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?
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."
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.
"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).
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'.
1. H. Laborit (1964) 'Sodium 4 - Hydroxybutyrate' Int J Neuropharmacol 3, 433-52.
2. M.-Y. Chin et al (1992) 'Acute Poisoning from Gamma-Hydroxybutyrate in California' 156, 380-84.
3. H. Laborit (1973) 'Gamma-Hydroxybutyrate, Succinic Semialdehyde and Sleep' Prog Neurobiol 1, 255-74.
4. M. Mamelak (1989) 'Gammahydroxybutyrate: An Endogenous Regulator of Energy Metabolism' Neurosci & Biobehav Rev 13, 187-98.
5. G. Tunnicliff (1992) 'Significance of Gamma-Hydroxybutyric Acid in the Brain' Gen Pharmacol 23, 1027-34.
6. C. Cash (1994) 'Gammahydroxybutyrate: An Overview of the Pros and Cons for it Being a Neurotransmitter and/or a Useful Therapeutic Agent' Neurosci & Biobehav Rev 18, 291-304.
7. W Dean et al, 'GHB, The Natural Mood Enhancer', Petaluma, CA: Smart Pub., 1998.
8. M. Vickers (1969) 'Gammahydroxybutyric Acid' Int Anaesthesia Clin 7, 75-89.
9. J. Takahara et al (1977) 'Stimulatory Effects of [GHB] on Growth Hormone and Prolactin Release in Humans' J Clin Endocrinol Metab 44, 1014-17.
10. R. Broughton & M. Mamelak 'The Treatment of Narcolepsy-Cataplexy with Nocturnal Gamma-Hydroxybutyrate' Can J Neurol Sci 6, 1-6.
11. M. Scharf et al (1985) 'The Effects and Effectiveness of Gamma-Hydroxybutyrate in Patients with Narcolepsy' J Clin Psychiatry 46, 222-25.
12. M. Mamelak et al (1986) 'Treatment of Narcolepsy with Gamma-Hydroxybutyrate. A Review of Clinical and Sleep Laboratory Findings' Sleep 9, 285-89.
13. L. Scrima et al (1989) 'Efficacy of Gamma-Hydroxybutyrate versus Placebo in Treating Narcolepsy-Cataplexy: Double-Blind Subjective Measures' Biol Psychiatry 26, 331-43.
14. L. Scrima et al (1990) 'The Effects of Gamma-Hydroxybutyrate on the Sleep of Narcolepsy Patients' Sleep 13, 479-90.
15. A. Boyd et al (1990) 'The Protective Effect of Gamma-Hydroxybutyrate in Regional Intestinal Ischemia in the Hamster' Gastroenterol 99, 860-62.
16. G. Pierrefiche et al (1991) 'Protective Effects of Gamma-Hydroxybutyrate on Alloxan Induced Diabetes in Mice' Res Comm Chem Path Pharmacol 71, 309-19.
17. J. Muyard & H. Laborit (1977) "Gammahydroxybutyrate' in Psychotherapeutic Drugs, Vol. 2, part 2, E. Usdin & I. Forrest, eds., 1339-75. N.Y: Marcel Dekker.
18. T. Oyama & M. Takiguchi (1970) 'Effects of Gamma-Hydroxybutyrate and Surgery on Plasma Human Growth Hormone and Insulin Levels' Aggressologie II, 289-98.
19. O. Lapierre et al (1990) 'The Effect of Gamma-Hydroxybutyrate on Nocturnal and Diurnal Sleep of Normal Subjects' Sleep 13, 24-30.
20. H. Kimelberg and M. Norenberg (1989) 'Astrocytes' Sci Am 260, 66-76.
21. S. Levine & P. Kidd, Antioxidant Adaptation, S.F. : Biocurrents Pub., 1985.
22. R. Bradford & H. Allen, Oxidology, Chula Vista, CA: R.W. Bradford Foundation, 1997.
23. P. Taberner et al (1972) 'The Action of Gamma-Hydroxybutyric Acid on Cerebral Glucose Metabolism' J Neurochem 19, 245-54.
24. J. Sagara et al (1993) 'Maintenance of Neuronal Glutathione by Glial Cells' J. Neurochem 61, 1672-76.
25. D. Reed (1986) 'Regulation of Reductive Processes by Glutathione' Biochem Pharmacol 35, 7-13.
26. J. Morgenthaler & D. Joy, Better Sex Through Chemistry, Petaluma, CA: Smart Pub. 1995.
27. L. Gallimberti et al (1989) '[GHB] for Treatment of Alcohol Withdrawal Syndrome' Lancet, 9-30-89, 787-89.
28. L. Gallimberti et al (1993) 'Gamma-Hydroxybutyric Acid for Treatment of Opiate Withdrawal Syndrome' Neuropsychopharmacol 9, 77-81.
29. L. Gallimberti et al (1994) 'Gamma-Hydroxybutyric Acid in Treatment of Opiate Withdrawal' Eur Arch Psychiatr Clin Neurosci 244, 113-14.
30. J. Sassin et al (1969) 'Human Growth Hormone Release: Relation to Slow-Wave Sleep and Sleep-Walking Cycles' Science #3892, 513-15.