Aftershock

Mamelak has also noted the unique ability of GHB to reduce brain glucose consumption, without toxic effect. Thus, he states: "An intravenous dose of 600mg/kg of [GBL, which is converted to GHB by an enzyme in the blood], for example, reduces glucose utilization in grey matter by 68% compared with 44% in white matter [of the brain]. Similar results have been reported with GHB. It is remarkable that in spite of these extraordinary degrees of metabolic depression full tissue recovery can take place.
Other [CNS] depressants such as the barbiturates also produce comparable effects on... energy metabolism, but doses of barbiturates which would be necessary to inhibit cerebral glucose utilization as much as that observed with [GBL] and GHB would likely be lethal." (4). By now it should be evident that (to put it politely) Chin et al may have exaggerated when they suggested (only by implication, if you read their statement carefully) that GHB might be a 'severe neurotoxin'.
And ironically comments made by Chin et al in their paper seem to contradict the implication that GHB might be a 'severe neurotoxin'. They point out that "The prognosis for those who experience GHB poisoning [sic] is quite good. There are no documented or anecdotal reports of long-term adverse effects or fatalities...." (2).
Don't you wish all 'severe neurotoxins' (e.g. Cobra venom) were that benign? (For a detailed dissection and critique of the Chin paper on GHB 'poisoning', see references 7 and 26). Far from acting like a toxin or poison, GHB has shown a remarkable range of protective effects in a diverse array of experimental and clinical conditions. Laborit reported in 1973 that "we observed... that GHB possesses a definite protective action against convulsions produced by strychnine, cardiazol and isoniazide," (3). While Mamelak notes that "GHB can block seizure activity induced by a variety of agents. Those induced by Kainic acid, strychnine, isoniazide and mercaptoproprionate may be cited as examples." (4).
Mamelak also reports a wide range of tissue-protecting actions of GHB. For example "500mg/kg of intravenous GHB protected rats against the lethal effects of 30 minutes of hypoxia. Under these conditions none of the GHB-treated rats died in comparison with 45% of the untreated control rats. Even lower doses of GHB, 200mg/kg, significantly reduced the subcellular response of the brain to hypoxia in rats exposed to [low oxygen] atmospheric pressures comparable to those at 10,000 meters [32,000 feet]." (4).
Mamelak concludes his section on GHB brain tissue protection by noting that "More so than any protective agent studied, including the barbiturates with which it is so often compared, GHB retards the disappearance of oxygen from anoxic cerebral tissue, again demonstrating the potent [and highly protective] energy sparing effects of this agent." (4).
Laborit reported in 1964 the anti-convulsive effects of GHB in protecting mice exposed to pure oxygen under 3.5 times normal atmospheric pressure. In the control animals this procedure routinely produced convulsions in all the (non-GHB) animals. "A hypnotic dose of 500mg/kg [GHB] protects all animals against convulsions (10 mice). With 250mg/kg doses, a convulsion is noted in one mouse out of 10; the seizure is retarded and of short duration. In 20 mice, with 200mg/kg, there were three slight and one typical convulsion." (1).
GHB has also shown a wide range of protective effects outside the nervous system, especially in conditions of anoxia or energy insufficiency. GHB has been used to reduce the pain of angina pectoris and myocardial infarction (heart tissue death). (4). GHB has also been shown to minimize the deterioration of heart function produced by massive haemorrhage. (4). Sodium and lithium GHB have been used to prolong the viability of kidney to be used for organ transplant. (4).
A 1990 study found an amazing effectiveness of GHB in preventing the intestinal lining damage that normally occurs when blood supply to the tissue is cut off (ischemia), and then blood is allowed to return to the tissue (reperfusion). Eight groups of 6 hamsters were studied in a blind experiment.
After 30 minutes of intestinal ischemia, 3 hours of reperusion were allowed. The animals' intestines were then subject to careful histological examination. In untreated animals, 75% +/-6% of the villi (microscopic finger-like intestinal lining projections) were damaged (haemorrhage and necrosis).
In GHB-treated hamsters, only 8% +/- 3% of the villi were damaged. Administration of the GHB following ischemia but before reperfusion also provided significant protection to the controls, with 26% +/- 3% of the villi damaged. In contrast, Vitamin E failed to provide any protection against the injury, with 71% +/- 4% of villi damaged. (15).
In a 1991 report Pierrefiche, Laborit and co-workers detailed the profound protective effect of GHB against alloxan-induced diabetes. Alloxan is a substance that is routinely used experimentally to destroy the insulin-producing beta cells of the pancreas. The rapid uptake of alloxan and an exquisite sensitivity to free radicals (which alloxan produces en masse) are unique features of these cells.
The toxic effects of alloxan, namely elevated blood glucose due to beta cell destruction, are prevented by a number of anti-oxidants. Different levels of GHB, from 1.5 mmoles/kg to 4.2 mmoles/kg, provided almost complete protection from the hyperglycaemia induced in the mice which received alloxan but no GHB. Fasting blood sugar in the alloxan-but-no-GHB mice typically tripled at 48, 72 and 96 hours after alloxan treatment, compared to control mice given only saline (salt) injection, but neither GHB or alloxan.
In the GHB-plus-alloxan mice, blood sugar levels at 48, 72 and 96 hours after injection remained virtually identical to the normal fasting blood sugar levels displayed by the saline-control mice.
Since the beginning of GHB studies in the early 1960's, GHB has been shown to have a wide range of metabolic effects in animals and man.
Perhaps the most well-documented effect of GHB on brain metabolism is the increase GHB causes in brain dopamine. "Systemic administration of GHB leads to decreased dopaminergic [nerve] activity. This is probably a reflection of GHB's inhibitory action on the cell body of dopamine-releasing neurons.
In the substantia nigra [the chief dopamine brain area where damage leads to Parkinson's disease] this initially leads to a decrease in dopamine release and an accumulation of dopamine at nerve terminals. Finally, a stimulation of dopamine release occurs." (5). Because of GHB's dopaminergic actions, it has been used with limited success in treating Parkinson patients.
"Major studies were conducted in Italy. One study showed that in 9 patients out of 10 a single dose of 400mg/kg... produced some improvement... within 24 hours, resulting in a sensation of comfort and regulation with improved ideation and renewed initiative. Within 2-7 weeks following initiation of treatment,... there was an improvement in tremors, hypertonia [muscle rigidity] and in the writing test. One female patient regained normal gait [walking] after having been confined to bed.... These results were confirmed by Ferrari et al." (17). GHB has moderate or little effect (depending on dosage) on acetylcholine, noradrenanlin and serotonin activity. (4).
GHB has been shown to induce major increases in plasma growth hormone (GH) levels. In 10 patients scheduled for surgery, intravenous GHB anaesthesia (100-150mg/kg) increased plasma GH levels 6-fold, from 2.2ng/ml pre-induction, to 13.8ng/ml at 45 minutes after GHB injection. GHB induced only slight increase in plasma cortisol levels, from 14mcg/ml to 23.6mcg/ml. (18).
In a 1977 report Takahara et al injected 2.5g GHB into 6 healthy men (25-40 years old). Compared to the GH levels after saline injection in the same 6 men, plasma GH levels rose 16-fold, from about 2ng/ml to 32ng/ml by 60 minutes after GHB injection. Plasma GH levels were still 6 times normal (13ng/ml) 2 hours after GHB injection. Plasma prolactin levels rose to a maximum of 5 times base-line levels at 60 minutes. (9).
It has been known since the 1960's that slow-wave sleep (EEG sleep stages 3 and 4) induces GH-release. Thus Sassin et al reported in 1969: "Those subjects with more frequent slow-wave cycles had initial peaks [of GH release] of greater magnitude and more frequent secondary [GH] rises.... We conclude from our data that [GH] release is related not only to sleep but particularly to non-REM portions of... sleep, especially... EEG stages 3 or 4.... Release of GH in sleep suggests an anabolic function of slow-wave sleep...." (30). And as is discussed in more detail below, GHB in normal subjects speeds up onset and increases amount of slow-wave (stage 3 & 4) sleep. (19).
GHB typically induces a slight slowing of the heartbeat (bradycardia). GHB also slows and deepens breathing, but does not depress the breathing centers in the brain stem, unlike e.g. barbiturates and benzodiazepines. Even with high doses of GHB the respiratory centers in the brain do not lose their sensitivity to carbon dioxide in the blood-the normal stimulus to breathing. (17).
GHB also induces a remarkable hypotonia, or extreme relaxation of the musculature. In medical contexts where GHB is used anaesthetically, this promotes easier insertion of breathing tubes into the throat. (17). GHB also induces a mild hyperthermia, apparently due to its decrease in brain and muscular metabolic rate. (4).
Perhaps the most striking physiologic feature of GHB is its rapid induction of sleep, even when given orally. Studies done in the 1960's showed GHB sleep to be essentially identical to normal physiologic sleep. Thus Okada et al in 1967 reported their study with 19 men who received GHB intravenously.
They slept deeply, with EEG records similar to natural sleep. "Awakening took place very rapidly, 3 hours after administration, without disorientation. The authors believe that the therapeutic effect of GHB is very similar to that of physiological sleep." (17).
GHB has been used therapeutically since the 1970's to treat narcolepsy, (a severe and disabling sleep disorder), with generally excellent results. It is generally agreed that GHB seems to consolidate and make more efficient the night-time sleep of narcoleptics, so that they don't fall asleep uncontrollably in the daytime. (10-14).
In a 1990 double-blind study, Lapierre and colleagues reported that GHB induced normal sleep in their subjects, but with an increase in the restorative (and GH-release promoting) slow-wave sleep (stages 3&4), and a more efficient REM (rapid eye movement) sleep, as well, while lessening time in the shallow initial stage of sleep (EEG stage 1). (19).
GHB is not a foreign substance which must be detoxified through the liver's detoxification system, unlike most other psychoactive drugs (e.g. barbiturates, benzodiazepines, SSRI's like Prozac®, phenothiazines, etc.). As Vickers notes, "[GHB] represents a unique development in the pharmacology of anaesthesia.
It is the first compound to exert a pharmacological action which is at the same time fully metabolized as an energy-producing substrate." (8). When GHB is catabolized (broken down), it is first converted into Succinic Semialdehyde (SSA). SSA is then converted to Succinic Acid, a Krebs cycle metabolite. The Succinic Acid is then oxidized through the Krebs cycle in the ATP-producing mitochondria, eventually becoming water and carbon dioxide, as has been experimentally verified following radioactively-labelled GHB administration. (17).
Thus, GHB leaves no 'toxic residue' in the body, unlike virtually all other drugs. GHB is rapidly metabolized in the human body, with a half-life of only 35-40 minutes. (7). Because it is so rapidly metabolized, its acute effects typically last only 2-3 hours.
The pioneering work of H. Laborit on GHB over several decades has led him to elaborate on extremely detailed explanation of the homeostatic normalizing, restorative, regenerative effects of GHB. (1,3,17). Laborit discovered that in effect, GHB serves as a switching agent to cycle brain/muscle activity from its high-energy output, "yang", daytime activities to a "yin," restorative/recuperative repair and rebuilding (anabolic) phase during night-time sleep.
Virtually all of the known properties of GHB, including its slowing of heartbeat and respiration, mild hypothermia, muscle relaxation, lowered brain and muscle energy consumption, increasing of the deep and restorative sleep phases (stage 3 & 4 slow-wave sleep), increasing growth hormone output, to name just a few, are involved in this integrated 'regeneration reflex'. At the center of Laborit's explanation of the therapeutic nature of GHB-induced sleep is what he terms the 'neuron-neuroglia as a metabolic and functional pair'. (3)
The human brain is generally 'guesstimated' to contain 10-100 billion neurons. Yet it also contains roughly 10 times as many glial or neuroglial cells, also called 'astrocytes'. The astrocytes completely surround neurons, and in effect comprise the second half of the blood-brain barrier.
Astrocytes completely surround blood vessels feeding the brain, and play a role in distributing at least some blood-borne nutrients to the neurons, as well as having key roles in disposing of some neuronal metabolite wastes. (20). Astrocyte neuroglia also secrete a number of growth factors for neurons. Some, like nerve growth factor, may stimulate the neuron as a whole, while others may increase growth of axons. (20). Neurons are the electrically active signalling cells in the brain, transmitting billions of electrical impulses between each other every second.
Neurons have the highest metabolic rate of any cells in the body, and are furious 'burners' of glucose (blood sugar) in the glycolytic-mitochondrial energy cycles to generate the massive ATP energy supplies they run on. Glial cells are metabolically more passive, 'burning' sugar primarily through the glycolytic and pentose shunt pathways. (3).
Drawing upon his own laboratory's research as well as the published research of hundreds of other scientists, Laborit discovered that GHB reverses the normal daytime pattern of energetic activity in the brain.
When we're awake, the glial cells are relatively quiescent, while the billions of neurons are intensely metabolically and electrically active. During normal sleep, and even more so during GHB sleep, the electrical-metabolic activity of neurons quiet down (especially during slow-wave sleep) and glial cells become more active. (metabolizing glucose through the pentose shunt, a non-oxygen using pathway).
The pentose shunt generates two key substances that are critically important for neurons to regenerate themselves during sleep, when they must restore their ion balances (sodium/potassium) and neurotransmitter stores, as well as engage in new protein synthesis.
The pentose pathway generates the 5-carbon sugar, ribose, which is the base of RNA. RNA in turn, as messenger, transfer, and ribosomal RNA, is the key to new protein synthesis. During sleep, neurons must repair the damage to their protein structures (e.g. the antenna-like neurotransmitter receptors on their cell membrane surfaces, microtubules, etc.) as well as elaborate new protein involved in memory consolidation.
The pentose pathway also generates NADPH, the chief 'reducing equivalent' of cells. (25). It is NADPH that ultimately allows neurons to repair the free radical damage created by the combination of their high daytime oxygen-using metabolic activity and the high polyunsaturated fat content of brain mitochondrial and cell membranes.
In the course of mitochondrial ATP bioenergy metabolism, neurons inevitably generate masses of hydrogen peroxide (H2O2). (22). Neurons are particularly vulnerable to damage by H2O2. (21,22). The main detoxifier of H2O2 is an enzyme called 'glutathione peroxidase' (GSH-Px). (21). GSH-Px in turn requires reduced glutathione (GSH) to dispose of H2O2 and the lipid peroxides ('rancid fats') that H2O2 creates in brain cell and mitochondrial membranes. (21).
GSH is also involved in protecting against/repairing oxidized proteins. (21). Unfortunately, neurons are unable to create GSH by themselves, and must depend upon glial cells to provide them with it. (24). When the neurons use GSH to detoxify H2O2, lipid peroxides, oxidized proteins, etc., the reduced glutathione (GSH) is 'burned up' and becomes oxidized glutathione (GSSG). And this is where the neuroglia 'come to the rescue'.
When GHB stimulates glial pentose pathway metabolism, this produces NADPH. The NADPH then combines with the oxidized glutathione (GSSG), regenerating it back to the free radical-quenching reduced glutathione (GSH). GSH is also essential for regenerating vitamin E and vitamin C after they have 'sacrificed' themselves to quench various types of free radicals. (21).
Thus, because GHB is such a powerful and effective stimulator of glial pentose pathway metabolism, (1,3,4,16,17,23). and because GHB simultaneously slows down the free-radical producing mitochondrial energy metabolism in neurons, (3,4). GHB, far from being a 'severe neurotoxin', in effect becomes the anabolic agent to promote healing and restoration of neurons during sleep!
GHB: Other Uses
Given the space limitations of this article, it is impossible to present an in-depth summary of the many uses of GHB reported in the scientific literature. From a life extension/enhancement perspective, the unique ability of GHB to promote brain structure/function regeneration during sleep must surely be its most important general use. Laborit details other uses for it, including psychotherapy, (17) anti-depressive and anti-anxiety therapy, (17) and sexual disorders. (17)
With regard to sexual disorders he notes: "Since GHB causes disruption of neocortical pathways, it suppresses inhibition and creates a special condition relaxing neurotic controls and defences. Greater emotional liability may thus develop and produce readiness for stronger affectivity [feelings].
This 'relaxing' effect has been used very efficiently in certain sexual inhibitions that produce anxiety syndromes or real infirmities (premature ejaculation, frigidity). This effect is not aphrodisiac, but rather an effective or libidinal action-stimulating relationship, associated with an objective... sensitivity which produces stronger [clitoral] and vaginal sensitivity in women and marked delay of ejaculation in men."
GHB: Cautions!
The published literature on GHB stretching almost 40 years has consistently shown it to be a safe and non-toxic substance, rapidly metabolized, usually within 2 or 3 hours. However, because of its powerful sleep inducing and muscle relaxant effects, it must be used with care and caution! In addition, GHB may potentate the neuro-depressive effects of other agents (e.g. alcohol, opiates, benzodiazepines, barbiturates, etc.), all of which can by themselves severely depress-or even stop!-breathing.
Thus the following cautions must be observed to ensure safe and responsible GHB use.
1) Do not EVER mix GHB with central nervous system depressants including but not limited to: benzodiazepines- 'minor tranquillisers' such as Valium, Librium, Xanax, or Halcion; 'major tranquillisers' such as Thorazine, Haldol or Stellazine; opiates-such as codeine, morphine, heroin, opium, or Vicodin; barbiturates such as phenobarbital; alcohol; or even various non-prescription allergy and sleep remedies.
2) Do not drive or operate dangerous devices or machinery (e.g. chainsaws, guns, power tools, construction machinery, etc.) while under the influence of GHB.
3) GHB has a rapid, but variable, onset of action when taken orally, and taking GHB after food may delay its action. Therefore it is unwise to delay going to bed after taking GHB. You may literally pass out on the couch, at the dinner table, going upstairs, etc. if you delay after taking GHB. Indeed, in most GHB sleep studies, subjects are advised to take GHB once they're already in bed. It is also best NOT to take GHB right after a meal (wait 2-4 hours, depending on meal size) as this may cause nausea or even vomiting in some individuals.
4) If you choose to 'cancel' your choice after taking GHB, a large cup of strong caffeinated coffee may counteract the GHB, depending on the dose of GHB taken. (4). This is not recommended as a 'standard practice', though.
GHB: Side Effects
GHB is generally considered to be without serious side effects. However, depending on unique individual health, emotional, metabolic, psychoactive drug history and liver status effects, GHB can have various 'side effects'. These may include fatigue and drowsiness, dizziness and 'light-headedness', nausea, diarrhoea, and occasionally, vomiting. Ataxia (clumsiness, poor co-ordination) may occur. Myoclonias (spasming or jerking of muscles, especially of limbs or face) may occur during the onset of GHB sleep. On rare occasions bed-wetting, confusion and sleepwalking may occur-although sleepwalking has only been reported in narcoleptics. These effects are temporary, and will usually dissipate with 4-24 hours after a GHB dose.
GHB: Contraindications
"There are only very few contraindications: severe alcoholics and epileptics..., patients with eclampsia, severe arterial hypertension, or bradycardia caused by conduction modifications. It should be noted that all hypolipemias with diarrhoea, vomiting, Cushing's syndrome, and renal duct lesions caused by chronic corticoid [cortisol, prednisone, etc.] treatment must first be thoroughly diagnosed and have potassium chloride prescribed before GHB treatment." (17).
GHB: Dosage
Sleep studies have typically used 1.5 to 3gms GHB at bedtime, with possibly a second or third (1-2.5gm) dose if subject awakens during night and can't return to sleep. Many people who use GHB as a sleep aid/restorative find their sleep need decreases 1/2 to 2 hours/night, yet they feel more rested than usual. Thus only those who demand their 'full 8 hours' of 'coma' before arising would be likely to need a third dose during the night.
For use as a sexual aid, probably only 1/2gm is needed (even slightly more, and sleep may ensue-that's usually not a 'sexual aid'!).
Some people have reported 1/2gm, used occasionally, is effective as an anti-anxiety aid, or to restore emotional equilibrium after an intense shock or emotional 'blow up'.

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"You are what you eat you can't possibly be anything else"

or put another way "eat sh*t look like sh*t!!"

Aftershock