# GHB Part 2



## Aftershock (Jan 28, 2004)

I've often said that anything can be abused. I've even pointed out that deaths have occurred due to water intoxication. Extremely relevant at this time is the recent death of a 53 year old male which was attributed by the Medical Examiner to "hypoxic encephalopathy due to acute GHB toxicity."

The autopsy report showed that the individual was brought in to the ER unconscious, with a sodium of 107 (which the admitting physician reported as incompatible with life-normal levels are 130-145). The history was that this long-time alcoholic and drug abuser had gone clean. However, within several months of discontinuing his other drugs, he began to feel badly, and occasionally became disoriented. His sleep was very poor, and he began to drink lots of water. He then began to take GBL to help himself sleep. It would help for a while, and it made him feel better. However, he became progressively worse, ultimately lapsing into a coma, and was taken to the hospital. Based on this history, the County Medical Examiner (Placer County, California) made the above diagnosis--"Due to Acute GHB Toxicity." However, there were no laboratory reports with the autopsy (lab was "pending" at the time of determination). I finally received the "missing" lab report which revealed a blood GHB level of 12.5 mg/L. There was no GHB in the urine. This amount of GHB is well within the range that is normally produced by the body after death. The fact that there was no GHB in the urine proves conclusively that the decedent had not taken any GHB prior to lapsing into the coma. The coma was due to low sodium, and had nothing to do with GHB. It is clear that the cause of death was a previously undiagnosed case of a disease known as diabetes insipidus, which causes excessive urination. This resulted in thirst and subsequent "water intoxication" which caused him to excrete excessive sodium, resulting in the profound hyponatremia (low blood sodium). The consumption of GBL in no way contributed to this death. The clinical presentation is certainly not consistent with a GHB overdose, and there is absolutely nothing in the scientific literature that would indicate that chronic use of GHB or its precursors would cause diabetes insipidus or hyponatremia.

This was a case where the death really was due to water - and got blamed on GHB!

Potential Problems that are Likely to Result from Passage of the Proposed Bill

GBL and BD are valuable industrial chemicals, available by the tank car load. Four hundred million pounds of GBL, and at least twice as much BD are manufactured each year. Because of the shear volume of these products produced annually, increasing the accountability and security of GBL and BD to the level of other "List 1 Chemicals" would probably bankrupt industry and eliminate many valuable consumer products (floor cleaners, paint strippers, acetone free nail polish removers, beer, pineapple ice cream, plastics, auto bodies, and many others).

Consequently, accountability and security requirements for these substances were waived in the recently-passed Federal Law (which I believe goes into effect on April 16th. Presumably, penalties for diversion would be those for other Class I chemicals which do have the statutory security and accountability requirements.

Because of the voluminous production of the two chemicals from which GHB can be manufactured/produced (12 million pounds), it will be difficult if not impossible to eliminate the production of GHB and/or its precursors (chemicals from which GHB is derived). Some GBL/BD will certainly be available through "illicit" channels. Stopping GHB production is going to be much more difficult than wiping out some poppy fields in Colombia, or spraying paraquat on marijuana plants in Mexico.

A lot of GBL and BD will probably be labelled "for industrial use only," and sold with a "wink." While in responsible hands, such a product can be diluted appropriately and be safely and beneficially consumed. Such users who could benefit include most adults of all ages, and even many children (GHB has been used successfully for autism and attention deficit disorder). Most "Industrial Grade" GBL actually is well within pharmaceutical standards of purity for contaminants and heavy metals (usually, the most common contaminant is water). "Pharmaceutical Grade" purity is often exactly the same product, but with a higher price.

However, because of the restrictions against dietary supplement use of GHB, there will be no instructions as to the proper dilution, and recommended dosage of the "bootleg" versions. Warnings against combining with alcohol and other central nervous system depressants will also obviously not be included.

Unfortunately, the consumers of this "bootleg GHB" will most likely be those most inclined to abuse it. Those who use GHB responsibly and benefit the most are generally law abiding adults-especially senior citizens. As we get older, sleep disturbances become more common. GHB normalizes sleep, resulting in deeper, more restful sleep, with consequent greater daytime alertness, improvement in memory, alleviation of depression, loss of body fat and increased musculature and bone density (due to release of growth hormone at night), reduction in cholesterol and reduction in oxygen requirements of the heart and brain (thereby actually protecting one against heart attacks and strokes). These are just a few of the well-documented benefits of GHB for "normal" people.

What Should be Done

First, since GHB meets the definition of dietary supplement in accordance with the Dietary Supplement Health and Education Act of 1994, I recommend that GHB be removed immediately from the list of controlled substances in Alabama.

Second, standards of purity and good manufacturing techniques should be established for the manufacture of GHB.

Third, appropriate warnings and dosage recommendations should be drafted to be incorporated on the label (just as on cigarette packs, [talk about dangerous drugs!])

Fourth, prohibit sales to minors. For example, in Florida, my children (11 and 13) cannot go into a K-Mart and buy a box of BBs. Florida law restricts sales of BBs to adults. I have to buy them.

Other considerations include possibly limiting sales in Alabama State Liquor stores (where ages are closely monitored)- although I really recommend separating these products from alcohol altogether. Taxes are another consideration.

Conclusion - Legal and Constitutional Considerations

Rape is a crime. Rape facilitated by a substance intended to incapacitate an individual is also a crime, with even more severe penalties. Adulterating someone's food or beverage is also already covered by the criminal code.

Although the Attorney General claims that criminal use of GHB has increased in Alabama, he has yet to provide us with any evidence of completed or pending prosecutions for a crime. Why increase the penalties for a crime for which no one has yet been punished.

The Eighth Amendment to the Constitution for the United States protects citizens from cruel and unusual punishment. Life in prison without parole for possession of a dose of GHB that will safely induce natural sleep for one night appears to me to be "cruel and unusual punishment." Especially when the same substance is about to be approved by the FDA for narcolepsy, yet which will admittedly (by Orphan Medical) be prescribed for a wide variety of legitimate uses. I doubt whether any rapists are imprisoned for life without parole.

The statements cited in this brief article can all be confirmed by scientific and public documents. One of the best sources of accurate information about GHB is the voluminous Investigational New Drug studies (INDs) on file with the FDA, which document over 25 years of research on the safety and clinical benefits of GHB. These documents have previously been placed into evidence in many court cases, and should now be considered public documents. I encourage investigative reporters and legislators to request these documents from the FDA.

The best proven oral agonist of GH was Gamma Hydroxy Butyrate (GHB), and it was no accident that GHB's sleep inducing affects must have contributed to its up-to 300% improvement of GH levels (as clinically studied by the Japanese). However the FDA and DEA ban on GHB because of its so-called "Date Rape" properties (and the UN's enforcement of that unscientific evidence in many other countries around the world), effectively rules out that "miracle molecule."

Discover The Regenerative Effects of GHB, the Elixir of Life!

By James South MA

GHB (Gamma-Hydroxybutyric Acid) is a hydroxylated form of the short-chain fatty acid. GHB is also closely related to GABA (Gamma-Aminobutyric Acid), the chief inhibitory neurotransmitter of the mammalian nervous system.

GHB was first synthesised in 1960 by H. Laborit, a French physician. Laborit was interested in studying the action of GABA in the nervous system, but GABA was known to be unable to cross the blood-brain barrier. Laborit hoped that by adding a hydroxyl (OH) group to butyric acid, the resulting molecule-GHB-would be protected from being destroyed by beta-oxidation (the process by which cells 'burn' fat), would cross the blood-brain barrier, and then serve as a precursor to GABA once in the brain. (1).

However, GHB turned out to be pharmacologically distinct in many of its actions from GABA, even though later research showed that GABA and GHB are interconvertible in the brain through a common metabolite- Succinic Semialdehyde (SSA). (2,4).

Somewhat surprisingly, in 1963 Bessman and Fishbein first reported GHB to be a naturally occurring molecule in the brain, and by 1970 the work of Roth and Giarman had proven conclusively that GHB is a normal, natural brain metabolite. (3),

It is now known that 0.08% to 0.16% of whole brain GABA is normally converted to GHB each minute. (4). And in a 1992 'mini-review' of the significance of GHB in the brain, G. Tunnicliff concluded: "There is little doubt that GHB is not merely a by-product of GABA metabolism.

Clearly it has distinct neuro-physiological and pharmacological actions, many of which are undoubtedly the result of the activation of specific GHB receptors.... The evidence is fairly substantial that GHB plays a role in the functioning of the central nervous system, perhaps as an inhibitory transmitter acting on dopaminergic neurons.... The ...actions of GHB make it a viable candidate as a neurotransmitter or neuromodulator in the CNS." (5).

Also somewhat surprisingly, research has shown that GHB is naturally present in kidney, heart, skeletal muscle, and brown fat, often at levels 10 to 20 times higher than whole brain GHB levels. (2,4).

In his detailed 1989 review of GHB as an endogenous regulator of energy metabolism, pioneer GHB researcher M.Mamelak stated: "Clinical and experimental work indicate that GHB can protect both central and peripheral tissues from the damaging effects of hypoxia or excessive metabolic demand.... GHB could function naturally to regulate cell activity when metabolic energy is in short supply." (4).

GHB has been the subject of hundreds of published scientific papers since 1960 (see the bibliographies in references 4 and 6). GHB is a legal drug in various European countries, including France and Italy, where it has been in clinical use since the early 1960's. It has been widely used as an anaesthetic- Laborit summarized the anaesthetic benefits of GHB in 1964, based on 6000 (!) case-reports. (1). GHB is also used to treat alcoholism, alcohol withdrawal syndrome, opiate addiction and opiate withdrawal syndrome. (7,27-29).

GHB has also proved useful in obstetrics. (8). GHB is also used in Europe to treat narcolepsy, a serious and disabling sleep disorder, as well as insomnia. (7). Yet in spite of the mere 40-year history of safe clinical and experimental use of GHB, in November 1990 the U.S. Food and Drug Administration (FDA) declared-through a press release-that GHB was an 'illegally marketed drug', and claimed that it was a danger to public health.

Since the U.S. Dietary Supplement Health and Education Act of 1994 (DSHEA) in effect classified GHB as a dietary supplement, not to be regulated only as a drug, and because the FDA had not bothered to legally classify GHB as a drug before DSHEA, the FDA has now backed off its claims that GHB is illegal at the federal level in the U.S. Instead, the FDA has orchestrated a campaign to get the various U.S. states to declare GHB an illegal drug, since DSHEA does not operate at the state level.

The FDA's smear-and-fear, disinformation and demonization campaign has been based in significant part on a brief 1992 paper by California medical bureaucrats Chin, Kreutzer and Dyer that claimed "The drug GHB is a substance with documented clinical actions consistent with severe neurotoxicity."

It is therefore necessary to look closely at the clinical and experimental record of GHB to ascertain if there is any documented evidence or general consensus of GHB as a "severe neurotoxin."

When scientists wish to determine the relative safety of a drug or nutrient, they perform experiments to establish a substance LD50. This is the amount of the substance (lethal dose) necessary to kill 50% of the test animals. The LD100 is the lethal dose that kills 100% of the test animals.

In his 1964 GHB review, Laborit reported: " In rat, the LD50 is 1.70gm/kg [of animal body weight]; the LD100, 2 gm/kg. The cause of death is respiratory depression, and under artificial respiration, rabbits can tolerate up to 7gm/kg. The dog is less sensitive.... In the rat no significant differences are observed between controls and the group injected daily with a 1/10th of the LD50, particularly with respect to weight, bone marrow, liver and kidneys [where toxic effects frequently show up]."(1)

In his 1969 review on GHB, anaesthesiologist M. Vickers wrote: "In acute experiments in animals, the LD50 has been 5 to 15 times the dose necessary to produce coma. Death was probably due to sodium intoxication rather than to any effect of the active drug.... No deaths have been reported in man attributable to acute toxicity.

The author [Vickers] has used doses of 20g to 30 g. [28,4 g = 1 oz] per 24 hours for several days without ill effect.... No toxic effect on the liver or kidney have been reported.... Its low acute toxicity may make it a safer sedative drug to prescribe when suicide is a possibility." (8)

While extrapolation from animal LD50 studies is at best an approximation of a drug's toxicity for humans, the rat LD50 of 1.7 g/kg of body weight would translate into 85 g (3 ounces) for a 50 kg (110 pound) person. This would equate to roughly 10 to 15 heaping teaspoons of GHB - rather more than anyone is likely to ingest at one time.

It should also be noted that Laborit's LD50 was based on injecting the GHB, rather than taking it orally, as humans normally do. Injecting GHB at least doubles its effect, as Laborit noted. (1) Thus a 50 kg/110 pound person would really need 170g (6 ounces) or 20 - 30 heaped teaspoons of GHB taken orally, to equal the rat LD50.

Another estimate of the human lethal dose is provided by the official package insert for the legal French GHB drug (Gamma - OH), where the human LD50 is stated as 4.28 g/kg. This would equate to an oral lethal dose in excess of 200g (7 ounces) for a 50 kg/110 pound person.

A perusal of the published GHB literature attests to the safety and low toxicity of GHB. In a 1977 report measuring the effect of 2.5g intravenous GHB given to 6 healthy young men, Takahara et al reported: "All volunteers except one fell asleep ... after GHB injection and slept for 30 to 150 min.

As side effects, one volunteer complained of nausea and another volunteer had orthostatic hypotension [dizziness upon arising] after test." (9) In a 1979 report on the use of GHB to treat 16 narcolepsy patients Mamelak and Broughton stated: "There have been very few adverse clinical effects with [GHB] treatment [3.75 to 6.25 gm, divided into 2 or 3 oral doses] and no abnormal laboratory findings.

Minor side effects of GHB have been seen for the first few days in a number of patients which consisted of a 'thick head', ocular discomfort, and other apparent hangover effects, but these were rare after one week.... The main disadvantage at present is its [GHB] short duration of action." (10) (Hardly a sign of "severe neurotoxicity a la chin and colleagues!)

In a 1985 report on treatin g 30 patients with narcolepsy, Scharf and co-workers specifically emphasize the toxicity and side effects of standard drugs used to treat narcolepsy (amphetamines, Ritalin, and tricyclic anti-depressants) .

They note that in contrast Our results confirm those of previous clinical studies of GHB, namely, that it is a safe, non-toxic substance...." (11). And in a 1986 review of 48 patients who took GHB for 6 months to 9 years as a narcolepsy treatment, Mamelak, Scharf and Woods report that: "Few adverse effects have been observed. All patients have been followed with serial liver, renal, and blood studies, periodic chest X-rays, and electrocardiograms; no abnormalities have been noted.

On the first few nights of treatment with GHB, two patients had enuresis [bed-wetting].... Patients who resist the sleep-inducing properties of the drug may become confused and emotionally [upset]...." (12).

In their 1989 double-blind study on GHB to treat narcolepsy, Scrima et al note: "The total number of adverse reactions [primarily upset stomach, muscle weakness, urinary urgency and dizziness] reported during GHB treatment was less than during the placebo treatment [!].... No patient discontinued participation in the study because of side effects. The blood test results... indicated that GHB did not cause hypokalemia [low blood potassium] or other marked changes in blood chemistry." (13).

And in their 1990 paper on GHB use with narcoleptics, Scrima et al remark: "GHB is a more appealing treatment for narcolepsy patients than other alternative treatments.... GHB has been found to cause only minor side effects that usually occur only during the first few days of treatment." (14).

In this remarkable paper integrating masses of GHB study data, Mamelak makes observations that clearly cast doubt on any claim that GHB is a 'severe neurotoxin'. "In man, oral or intravenous doses greater than 50mg/kg [=3.5g for a 70kg/154 pound person] produce anaesthesia.... The drug is rapidly metabolized and the central [nervous system] effects of an intravenous dose of 60-70mg/kg run their course in about 2 hours.... In the rat... 600mg/kg [=42g for a 70kg person]... produces a reversible continuum of EEG changes... Complete recovery occurs about 2 hours after the drug has been given.... As much as 1000mg/kg [=70g for a 70kg person] have been given to monkeys without harmful effects.... As has been demonstrated in other circumstances, GHB appears to promote survival under hypoxic [low oxygen] conditions." (4). Does that sound like any 'severe neurotoxins' you know?


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