GHB, a now illegal compound once sold in health food stores, was discovered in 1963 as a naturally-occurring substance in the human brain [Nature 1963;200: pp.1207-8].
For a summary of the history and actions of GHB please visit our GHB Summary page.
Researchers have suggested that GHB acts as a neurotransmitter, but the mechanism of action producing the clinical effects is unknown.
See the link between Alcoholism and GHB.
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.
In a rigorous, double-blind, placebo-controlled study conducted on alcoholics, "...nearly all withdrawal symptoms disappeared within 2-7 hours" after administration of GHB. On a severe-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].
GHB induces "remarkable hypotonia" (muscle relaxation) [Vickers, 1969] and is now gaining popularity in France and Italy as an aid to childbirth. GHB 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) [Vickers, 1969; Laborit, 1964].
GHB stimulates 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 2.5gm of GHB in 6 healthy men between the ages 25-40 [Takahara, 1977]. GH levels were still seven-fold higher after 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.
GHB has been reported to help decrease pain and improve sleep amongst fibromyalgia patients.
In a study of 100 patients at the Warsaw Institute of Hematology, GHB was shown to lower cholesterol levels.
An IND (Investigational New Drug Application) has been filed with the FDA for GHB's proposed action on improving poor memory.
GHB has been report to help decrease hyperactivity and learning disabilities in some children.
GHB has been reported to reduce schizophrenia symptoms, but must not be used with some psychotropic drugs, such as Valium, Thorazine, Dilantin or Phenobarbital.
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, 1969]. 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.
Several independent investigators have reported beneficial effects by GHB against narcolepsy, with two double-blind studies having been published [Scrima et al, 1989 and 1990; Lammers et al., 1993]. Based on these two reports, there is little doubt that the drug is helpful to narcoleptic patients and several other independent investigators have confirmed the findings.
GHB was used in the 1970s to treat sleep disorders, and some interest in this use continues. Some doctors feel it is the most reliable medication for inducing sleep that exists. It is thought to induce rapid eye movement sleep, decreasing symptoms of narcolepsy. Many prominent doctors have been outspoken about the unnecessary legal restrictions placed on this naturally-occurring substance. Medical use in the treatment of narcolepsy is usually 50mg/kg per day.
The most consistent and least controversial effects are improved cataplexy and improved nocturnal sleep disruption with GHB treatment [Scrima et al., 1990; Broughton and Mamelak, 1980: Bedard et al., 1990]. Further investigations would be needed to confirm a possible beneficial effect for daytime sleepiness. Importantly, GHB's anti-cataplectic effects are clearly mediated by a different mode of action when compared to those produced by antidepressant compounds. As such, patients who do not tolerate classical antidepressant treatment because of side-effects, tolerance or contraindications would not have any other choice if GHB were not available to them.
An IND (Investigational New Drug Application) has been filed with the FDA for GHB's proposed action on reducing nocturnal myoclonus (painful leg cramps at night).
GHB has been called "almost an ideal sleep inducing substance" [Smart Drugs 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 both normal and GHB-induced sleep, the central nervous system 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, 1964].
The primary disadvantage of GHB's use as a sleep aid is its short term influence – some 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 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. Some people never achieve sleep even with the doses normally used for such purposes. In addition, Takahara (1977) reported in a growth-hormone study that one man remained conscious even though he had received GHB intravenously at a dosage which rendered the rest of the participants unconscious.