine specialists but there was a social rule that women should not smoke. The only time women were allowed to smoke was in apre-sexual context. Everybody believed ganja was an aphrodisiac, they said it made both sexes more powerful, makes you like sex more, makes you concentrate on lovemaking more. It was not used as a clandestine seduction tool like alcohol. That's not to say that like at a dance if young men were smoking, a young woman wouldn't say "Give me a draw," but it was very innocent, never saw an attempt to use marijuana as seduction or date rape. Back then, women were smoking secretly. If a man didn't finish the whole spliffthen after he went to work the women might smoke a little. Women said it helped them do their housework and be good to their children. So the women had to sneak around to smoke it but they were expected to openly administer its medicinal use. The real focus of the women was to have marijuana to prepare for tea for their children to make them healthier and smarter and help them have better school performance and help them concentrate. Has your subsequent research found changes in the use of ganja by Jamaican women? Yes, as the role of women has changed economically and socially, some women have been able to smoke ganja „ openly with the men. They're called "roots daughters", which is a term of Rr 3 respect meaning that they can smoke as hard as a man and maintain a dignity of conversation and behavior. They can smoke ganja and reason with men, have debates about serious topics like politics and religion. They are considered to be principled women who are astute and trustworthy. Another characteristic of these women is they tend to be economically independent and resourceful. fhe y don't expect that men will have the sole burden of supporting households. Many of these women are working for themselves, and a significant number of them are involved in ganja sales, along with work such as farming and other commercial enterprises. They build their own houses and become less dependent on men, or on one man, for their livelihood. Part of this change came from Rastafarianism, because Rasta women do smoke ganja chronically as par[ of their religious rituals. Older women have built up their roles as ganja administrators, while older men may have to decrease their ganja use once their days in the fields are over. The society is changing experience with ganja is changing, and women smokers are becoming more visible then before. Give us a general overview of the studies you've done on ganja use during pregnancy When [noticed that increasing numbers of women were smoking marijuana, I decided to study prenatal marijuana exposure and its effects on children. Most of the studies done in North America had serious confounds and results which just did not hold up under scrutiny. We did ethnographic studies which examined the lifestyles of mothers who used ganja and mothers who didn't use ganja, and compared behavioral characteristics of neonates from both groups in the first month of life. We later went back and looked at the children with afive-year follow-up study. How did your studies differ from other studies? Up to that point, most studies which examined marijuana use during pregnancy were flawed by serious methodological problems. They couldn't control for so many variables, and the negative effects they blamed on marijuana could well have been caused by other things. My studies are among the few which actually measured how much ganja a woman has consumed. I wasn't sitting in a clinic somewhere divorced from women's lives asking them how much marijuana they'd used - my research team is in a community and in the Feld where we can observe these women and check out their reports. We know how much ganja, and what type and potency, they are consuming. We had ways of verifying the amount of ganja they consume; neighbors would come and tell us what was going on, so we could compare that to _ what we had been told by the mother We had a setting in which we knew that the women were only exposed to marijuana. In most North American studies the women were using all kinds of drugs like alcohol, tobacco, speed and cocaine during prenatal studies, and there was no way for the researchers to know what or how much. We knew what our test subjects were doing and this gave extra credibility to our work. A lot of media publicity had been given to US studies which purported to show that marijuana caused birth defects or serious developmental problems, but most of this research involved participants who were multi-drug users who had a terrible social support network that probably caused the problems. Instead, these problems were blamed on marijuana. 4 Is it possible that American women didn't know how to use marijuana intelligently? Did you find that Jamaican women had more ganja wisdom? American drug use often takes place without cultural rules and in an unsupervised context. The Jamaican women we studied had been educated in a cultural tradition of using marijuana as a medicine. They prepared it with teas, milk and spices, and thought of it as a preventive and curative substance. Smoking it during pregnancy was a way of relieving nausea, increasing appetites, combating fatigue and depression, providing rest and relaxation. Some of these women were in dire socioeconomic straits, and they found that smoking ganja helped allay feelings of worry and depression about [heir financial situation. Our testing showed that the children of women who used ganja had better alertness, stability and adjustment than children of women who didn't use ganja. This was measured at the age of one month. We measured children again at four years and at five years of age, and found that there were no apparent deficits in the children of marijuana-using mothers. In fact, in many ways, they were better oft than children ofnon-smoking mothers. The ganja-using mothers also seemed better off than non- users. Since these results contradicted the hysteria of drug war assertions, did you find it hard to get your studies published? I insisted on publishing in a medical journal - I wanted the academic community to understand that thejury was still out on marijuana and that's why we do cross-cultural studies to determine how drugs really affect people. It isn't logical to look just at one culture's problems with a drug and conclude that that's a universal situation. The medical community needed to see that these results, which came from very solid research methods, were far different than what they are usually exposed to. They needed to see that women who smoked marijuana are not bad mothers. I am so damned sick of picking up a woman's journal or a tabloid and seeing some article saying that if you smoke even one marijuana cigarette during pregnancy you are a bad mother and you're doing permanent damage to your baby. There's no evidence to back up these warnings, and in my studies the evidence points in the other direction. It sounds like you're frustrated about the influences of politics and inaccuracy in the reporting of marijuana research findings. I just want researchers to use good research methods and to tell women the truth. I think these hyperbolic warnings about marijuana and pregnancy have made women absolutely nuts. 1 got a call from a woman who was in tears because she and her husband had waited several years to adopt a baby and finally she had found a baby to adopt, but somebody told the couple they couldn't adopt the baby because the baby had tested positive for marijuana. "Oh for god's sake," [said, "Go adopt your baby. Love your baby. Your baby is going to be just fine." Now they're talking about charging women with child abuse if they test positive for drugs during pregnancy. It's a slippery slope. Where's it going to stop? Are we going [o arrest women for sitting on the couch eatingjunk food watching television during pregnancy? We are on the way to the Stepford Wives. So one of my goals with this research was to get the message to physicians: so women smoke a little marijuana -big deal. Let women enjoy their pregnancies. If there's something seriously wrong with their baby it would have occurred no matter what -marijuana or not. Things have gotten so strange in regard to babies. We have to have the perfect baby and if not, well somebody or something has to be blamed. It must have been a whiff of paint she smelled, or a glass of wine, or a cigarette, or a draw of marijuana... It's ridiculous. 5 Can you comment on the issue of crack babies? I have tended to be vary skeptical of crack baby findings. 1 have studied cocaine use in Jamaica, and have studied children exposed to crack pre-natally who are doing fine. 1 think the problem with crack is what happens after birth. The babies are often abused by mothers or others in the home; cocaine is just part of a terrible environment. Ironically, Rastas are the only group who refuse to participate in the cocaine trade. They think it's poison. Women use ganja to kick cocaine withdrawal; they use ganja during cessation to get enough of a comfortable anti-depressant feeling so that they don't have to use crack. Some start using what they call a seasoned spliff, which is a marijuana cigarette seasoned with crack. Having the pot in there seems to relieve the precipitous drop from the crack high to a paranoia which would otherwise force them to smoke crack immediately again. They are high enough on the pot and the crack drop doesn't make them crazy like it would if they were using crack by itself. The American government's approach to cocaine and ganja in Jamaica has been very counterproductive. The DRA finds it easy to see and go after ganja fields, but almost nothing is being done to stop cocaine, which is ravaging the country. It's very sad. I heard that political pressure influenced your subsequent research grants and the academic journal that you were going to publish your findings in. It did take us a while to get published. We had to do revisions that t thought were unnecessary. It would be hard to classify the request for us to do revisions as politically motivated. 1 just thought that these people who wanted the changes made haven't got a clue about Jamaica or ethnographic research. They went on vacation once to Jamaica and drew some incomplete conclusions. felt that the revisions suggested were often based on ignorance of Jamaican culture and prejudice against ganja. The same problems were evident in letters that the journal received after publication. The letters contained unfounded criticisms, and I had to explain that I was doing anthropological research that nobody else was doing. I wasn't measuring physiology with test tubes. I was measuring behavior, reporting how these women and their children acted. These babies are doing great. It wasn't necessarily due to marijuana, but pot-smoking mothers were apparently good mothers and the marijuana didn't appear to be hurting the babies. I have said repeatedly that I am not recommending that you smoke pot to have a healthy baby, but I am saying let's not castigate women who use a mild substance during pregnancy. After doing research in Jamaica funded by the National Institute on Drug Abuse (NIDA) from 1988 to 1991, 1 submitted two follow-up proposals in 1993 and 1994 and got news that never ever do they want to see those proposals again. They had done one of the worst reviews of a proposals that I had ever seen. Really weak. o; 1 thought 1 should call NIDA and tell them this shows a lack of understanding of any type of unbiased research on the issues involved and what we're trying [o do. It was a damning review, misguided and misinformed. I have to think that this was due to a political consideration, not an honest review of my work. t I'm 55, in my 15th year as dean, 1 testified in a trial and the prosecution brought out that I was once on the board ofNORML, and involved with a group called POT (Patients Out of Time) and wrote an article for a 6 medical marijuana book. So what? 1 am a good researcher. Nobody knows more about marijuana use in Jamaica than I do, and t am prepared to speak about that and don't care what people try to do against me because of it. I felt that this last denial at NIDA was motivated by anti-pot ideology, but since that time [was funded by the National Institute of Health. Has your career suffered because you've objectively researched marijuana? Do you feel you've been persecuted because of your research? There may well be persecution, but if there is, 1 don't obsess over it. I'm a very good dean and highly regarded in the nursing and academic communities. Somebody asked me if I was worried about DARE coming after me, and I thought: Isn't that the organization that gets children to report on their parents? I am going to continue doing good research and disseminating the results. Am I worried about persecution? Well, 1 have a secure academic position and could be a nurse again if 1 had to, but some of these researchers haven't got something to fall back on so they have to please NIDA and find what they're supposed to find To a large degree, the politicization of such research has corrupted the research process. I'm never going to be a part of that. 7 Use of the NMDA-Receptor Blocker Dextromethorphan and Nutritional Support to Reduce Cravings and Increase Success in Acute and Post-acute Amphetamine Withdrawal *Laura Moire, M.D. & **Michael T. Hyson, Ph.D. *PresidenL Volcano Healing An Centre Post Office Bos 1077, Mountain View. Hanoi' i 96771 Phone: 808A87-765 Fas: 808-968-8937 Enuvl: healing_music6hotnli~il.com **Research Director. Sirius Institute, P.O. Bos 1979, Pahoa. Hawaii 96778 Phone: 808-965-1607 or 808-96.5-9667 Email: michaellwson6vahoo.com Summary The use of NMDA antagonists with nutritional support promises to increase success in the treaunent of amphetamine dependence. We propose an alternate treatment for acute and post-acute atphetamine withdrawal utilizing destromethorphan and nutritional support. Use of antagonists of the N-meths 1-D-aspartate (NMDA) receptor reduces cravings for a varieh of drugs. One Basil} available NMDA antagonist is destromethorphan (DM). found in cough scraps. Administration of destromethorphan should ease acute and post-acute amphetamine withdrawal and lead to higher rates of success in dnig treatment. Drug use o8en depletes stores of nutrients adding to the problems of withdrawal and recovery. Nutrients will be used to support and restore normal nutrient levels during acute and post-acute withdrawal. For example. the nerve transmitter serotonin is often depleted with chronic drug use. The Levels of serotonin can be restored through the supplementation w ith precursor molecules like 5- hydros~tr<ptophan. This and similar nutritional support aids recoveq, eases ~cithdrawal and further reduces cravings. B}-using these safe_ over-the-counter, low cost agents, we can effectively treat the large number of people now adversely affected b~~ amphetamines. This protocol, once established, can be included in many existing programs and add value to them be improving their success. Based on large European studies that utilized interventions to reduce cravings in alcohol addiction, eye theorize that the current relapse rate (85-90"/0) can be improved and look to achieve a ~0% or more sustained sobriet} b}-the addition of these interventions to curreut programs. Background Amphetamine addiction is a major problem throughout the nation and especialtc in Hawai i. Amphetamine use is linked to violent crime. T7tis is a crisis of such epic proportions that it is overcrowding the jails and the public has expressed a resounding en~ for assistance. Hawai' i Governor Lingle and Lt. Governor Aiona have expressed support to implement this specific project. In addition_ Amoore Health Group ~~hich is involved in the development and implementation of eomprehensi~ ~ behavioral health treatment programs across the count} has offered financial and grant development assistance. The addition of the sU•ateg} of our grant proposal -utilizing medications and nutritional support -promises to groath improve treatment success. Long-term users of amphetamines develop classical habituation and addiction. When the drug is withdrawn_ sG'ong cravings remain. Cravings originate, in part. with [he operant conditioning of 1 nerve cell receptors wfiich come to expect the presence of the drug. Cravings must be overcome during recoveq in acute and post-acute amphetamine withdrawal. Mane succumb to the cravings and return to drug use. B} reducing cravings, we can improve the success rates of treatment programs. Gavings eau be ameliorated using N-methyl-D-aspartate (NMDA) receptor antagonists. For example, NMDA receptor antagonism is a major mode of action of ibogaine which is known to greatl} or perhaps permanently reduce mangy existing drug cravings. In contrast to medications like: ibogaine however, dextromethorphan is currently over-the-counter, approved for all age groups and has a low side effect profile. Besides being a safe, over-the-counter NMDA-antagonist. wide( used and easik available (for example. in cough s~ rnps) de~Uromethorphan is also quite low cost. As an effective NMDA blocker, it will reduce drug cravings. Dr. Luigi Pulvirenti, Universitc of Rome and Scripps Institute has shown this in animal studies. Considering the widespread nature of the amphetamine problem, ice need such available, safe. effective treatments. Study Design To determine the effectiveness of the proposed treatment, w e will test } oung adult malt imnates in Hawai' i~s prisons and `Drug Court ~ programs that are known users of amphetamine in a pilot. We will test the results of treatment with: 1) Destromethorphan 2) Nutritional Support 3) DexU'omethorphan+Nutritional Support d) Control group using standard treatnents/Placebo All groups will be statisticall} matched. To uisure statistical significance, each group should have up to ~0 members with a minimum of 2~. The software package SPSS will be used to evaluate the results and their statistical significance. We will be able to compare the control/placebo group with the groups receiving DM, DM +Nutritional Support, and Nutritional Support onh . Long-acting (even- 12 hours) De~iromethorphan azid identical(- appearing placebos can be obtained through bulk purchase from phannaccutical manufacturers. The nutritional support formulas were developed b~ Dr. Richard Ikauffinan and are cwrently marketed through "Recover} Essentials~~ at www.recovervessentials.com . Thee constitute state of the azt "nutriccuticals.° See the Appendices for descriptions and references for these formulas. Other similar products exist or can be developed. Amoorc Health, Inc. will be involved in all stages of grant/studv development Amoore Health will assist with budget and staff development as well as the bulk purchase of the medication and nutritional support. We will negotiate with the Communit} College, hapiolani. and Universitc of HawaP i Schools of Nursing to help us run the stud} . Thee kill assist in data collection and administer the standard available pscchiatric evaluation tools for mood. cravings, and other variables applicable to potential for relapse along with evaluation for co-occurring disorders 2 This will be a double blinded study. Our proposed study in turn will provide nursing students and/or post graduate students with valuable research experience and seed further studies and grants. We will negotiate with existing residential amphetamine recovery treatment programs and Public Safety (prison/jail) personnel to incorporate our study as an added value to their existing programs. We will consider using subjects on all islands. This will involve the project in travel to and from the various facilities. Paradise Newland will help in negotiation and coordination and act as liaison with the various agencies and staff that are involved. Her diplomatic and language skills will improve communication throughout the project. We will be reporting our progress to Governor Lingle and Lt. Governor Aiona. Since the standard "Drug Court" assignment to residential amphetamine recovery treatment programs extends to two years, we will use atwo-year study period. These programs as well as the prisons/jails have medication distribution systems in place for distribution of methadone and other routine medications. We will utilize the existing medication distribution system to distribute the dextromethorphan and "nutriceuticals," and placebos. Therefore, the administration of the DM and nutrients should be a straightforward addition to existing programs. We expect that the subjects will be in a "Nare-Anon"-like program in addition to our interventions. We feel that this is fine, and that our protocol will only add to other positive pre-existing programs. Prisoners entering the system through "Drug Court" and other paths will be evaluated for use in the study. We will develop informed consent documents and videos describing the study and these will be shown to prospective subjects so that they can make an informed choice in language appropriate to their level of understanding and culture. The choice to be in the study will comply with the National Commission on Correctional Health Care standards and comply with other human subject review board requirements. Entry into the study will comply with all laws regarding prison/detention subjects. We will use standard psychological evaluation tools and existing toxicological (drug use/relapse) testing to determine use patterns, degrees of craving, and monitor the mood and state of the study subjects. During the study, degrees of craving will be assessed weekly. Data collectors and those administering assessment tools will be "blinded" to the subject's use of DM and nutriceuticals. The subjects will likewise be "blinded" to their category. This will be a "double-blind," placebo controlled, "cross-over" study. Therefore we can use "factor analysis" to determine the effects of DM and the nutriceuticals both individually and in combination. Since full withdrawal and readjustment of nerve receptor numbers can take several months, we will administer the DM and Nutrients on a daily basis for at least the first 6 months. We feel this should allow sufficient time for rebalancing the subject's biochemistry. It is suggested that the long acting Corm of DM up to 50 mg be administered two times per day. Following the first six months of the program, we may be able to reduce the amounts of DM. The amounts given will be evaluated and determined in part through the psychological assessments of cravings and sustained sobriety in the subjects. 3 In all test cases, the DM and nutrients should be made available at any time the subjects are troubled by cravings. The placebo group will be similarly provided. The study should show significant results within 6 months to a year. We will continue to follow the subjects through the second year to determine the success of the program through monitoring the sobriety rates. Optionally subjects could be followed longer to assess success over the years. Staffing Principle Co-Investigators: Laura Moire, M.D. and Michael T. Hyson, Ph.D. Consultants: Paradise Newland -Inter-agency Coordinator and Community Liaison Margaret Fischl, M.D. -Standard Operating Protocols for Prisons Luigi Pulvirenti M.D., Ph. D-Biochemical Consultation on the action of DM Richard Kauffman, Ph.D. Recovery Essentials Nursing Schools -data collection Budget Co-PI I /2 time $ 40,000.00 Co-PI 1 /2 time $ 40,000.00 Project liaison & Coordinator $ 40,000.00 Consultants: Luigi Pulvirenti $ 2,000.00 Margaret Fischl $ 2,000.00 Richard Kautlman $ 2,000.00 Nursing student assistants $ 50,000.00 Data Entry $ 5,000.00 Data Analysis $ 10,000.00 Office & Overheads (25%) $ 47,750.00 Travel 10 trips @400/trip $ 40,000.00 Drugs for Study Placebos (estimate) $ 10,000.00 Dextromethorphan Liquid Gelcaps Qty 30 Good for IS days/person 15.63 For I year - 10 x 2groups x 365 $ 19,016.50 4 Recovery Essentials Maximum of $5/day/person Two groups of 50 for 1/2 year $ 91,250.00 TOTAL FOR GRANT FOR 1 YEAR $399,016.50 5 APPENDIX L NMDA ANTAGONIST REFERENCES Glutamate During The Natural History Of Psychostimulant Depeudence: Synaptic Plasticity And Medications Development Luigi Pulvirenti, M.D. University of Rome -Tor Vergata, Italy The natural history of drug dependence is characterized by phases of acquisition, maintenance, extinction and relapse of drug taking. All these phases have now been successfully mimicked using a rodent model of intravenous drug self-administration and the psychostimulant addiction cycle has been extensively investigated. Much evidence suggests that glutamate may play a critical role. During the first days of acquisition of cocaine-seeking behavior aglutamate-dependent enhancement of synaptic efficacy was found using evoked field responses in the rat nucleus accumbens, a critical neural substrate mediating cocaine self-administration. Furthermore, intact glutamatergic neurotransmission was shown to be essential for the full expression of the reinforcing properties of cocaine during the maintenance phase of cocaine self-administration. Later phases of cocaine dependence were also found to be affected by indirect glutamatergic manipulation. Inhibition of nitric oxide synthesis reduced the reinforcing properties of cocaine, cocaine craving during the extinction phase and later relapse into cocaine-seeking behavior. Therefore, a potential for medication development targeting glutamate neurotransmission exists and is further supported by preclinical observations showing that dextromethorphan, actinically safe medication with glutamate antagonistic properties, reduced the absolute reinforcing properties of cocaine. Glutamate-dependent changes of synaptic efficacy within critical limbic circuits may therefore be part of the early events of the addiction cycle leading to the development of abuse and part of the long-lasting behavioral changes of the natural history of dependence, warranting further studies on pharmacological intervention at the glutamate level for the therapy of drug abuse. Glutamate-Mediated Neuroplasticity: Role In Amphetamine Addiction Marina E. Wolf, Ph.D. The Chicago Medical School Work from our laboratory and others has demonstrated that the development of sensitization requires glutamate transmission, suggesting mechanistic similarities to other forms of neuronal plasticity. More recently, we have shown that sensitization involves adaptations in glutamate transmission in the mesoaccumbens DA system. After repeated amphetamine, VTA DA cells are supersensitive to the excitatory effects of glutamate and AMPA. This is transient, present after 3 but not 14 days of withdrawal, and does not reflect increased expression of AMPA receptor subunits (measured at protein or mRNA levels). NAc neurons show subsensitivity to glutamate, NMDA and AMPA at both withdrawals. Decreased levels of mRNA and immunoreactivity for GluRl, GIuR2 and NR] subunits were found in NAc at the 14 day withdrawal time, which may in part explain the electrophysiological findings. We also examined PFC, a major source of glutamate projections to VTA. After 3 days' withdrawal, we found increased GIuR I expression and increased sensitivity of PFC cells to glutamate. This may contribute to transient increases in excitatory drive to VTA DA cells thought to mediate induction of sensitization. Increases in excitatory drive may also reflect effects of amphetamine within the VTA, since microdialysis studies have found a delayed increase in glutamate efflux after systemic or local amphetamine. This is prevented by agents that also prevent sensitization (MK-801 and SCH 23390), suggesting a link between increased glutamate efflux and induction. The link could reflect LTP-like mechanisms or mild excitotoxic damage to DA neurons, either of which could result in transient hyperexcitability. (Supported by DA09621.) NMDA ANTAGONISTS MODIFY OPIATE DRUG-SEEKING: PRECLINICAL AND PRELIMINARY CLINICAL FINDINGS 6 Piotr Popik, M.D., Ph.D. Institute of Pharmacology Palish Academy of Sciences, Poland Traditional "anti-addictive" pharmacotherapies are "drug-targeted," despite the fact that all of the drugs of abuse produce the same reinforcing (rewarding) effects and their long term administration results in drug addiction. However, the same inhibitory actions ofN-methyl-D-aspartate (NMDA) receptor antagonists on phenomena related to drug seeking behavior produced by all addictive substances suggest that glutamatergic receptors may be a final common pathway to all addictions and a possible therapeutic target. Presented are the data illustrating inhibitory effects of NMDA receptor antagonists on the expression and maintenance of physical and motivational aspects of morphine dependence in rats and mice. Next, the data concerning inhibitory effects of several (uncompetitive: memantine, glycine/NMDA: L-701,324 and competitive: NPC 17742) NMDA receptor antagonists on the acquisition, expression and extinction of morphine-induced conditioned reward are discussed. Brain areas sensitive to the treatment with NMDA receptor antagonists have been identified as the administration of NPC 17742 into the nucleus accumbens and ventral tegmental area produced the same, inhibitory effects on the expression of morphine-conditioned reward. These preclinical data are followed by presentation of preliminary clinical findings suggesting that the uncompetitive NMDA antagonist, dextromethorphan may facilitate detoxification from heroin and inhibit craving for this drug in human addicts. Despite the "bad reputation" of some NMDA receptor antagonists that produce ataxia, memory disturbances and psychotomimetic effects, some low affinity, highly voltage dependent uncompetitive antagonists like memantine and dextromethorphan as well as glycine/NMDA site antagonists may have beneficial effects on drug dependence and addiction. Therapeutic Potential Of NMDA Receptor Antagonists In The Treatment Of Alcohol And Substance Use Disorders Bisaga A, Popik P, Bespalov AY, Danysz W. New York State Psychiatric Institute, Unit # 120, 1051 Riverside Dr., New York, NY 10032, USA. bisagaa@pi.cpmc.columbia. edu Expert Opin Investig Drugs 2000 Oct; 9(10):2233-48 ABSTRACT Despite the fact that the use of alcohol, nicotine and other drugs is the major external factor contributing to mortality in industrialised countries, there are few medications available to treat alcohol and substance use disorders. [n recent years, major advances have been made in the understanding of the neurobiological basis for these disorders and these advances should lead to the development of new pharmacotherapeutics. Asubstantial amount of the research suggests that N-methyl-D-aspartate (NMDA) receptor neurotransmission contributes to mediating the behavioural effects of alcohol and other drugs of abuse. This research supports the therapeutic potential of NMDA receptor antagonists in alcohol and substance use disorders. In this paper the authors present their opinion on the goals and stages of pharmacological treatment of these complex psychiatric disorders. Available preclinical research using designs that model aspects of alcohol and substance use disorders is summarised, with an emphasis on research published in the last two years. In animal models, NMDA antagonists inhibit physical dependence and the reinforcing effects of a variety of abused substances. The ability of NMDA antagonists to inhibit tolerance to drug 7 effects and contribute possible antidepressant and anxiolytic effects are also important from the perspective of drug development. This review summarises the relevant clinical laboratory and treatment data. Finally, it presents the status of the current development of NMDA receptor antagonists and discusses candidates with the greatest potential for clinical development. Clinically Available NMDA Receptor Antagonists Memantine And Dextromethorphan Reverse Existing Tolerance To The Antinociceptive Effects Of Morphine In Mice Popik P, Kozela E, Danysz W. Institute of Pharmacology, Polish Academy of Sciences, Krakow. nfpopik@cyf-kr. edu.pl Naunyn Schmiedebergs Arch Pharmaco12000 Apr; 361(4): 425-32 ABSTRACT The tail-flick test was used to investigate the effects of chronic administration of the N-methyl-D- aspartate (NMDA) receptor antagonists, dextromethorphan, memantine and MRZ 2/579, on the development and reversal of morphine tolerance in mice in three separate experiments. Experiment 1 investigated the effects of NMDA receptor antagonists on the development of tolerance. Morphine (10 mg/kg for 6 days, twice daily) produced a 5.9-fold rightward shift of the cumulative dose- response curves. Co-administration of dextromethorphan, memantine or MRZ 2/579 between tests 1 and 2dose-dependently (5-] 0 mg/kg) inhibited the development of morphine tolerance. In experiment 2, in which the effects on the reversal were investigated, morphine-tolerant mice were treated b.i.d. for an additional 6 days (between tests 2 and 3) with vehicle+vehicle, NMDA receptor antagonist+vehicle, vehicle+morphine or NMDA receptor antagonist+morphine. Morphine-tolerant mice treated with vehicle+vehicle remained morphine tolerant, whereas this residual morphine tolerance was inhibited by administration of all three NMDA antagonists (each 10 mg/kg). Morphine- tolerant mice receiving vehicle+morphine injections demonstrated an unchanged degree of antinociceptive tolerance. In these mice, the co-administration of memantine and MRZ 2/579, but not dextromethorphan, resulted in the reversal of morphine tolerance. In experiment 3, memantine and MRZ 2/579 (10 mg/kg) inhibited the acute antinociceptive effect of morphine, but dextromethorphan did not. These data indicate that low-affinity, clinically available and/or therapeutically promising NMDA receptor antagonists may be used to inhibit ongoing morphine tolerance. Amphetamine Chemistry Powder methamphetamine is the hydrochloride salt form which is strongly hydrophilic (absorbs water from the air quickly). The HCI salt can be smoked as is. Crystal meth "Crystal Meth" or "Ice" refer to methamphetamine grown into crystals. Though many people believe that Crystal Meth is [he freebase form of methamphetamine HCI, this is wrong. Growing the HCI salt it into crystals makes it easier to smoke. Meth in visible crystals (rather than powder) is likely to be relatively pure as it is difficult to grow crystals from impure material. Methamphetamine freebase is an oil and is more rare on the street. 'Ice' is recrystalised methamphetamine hydrochloride, a potent stimulant. Ice will dissolve in water and break down to smaller particles. It generally takes the form of clear crystallized chunks. Ice induces a profound sense of euphoria in the user by blocking the reuptake, and stimulating the release, of dopamine and noradrenaline in the central nervous system. Problems from Using Amphetamines 8 Amphetamine use produces a wide range of short term and long term problems that may have serious consequences. Short-term problems from using amphetamines: • Disturbed sleep patterns • Loss of interest in friends, sex, or food • Itching, welts on skin Nausea, vomiting, diarrhea • Excessive excitation, hyperactivity • Shortness of breath • Moodiness & irritability • Anxiousness & nervousness • Aggressiveness • Involuntary body movements • Panic, suspiciousness & paranoia • Aggressive and violent behavior • Severe depression, suicidal tendencies Potential problems from long-term use of amphetamiues: • Fatal kidney and lung disorders • Brain damage Malnutrition & anorexia • Permanent psychological problems • Lowered resistance to illnesses • Liver damage • Stroke 9 Withdrawal symptoms from long term use of amphetamines: • Craving • Exhaustion • Depression • Mental confusion • Restlessness and insomnia • Deep or disturbed sleep lasting up to 48 hours • Extreme hunger • Psychotic reaction • Anxiety reactions Risks of injecting Amphetamines • The dose reaches the brain almost immediately, increasing the possibility of an overdose. • Impurities are introduced directly into the bloodstream that may cause septicemia and other infections. • Repeated injections damage the veins, leading to thrombosis and abscesses. • Sharing syringes can cause hepatitis and H[ V, the virus that can cause AIDS. Contraindications • Avoid taking amphetamines if you are currently taking an MAO. MAOs are most commonly found in the prescription anti-depressants Nardil (phenelzine), Parnate (tranylcypromine), Marplan (isocarboxazid), Eldepryl (1-deprenyl), and Aurorex or Manerix (moclobemide). Ayahuasca also contains MAOIs (harmine and harmaline). MAOIs and Methamphetamin are a potentially dangerous combination. Check with your doctor if you are not sure whether your prescription medication is an MAO. • Avoid taking amphetamines if you have any kind of heart disease (i.e. arteriosclerosis, hypertension) as Amphetamine use can be hard on the heart. • Avoid amphetamines if you are pregnant. Research shows that amphetamines used during pregnancy may decrease the birth weight of the baby as well as increasing the likelihood of cardiac abnormalities (heart problems) and possibly other birth defects. 10 . Avoid taking amphetamines if you are breast-feeding. Amphetamines are believed to be transferred through breast milk. 11 APPENDIX IV. NUTRITIONAL SUPPORT FORMULAS Meth DEFENSETM'...brain and nerve protection. L-Carnosine L-Carnosine is a dipeptide that neutralizes the damaging hydroxyl radicals that are generated by amphetamines. It also prevents DNA oxidation and blocks excitatory neurotransmitter toxicity, implicated in the neurotoxic process. L-Carnosine prevents lipid oxidation and cross linking (abnormal molecular bonds) which occurs when aldehydes like those formed during degradation of dopamine (and sugars) react with protein amino groups and polymerize. R-Lipoic acid R-Lipoic acid is the biologically active form of alpha Iipoic acid and up to 10 times more potent. It reaches higher blood levels than alpha Lipoic, crosses the blood brain barrier and boosts glutathione, the body's major antioxidant enzyme. R-Lipoic acid is one of the most important protective nutrients for amphetamine users. Alpha-Lipoic acid Alpha-Lipoic acid is a master antioxidant that protects cell membranes both in the aqueous and fatty bi-layers. It recycles Vitamin C and Vitamin E, CoQ10 and boosts glutathione. This is one of the most important protective nutrients for amphetamine users. Quercetin Quercetin is a catechol-type flavonoid that localizes near the surface of phospholipid bilayers of membranes and scavenges aqueous oxygen radicals. The actions of Quercetin prevent the consumption of Iipophilic alpha-tocopherol (Vitamin E) and the peroxidation of neuronal membranes. Calcium ascorbate Calcium ascorbate is a neutral salt form of vitamin C. Vitamin C is a major component of the body's antioxidant defense shield. The highest accumulation of Vitamin C is in the adrenal glands. The second highest is in the nerve terminals; the location where amphetamine induced damage occurs. Selenomethionine Selenomethionine is the most bioactive form of selenium, bound to the sulfur containing amino acid methionine. Selenium substantially reduces lipid peroxidation. Astaxanthin Astaxanthin is a new commercial antioxidant concentrated from an algae that anchors itself between the faUwater interface of cell membranes, the exact location where amphetamine induced free radicals exert their damage on serotonin and dopamine nerve terminals. Astaxanthin blocks lipid peroxidation. Next to R-Lipoic acid and Vitamin C this may exert more protection against amphetamine induced free radical oxidation than any other nutrient. Grapeseed Standardized Extract (90-95% proanthocyanodins) Grapeseed Standardized Extract contains proanthocyanodins; agroup of powerful flavonoid antioxidants that cross the blood-brain barrier, reduce inflammation and protect neurons from a variety of free radicals. Schizandra Standardized Extract Schizandra Standardized Extract (9% schizandrins) is a traditional Chinese herb that increases glutathione, a major component of the endogenous antioxidant shield. Schizandra antagonizes the adverse stimulatory properties of amphetamines. 12 Vitamin E (Vitamin E succinate, Mixed Tocopherols, Tocotrienols) Vitamin E is the official designation for alpha tocopherol, afat-soluble nutrient found in the diet in varying amounts. The term vitamin E is used to refer to all loco (mixed tocopherols) and trienol (tocotrienol) derivatives. The tocols are alpha, beta, delta and gamma tocopherols; the trienols are alpha, beta, delta and gamma tocotrienols. All of these substances have vitamin E activity and until recently it was thought alpha tocopherol was the most active form. As such, only official vitamin E activity (IU) is given to alpha tocopherol. Recent research however, suggests that gamma tocopherol is as biologically active as alpha tocopherol and that vitamin E products should contain tocopherols and tocotrienols for maximum benefit. Vitamin E succinate is the most active form of vitamin E and protects cell membranes from oxidation better than other forms of natural or synthetic vitamin E. Mixed tocopherols are the balanced and complete natural spectrum of tocotrienols enhancing antioxidant effects. Tocotrienols are apalm-oil derived antioxidant faction of vitamin E with more protective power than vitamin E alone. They work synergistically with Vitamin E and the other ingredients to protect cell membranes from oxidative stress of peroxyl radicals. Jitter EndT"'...jaw and muscle ease Calcium (Calcium Citrate & Calcium Malate) Stimulant drugs may produce a marginal drop in ionized calcium levels that produce a state of nervous and muscular hyperactivity. Taking calcium helps prevent the symptoms of tremor, muscle spasms, anxiety, tension and cramps from low calcium levels. Magnesium (Amino Acid Chelate) Magnesium ions modulate the tone of muscles by influencing the availability of calcium ions at various intracellular locations. Magnesium actively promotes smooth muscle relaxation, offsets calcium-dependent excitation contraction coupling and decreases cellular responsiveness to depolarizing stimuli. Supplementation of Magnesium eases muscular tension and cardiac over- excitation from the stimulatory effects of amphetamines. Pantothenic Acid (Vitamin BS from Calcium Pantothenate and Pantethine) Pantothenic Acid helps with the anxiety, tension, muscular cramps and stress from amphetamine use. DowntimeT"'...comedown, chill out and rest Vitamin B6 (pyridoxine HCI) Vitamin B6 (pyridoxine HCl) is a necessary co factor for the brain to assist in replenishing neurotransmitters. Tocotrienols Tocotrienols are palm-oil derived antioxidants with more protective power than vitamin E alone. They work synergistically with Vitamin E and the other ingredients in Downtime to protect cell membranes from oxidative stress. Schizandra Berry Schizandra is a traditional Chinese herb that increases the glutathione; a major component of the endogenous antioxidant shield. It also antagonizes the adverse stimulatory properties of amphetamines. 5-Hydroxytryptophan (SHTP) 5-HTP is the immediate precursor of serotonin, one of the neurotransmitters most adversely affected 13 by amphetamines. It helps diminish the post amphetamine "crash" and depression on subsequent days following amphetamine use. It helps alleviate headaches and muscle pain. SHTP may be beneficial for the acute aggressiveness and psychotic effects from amphetamine abuse. SHTP also has antioxidant properties and assists in recovery by promoting deep restful sleep and circadian rhythm synchronicity. Bacopa Monneiri Standardized whole plant extract (Bacosides A & B) Bacopa is an Indian adaptogenic herb with antidepressant and tranquilizing properties. It has been shown to have a positive effect on serotonin metabolism and may help normalize serotonin levels. Bacosides A & B repair damaged neurons by enhancing pre and post synaptic proteins. Bacopa prevents lipid peroxidation, boosts memory and reduces anxiety and fatigue without producing stimulation. All of these effects may benefit the amphetamine user during both short and long term recovery. Valerian Root Standardized Extract (Valerenic Acid 0.8%) Valerian Root Extract acts as a sedative and improves sleep quality without producing negative side effects. Trimethylglycine (TMG, Betaine) Trimethylglycine (TMG, Betaine) is methyl donor which boosts the COMT enzyme, responsible for elimination of Dopamine metabolites. St John's Wort Standardized Extract (Hypericin) St John's Wort acts as anon-selective reuptake inhibitor of monoamine neurotransmitters and fias been called an herbal "Prozac". The hyperforin in St John's inhibits the reuptake of monoamines, serotonin, dopamine and noradrenaline and the amino-acid neurotransmitters GABA and glutamate. Unlike standard reuptake inhibitors, St Johns Wort exerts this reuptake inhibition non-competitively by enhancing intracellular Na+ ion concentrations. These actions produce most of the anti-depressive effects St. John's Wort extract. Melatonin Melatonin is a powerful scavenger of hydroxyl radicals produced by amphetamines. It helps reset the biological clock disrupted by staying up all night. GOT"'...daytime energy and alertness Vitamin B6 (pyridoxine HCI) Vitamin B6 is a necessary cofactor for replenishing neurotransmitters in the brain. It is required to manufacture norepinephrine, dopamine, serotonin and phenyl ethylamine from Phenylalanine. L-Tyrosine L-Tyrosine is an amino acid precursor for catecholamines (phenethylamine, dopamine and norepinephrine) that activates the catecholamine energy production pathway. L-Tyrosine increases brain energy, combats stress maintains circadian rhythm synchronicity and reduces depressive symptoms. L-Phenylalanine L-Phenylalanine is an amino acid precursor to L-tyrosine that boosts catecholamines (phenethylamine, dopamine and norepinephrine), increases brain energy, combats stress and reduces depressive symptoms. DMAE Bitartrate DMAE helps remove metabolic waste products, scavenges hydroxyl radicals from brain tissue and 14 acts as a precursor for acetylcholine, the transmitter most associated with memory and learning. Schizandra Root Extract (standardized for Schizandrins-9%) Schizandra Root Extract is a traditional Chinese herb that increases the glutathione, a major component of the endogenous antioxidant shield. Schizandra antagonizes the adverse stimulatory properties of amphetamines. Ginkgo Biloba Standardized Leaf Extract (24%) Ginkgo Biloba is a brain penetrating antioxidant that increases cerebral blood flow and enhances cognitive functioning. Vinpocetine Vinpocetine is a nootropic derivative of the periwinkle plant that functions to boost memory, enhance cognitive functions and cerebral blood flow. 15