Loading...
HomeMy WebLinkAboutCOM 0078.006 1996-1998 h euet tlio-AgnCUltural ~KwCe9 lnc. II BOB-32B-9760 751131197 'J 2:1 B NM lJ 1/1 4 .,v„Q„ RE ~-IVED Tltne..-_'-' - By 7'-------------_' Department Counry Council of Health Services wrote a report on ten "poisonings" associated with GHB. The authors, Chin and Kreutzer, warned of GHB's "tremendous potential for abuse." They observed that "all interviewed patients reported a pleasurable sensation or a 'high.' Several of them...continued taking [GHB] because it made them 'feel good'." Apparently, the authors construed feeling good in and of itself as a potential threat to public health. Despite such dire language, the report acknowledged that "there are no documented reports of long-term [detrimental] effects. Nor is there any evidence for physiologic addiction." Of the ten "poisonings" reported, four involved "unknown doses," four featured the "coingestion" of other drugs, (usually alcohol), one involved unmedicated epilepsy, and another a history of grand mal seizures. Since alcohol and other central nervous system (CNS) depressants are not recommended with GHB, and because GHB is contraindicated for epileptics, such cases are not unexpected. Chin and Kreutzer acknowledge that the "more severe reactions...generally occurred when patients took an unmeasured dose, a particularly large dose, or several doses within a short period of time." Such problems are easily avoided by following the directions for GHB's use. Although the specific clinical details of these ten cases are too lengthy to go into here, one point needs addressing the use of the terms "coma" and "seizures" in descriptions of these cases. At a sufficiently high dose, GHB can cause clonus, a rapid, rhythmic contraction and relaxation of muscles which would be better described as muscle spasm or uncontrollable twitching than a seizure. GHB can also cause intense drowsiness, abrupt sedation, and deep sleep which is probably better described as unarrousability or deep sedation than coma. Vickers [1969] described ii as a "nontoxic coma," which blunts some of the inflammatory connotations of the term coma. 7g O` Coma~? Diw_.~..,,_ H11e loo. HCr+ Htef. '!'ot Prosented 4 ~v~ 7 19SI7 Fief. L?ate_ Feuat &o-Agricultural services Inc. 4 BOBJ2B-9760 i$1/31/97 a 2:19 PM ~ Z/16 Regardless of their alarmist tone, the authors confirm that "there have not been any reported deaths" and that "if product use is discontinued, f II recovery with no long-term side effects is universal." They conclude that "the prognosis for people who experience GHB poisoning is quite good" The degree to which the pleasant state of GHB euphoria may be psychologically addicting may not be fully appreciated. Anybody with known attraction or addiction to tranquilizers or alcohol should pay special heed to this possibility. In the few cases of GHB abuse that we have investigated, there were pre-existing use/abuse patterns with alcohol and/or tranquilizers. Ironically, it was GHB's lack of toxicity that led to increased frequency of use (numerous times per day) that characterized what can only be called classic cases of psychological addiction. Without the dehydration and CNS irritation of alcohol, or the side effects of tranquilizers, there was no incentive to moderate or curtail GHB use. Fortunately, few people seem to have such overwhelming attraction to the GHB state. Even Chin and Kreutzer minimize GHB's abuse potential by stating, "No investigator [has] reported any long-term adverse effects, addictive or dependent qualities associated with discontinued usage of the drug." Why Was GHB Banned? It seems likely, then, that at least some of the motives behind the 1990 FDA ban of GHB were other than those of public safety. Such a ban constitutes the only means of Federal control of a substance neither scheduled by the DEA nor approved by the FDA as a drug. In the absence of a genuine public-health concern, such control might have been motivated by a desire to protect the pharmaceutical industry (with which the FDA is closely intertwined) from competition from a safer, more effective and less expensive alternative to sleeping pills. Is it a coincidence that the FDA has also banned L-tryptophan, another nutrient that functions as a safe and Feuri &o-Apiwltural Ssrwceo Inc. 4 802-328-9760 iTi 1IJ1197 G~2:19 PPA ~ 3/14 effective sleep aid? ' What Are the Real Concerns? As with most substances, unpleasant and possibly dangerous side effects can be associated with excessive doses of GHB. A dose usually only about twice the amount required for relaxation or a prosexual effect can, as one user put it, "knock you out but fast." In this respect, GHB is probably comparable to alcohol: if you drink twice as much as you normally would, you probably wouldn't function very well. Despite its general safety and lack of toxicity, the safe use of GHB requires information, preparation, caution, and good judgment. In other words, follow the usage guidelines! How Does It Feel? Most users find that GHB induces a pleasant state of relaxation and tranquility. Frequent effects are placidity, sensuality, mild euphoria, and a tendency to verbalize. Anxieties and inhibitions tend to dissolve into a feeling of emotional warmth, wellbeing, and pleasant drowsiness. The "morning after" effects of GHB lack the unpleasant or debilitating characteristics associated with alcohol and other relaxation-oriented drugs. In fact, many users report feeling particularly refreshed, even energized, the next day. The effects of GHB can generally be felt within five to twenty minutes after ingestion. They usually last no more than one and a half to three hours, although they can be indefinitely prolonged through repeated dosing. The effects of GHB are very dose-dependent. Small increases in the amount ingested lead to significant intensification of the effect. Higher levels feature greater giddiness, silliness, and interference with mobility and verbal coherence, and maybe even dizziness. Even higher doses usually induce sleep. Feum Bio-,agiculturol Services lnc. ?808-328-9760 i$~ip1/97 62:20 PM X414 The Actions of GHB in the Body GHB temporarily inhibits the release of dopamine in the brain. This may cause increased dopamine storage, and later increased dopamine release when the GHB influence wears off [Chin and Kreutzer, 1 992]. This effect could account for the middle-of-the-night wakings common with use of higher GHB doses, and the general feelings of increased well-being, alertness and arousal the next day. GHB also stimules pituitary growth hormone (GH) release. One methodologically rigorous Japanese study reported nine-fold and sixteen- fold increases in growth hormone 30 and 60 minutes respectively after intravenous administration of 2.5 grams of GHB in six healthy men between the ages of twenty-five and forty [Takahara, 1977). GH levels were still seven-fold higher at 120 minutes. The mechanism by which GHB stimulates growth-hormone release is not known. Dopamine activity in the hypothalamus is known to stimulate pituitary release of growth hormone, but GHB inhibits dopamine release at the same time that it stimulates GH release. This suggests that GHB's GH-releasing effect takes place through an entirely different mechanism [Takahara, 1977]. At the same time GH is being released, prolactin levels also rise. Serum prolactin levels increase in a similar time-dependent manner as GH, peaking at five-fold above baseline at GO minutes [Takahara, 1977]. This effect, unlike the release of GH, is entirely consistent with GHB's inhibition of dopamine. Other compounds which lessen dopamine activity in the brain (such as the neuroleptic Thorazine) have been shown to result in prolactin release. Although prolactin tends to counteract many of the beneficial effects of GH, the sixteen-fold increases in GH probably overwhelm the five-fold increases in prolactin. Faust Bio-Agricultural 5srviceo lnc. ~80B-32B-9760 $1/31/97 62',21 PM p5/14 GHB induces "remarkable hypotonia" (muscle relaxation) [Vickers, 1969]. It is now gaining popularity in France and Italy as an aid to childbirth.HB causes "spectacular action on the dilation of the cervix," decreased anxiety, greater intensity and frequency of uterine contractions, increased sensitivity to oxytocic drugs (used to induce contractions), preservation of reflexes, a lack of respiratory depression in the fetus, and protection against fetal cardiac anoxia (especially in cases where the umbilical cord wraps around the fetus' neck) [Vlckers, 1969; Laborl>:, 1984]. GHB is completely metabolized into carbon dioxide and water, leaving absolutely no residue of toxic metabolites [Vickers, 1 969; Laborit, 1972]. Metabolism is so efficient that GHB can no longer be detected in urine four to five hours after it is taken by injection [Laborit, 1964]. GHB activates a metabolic process known as the "pentose pathway" which plays an important role in the synthesis of protein within the body [Laborit, 1972]. It also causes a "protein sparing" effect [Laborit, 1964] which reduces the rate at which the body breaks down its own proteins. These properties, along with GHB's effect on growth hormone, underlie its common use as an aid to muscle-building and fat loss. Anesthetic (large) doses of GHB are accompanied by a small increase in blood sugar levels, and a significant decrease in cholesterol. Respiration becomes slower and deeper. Blood pressure may rise or fall slightly, or remain stable, but a moderate bradycardia (slowing of the heart) is consistent [Vickers, 1969; Laborit, 1964]. A slight drop in body temperature also occurs [Laborit, 1964]. GHB also stimulates the release of acetylcholine in the brain [Gallimberti, 1989]. GHB and Sieep GHB has been called "almost an ideal sleep inducing substance" [Smart Drugs Feuer Bio-Agricultural Ssrvicse Ina iQ 808]28-9760 $1131197 G 2:21 PM ~ 6116 fi fi t II, p. 245]. Small doses produce relaxation, tranquility and drowsiness which make it extremely easy to fall asleep naturally. Higher doses increase the drowsiness effect and decrease the time it takes to fall asleep. A sufficiently large dose of GHB will induce sudden sleep within five to ten minutes [Laborit, 1964]. Many other hypnotics interfere with various stages of the sleep cycle thus preventing the body from achieving a complete and balanced session of rest and recuperation. The most remarkable facet of GHB-induced sleep is its physiological resemblance to normal sleep. For' instance, GHB sleep is characterized by increased levels of carbon dioxide in the arteries, as in normal sleep [Vickers, 1969]. During normal and GHB sleep, the CNS continues to be responsive to "noxious stimuli" (pain and other irritations), a factor which sets limits on GHB's uses in anesthesia [Vickers, 1969]. GHB facilitates both REM (rapid eye movement) sleep, and "slow-wave" (non-REM) sleep, the stage of sleep featuring increased release of growth hormone [Laborit, 1972]. And unlike the unconsciousness induced by other anesthetics, that triggered by GHB does not feature a systemic decrease in oxygen consumption [Laborit, 1 964). The primary disadvantage to GHB's use as a sleep aid is it's short-term influence about three hours. During GHB's influence, sleep is deeper and more restful, but after the GHB has worn off, people have a tendency to wake up. The higher the dose, the greater is this tendency. Some have called this pattern the "dawn effect" and have speculated that it is related to the release of stored-up dopamine. Some people minimize this effect by taking minimal doses of GHB. Others take advantage of this effect by getting a couple of hours of work done in the middle of the night. Still others choose to take a second dose of GHB to sleep for another three hours. It should be noted that not everyone can be put to sleep by GHB. We have spoken to three men who have never achieved sleep even with the doses normally used for such purposes. In addition, Takahara [1 977] reported that one of the six men in the growth hormone study cited above remained conscious even though he had received two and a half grams of GHB Feuat&o-Ayiculturel 5srwceo lnc. 4BOB-32B-9i60 ~$1131l97 G2:22 PM ~il14 intravenously, a dosage which rendered the rest of the participants unconscious. GHB, Alcohol and Alcoholism GHB shows great promise in the treatment of alcoholism. In Europe, one of its primary uses is to relieve withdrawal symptoms, cravings, and anxiety among alcoholics. UL In laboratory rats addicted to alcohol, withdrawal symptoms closely resemble those exhibited by humans, including tremors, convulsions, and hypersensitivity to sound. All of these symptoms were blocked by sufficiently high doses of GHB [Fadda, 1989]. Administration of GHB has also been found to prevent alcohol consumption among rats that voluntarily ingest alcohol [Fadda, 1989; Gallimberti, 1989]. In a rigorous, double-blind, placebo-controlled study conducted of human alcoholics, "nearly all withdrawal symptoms disappeared within two to seven hours" after administration of GHB. On asevere-moderate-mild-or-none scale, withdrawal symptoms remained below moderate during the entire period. The only side effect observed was slight, occasional, and transient dizziness. The researchers concluded, "the results clearly indicated that GHB is effective for the suppression of withdrawal symptoms in alcoholics" [Gallimberti, 1989]. Other Uses of GHB GHB has a decades long track record of use as a general anesthetic. Administered intravenously, an anesthetic dose of GHB is in the range of 4-5 grams fora 1 50-pound person [Vickers, 1969]. Its advantages as an anesthetic include low toxicity, relatively few contraindications, slowing of the heart rate without loss of blood pressure, the absence of irritation to the veins with intravenous administration, muscle relaxation, absence Fauot Bio-Agricultural Ssrvinslnc. 4808-326-9760 [$1131/97 62:23 PM ?6/14 of respiratory depression (usually), reduction of body temperature (hypothermia), and various protective and anti-shock actions [Labor 1964]. However, GHB can almost never be used in anesthesia withoutthe additional administration of other drugs [Vickers, 1969] because it does not produce complete surgical anesthesia except in children [Laborit, 1964]. The autonomic nervous system remains active during GHB-induced anesthetic coma, and thus the body continues to respond to surgical stimuli through increases in heart rate, blood pressure, and cardiac output, as well as through sweating, peripheral vasoconstriction, vocalization, and reflex muscle action [Vickers, 1969]. Local anesthetics or other drugs which suppress these responses must therefore also be used, like the way a dentist or orthodontic surgeon might use Novocaine to kill pain along with nitrous oxide to render a patient unconscious. It is suspected that part of GHB's protective function involves a slowing of the metabolism of brain cells, thus reducing their requirements for oxygen and glucose [Chin and Kreutzer, 1992; Artru, 1980]. Another factor in GHB's anti-shock capability may be the marked vasodilation induced in the liver and kidney, thus increasing blood flow to those vital organs. GHB's efficacy for treating anxiety has been positively demonstrated in tests involving schizophrenic subjects [Laborit, 1964]. Its sedative properties have earned it a role as a psychotherapeutic adjunct [Vickers, 1 969]. It has also been used to assist the process of "abreaction," or the release (usually through verbalization) of repressed emotion [Vickers, 1969]. Unlike other "anxiolytic" (or anti-anxiety) drugs, GHB's effect is non-toxic. Furthermore, GHB's reduction of inhibitions, its tendency to encourage verbalization, and the typical lack of fear during the GHB experience would seem to provide an ideal context for the verbal exploration of difficult emotional territory during therapy. GHB and Sex Fewt Bio-Agnculturnl Ssrvicsa lne. 4608-328-9760 $11J1/97 62:23 PM C9/74 Scientists and doctors have traditionally been reluctant to ascribe aphrodisiac properties to any substance, although this tendency may have abated somewhat in recent years. It is a testament, then, to the power the GHB's sexual effects that they were clearly acknowledged in the scientific literature by 1972. Dr. Laborit wrote: "A last point should still be mentioned: the [GHB] action on Man which could be called 'aphrodisiac.' We cannot present any animal experiments on this subject. However, the oral form has now been sufficiently used so that, as generally agreed, no doubt can subsist as to its existence." We have identified four main prosexual properties: 1) disinhibition, 2) heightening of the sense of touch (tactility), 3) enhancement of male erectile capacity, and 4) increased intensity of orgasm. Perhaps the foremost prosexual property of GHB is disinhibition. Some users suggest that GHB's other sexual benefits are secondary effects, made possible (or at least amplified) by this loosening of psychosomatic constraint. A number of people have commented that this disinhibition is particularly marked among women. Women often report that GHB makes their orgasms longer and more intense, as well as more difficult or time-consuming to achieve, especially at higher doses. As with its other effects, GHB's impact on female orgasm seems highly sensitive to small adjustments in dosage. Legal Status and Availability GHB is not approved in the US and has been banned from over-the-counter sale by the FDA. GHB has not yet been "scheduled" as a "controlled substance" by the DEA, and therefore simple possession is not illegal. GHB continues to be sold to legitimate laboratories and scientists for research purposes, but selling it specifically for human consumption, especially while making Faum Bio-Agiculturel Ssrvicea Inc 4 BOB-32B-9760 I$~1131/97 G 2:24 PM ? 10/14 claims about its health benefits, is a violation of current FDA regulations and policy. In some European countries, GHB is an approved drug available by prescription. Local doctors, pharmacists and government bureaucrats should be able to provide country-by-country specifics. GHB is growing in popularity and seems to be widely available in the underground "gray market." Since most of the GHB available through such channels is of the "bootleg" variety, manufactured by non-professional "kitchen" chemists, concerns about quality and purity should be kept in mind. Caveat emptor (buyer beware)! Safety Issues As has been emphasized, the overall safety of GHB is well-established, and no deaths attribu*_able to GHB have been reported over the thirty year period that this compound has been in use [Vickers, 1969; Chin and Kreutzer, 199Z]. In fact, as of 1990, only forty-six adverse reactions had been reported in the United States surely constituting only an infinitesimal fraction of actual usage, all followed by rapid and complete recovery [Chin and Kreutzer, 1992]. Unlike a large proportion of other drugs including alcohol and even Tylenol, GHB has no toxic effects on the liver, kidney or other organs [Vickers, 1 969; Chin and Kreutzer, 1 992]. One program of sleep therapy using six to eight grams daily for a period of eight to ten days produced no side effects. Vickers [1 969] even reports that doses as high as twenty to thirty grams per twenty-four hour period have been used for several days without negative consequences (don't do this at home kids!). In the Canadian studies of narcolepsy mentioned earlier, the nightly use of two to six teaspoons (one teaspoon equaling roughly 2.5 grams) for several years resulted in no reports of long-term adverse effects, or problems with issues Fewt Bio-Ag~iculturel Services Int. ~ 608-329-9760 $1131/97 ~ 2:25 PM 11/14 of addiction or dependence. In one of these studies, one patient inadvertently ingested fifteen teaspoons without adverse consequence "other than deep sedation and headache the next day" [Chin and Kreutzer, 1 992). And in France, sub-anesthetic oral doses were used by "a large number of patients for about six years" without untoward effect [Laborit, 1972). Side Effects According to Dr. Gallimberti [1989), the action of GHB is "without serious side effects." Some research programs have reported no side effects at all. Nonetheless, it's clear that some minor side effects can occur. Those most commonly experienced are drowsiness, dizziness, nausea, and sometimes vomiting. As asedative-hypnotic, GHB's effects bear some similarity to those of alcohol and tranquilizers. GHB not only "may cause drowsiness" like these other drugs, it will almost invariably do so. Ataxia, or incoordination, can also be a side effect of GHB. Do not drive a vehicle or operate dangerous machinery while under the influence of GHB. As mentioned, clonic movements (muscle contractions or "seizures") have been observed during the onset of GHB-induced sleep. Headache is sometimes reported. A moderate slowing of the heart rate is a consistent effect, and small changes in blood pressure can take place. Likewise, orthostatic hypotension (a sudden drop in blood pressure caused by standing up quickly) has also been reported. Sometimes this is experienced as brief dizziness, and rarely people can briefly lose consciousness. At very high doses, cardiac and respiratory depression can occur. Sufficiently large doses of GHB can cause sudden sedation and loss of consciousness. Do not take such doses except when reclining on a bed or sofa. It is also a bad idea to take such doses in the presence of people who don't know anything about GHB. You may alarm your family or friends and wake up in an emergency room (with a large medical bill). F Bust Bio-AyicWtural Services Inc. 4 806-328-9760 :31 /31 /97 r,~2:26 PM _,12/14 More unusual and extreme reactions have included diarrhea, lack of bladder control, temporary amnesia, and sleep-walking. Whatever side effects may be noted, they are often much more severe when GHB is combined with other central nervous system depressants [Chin and Kreutzer, 1992, Gallimberti, 1989; Takahara, 1977; Vickers, 1969]. Contraindications r Although contraindications for GHB have been described as "remarkably few" [Vickers, 1 g69], those who suffer from any of the following conditions should not use GHB: severe illness of any kind, epilepsy, eclampsia (convulsions), bradycardia (slowed heart-beat) due to conduction problems [left-bundle-branch-block is an example of conduction difficulty], Cushing's syndrome, severe cardiovascular disease, hyperprolactinemia, and severe hypertension [Gallimberti, 1989; Vickers, 1969]. Severe alcoholism is sometimes mentioned as a contraindication for GHB [Smart Drugs II, page 244] even though GHB has been used quite successfully in the treatment of withdrawal symptoms. The explanation for this seeming contradiction probably lies in the likelihood that severe alcoholics may combine GHB with alcohol. GHB should not be used with benzodiazepines ("minor tranquilizers" such as Valium and Xanax), phenothiazines ("major tranquilizers" like Thorazine and Stellazine), various painkillers (barbiturates and opiates), alcohol, anticonvulsants (Dilantin and phenobarbital) and even many over-the- counter allergy and sleep remedies without direct medical supervision. Dosage Determining the ideal dose is probably the trickiest aspect of working with Feuat Bio-Agricuiturnl Sxvicea Inc ~ 90Q-32B-976° ITi 1131/97 .:d:27 PPd 13/14 GHB. The amount required for a given level of effect will vary from person to person, and the dose-response curve is fairly steep. Overestimating the dose can have consequences ranging in seriousness from ruining you plans for the evening to waking up in the emergency ward as a result of panic on the part of concerned-but-uninformed friends or relatives. Once you have found the levels that give you the effects you desire, they will remain consistent. Tolerance to GHB does not develop. However, recent (not current) alcohol consumption may decrease the effect of a given dose of GHB [Fadda, 1989]. Most people find that a dose in the range of 0.75-1.5 grams is suitable for prosexual purposes, and that a quantity in the range of 2.5 grams is sufficient to force sleep. Some people think that GHB might lower potassium levels and should therefore be taken with potassium supplementation. Some research papers have identified such an effect, others have not. If you want to play it safe, take a potassium supplement equal to 10% of the GHB dose. This article is excerpted and adapted from a chapter of a forthcoming book, Better Sex Through Chemistry available from CERI and Smart Publications, PO Box 4667, Petaluma, CA 94955 (phone: 707-769-8078, fax: 707-769- 1062, CompuServe: 71221,1427). References: Artru AA, Steen PA and Michenfelder JD. gamma-Hydroxybutyrate: Cerebral Metabolic, Vascular, and Protective Effects. J Neurochemistry. 35(5): 1114-9, November 1980. Chin MY, Kreutzer RA and Dyer JE. Acute poisoning from gamma- hydroxybutyrate in California. West J Med (United States). 1 56(4): 380-4, April 1992. Fewt&o-Agricultural Services lac QBOB-326-9160 1$1/31197 G2:2i PPd ~'_'1U14 Fadda F, Colombo G, Mosca E and Gessa GL. Suppression by gamma-hydroxybutyric acid of ethanol withdrawal syndrome in rats. Alcohol and Alcoholism [Great BritainJ. 24(5): 447-51, 1989. Gallimberti L, Gentile N, Cibin M, Fadda F, Canton G, Ferri M, Ferrara SD and Gessa GL. Gamma-hydroxybutyric acid for treatment of alcohol withdra•,val syndrome. The Lancet, 787-9, 30 September 1 989. Kleimenova NN, Ostrovskaya RU and Arefolov VA. Effect of sodium hydroxybutyrate on the ultrastructure of the cross-striated muscle tissue myocytes during physical exercise. Byull Eksp Biol Med 88(9): 358-61, 1979. Laborit H. Correlations between protein and serotonin synthesis during various activities of the central nervous system (slow and desynchronized sleep, learning and memory, sexual activity, morphine tolerance, aggressiveness, and pharmacological action of sodium gamma- hydroxybutyrate). Research Communications in Chemical Pathology and Pharmacology 3(1): January 1972. Laborit H. Sodium 4-Hydroxybutyrate. Int J Neuropharmacology [Great Britain). 3: 433-52, 1964. Ostrovskaya RU, Kleimenova NN, Kamisheva V, Molodavkin GM, Yavorskii AN and Boikko SS. Effect of sodium hydroxybutyrate on functional biochemical and morphological indexes of physical working ability. Farmakol Regul Protsessov Utomleniya [Moscow, USSR] 39-56: 112-17, 1982. Takahara J, Yunoki S, Yakushiji W, Yamauchi J, Yamane J and Ofuji T. Stimulatory effects of gamma-hydroxybutyric acid on growth hormone and prolactin release in humans. J Clin Endocrinal Metab 44: 1014, 1977. Vickers MD. Gamma-hydroxybutyric Acid. Int Anaesthesia Clinic 7: 75-89, 1969. heum tlio-Agnculturai Servmeo Ina Y 808-328-9760 X1/31197 U 2:30 F'Pd ~ 1/11 i My Testimony on County of Hawaii country Bill 28 to Ban GHB by Robert H. Faust Ph.D. The banning of GHB by Hawaii County is unconstitutional. GHB is a beneficial nutrient and not a drug, and it is used medicinally by hundreds of people on this tsland. It is legal to possess and a M.U. can write a prescrtpttonftor it and it can be legally obtained. Passing this bill will turn hundreds of people into "criminals", even those with a prescription and legitimate medical use. GHB is widely used and prescribed by Doctors in Japan, Europe and most of the rest of the world. Wtth this law tourists from other countries bringing GHB into Hmvaii would be criminals here. How can this right be taken away when it is a legal nutrient and beneficial health aid in the rest of the world, including the U.S.? The Proposed Bill #Z8's stated justification for the ban is simply not true. As stated, and I quote, "GHB has been determined to have deleterious effects on human health, including depression of the respiratory system." This is completely untrue and easy to refute. It has never been deleterious to human health, quite to the contrary it is a beneficial nutrient that has helped millions all over the world. It is a prescription medicine used to treat depression, cure alcoholism and many other diseases. The claim to respiratory depression has no basis in fact and is opposite to the published scientific literature which says "GHB may protect the brain and heart during conditions which depress vital functions or decrease oxygen availability". The other lie is that GHB decreases oxygen to the brain causing unconsciousness. This is also totally untrue, as GHB flas shown to do Lust the opposite and works by by tnhibtting the release of dopamine from nerve endings which creates a higher level of dopamine in the brain cells.Dopamine a normally occurring neurotransmitter and the body's natural on ti depressant. This is why GHB is not a drug, because it's effects come from a natural release of dopamine. There are not direct effects from GNB, the effect is from the bodies own dopamine. Nor has there ever been a death caused by GHB in the 30 years it has been to use worldwide. To say that tt has killed people or can kill is another lie. It is totally non-toxic even a 100X dose. Alcohol and opiates do kill, and any cases of death or poison have come from the combination of GHB and alcohol or heroin, so why not ban alcohol because this is what causes death and date rape in teens. GHB in pure form is incapable of causing death or injury so flow can death be nttributed to GHB when only the alcohol or opiates are capable of causing death. The scientific data cited at the end of this report are clear evidence to the lack of truth in this bill as stated above. The County Council should at least base a new ordinance on truth and get the rue ~a rtyn~ oe tore procccu viy. nits iuw to yotny w ~u he urvuy peopie'a rtyins and violate the state constitution concerning rights of privacy and the U.S. Constitution in terms of rights to life, liberty and the pursuit of happiness, as it is not noiv illegal under U.S. law. By making this illegal is only protecting the alcohol, pharmaceutical arld illegal drug industry. Making it illegal will put profits into the Illegal drug dealers hands and an unknown product strength and contaminated bathtub products could cause problems. At leost get the facts right before our rights are taken away and we are made into criminals because we want to increase our health and longevity by taking something that is PROVEN harmless and beneficial and is in use by millions in civilized countries across the r^iorid. I can supply scientific data that easily refutes the lies in this proposed ordinance. This law is a sham and reflects an Inquisition mentaltty, a by- Feuot&o-l.giculturnl Ssrwcas lnc 1Q BOE-32B-9760 $1131197 62:31 PM 02111 product of the war on drugs. This is not a drug, it is a legal medicine. There has been no documented death from GHB and the use of GHB as a date rape drug is a myth with no basis. I would bet that in Hawaii County not one case of date rape with GHB has ever occurred. GHB can not be used effectively as a date rape drug because tt won't work on a full stomach and eating a ltttle food or candy or coffee rapidly negates the effects. Alcohol, on the other hand has always been the date rape drug of choice and has caused the death of hundreds of teens on this island. Do we need to make alcohol illegal? We tried that in the 20's and it failed - why do we think prohibition will solve this so called problem! GHB wtll be come more popular and available AhItK the ban! I believe the motivation behind this bill is to protect the alcohol beverage and Prozac market, because the first dose of GHB I took totally eliminated a 30 years craving for alcohol and I haren't wanted any since that first dose 7 months ago. GHB is the world's best natural anttdepressant and people are able to give up Prozac, and they use GHB in Europe to get people off of heroin and cocaine, many people in Hawaii are using it for the same purpose. Who's side is the Country Council really on? It is the job of the County Council to protect the rights of the citizens, not limit their rights. This law, if passed, will popularize GHB and put it into the hands of criminals and take it away from Doctors. Na law against drugs has ever stopped the availability, but usually enhances it. The Country Council is playing Into the hands of drug dealers and the police-state apparatus that operates to Hawatt. This btll is clearly wrong and motivated by powerful interests and not the desire to protect the utrrena, nhu wrll he ~unrerteU rntu ~r unrnuls ri rt pua~ea. the irony of the situation is that in a state with already over 349 of the people in prison are there for drug offenses, this non-drug nutrient can get people off of drugs arld be beneficial to all. If date rape is a problem then there are rape laws already. If the country find the it needs to prevent date rape with various drugs, it is clear that that using any drug including alcohol for attempted rape should be made a crime, assault with a drug or attempted rape. Punish the guilty not the 99.99a innocent, honest people who use GHB for health purposes on a daily basis on this island. This is an amazingly Draconian step for the county to make, when the only use of GHB has been beneficial to society on this island. I am not willing to see my tax dollars used to put more people into prison for the effect of their own nurotransmitters. The county should not become "brain police" and take mvay choices for Doctors. Safety Issues (From Joy and Mogenthaler 1995) As has been emphasized, the overall safety of GHB is well-established, and no deaths attributable to GHB have been reported over the thirty year period that this compound has been in use [Vickers, 1969; Chin and Kreutzer, 199Z]. In fact, as of 1990, only forty-six adverse reactions had been reported in the United States surely constituting only an uifinitestmal fraction of actual usage, all followed by rapid and complete recovery [Chin and Kreutzer, 1992]. Unlike a large proportion of other drugs including alcohol and even Tylenol, GHB has no toxic effects on the liver, kidney or other organs [Vickers, 1969; Chin and Kreutzer, 1992]. One program of sleep therapy using six to eight grams daily for a period of eight to ten days produced no side effects. Vickers [1969] even reports that doses as high as twenty to thirty grams per twenty-four hour period have been used for several days without negative consequences (don't do this at home kids!). In the Canadtan studtes of narcolepsy menttoned earlier, the nightly use of two to six teaspoons (one teaspoon equaling roughly Z.5 grams) for several years resulted in no reports of long-term adverse effects, or problems with issues of addiction or Paum &o-Agiwltvral Ssrvicu Inc ~ BOB-328-9760 $1131/97 G 2:R PPd 03/11 dependence. In one of these studies, one patient inadvertently ingested fifteen teaspoons without adverse consequence "other than deep sedation and headache the next day" [Chin and Kreutzer, 1992]. And in France, sub- anesthetic oral doses were used by "a large number of patients for about"{ six years" without untoward effect [Laborit, 1972]. The Demonisation of Gamma-OH in North-America: A New Form of Inquisition By Dr. Clautle Rltal, Blologlst In Swlizerland antl GHB researcher. GHB Is a prescrlptlon nutrient In Swltz. We are living since the I960's,in a world of INQUISITION against alt psychotroptc molecules which generate some forms of pleasure. This modern Inquisition started in America as a puritanical expression of American society to ban pleasure from life. This Inquisition should be fought against as it has halted the development of scientific research on the mind. 30 years of research have been lost because Americans imposed an INTELLECTUAL EMBARGO on many research involving the mind. For instance, all research on the hallucinogens was stopped, thanks to this perverse Inquisition. This intellectual embargo should be lifted and scientists and laymen should fight for that. No Inquisition can be accepted to the scientific field. American society has systematically demonised all psychotropic molecules which can give pleasure. (Even alcohol was demonised but this demonisation was not successful and was abandoned when it was noticed that the creation of Al Capone and other similar people was a consequence of this demonisation!) This is sheer madness and should strongly be opposed. The right to use our brain in the way we want should be a FUNDAMENTAL RIGHT OF MAN and put in the Declaration of Human Rights. I hope this goal will be achie~~ed in the future. One of the reasons rvhtch motivated me to write what you are reading is that GAMMA-OH has been in use, for knowledgeable people in Europe, for decades. Now it reached the USA, unfortunately, because, as usual, some American INQUISITORS are trying to demonise this very useful molecule. These pseudo-scientific AYATOLLAHS should be put back in their middle-ages churches. In Iran, ayatollahs are condemning sex. In America, the American ayatollahs want, desperately, to control the use of our mind. This is an intolerable situation. Progress is made through freedom and knowledge, not under the guidance of any ayatollah. Let us make a grassroots movement against all these ayatollahs! Ayatollahs and similar Inquisitors should go back into their dungeons!!! The Middle-Age is over. The quest for Freedom is a never-ending quest. It is surprising that you do not need, yet, a prescription for Champagne, wines and other alcohols in North-America because if alcohol were judged by pharmaceutical standards it would have been banned a long time ago. Gamma-OH in France and North-America Gamma-OH ryas invented by Dr. Wermuth, in France, for Dr. Henri Laborit who is the father of chlorpromazine and modern psychopharmacology. Wermuth created gamma-hydroxybutyrate in I96I in the search of a GA BA analog which could, readily, penetrate the blood-brain barrier. Gamma-OH soon went to the market as an hypnotic which could be obtained with no medical prescription. The french, until I started to study this molecule, were unable to classify it under any class. For sometimes,it ryas an hypnotic inducing a form of sleep very similar to normal sleep, then it became a pre-anesthesiser, etc. About IS years ago, I finally discovered that Gamma-OH was, in fact, a molecule to be classi ried under the novel class of the Sociabi lasers, together with its butyrolactone form which is, readily, transformed into Gamma-OH in the blood by a non specific lactonase. In fact,butyrolactone is a pro-drug giving rise to gamma-hydroxybutyric acrd. Gamma-OH has a recognized pertpheric oxytocinergic action while its central oxytocin properties are still to be Faust B~o-AgnculturelSwvicea lac. 4900-329-9760 X1131197 62:33 PM ?411 4 demonstrated but seem very likely. Gamma-OH is known in France through the many books of Henri Laborit and his conferences! Laborit always praised the properties of Gamma-OH and, as France is definitely uui u puriiunicul auciety Uunniny pleusure frum existence, Gunuuu-OH liua ulwuya been available, even though its stimulates pleasure. Laborit always advocated the general use of Gamma-OH in society, like butter or milk! Why? Because it takes away your stress, makes you more positive towards life, suppresses selectively, like a kind of "psychological diode" your painful feelings, stimulates your sociability and makes you more tender, more loving, more concerned of others. Also you become keenly aware that you ha~~e only one life and that life should be a quest for happiness. Gamma-OH makes you realize how much you need others (not something for businessmen and militaries or gangsters!!!) and this is a highly positive thing. I always knew that when Gamma-OH would arrive in puritanical North-America it would, one day, be demonised...Unfortunately for North-Americans, the ayatollahs of the pleasure INQUISITION have struck again and banned gamma-hydroxybutyrate! Laborit just died recently, a few months ago at an old age. Sometimes, he used to joke that Gamma-OH made him live longer as he would suppress his stress with this "drinkable gold", in case of need!!! He always said that his two greatest discoveries were chlorpromazine and Gamma-DH but he never fully realized that Gamma-OH could open a nely era in the management of depression and anxiety. He never fought in order to promote the study of the psychotropic effects of Gamma-OH, he never discovered that Gamma-OH was the first molecule of a novel class: the sociabilisers. He just enjoyed Gamma-OH with his friends, while conducting other researches. All the people who have surrounded Laborit have, naturally, more or less been exposed to Gamma-OH! I was lucky to be one of these people. Gamma-OH is still a crude medicine. It should be properly studied and better analogs should be invented. The use of sociabilisers may have tremendous effects on our societies, reducing intraspecific aggression and enhancing cooperation instead of competition. Gamma-OH is a convivial medicine as it shows you that you need others to be happy. Long term on and off use seems to make you more immune to stress and dysphoria, more loving towards people in general, more active in your life as it stimulates your enthusiasm because you are so aware that life can be a fantastic thing, everyday.T he general use of sociabilisers may be a temporary solution for the intraspecific aggressivity of the human kind. Can Gamma-OH and novel analogs reduce wars, at last? I leave this question opened for your reflection. I will summarize now, the psychotropic profile of Gamma-OH, something which I have done in a lengthy paper many years ago,in French. Description of the Psychotropic Effects of Gamma-OH (I985) Gamma-OH has the following properties: A. It stimulates sociability which means that you feel like communicating with other people in all ways: emotional, intellectual, sexual. And from this communication you feel a very strong and deep happiness. Why? Because, probably, Gamma-OH inactivates a system which, normally, controls our base- ltne level of paranoia. Gamma-OH seems to dissolve paranoia and induce trust. It would had been very interesting to give Gamma-OH to both Mr.6ush and Saddam Hussein before they started their silly war! B. Gamma-OH gives you a strong desire to TOUCH others, physically and psychologically. C. Communication becomes extremely gratifying as you feel you want to become close to people, not to isolate yourself. D. Gamma-OH induces a strong sense of BEAUTY. Everything looks so beautiful, so VIVID, so enjoyable, so pleasurable, so important, so "deep". C. The perception of movement is enhanced. Feust Biu-Ay'iculturel3v viuslnc. '~B00-J20-9760 $1/Jt/97 ~2.JJ PM r^~5/11 D. Three-dimensional perception is enhanced and vision seems more clear, better than usual. GHB Information- from "Better Sex Through Chemistry" by John Morgenthaler & Dan Joy reviewed by Ward Dean M. D. GHB, or gamma-hydroxybutyrate, is a normal constituent of mammalian biochemistry. It is found naturally in every cell in the human body. In the brain, the highest amounts occur in the hypothalamus and basal ganglia [Gallimberti, 1989]. GHB is found in even greater concentrations in the kidney, heart, skeletal muscles, and brown fat [Chin, 1992]. It is believed to be a neurotransmitter, although the )ury is still out as to whether it exhibits all of the properties requiretl for fulidlment of this function Chin, 1 992]. II is both a metabolite and precursor of the inhibitory neurotransmitter GAGA (gamma-aminobutyric acid), to which it bears a close relationship of chemical structure. GHB, however, does not act on GAGA receptor sites [Chin, 1992]. GHB was first synthesized about thirty years ago by H. Laborit, a French researcher interested in exploring the effects of GABA in the brain. Direct administration of GABA would not be effective for this purpose because it does not cross the blood-brain barrier. Laborit's alternative was to administer GHB, which does cross the blood-brain barrier, and some of which, once inside the brain, metabolizes into GABA [Vickers, 1969]. Independently of its relationship to GABA, however, GHB turned out to be a drug with its own range of effects. It has since been widely used and researched, finding applications in obstetrics and general anesthesia. and in the treatment of alcohol withdrawal syndrome, narcolepsy, insomnia, and other arenas. During the 1980s, GHB was widely available over-the-counter in health-food stores, purchased largely by body-builders for its ability to aid in fat reduction and muscle-building. In the last few years it has been gaining popularity as a "recreational" drug offering a pleasant, alcohol-like, hangover-free "high" and potent prosexual effects. The Demonization of GHB If the long-lived media truism holds "all publicity is good publicity", then the recent history of GHB might serve as a case in point. Most of those who've heard of GHB probably first became aware of it by way of a widespread rumor-unsupported by the subsequent coroner's report-it played a role in the death of actor River Phoenix in the Fall of 1993. An article in the December 6th issue of Newsweek reported this piece of hearsay-despite its alarming nature-inspired a groundswell of demand for GHB in the nightclub drug underground. Newsweek reported: "The hunt was on. 'I'd never heard of GHB before. No one in New fork had,' said a Manhattan drug user. 'This month it's the only drug"' [Rogers, 1993]. The facts were widely misrepresented in the popular media, which vastly, exaggerated GHB's so-called "dangers"-and usually left them unspecified. Fur instance, Newsweek sensationally described GHB as "an obscure and dangerous steroid substitute occasionally gulped down by 1Nest Coast thrill seekers" [Rogers, 1993]. (Although it can be used to increase muscle mass, GHB is neither a "steroid" nor in any other way "steroid-like," as it was often rendered in even more distorted reports.) A guide to aphrodisiacs published in 1993 made a vague reference to "dangerous side effects" in the first sentence of its description of the drug [1^Jatson,1993J. In 1992, a report written by epidemiologist Ming-1'an Chin and Richard A. Kreutzer, MD, both staff members of the California Department of Health Services, warned sternly of GHB's Faust&o-Agricultural Services lnc. ~BOB-329-9760 $'1/31/97 62:34 PM D6/11 y "Vemendous potential for abuse." Nonetheless, the authors went on to conclude: "There are no documented reports of long term [detrimental] effects. fJOr is there any evidence for physiologic addiction." (See "Addictive potential" in the "Safety Issues" section.) [Chin, 1992]. NJhat, then, was the source of their concerns By way of explanation for "sounding the alarm," Chin and Kreutzer offered only the following statement: "All interviewed patients reported a pleasurable sensation or a'high.' Several of them expliatly noted one reason they continued taking the drug was because it made them feel good."' It would seem ilia authors consVued "feeling good'-in and of itself-as a threat to the public health in whose service they were ostensibly employed. For whatever reasons, the FDA banned the over-the-counter sale of GHB on November 8th, 1990 [Chin, 1992]. Setting the Record Straight More than twenty-five years of scientific research into the effects of GHB-right up to 1989, one year prior to the FDA ban-clearly contradicts GHB's U.S. media image as a menacing poison. It will become clear as this chapter unfolds numerous beneficial physiological effects-in the absence of significant negative physiological consequences-are well-documented in the scientific literature. Additionally, there is strong anecdotal evidence for psychological and sexual benefits. In fact, prior to the FDA ban, GHB's high degree of safety was practically taken For granted in the suentific literature. A 1964 report lists "very low toxicity' as one of the "principle elements" of the GHB's pharmacology [Laborit, 1964]. A 1969 summary of its anesthetic uses called GHB "a truly nontoxic hypnotic," repeatedly emphasized its "lack of toxicity," and cited evidence which demonstrates "no toxic effects on the liver and kidney" [Vickers, 1969]. In describing the way GHB is metabolized, a 1972 paper mentions "the absence of any need of detoxication by the organism" [Laborit, 1972]. As recently as 1989, this scientific picture of GHB's benign nature remained unchanged. One study on its uses in treating alcohol withdrawal in humans notes "GHB action seems to be without serious side effects." The same report's almost off-hand reference to the "safety of GHB" shows how well-established this property of the drug had become [Gallimberti, 1989]. Worst-case scenarios Chin and Kreutzer's 1992 document, summarizing ten cases of "Acute poisonings associated with gammahydroxybutyrate in California," thus represented a radical departure from the previous consensus. (It is worth noting "poisoning" was never defined in this paper.) Four of the cases reported involved "unknown doses." Four featured the "coingestion" of other drugs, usually alcohol. One involved unmedicated epilepsy and another a history of grand mal seizures - conditions specifically contraindicated for GHB. Chin and Kreutzer acknowledged the "more severe reactions... generally occurred when patients took an unmeasured dose, a particularly large dose, or several doses within a short period of time." The two most severe incidents of adverse reaction out of the ten included in Chin and Kreutzer's document are by far the most extreme cases encountered in the wide-ranging research on GHB performed for this book. Both of these cases involved the ingestion of central nervous system depressants in addition to GHB. (Combining GHB with central nervous system depressants, such as alcohol or tranquilizers, is generally considered inadvisable.) They are included here as "worst case scenarios" to guarantee the complete spectrum of GHB's potential effects is Faust BicAyicultural Services lnc 4909-329-9760 ~~113t/97 62:35 PMT ?7l11 represented. One of Chin and Kreutzer's case histories relates [he story of a "previously healthy 39-year old Caucasian woman." During the period of her experimentation with GHB, she was also using Vicodin, a prescription painkiller containing a central nervous system depressant. She "experienced numbing of the legs, dizziness, and a tight chest" after her first dose of GHB (consisting of one teaspoon) purchased from ahealth-food store. Nonetheless, this woman resumed taking GHB three weeks later. For one month thereafter, she took one-half teaspoon of GHB on a near-daily basis without negative consequence. However, after the last of "three or four doses" consumed on a day during which she departed from this regimen, "she experienced a 'high'...the 'jabbers' (pressured speech and ebullience), intense drowsiness, confusion, trouble breathing, and uncontrollable twitching in her arm. Her children found her and reported her eyes were rolled back, her body was tense, and'-although no mention is made as to how the children were able to make such adetermination-"she was hallucinating." She was admitted to a hospital for a night, where, despite the disturbing nature of the ~ymptom~ recounted above, it was determined "her pulse, blood pressure, and respiration were normal." Her physical exam was deemed "unremarkable except for alternating wakeful and sleepy states with irregular leg twitches." Her case history concludes: "she experienced a full recovery with no lasting symptoms." The second case involves a "28-year old Caucasian woman" who took an unspecified quantity of GHB in addition to some mixed drinks" at a nightclub. The report continues: "she experienced confusion and uncontrollable shaking followed by a seizure and then coma. A witness states she was banging her head on a wall before becoming unconscious. Patient vomited and was suctioned before transport. Paramedics reported she alternated between combativeness and unresponsiveness as she was taken to the emergency room. She arrived with good respiratory effort but with long apneic periods [lapses of breathing)." Her recovery was complete, with "no adverse side effects" since the incdent. Several points regarding this case are worth keeping in mind. The woman's blood alcohol level was assessed at the hospital and was found to be quite high. Furthermore, it seems likely from the context of Chin and Kreutzer's presentation the GHB may have been acquired at the nightclub where the incdent took place. Under such circumstances, and in light of the severity of the woman's reaction, the possibility must be taken into account the substance in question may in fact not have been GHB at all. Lastly, the report of "seizure and then coma" need not be the great cause for alarm as it at first seemed. In any case, this woman's "coma" must have been rather short-lived in order for her to be able to behave in a "combative" manner towards paramedics. Another of Chin and Kreutzer's cases is worthy of mention not for its severity but for its mildness. In this incident, a "39-year-old Caucasian man" took a rather large quantity of GHB (one and a half teaspoons, or nearly four grams) along with twenty-five milligrams of diphenhydramine hydrochloride (another central nervous system depressant, marketed over-the-counter both for allergies and as an aid to sleep). The only reported symptom is he became "lethargic." This effect hardly seems disturbuig given he had just taken two known hypnotics (although it apparently disturbed his wife, who called 91 1 and had him taken to an emergency room- from which he was released in two hours). It is especially difficult to Fnuat Bio-AgriculturelSwvmea lnc. ~BOB-32B-9760 01131/97 G~2:36 PM°, ~9l11 iy. understand why this case is included among so-called "poisonings." Despite their alarmist tone, the authors acknowledge "there have not been any reported d aths" and "if the product use is discontinued, full recovery with no long-term side effects is universal." They concluded "the prognosis for people who experience GHB poisoning is q' ite good" Summarizing the results of Canadian research into GHB as a treatment for narcolepsy, authors Chin and Kreutzer further undermine their own stated position on GHB's abuse potential by reporting: "Several researchers consistently describe the beneficial clinical effects One Canadian researcher has noted adverse effects no worse than abrupt sedation, ataxia [lack of coordination], sleepwalking, unarousability, and decreased inhibition in normals [meaning persons free of narcolepsy or other major disease conditions] taking two to six teaspoons twice a night for several years. One patient who accidentally took fifteen teaspoons on one occasion suffered no adverse reactions other than deep sedation and a headache the next day. No investigator reported any long-term adverse effects, addictive or dependent qualities assocated with discontinued usage of the drug." (See"Addictive potential" in the Safety section.) Chin and Kreutzer acknowledge "Researchers working with narcoleptics consider GHB a relatively harmless and effective drug" [Chin, 1992]. "Comas and Seizures" or 'Sleeping and Twitching"? Negative press on GHB frequently mentions the possibility of "seizures' and "coma." These are certainly frightening words-until their meaning is closely examined in context. With regard to GHB, "coma" refers merely to the state of deep sleep or unconsciousness induced by higher doses, from which people often cannot be aroused until the GHB has worn off. This "coma" is of short duration-one to two hours-and provides the basis for GHB's use as a general anesthetic. In fact, one researcher even described it as a "nontoxic coma," [Vickers, 1969] defusing much of the fear inspired by the use of the word coma. This state of "coma" could just as easily-and accurately-be described as one of "unarousability" (the key term in the definition of "coma") or "deep sedation." In Fact, these are the words used by Chin and Kreutzer themselves in their summary of research results from Canada, quoted above. Their phrases "adverse effects no worse than unarousability" and "no adverse reactions other than deep sedation" would have quite a different impact if the word "coma" was inserted in place of its synonyms. In fact, the alternate phrases created thereby "adverse effects no worse than coma" and "no adverse reactions other than coma"-appear blatantly self-contradictory. Nevertheless, there is no significant difference here in meaning, only in choice of terminology. The point here is the words chosen by the major media and other sources in public discourse about GHB have carried a substantial negative load. Like "coma", the Nrord "seizure" becomes much less frightening when it is replaced by alternatives which are considerably less "loaded" but nonetheless equally accurate in terms of GHB's actual observed side effects. The "seizures' sometimes associated with GHB are usually Faust Bio-Agriculturpl services Ire. ~ 808-328-9760 I~'1/31l97 G~2:37 PM 119111 i. c,' described as being of the "clonic" variety [Vickers, 1969; Chin, 1992]. This word refers to "a forced series of alternating contractions and partial relaxations of a muscle' [Webster's 7th New Collegiate], as in one researcher's statement that "During the onset of [GHB] coma..: random clonic movements of the limbs or face are frequently seen." This activity could alternatively-and correctly-be described as "muscle spasms' or "twitching.' Thus, adire-sounding warning such as "a large dose of GHB can cause coma and seizures" could be translated into the relatively innocuous statement that "a sufficient dose of GHB may result in a few Bows of deep sleep from which die uses cannot be aiuused, and the enuy inlu unconsciousness may be accompanied by some twitching of the face or limbs." Why Was GHB Banned? It seems likely, then, at least some of the motives behind the 1990 FDA ban of GHB were other than those of public safety. Such a ban constitutes the only means of Federal control of a drug neither scheduled by the DEA nor approved by the FDA for prescription use. (The latter status requires considerable expenditure of time and money on the part of a pharmaceutical firm in an investment which can usually be recovered only when the company in question holds an exclusive U.S. patent. In the case of GHB, no such patent exists.) As physician Ward Dean has put it, "the FDA doesn't like drugs people use just to'feel good' or unwind after a hard day's work. In fact, the aphrodisiac properties of GHB may well have been part of the motivation for the ban" [Dean, 1993]. What Are the Real Concerns? The purpose of this section has been to make clear the dangers widely atVibuted to GHB have been greatly exaggerated. 1^Jere this not the case-and were not the benefits offered by GHB both substantive and well-documented, a drug so controversial, and so ambiguous in legal status, would not have been included in this book. Such an argument having been made, it must be emphasized, as with most substances, unpleasant, although not ultimately dangerous, side effects can be associated with GHB. Furthermore, there is one potentially significant hazard which must be taken into account when self-administering GHB: a sufficient dose-usually only about twice the amount required for a pleasant prosexual effect-can, as one user put it, "knock you out, but fast." (To keep things in perspective, remember alcohol-a drug of exponentially greater toxicity and health nsk than GHB-and many approved prescription drugs can also function in this manner.) Durk Pearson and Sandy Shaw's book Life Extension: A Practical Scientific Approach features a chapter entitled "Is There Anything Perfectly Safe7" The entire text of this chapter consists of a single capitalized word: "NO" [Pearson & Shaw, 1982]. This succinct statement applies to GHB. In spite of its general safety and lack of toxicity, the intelligent use of GHB requires preparation, information, care, caution, and good judgment. These issues will be fully discussed in the sections called "Safety Issues" and "Self-Administration." References Artru, AA; Steen PA; Michenfelder JD. Gamma-Hydroxybutyrate: Cerebral metabolic, vascular, and protective effects. Journal of f~leurochemistry. 35(5): p.114-9, November 1980. Cash, CD. Gammahydroxybutyrate: An overview of the pros and cons for it being a neuro- Feum Bio-Agricultural Sxvices Inc. iQ 809-329-9760 X1/31/97 G2:aB PM p 10/11 , transmitter and/or a useful therapeutic agent. Neuroscience and BiobehaWorat Reviews. 18(2): p.291-304, 1994. Chin, MY; Kreutzer RA; Dyer, JE. Acute poisoning associated with gamma-hydroxybutyrate in California. (Nest J Med (UNITED STATES). 156(4): p.38O4, Apr 1992. (California Department of Health Services, Environmental Epidemiology and Toxicology Branch, Emeryville 94608.) Cooper, JR; Bloom, FE; Roth, RH. The biochemical basis of neuropharmacology, 2nd edition. New York, London, Toronto: Oxford University Press, 1974. Dean, W; Morgenthaler, J; Fowkes, S. Smart Drugs II.' The Next Generation. Petaluma, California: Smart Publications, 1993. ~ Fadda, F; Colombo G, Mosca E; Gessa GL. Suppression by gamma-hydroxybutyrir. acid of ethanol withdrawal syndrome in rats. Alcohol & Alcoholism. 24(5): p.447-51, 1989. (Printed in Great Britain.) h-owkes, S. (~&A. Smart Urug News. Z(L): March 1993. (UEKI, PUti 4UL9, Menlo Park, LA, 9'1026 '1029, tc1:~15 321 237, fax:~15 323 386'1) Gallimberti, L; Gentile N; Cibin M; Fadda F; Canton G; Ferri M; Ferrara SD; Gessa GL. Gamnia- hydroxybutyric acid for treatment of alcohol withdrawal syndrome- The Lancet. p.787-9, 30 September 1989. Kleimenova, NN; Ostrovskaya RU; Arefolov VA. Effect of Sodium hydroxybutyrate on the ultrastructure of the cross-striated muscle tissue myocytes during physical exercise. Byull Eks-p Biol Med. 88(9); p.358-61, 1979. (Inst Pharinacol, Moscow USSR.) Laborit, H. Correlations between protein and serotonin synthesis during various activities of the central nervous system (slow and desynchronized sleep, learning and memory, sexual activity, morphine tolerance, aggressiveness, and pharmacological action of sodium gamma- hydroxybutyrate). Research Communications in Chemical Pathology and Pharmacology. 3(I): Jan 1972. Laborit, H. Sodium4-hydroxybutyrate.lnt. J. Neuropharmacology. 3:p.433-52,1964. (Pergamon Press- Printed in Great Britain.) Ostrovskaya, RU; Kleimenova NN; Kamisheva V; Molodavkin GM; Yavorskii AN; Boikko SS. Effect of sodwm hydroxybutyrate on functional biochemical and morphological indexes of physical working ability. Fannakot Regul Proisessov Utomieniya (Moscow USSR). 39(56): p.l12-17, 1982. Pearson, D; Shaw, S. Life Extension: A Practical Scientific Approach. New fork: Wamer Books,1982. Pearson, D; Shaw S. Durk Pearson & Sandy Shaw's Life Extension Newsletter. Z: October 1988. Rogers, P; Katel P. The new view from on high. Newsweek. 6 December 1993. Foust 9io-l+gricuitural Services Inc. 4 808-328-9760 X1131197 2:39 PPd ~ 11/11 , Takahara, I; Yunoki S; Yakushiji W; Yamauchi J; Yamane J; Ofuji T. Stimulatory effects of gamma-hydroxybutyric acid on growth hormone and prolactin release in humans. J Clin Endocrinal Metab. 44: p.10-14, 1977. Vickers, MD. Gammahydroxybutyric acid. Int Anaesthesia Clinic. 7: p.75-89, 1969. Watson, CM. Love Potions: A Guide to Aphrodisiacs and Sexual Pleasures. Tarcher/Perigee, 1993. The above is from books by John Mogenthaler and Ward Dean M.D. Bio Of Ward Dean, M.D. and the Center for BioGerontology Dr. Ward Dean graduated from the U. S. Military Academy, West Point, New York. Ht served as an infantry officer for six years, during ~Mhich lime ht was an instructor at the U. S. Army Ranger School and combat advisor to the Vietnamese Rangers. He received his M. D. degree from Han Yang University, Seoul, Korea. During seven more years of sere-ice, Dr. Dean participated in a number of classtfied misstons as Flight Surgeon for the Delta Force, America's top- secret counter-terrorist unit. Or. Dean is now the Medical Director of the Center far BioGerontology in Pensacola, Florida. He has published more than 70 articles and reviews in professional journals, and is the author of Biological Aging Measurement--Clinical Applications [1988], co-author of The Neuroendocrine Theory of Aging and Degenerative Disease (with the late Professor Vladimir Dilman) [1992], and co-author of Smart Drugs & Nutrients [1990] and Smart Drugs II [1993]. Fewt eio-AgneWturel Serwcee lne. 4806-J26-9760 $1/31/97 ( 2:46 NM L71/B GAMMA•OH (Gamma-Hytlroxybutyrate): The First Authentic Antl-Depressant ClaudeRAat,Bbloglst(S UISSE) Introduction Recently, the whole world was brainwashed by Lilly Company with a severe bllizkrleg propaganda on an allegedly "new" antl-depressant called Iluoxetlne or PrOZaC. Lilly Iled when It presented PrOZdC as being the "first" marketed anti-depressant of a "new" generation! The Ilrst marketed anti-depressant of Asira, In Europe, as NOrmUtl, and develOpped In Scandinavia. Zlmelltllne Was IOIIOwed by INDALPINE In France (Upst SBoO (Je) and then by FLUVOXAMINE In Holland (Floxylral). Only FLUVOXAMINE withstood the test of time as zlmelldlne and Indalplne had some unwanted side~ etl@C15, even though Indalplne proved to be a remarkable molecule IOr some treatment resistant persons. Fluvoxamine was marketed In Europe perhaps 8 YEARS BEFORE Its amerlcan equivalent Prozac! Even though It did not reach the US market because American pharmaceutical companies COUId not yet compete with Europeans... So Fluvoxamine was blocked to reach the US market until Americans could develop properly their own SSRI! Thls Is what amerlcan businessmen, usually, call "talrplay". By tloing so, millions of Americans did not benellt of Fluvoxamine and, surely, many Ilves could had been saved In America by FIUVOxamine.... AIdS, these Ilves WERE NOT saved because 01 the greed and Unfair practices of the amerlcan system towards novel medications Invented elsewhere. Millions of depressed Americans were dented access to Fluvoxamine, for commercial purposes only. This Is a moral perversion of the ethic of medicine. The sad Irony of this situation Is that Fluvoxamine Is superior, In all respects, to Prozac! For Instance, Prozac has some unwanted side-ellecis which Iluvoxamine does not have. Moreover, Iluvoxamine can SUPPRESS the slde•ettects of Prozac! So why use Prozac at all? Thls Is due to the fact that Lilly was very successful In launching a bllizkrleg propaganda campaign, superbly Ignoring our european product antl Its anlerl0rity. Moreover, the Idea of developping a SpeCItIC SerOtOnln reUpiake blocker was a european Idea and not an amerlcan Idea as Americans did not believe In the antl-depressant etiecis of serotonln but favoured noradrenallne... Prozac, frequently, Intluces Insomnia and heatlaches while It Is also sllghly sub•halluclnogenlc. Fluvoxamine, on the contrary, promotes sleep antl alleviates headaches. Also no subhalluclnogenlc phenomena can be detected. One reason why Prozac has these side-etiects Is because Prozac should, preferentially, Indirectly activate serotonln 5•HT2A receptors. Activation of these receptors Is a common ettect of the hallucinogens. Normally the TYPICAL SSRIS have antl•halluclnogenlc properties, meaning that they are not eltectlve at 5-HT2A receptors, contrary to Iluoxetlne which Is,ihus,an ATYPICAL SSRI. All the unwanted side-ellecis ol, let say a dose of 40 mgr of Prozac are abolished by an equlpotent dose of l0O mgr of tluvoxamine. Fluvoxamine also suppresses rapidly moral suffering (the Hard-core of depression) and suicidal Ideation while Prozac Is slower on onset. So the big commercial problem for amerlcan companies was that tluvoxamine was Invented not In America but In Europe and marketed about 8 years before they could SELL their own similar products.... Moral perversion, as I said, and totally unacceptable. Just recently was tluvoxamine accepted. No comments! What Is Interesting Is that In Switzerland Prozac's name has been changed Into Fluctlne, probably for commercial reasons. In addition to Iluvoxamine, cltalopram, paroxeilne and ser(rallne are available here. So Swiss people seem to have been less stupid In front of the bllizkrleg for tluoxetlne! Another very good european antl•depressant of which Americans have no equivalent Is AMINEPTINE (Survector) and, naturally, Amineptine Is not marketed In the USA even though It Is a dopaminerglc anil- depressant antl dopaminerglc antl-depressants are known to be more etiectlve In treatment resistant pattenls. Why Americans have not yet marketeU dopaminerglc antl•depressants remains an enigma. As Japanese say: "kaoua SB}=01 (JSO"for amerlcan patients, meaning amerlcan patients are most unfortunate (because money always comes before morality In the US). Intact, the activation of dopamine seems more crucial In order to obtain a cast antl•tlepressanl ettect than modulation of other neurotransmitters as the iunctlon of dopamine In the CNS Is to metabolically activate neuronal systems. Fewt eio-Agriculture! Ssrvicsa Inc. ~ BOA-329-9760 $1131!97 62:47 PM 11219 Dopamine Is an ubiquitous metabolic activator while serotonin has, most frequently, the opposite action (this Is calletl the DopaminelSerotonln balance hypothesis; there Is also a SerotonlNSerotonln balance hypothesis. This hypotheses states that the global metabolic action of serotonin Is the ratio of activation o1 serotonin receptors diminishing tlopaminerglc activity to those serotoninerglc receptors which Inc~,ease dopamine activity, such as the 5•HT2A receptors). Concerning novel anti-depressants the French.have Invented the very Ilrst Selective serotonin reuptake Accelerator (SSRA): Tlanepilne. Tlaneptine acts In an opposite way as the SSRI but, still, Instead of Inducing depressions cure depressions! In the Halve untlerstanding of serotonin In depression such a tact cannot be understootl... We will explain later on why tlaneptlne Is, In tact, an ant!-depressant and even the FIRST authentic serotoninerglc anti-depressant! i So we are left with the morally unacceptable tact that America has banned superior european antl- tlepressants because the same equivalent protlucts tlld not yet exist In America. This behaviour of the amerlcan pharmaceutical companies has been systematic. For Instance a good anti-depressant Invented In Italy antl called TRAZODONE was, recently, Imitated In America with the creation of NEFAZODONE (Serzone) In order to get more money! And another novel antl-depressant Inventetl In Europe, VILOXAZINE (the first selective noratlrenallne reuptake Inhibitor), apparently neverreachetl [he US market, etc, etc. Gamma-OH Is the French brand name for GHB Now I will come to a iantastlc antl•tlepressant called GAMMA-OH (brand name), and which could save lots of tlepressed people Ii If were marketed to that effect. GAMMA-OH has never been studied as an anti- depressant because of what Is called the IMIPRAMINOMIMETIC DOGMA .This dogma states that antl• depressants can only be found by those pharmacological methods which have been applletl to discover rlmlpramine, the first alleged antl•tlepressant! Clearly, Ines tlogma Is nonsense and It has hampered research On antl•depre55ani5 since more than 30 years, lorbltltling the tllscovery of true last-acting anti- depressants. This dogma also states that It Is not possible to achieve an antl-depressant etiect Immetllalely but that one has to sutler for weeks before starting to !eel better with medication... What Is tunny with this grotesque dogma Is that Imlpramine was tllscovered by chance! At that time nobody bellevetl In Imlpramine except one lone researcher whose obstinate perserverance was rewartletl... GAMMA-OH (or gamma-hydroxybutyrate, a quite simple molecule with a vast array of psychotroplc properties) has proved that this statement was sheer nonsense. GAMMA-OH was discovered by a Irlend of mine (the late Dr.Henrl Laborlt who Introduced the use of chlorpromazine In psychiatry around 1952) In 1967 In France antl since that time sclentlsis were unable to discover some rather exiraortllnary properties of this molecule on depression, anxiety and soclablllty! Why? Because nobotly seriously studletl the psychotroplc eitecls of this molecule until I startetl to tlo the Job. This stems from the tact that most "sclentlsis" are not real scientists or savants but only civil servants: they work to earn their food, not to really discover nature's mysteries. These civil servants (called "tonctlonnalres", In French, a simpler word) work Ilke soldiers In an Army, not Ilke true researchers because they are not authentic researchers! They have Ideas and Interests of "tonctlonnalres" not of savants. For some years GAMMA-OH was used as an hypnotic In France but people complained that they did not sleep long enough with that and would awake too early In the morning! Then, according to Henri Laborlt, came May 1968 and Gamma•OH was considered subversive: It thus became a medicine only available on prescription. And of course a medicine which can enhance soclablllty Is, Indeetl, subversive because soclablllty does not go well along with business and merchants! To be a good merchant you need, psychdl0gIC211y, to block your sociable leelings: you should cease to consider other Human beings as human beings but Just as things which can bring you money and power. You have to learn to be selfish, that Is non-sociable! GAMMA•OH Is a remarkable molecule because It can suppress depressive Ideation and anxlely sometllnes within less than 30 minutes. It also seems to be Immediately active on the most severe and treatment resistant forms of tlepresslon. Because of such remarkable properties I usetl to call, Jokingly, GAMMA-OH "Or Potable", In French, which means "potable gold"! Indeed a molecule which can block yuur Uepresslun and sulcklal iueas, anxlely, elc, In such au elnclenl way Is as precWUS as yulu because II Feum Bio-Agnculturel Services inc. X806-328-9760 !$1/31197 G2:4B PM (,'3l9 ~ , can save your Ilte. GAMMA•OH saved my own Ilte many times when all other antl-depressants tailed. For years I sutle~~'rred of depressive eplsotles which tlltl not react to conventional "anti-depressants". Why? Because, In tact, most antl•depressanls (an anti-depressant Is also called a THYMOANALEPTIC. A ihymoanaleptlc Is a molecule which stimulates mood) are not really "anti-depressants" per se but THYMOANESTHESISERS. A ihymoanesiheslser Is a molecule which ANESTHESISES emotions and which, thus, blunt leelings. For Instance, II you glue "antl•depressants" to, let say, two lovers together you will notice That their love leelings towards one another become anestheslsed, blunted... Clearly, a molecule which blunts rewarding emdtldn515 detinltely not an authentic anti-depreSSant but rather, a "mind Xylocalne" (xylOCalne Is an anesiheslser used for hemorholds and all kinds of slmllar pains!). A Ihymoanestheslser takes away a part o1 your pelsonailty and makes you a bit slmllar to people suttering from negative schizophrenia. On the contrary It you administer gamma•hydroxybutyrate to a pair o1 lovers you will notice that It will enhance their love ieelings because If stimulates soclablllty. Prozac and Fluvoxamine and all SSRI are,ln lact,thymoanesiheslsers not authentic thymoanaleptlcs.They block depression by SUPPRESSING or reducing leelings, euphoric or tlysphorlc and you become a k!ntl of satlstled zombie! Another ihymoanesiheslser, which Is not a SSRI, and which blocks quite spectacularly love leelings Is MAPROTILINE, a slightly motlltletl irlcycllc.ln my opinion, maprotlllne Is psychotoxlc because It can Induce Indliterence In otherwise normal subJecis. No more suttering but no more real happiness. On the contrary, AMINEPTINEdoes not suppress emotions but It does not Intensity Them either. So amineptlne Is anantl-depressant but 51111 not the Ideal Ihymoanaleptic. Now we can come back to tlaneptlne. Why tlaneptlne Is an antl-tlepressant? We have seen that serotonlnerglcs alleviate depression by REDUCING emotions. Enhancing serotonln neurotransmisslon, In tact, anesiheslses emotions. Thus It Is logical that reducing serotonln neurotransmisslon (In some unknown brain areas ) should STIMULATE the expression of emotions. This Is demonstratetl by tlaneptlne and by some tryptophane hydroxylase Inhibitors such as MDA or MDMA. What Is more Interesting Is that even though MDMA selectively destroys the axons of the raph SBq=01 (Jnucleus the behavioural consequences of that are, apparently, non-existent (But damages can be demonstrated In MDMA treated persons through Fluvoxamine). Further reducing serotonln neurotransmisslon In MDMA subJecis having a depressive episode, with tlaneptlne, can suppress depression In these people! nne person who had taken MDMA at high doses for 5 years and who became depressed reporetl that, under tlaneptlne, he would ieel Ilke under MDMA!!! Ot course n0 normal patient has ever reported an MDMA-like eeect with tlaneptlne... As tlaneptlne activates emotions Instead of reducing them TIANEPTINE CAN THUS BE CONSIDERED AS THE FIRST AUTHENTIC SEROTONINERGICANTI-DEPRESSANT. But who knows tlaneptlne In North-America? Nearly nobotly because the French are very, very bad businessmen not Ilke those of Lilly! French can Invent good novel products but are not good at propaganda. Lilly Invented a mediocre product but persuaded everybody that their product was Ine best ever... Ii the French had been so clever as Lilly, Amineptlne, for Instance, would have Invaded the whole world years and years ago, not to speak about tlaneptlne! The French have Invented many novel anti-depressant but did practically nothing to spread them. Some of these are:m SBgE (Jlloxamine(CI SBgE (Jlaq, minaprlne(Cantor), Vlloxazlne(Vlvalan), not to speak about amineptlne and tlaneptlne! What's more they Invented (by chance!) Gamma-OH and never discovered that this was a very novel anti- depressant! Knowledgeable people Just used Gamma-OH Ilke Champagne or BeauJolals but tlltl nothing more... Gamma-OH stayed for the elite antl the elite was not Interested to study the peculiar psychotroplc elleCiS Ol ih15 m010001e! Alter years of reilexlons on depression I realised, one tlay, that a real antl-depressant should STIMULATE SOCIABILITY. \Nhy? Because depression Is, basically, a detect of soclablllty. Depression Is a state of LOWERED SOCIABILITY and when natural soclablllty Is lowered In a human brain (tor Instance through competition, etc) then this brain starts to sutler morally. Experience has shown that when soclablllty Is ENHANCED then depression vanishes. GAMMA-OH Is the first molecule discovered which does Just this: It STIMULATES SOCIABILITY. This is vwlly GAMMA-OH Is calletl a SOCIABILISER. Feum Sip-Agnculturpl Ssrvicsa Ina ~ 60Q-32B-9760 ZL 1131197 ,'2:49 PM = 4/B , GAMMA-OH Is hypoiheslsed to cure depression by stimulation of brain OXYTOCIN neurotransmisslon. ~xytOCln Is a very Important molecule responsible 01 sOClable states, 01 the maternal InsllnCt and 01 all activities related to the malntalnance o1 Ilte. For Instance,Qx ytocln Is Involved In sex and orgasm and orgasm Intensity seems dlrecllV linked to enhanced oxytocln neurotransmisslon. GAMMA-OH suppresses depressed Ideation with amazing rapl(1Ity.YOU may feel uncurable dysphorla wlih suicidal Ideatl0n, anxiety, etc, and think that no medicine Or no one Could help you Until you try_gamma• hydroxybutyrate! Alter you may_JUSI think how CraZy_y0U were and leel how Ille I5 beautiful and deserves IO be Ilvetl and enJOyetl! amnia-hytlrOxybUtyrate strongly stimulates the desire to be and 10 remain alive despite unfavourable circumstances. No conventional so-called antl•depressant does that. Gamma-OH Is the fastest anti-depressant known and can,oiten,suppress severe depressive Ideation within Just hours while conventional thymoanesiheslsers take WEEKS or MONTHS to alleviate sutiering... GAMMA-OH therapy Is also very short: less than a month of treatment Is etiecllve, as opposed 01 months or years of treatment with other treatments. HOW 10 USe Gamma•OHGAMMA•OH (thlc Ic iha hranrt nano nt thlc mnlor,Ut?.In.FYanCe,-a5! 58!d.re!.ore) snould be used as rouows: Three doses of 2 gr per day on an empty stomach.FOr Instance,2gr In the morning, then 2gr before eating your first meal, at noon, then the last dose at around 6 In the evening. GAMMA-OH should always be associated with CLOiJAZEPAM(Rivotrll)Imgr taken In the morning. II you sUlter Irom Intractable moral pain you will be surprised to feel that your blocked gralliying emotions come back very, very last! GAMMA-OH Is a self-limiting medlclne,which means that you discover by yoursell when It Is time to stop medication. Why? Because GAMMA-OH Induces EMOTIONAL SATIETY and when you are emotionally satiated you do not leel Ilke asking for more Joy as you feel already led up with happiness!!! Yes, you can be fed up with happiness! Thls I5 why people using GAMMA-OH tl0 not become addicted. Intact, GAMMA•OH Is even used to treat alcohol and opiate addicts. GAMMA•OH glues you a strong DESIRE TO LIVE whatever are the circumstances. This Is why It Is the only authentic antl•depressant avallabie. Gamma•hytlroxy butyrate was the itrst soclablllser which I discovered through Henri Laborlt. Laborit Is well-known In France for his many books on society. He used to drink GAMMA•OH 3 times a week, which maintained him In an amazing shape! However, Gamma•OH, normally, cannot be taken for a long period of time continuously as II lends to Induce latlgue and, sometimes, anxiety. So emotional satiety or latlgue, etc, make Gamma-OH a non-addictive medicine as people will, spontaneously, slop medicailon when they feel these phenomena! GAMMA•OH Is a so-called Gaba B agonlst and a TYROSINE HYDROXYLASE ACTIVATOR. At pharmacological doses, It has, recently, been lountl, In Sirasbourg(France),to be a lryptophan hydroxylase activator. At the normal doses used for depression and anxiety Gamma-OH has a small regulatory dopaminerglc activity: It regularises tlopaminerglc activity. Gamma-OH Is found, naturally, In the brain togetherwlih another more rigid analog called GAMMA-HYDROXY-TRANS•CROTONATE (G.H.T.C). GHTC Is a close analogue Of GAMA•AMINO-TRANS•CROTONATE(G.A.T.C) which IS one 011he most potent agonlst of the newly discovered Gaba C receptors. II I5 not known yet whether Gamma-OH or GHTC bind to these Gaba C receptors. There are specific receptors to 4.OHB(another name of Gamma•OH!)and GHTC In the brain. These receptors are called GHB receplors.French scientists have lountl that some benzamlde neuroleptlcs bind with high affinity to these receptors. Nobody knows yet what 4-OHB and GHTC do, exactly, In the brain! They may serve as neuromotlulators.Tke only rather clear Ihing we know Is Feuat 6io-Agricultural Ssrvicea inc. 4BOB-32B-9760 iSl1/31/97 G2:50 PM CS/B _ that stimulation of these receptors could be Involved In the generation of "petit mat"epilepsy. Gamma-OH can Induce, very rarely(and ih15 Is not dose•dependent!) slight SUbJBCllue effects reminlSCent of petit mat epllepsy.These etiecis are adequately blocked by CLONAZEPAM and this Is the reason why Gamr~na-OH Should, alway3, baftel' be dt731/rbCd WItl1 GIUnd LCpdm GI' i~th@I' bzn¢Vd1aZ@pInC3. BZ nZGUIdZCplna3 3d6m to nave a good protective etiecis against the eventual minor side-effects of Gamma-OH. For Instance, Short term use of Gamma•OH IS strongly anxlolyllC and a Very elleCllve medication IOr panic attacks which are reversed wlthln IS to 20 minutes(on an empty stomach only). However, It Gamma-OH Is taken for weeks II can Induce what looks Ilke a "rebound" anxiety phenomenon. This anxiety manllesis Itself as plain anxiety or a panic attack Just when the psychotropic effects 01 Gamma-OH start to wane. In such Cases of anxiety, clonazepam(2mgr), mldazolam(ISmgr), trlazolam(O.Smgr) or chloraz SBgO (Jate(Tranx SB00 (Je,25 mgr) should be used. Gamma-OH Invariably Induces vomliing In people Chronically Intoxicated with alcohol or people having Ilver problems. Intact, Gamma-OH can be used as a lest of Ilver lunctloning! However, as Gamma-OH stimulates dopamine actlvlty II can glue rise to nausea and vomlting wlih very slight Increases In the normal dose range which should NEVER exceed 2.Sgr wlthln 6 hours. Itallanshave Used Gamma-OH , to treat alcoholics and opiates addlCiS, without SerI0U5 Sltle effects. They nave been using Shorter time Interval than what I recommend and big dally doses wlih Heroin addicts with no apparent serious side-effects. This Is In contradiction wlih what Americans have reported... So Is ihere,now,an American and a European science??? Why Gamma•OH slde•eilecls are "serious" to North-America and "neglgglble" In Europe (Italy)? Are these differences of OpInI0n5 related 10 science OR culture??? My_ opinion Is that demonlsatlon of so and so Is strongly eniranched In North-American culture. In North- Amerlca things have IO be good OR bad, black OR white. Something cannot be good and bad at the same Ilme, out there... This Is an ayatollah way of thinking: It Is cultural Inquisition. \Ne are more realistic and pragmatic In Europe. Even water can lead to Intoxication It taken In sutllclenl amount... Words can also Intoxicate but words are far more potent than molecules! Adolf Hitler could Intoxicate and make millions of people hallucinate Just wltn a few words... The words Ot Hiller were hdIIUCInOgenlC and tar, tar more potent Than lysergamlde(LSD)! Hlllerwas a potential emollonnal hallucinogen, Ilke some mushrooms are potential hallucinogens. But this Is a philosophical discussion wnlch does not have Its place Here! Just good to know because some nortn-amedcan "sclentlsis"are also halluclnogenlc and spread halluclnatlons... The whole north-amerlcan system Is strongly halluclnogenlc wlih IIS Insidious commercial and puritanical flavour. This Is another debate... Concerning hallucinogens, Shulgln(a famous sclentlst)speculated once that 5-Methoxy-DMT (a hallucinogen!) might Iltt rapidly depressive Ideation. Hallucinogens have not been experimented asants-depressants yet but some lack suggest that some might have an action. This remains to be determined. Many years ago i discovered a second class of 3oclablllsels(though less potent because of a mixed pro- serotonlnerglc actlon)called the TRYPTOPHAN HYDROXYLASE INHIBITORS, such as MDMA (3,4 methylenedloxymethylpnenyllsopropylamine) or MDAI (5,6 methylenetlloxyaminolntlane). Tne soclablllsing actions per se of MDMA are slmllar but GAMMA-OH Is more potent and Oerlectly sate whsle MDMA Is neUr0I0xIC and CardI010xIC. MDAI IS a nOn•neUr0I0XIC analogue Oi MDMA. New analogues OI both GAMMA-OH and MDMA nave been Invented but not yet tested. The soclablllsing action of MDMA Is related to Its Indirect blocking of SEROTONIN neurotransmisslon In a brain structure Called the MEDIAN RAPHE NUCLEUS. When the Medlars Raphe Nucleus IS Inactivated than snclablllty, spontaneou sly, appears. In fact, both rGMMG-nN and MDMd could act at a common site modulating oxytoclnerglc neurotransmisslon. I have now a hypothesis which could Ilnk the eitects on sOClablllfy 01 these Iwo m010001e5. B2siCally inls hypO1he515 Stales that MDMA might be an Indirect tyrosine hydroxylase activator by suppressing the action of serotonln at post-synaptic S-HT-IA heteroreceptors, thus ennancing the actlvlty of tyrosine hytlroxylase In some unitlentliled locus. Tnere exists one molecule, called NAhI.190, whlcn could help In evaluating this hypothesis. GAMMA-OH Is a pure soclablllser while MDMA and MDMA-mlmetlcs are partial soclablllsers. At low doses of MDMA the soclablllsing action of this substance Is masked by a pro-serotonlnerglc action as MDMA Is, also, a serotonln releaser. This etiect of MDMA produces a psychotroplc action slmllar to the serotonlnerglc Ihymoanestheslsers such as iluvoxamine, cltalopram, serirallne, etc. At higher dosage the soclablllsing action of MDMA becomes manifest. Sub~ectlvely speaking 2.Sgr of GAMMA-OH are equivalent to 200 Faw~Bio-Ag~iculturel Services inc. 4808-329-9760 $1!31/97 62:51 PM 0618 t' J mgr of MDMA. Haloperldol Imgr does not block the soclablllsing actions of Gamma•OH while II blocks the dopaminerglc ettects of a dose of 20omgr of Amineptlne, a dopamine re-uptake blocker. Haloperldol might block the soclablllsing ettects of MDMA. This I5 not clear yet. GAMMA-OH mlght,theoretlcally, be x150 ettectlve against the negative Symptoms of schizophrenia but this remains to be tested. GAMMA-OH should never be mixed with alcohol, opiates, antibiotics, or anything else except benZOdldzeplnes, Amineptlne, or Fluvoxamine. The pSyChOtrOpIC e1IeCI5 of IOOmgr of iluvoxamine will be suppressed, for about one hour and a halt, by a dose of 2.Sgr of Gamma•OH. Amineptlne does not seem to modify the psychotroplc ettects of Gamma-OH while L•DOpa Intensities the hypnotic ettects of this molecule. The recommended dose of Gamma•OH should NOT be exceeded. It you overdose, you tall Into a hypnotic sleep from which you cannot be awaken for hours. Moreover, It could promote "petit mat" epilepsy In such overdoses, plus nausea and vomiting. Vomiting Is a clear sign of relative over-dosage of Gamma-OH and Is related, apparently, both to the dopaminerglc activity 01 ih15 molecule and Io Ilver function. Anyhow there Is no need for overdosing. II used as prescribed here It Is a very sate ant~~ depressant and antl•panic medication. GAMMA•OH Is available only on prescrlptlon. I advise those people who see everything In term of white or black (this Is very entrenched In the psychology of white Anglo-Saxons protestanls) to consider the considerable benefits for sufiering people that Gamma-OH could bring Ii Il Is demonstrated to be the superlorantl-depressant which I claim here. Afterwards, more research will, very cenalnly, lead to relined versions of Gamma-OH with minimal side-ettects. The demonlsatlon of Gamma-OH In North-Amerlca:A New Form of Inqulsltlon We are living since the, 1960'5, In a world of INQUISITION against all psychotroplc molecules which generate some corms of pleasure. This modern Inqulsltlon started In America as a puritanical expression of amerlcan society to ban pleasure Irom Ilfe. This Inqulsltlon should besought against as It has halted the development Ot sclentlilc research On the mind. 30 years of reSearCh have been IOSt because Americans Imposed an INTELLECTUAL EMBARGO on many research Involving the mind. For Instance, all research on the hallucinogens was stopped, thanks l0 Ihls perverse Inqulsltlon. This Intellectual embargo ShOUId be Iltted and scientists and laymen should tight for that. No Inqulsltlon can be accepted In the sclentlilc 11eId.Amerlcan society has systematically demonised all psychotroplc molecules which can glue pleasure. (Even alcohol was demonised but this demonlsatlon was not successtul and was abandonned when It was noticed that the creation of AI Capone and other slmllar people was a consequence of this demonlsatlon!) Thls Is sheer madness and should strongly be opposed. The right to use our brain In the way we want should be a FUNDAMENTAL RIGHT OF MAN and put In the Declaration of Human Rights. I hope this goal will be achieved In the tuture.One of the reason which motivated me to write what you are reading Is that GAMMA-OH has been In use, Tor knowledgeable people In Europe, Tor decades. Now It reached the USA, unfortunately, because, as usual, some amerlcan INQUISITORS are trying to demonise this very useful molecule. These pseudo-sclentlilc AYATOLLAHS should be put back In their middle-ages churchs. In Iran, ayatollahs are condemning sex. In America, the amerlcan ayatollahs want, desperately, to control the use of our mind. This Is an unlolerable situation. Progress Is made through freedom and knOWledge, not Under the gUldanCe Oi any ayall0lah. Let US make a gra55r00t movement against all these ayatollahs! Ayatollahs and slmllar Inquisitors should go back Into their dungeons!!! Middle-Age Is over. The quest for Freedom Is a never-ending quest. It Is SUrprl5ing that you do not need, yet, a prescrlptlon for Champagne, wines and other alcohols In t~lonh-America because ii alcohol were Judged by pharmaceutical standards it would nave been banned a long time ago... Faun &o-Agiwltur¢I Ssrwcsa Inc. ~ 608-326-9760 i$1131/97 ~ 2:52 PM ~ 7l8 , Gamma-OH In France and North-Amerlca Gamma•oh was Invented by Dr. Wermulh, In France, for Dr. Henri Laborlt who Is the latherol chlorpromazine and modern psychopharmacology. Wermuth created gamma•hydroxybutyrate In 1961 In the search of a GABA analog which could, readily, penetrate the blood•braln barrier. Gamma-OH soon went to the market as an hypnotic which could be obtained with no metllcal prescrlptlon. The French, until I started Io study ihls molecule, were unable to classliy It under any class. For sometimes, It was an hypnotic Inducing a form of sleep very slmllar to normal sleep,then It became a pre•anestheslser, etc. About IS years ago, I, Ilnally, tllscoveretl that Gamma•OH was, In tact, a molecule to be Classltled under the novel Class of the soclablllsers, together wlih IIS butyrolactone form whlCh Is, readily, transformed Info Gamma•OH In the blood by a non specltlc lactonase. In iact, butyrolactone Is a pro-drug glving rise to gamma•hytlroxybulyrlc acid. Gamma-OH has a recognised peripherlc oxytoclnerglc action while Its central oxytocln properties are still to be demonstrated but seem very Ilkely. Gamma•OH Is known In France through the many books of Henri Laborlt and his conferences! Laborlt always pralsetl the properties of Gamma-OH and,as France Is deilnltely not a pudtanical society banning pleasure Irom exlstence,Gamma•OH has always been available, even though Its stimulates pleasure. Laborlt always advocated the general use of Gamma-OH In society, Ilke butter or milk! Why? Because It takes away your stress, makes you more posltlve towards Ilte, suppresses selectively, Ilke a kind of "psychological diode", your palnlul leelings, stimulates your soclablllty and makes you more lender, more loving, more Concerned by others. AISO yoU become keenly aware that yoU have Only one Itle and that IIIe should be a quest for happiness. Gamma-OH makes you realise how much you need others (not something for businessmen and mllltarles or gangsters!!!) and this Is a highly posltlve ihing. I always knew that when Gamma-OH would arrive In puritanical North-Amerlca Ii would, one day, be demonised.. Uniortunately for North-AmerlCans, the ayal011ah5 0l the pledSUre INQUISITION have Struck again and banned gamma•hydroxybutyrate! Laborlt Just died, recently, a few months ago at an old age. Somellmes, he used 10 Joke ihal Gamma-OH made him Ilve longer as he would suppress his stress with this "drinkable gold", Incase o1 need!!! He always Bald that his Iwo greatest discoveries were chlorpromazine and Gamma- OH but he never iully realised that Gamma-OH could open a new era In the management of tlepresslon and anxlefy. He never lought In order to promote the study of the psychotroplc eltects of Gamma•OH, he neverdlscoveredfhat Gamma•OH was the Ilrst molecule of a novel class: the soclablllsers. He Just enJoyed Gamma•OH, wlih his Irlends, while conducting other researches. All the people who have surrounded Laborlt have, naturally, more or less been exposed to Gamma-OH! I was lucky to be one of these people. Gamma-OH Is still a crude medlclne.lt should be properly studied and better analogs should be Invented. The use of soclablllsers may have tremendous etfecis on our soCletles, retlucing Inira•specltlc aggression and enhancing cooperation Instead of competition. Gamma-OH Is a conulvlal medlclne as 11 shows you Ihal you need others to be happy. Long term on and oit use seems to make you more Immune to stress and dysphorla, more loving towards people In general, more active In your Itle as II stimulates your enihuslasm because you are so aware that Isle can be a tantastlc ihing, everyday. The general use of soclablllsers may be a temporary solution torihe intra-specltlc aggresslvity of the human kind. Can Gamma-OH and novel analogs reduce wars, at last? I leave this question opened for your reilexlon. I will summarise, now, the psychotroplc protlle of Gamina•OH, something which I nave done In a lenghty paper many years ago, In French. Descrlptlon of the Psychotropic Effects of Gamma-OH (1985) Gamma-OH have the iollowing properties: A. II stimulates soclablllty which means that you feel Ilke communlcaling with other people In all ways: emotlonnal, Intellectual, sexual. Ana Irom ihls communlcatlon you feel a very strong and deep happiness. Why? Because, probably, Gamma•OH Inacth~aies a system which, normally, controls our base- Ilne level of paranoia. Gamma•OH seems to dissolve paranoia and Induce trust. It would had been very Poust Bio-Agricultural Services Inc. ~ 808-328-9760 !$1131197 G 2:53 PM ~ 6!6 ~ , Interesting to glue Gamma•OH to both Mr.Bush and Saddam Hussein before they started their silly war! B. Gamma•OH glues yoU a Strong desire Io TOUCH others, physically and psychologically~;e C. Communication becomes extremely gratifying as you teal you want to become close teople, not to Isolate yourself. D. Gamma•OH Induces a strong sense of BEAUTY. Everything looks so beautiful, so VIVID, so enJdyable, so pleasurable, so Important, so "deep". C. The perception of movement Is enhanced. D. Three•dlmenslonal perception Is enhanced and vision seems more clear, better than usual. E. The contrast of colours between obJects Is Increased. A yellow "pissenllt" (dandelion), or a rose, etc, situated In Iront ot, let say, green grass look brighter, more real, closer to you. F. You can feel a sense of Ireshness on your lace (this effect has also been noticed with Nomlienslne, a dopaminerglc thymoanaleptlc). G. You teal very hungry.This may be useful In treating anorexics. H. II you are a man, a woman well look magnitlceni and very attractive. She may become Just Ilke a goddess to your eyes. Women will experience the same feelings towards men. However, these kinds of teelings depend of your cultural background. For Instance, a simple Siamese woman will not feel such Intense teelings but will report that she feels drunk! Gamma•OH Is a very Important tool In order to Investigate the emotlonnal background of a person. For Instance loving persons well become more loving wnlle people devoid Ot these teelings will Just feel In good m00d,dnly. Some people may cry, WhICh demonstrates Ihal they have a tot of repressed materials In Ihemselves,etc. Crying under Gamma-OH Is a very liberating experience because you can take out and release things which, normally, you keep deep Inside and which thus hurt you. Crying under Gamma-OH takes away accumulated Inner moral pains. I. Sensuality becomes very Intense. You want to touch, to kiss, to caress, to hold, to love, to hug, 10 make love. In summary, you want to contact others through any mean available because you are Just highly sociable! J. According to Henri Laborlt, Gamma•OH renders the clitoris more sensitive. Moreover, Gamma- OH Increases love and sexual desires both In women and men.HOwever, II has a tendency to lower erection abllltles In man! Making love with Gamma-OH Is an extraordinary experience! Love teelings are Intensltled and the person you love can, even, look to you Ilke a deity. K. You can sometimes feel a deep sense of "meaningfulness". Things become meaningful to you, even you are unable to sclentlilcally define such a mystical feeling. This meaningtulness of reality Is a very Interesting phenomenon from a sclenllilc point of view as II seems to show that there exists a "clrcult" of meaningtulness In our nervous system. Non-specific activation of this clrcult, under Gamma•OH, would glue us a "deep" sense of "meaningtulness" which Is, of course, Imaginary. L. Gamma-OH stimulates your recall abllltles related to previous Gamma•OH experience. Each time you take Gamma•OH you can, often, remember very well memories stored under another Gamma-OH context. Emotions are, especially, 14~e11 remembered and reexperlenCed. From these and other observations, I think Gamma•OH should be a tool of choice In psychoanalysts. M. Some people feel an urge 10 defecate alter Gamma-OH, probably because of muscle relaxation! One of the ilrst reaction from a colleague of mine, alter Gamma-OH, Is to go to the toilets!!! N. In tact, Gamma•OH Induces a very pleasant sense of muscle relaxation, especially In the legs. 0. One of the most remarkable action of Gainma-OH Is that II gives you a STRONG DESIRE TO LIVE AND TO REMAIN ALIVE, DESPITE UNFAVOURABLE CONDITIONS. This Is what we Should expect Irom authentic anti-depressants. Gamma•OH shares some properties with another Tyrosine hydroxylase activator which Is NOT classllled as a soclablllser, despite the tact that It can, sometimes, Increase sociability and decrease depressive Ideation. On the contrary, this other molecule has been reported to have anti-depressive and depress ogenlc properties, simultaneously. When Gamma-OH Is contralndlcated? Unueareu epuepsy, ecianipsia, uyp~Kaienua, aevere nypenenaion, aicohuusni, assoaauun wmi upiales, antibiotics. For depressed patients, Gamma-OH should be taken only under the supervision of a medical Doctor. (In Switzerland where It Is a prescription drug) ~ ~ ~O N u b ~ u w ~ ~ T~ N w C O ^a 'm b O [ K ~ O A ~ .N. V ~ J ~ '.A m ~ C ~ V ~ G' b p n v 'Cy 'C ~ y C E T r O== m u m G ~ u 0 _ o ea .a ~ dm 3 a J m ~~U~~ hod c U~v r'°'c Ems... D. b c u m 3 T ~ L Q' i CY7 c= r t ~ ~o ~ a c U N e j ~ T ° c ~ ,e o L :t a I •c E c ~ `u r '-NC s N m ~ G ~ G- A ~ ° •v ami c x 4 ~ u v " h cmb ° ~ = .4 ~ G m a0 a 4= .c .e ~ -Y v- J C v N~ ~ .n O :v O T N xn o c ~ n~° E~ 2 0 .E -'~am -5 E m o te `o N s v .c m E ~ c 'v' 9 ° c e, i ~ _ aN a N E r3 ~ ~n n N O. ~ ~ S ep ~ ~ u ° u C m . t 'JJ _M S T G ~ O` C v -a C G ` T u C O E N G x (.J• ~ A LL - V H U s N O f0 "J N N` U Cl C E ~ 9 u u ~ E O. M u j C ~ v •v V _ 3~ iO ~ N u~ G m ° ~ a 'c 3 N o ~ ` ~ .A L E ,u, 7 ~ c y u rid ,c°. .T 9 U ^J 'S 7~ V G ~ N~ L 0 C A T G' J m U .p c q 2 c N ~ ~ A > ^ N s 3 c N N m S E Y.n y V t_ G N OI O N lI N`~ L°~ O\ L T • m E o o .c ~ G o E E ,g c T T y N s .c v Z m c c A 0 D4 ~l ti S J G? C ~ C V V q. 9 0 ? Q o~ G~~~ ~ ~ c F c s c E .E c ? q •m u~ ~ 9 L L ~ ~ O ~ O ti. G .p t 3 h j G L. ~e O 99~ c 3 ° ~ ~c. m U ;v 3 ~ ~ n ~O ~ c i .c ~ C ~ c_ n v _ N ' V ^J U q K Y C N~ V -0 L x ~p t N ak. O~ G .y `4 R N v 0 3 c .r., ~ ~ c c a 3 c z? ~ a+ 'u- u S ~ Z d c •C > N T p u a 'J oQ N K u j ~ 0 N n w L iJ L ED O ~ N vCi CO ° y ~ G ~ ^ X q N > ~ o G~ O- u a O G~= C T~ a ~ n 7 O~ c v~~~ ~ d ? o G d> o r.D c iy n u d E v n y m 0-¢ E~ ~ N a ~ ij ~ ~ ¢ ~ N ? ~ E C L 'J ~ 'N ~ N C ~ C ~ d ? u ? :4 N _ _ N CD L Y 4 L O 3 a v~ ~ ..iO O. r N u 0• u G 9 ~ J •N O G N riuj a\ C7 e N H c A w vc -c .c - i o- c c a ~o CY Q~ u E - N C C~l N m V IJ ~ Gl ~ 3 e a ~O N C7 d ~ J p d 7i 7^ .C ~ Ij- N ° C1 V> O m m> O~ .p m m L m > m Fj L j L m "J y m DD O~ C 1~ .L-. ~ O . L L ~ m m A r.~ U ~ 3 N u C e 3 ~ 'S 2 c m m ~ - ~m c L m m- m} r 3 N ~ 3~ m'c aL °'>4m ~ m:4a .=~b° m a - C A _ 7 ¢ 'S z 0 t~ 0 0 O "G .c. t~ O y _ C L N' ~ 'm. > X m in 0 ~ U O m N u u T o0 G L C Ol m O O m 'd'U.O -m 0 U ` ¢ oV= <d ~A°o .E g 30,5 =mm~E ~cmydub cE U u v r Q a v m A o ~ p o c `m T' G m v_~ O ~.,~.Y a~ b m,. 3 a o o. ~ .q a .m ..'o w~.~,L ~ ~'E y. m W O C• E_ P V N ~O G > .G L w° O~ E m L L ° ~ ~ C O cC N `v t° ~ 3 ~ ° y O O m ti o E N 3 ~ oc_o JE ra T b ~ m o ~ m.~La'ni1-' 10t ro E ~ ° ro ~ m.~ m~'° c~_°y LoY~m. ooh°~YC7 °c'm d .n y''! F G V A; C m j b y:O y.mb m O m° , m 5°' °c>.~° cmc'";~ ~nE'.m.c.,=dvtauc ay E ~ ~ n .7 e~ 'S A5g. A ~ A 2 0 c ° fp r..L ~ .c c ~ ° c ° b L m a u E E m .G c a E r b O b ~ m' C O m °C O L m y L p m A .`v m 'S A b O Y .u.. O b m m'^ C >b--._d ry C C'y QA.m,- y O.= of < 3 a N c m ;p m m y: m u ~ y .o . m]° Y L Q.. `-~cA~~m°~~~~°'am Noomm ~m>oamo.rnm`ny.o ux.A.. Q Q. = 0 0 2 ,O »O ~ C ° y L~ T m m-> y..C O C~ m U ~'m. a ~.~,c o ~v, oo a'35 ?.yc cc7 'y `_~.a ~`o.m' m.n.~> mmb.. C 6 T R~p~ lj y. ~ G~ CO y C N m 10 y ~A m y O .O Y ,a. m 'v_~%'L O~CNpe~,g N'~cc >LA ao y:m~Am °m m,y~om c.m m. N•~ooo~~n~I3~o v ~ym>y YL•-°Oti-yEm~-u~~>-, ~,O'`.~.. .,a °c N o c ,vo~~ m c o m~- •;t C mob m m. o A F ~ c m 'n y> t m Q~O o m E L ,c m w u ¢i~~c`coo~EQr~ct _m'>Lb~>i 39~m'a'nim mLmyO m~o~fn 0. cv Q " o E ~ ~pC ~ r f- ~ c m m Y. ~2. omi ~ s. A m ai @ > E y Y_, ~ L7 x G u .o Z P A w ~C ~ ~ ~ Q' E Q' 01 'L m. - Q ~/f L .O b _ O Q N i0'd P. 0: ~ o a g t c o •o ~ ~ o ~ °T' 'S o~ ~ v o Q~ 'c° v o N m ~ C O ~ L G T 'J V T ~ u N n~ N .C O N N, y 3 to 'S ~ a ~ ~ o ~ U W ~ o •5 to L m ~ u u ? `N° °'o> 10Q1 •5 L rJ' d °OC t~ i`- m Y V p~ N N L A~ yy~ L C~. J C % E L Y ° V O~`. O T A~ l9 a to > ~ Y Y tC ; C Q 4~ N' O HEd Xl ~ A ~f ° E - a O •p o r w° n c ~'C L G E 7 e3 N L '4^ ~ .y ~ O C y E~ ~ 3 ~ ~~n u o .`a .Ci ~ ~ C O ~ u d ~ 'O ~ ~ y y C1 ~ N ~ i0 L y0 n 0] ~ .5 C o O C 00 b o .e v 3 ~ y~ ~ E ~ p~ o y a V c c v Z u. ro E ~ ~ .Np ~ d ~ a y ~ G o ~ ~ ; y 3 y u ~ u ,d ea ~ ~ o G V 0. C C O u C O V > A D G T N a`Z U G L O m u 3 ' o~ vC o E E o w~ t m Z~ u v v 3 u ~ .n 5 v0 ~ N~ O A V i C y G a c t' O ~ O ~ L7 T y C ~e 'O Y ~ 0. d 7~ C y$ u v. y E ~ 00 [C ~ - ~ ~ DD N V UU E ~ u is ~ ~ v 9 _ c v_i p m a .c a ~:.5 ~ o 6 d ~ V N ~G y 'S O ~3 u~~ ~ N 0$ y~ CL ~ - 3 s :L M y d= N~ O ~o u~ °i c V G ~ > v E c dcN T r~ v a W° • E G' r$ ~ y N cue ~ ~ ~ $ o° u ~ " n ~ ° ~ 'a ~ v .y ~ ° ~ ~ x `u b S ~ c y ~ N 3 o ay u o ~n o.°_ ~ c a~ c c °u' o C1 ` E c~ d ,0. au r U~? ~ X •S -i N c 9 ~0 3 ~ c v 6 m n .Z TU ~ 43 ~ T v v H m ~ ~ ~ ~ ~ b ~ ~ 8 o yj ~ 3 ~ {.E~3.u}~ 'E ~ 3 ~ D ° y .E c b ~ c ~ A `~x~0• ° ~ V • 1 O W d G ~V ~ CI N ~ ° • ~ 61 ~ ~ ~ dya ° N ~ E L rd O V ~ C N u tU~ ~ u ~ V V N O ti V N ~ ~ V V O~O O~ N G i6 •4 ~ G~ ` y 6l DbD ~ ~ < ~ 8 s .c se ° .s 'S .6 .o ~ .e c .5 U. 7 ~ ~ > 41 5 i rv av ea u u < oo ~ v u ~ r, u ~ _ y v . e C_ p V+ _ of ~ R C ~ v !J. Q C~ t: .C 3 c L ~ v o E 'C C V m 'r C C E ,v s o c L' c °a ~ ~ u o o y rte, v O• D r j~ c. 3 0~ ~ O G = i C u V v~ C 'y C t r G ~ r ~ N N v O t a`i ~ ~ ' ea L 'S E c ~ v ~ h rn C `~d ~ " ° d .z ~ v U c u w ~ ~ ~ n ° q ~ ' ~ > ° Q E G i ' ' to ~e " Z G ~ s 6 u v 3 t R v ~ f`. ~ v ~ 'J C ' i. y V L GO .G O ~ v C OD C q m V N C V Y~ L O N n x ' F+ i0 ~ L~ O J .7 P L J~ j y C ~ u. V D` C = rv~ A ~ m N~ r. v k c 3 c ~ c T ,~g v E :d c v 'u m, c y V E L O S C - v L V_ < K N 1 ~X G H U u y~~ n r h c~ b ° cco N L a°' _ c ,cv E r u°~ u s y i ~ ~ ~L 3 cU _ o E ~ ~7 ? _ ~ uQ ~ u.~v ~"'t1i A ¢l Y 8 o u. rn rn A rn~~ c 3= c o°_ Z o T 'c o 2 6 .c ~ E ~ 0. u _ ` " s ~a y a ~ ~ 1 a V L v T p 6] N J 'O v L C O 'E O 'r T C N 'J u ? ~ 3 ~ 7 en ~ 2 .c c u N ~ V ~ ~ $ s L u _ ~ `u y ~ m e o v o C re ° s~ v y y U ~ -Ci oD ~ E~ O v X L ra cu m V y' K ~ v t 3 3 aCi C N m y i u ca 3 2_ v o o A o ~ C H rj ~ ~ ~ C ~ ~ f.] O 'D ~ •Oi ~ A C C r ~ V C A - T 'O ° ? ~ n c ~o u~ t~ c~ 3 Z v 0. .eo ~ L u~ R a ~ E `O u r v~ y v rte. o v 07 0 o v- ,h Jn ` c C ro u a .y N c ~ ee N° c' J G C t ~ u LL. O ~ G~ v o` p g L U i> `n $ r O~?°< ~ E O ~ L ,d 0. u~ v C~ ~ ~ u .y. w ~ h Y c E v~ C j n ~ in r o G~ 'a m (!7 u~ n a o. u n c..= V w u 'o - E c n~ u