Abuse Of Gamma-hydroxybutyrate Research Articles

Sodium Oxybate: a Substitute for Alcohol?

Gamma-hydroxybutyrate (GHB) is a neurotransmitter found naturally in the human brain. Sodium oxybate (SO) is the sodium salt of GHB. In 2000 GHB was classified a Schedule I controlled substance, while SO became a Schedule III controlled substance for medicinal use under the Controlled Substances Act. SO and alcohol share a similar pharmacological profile. GHB acts on GABAB receptors and extrasynaptic GABAA receptors resulting in alcohol-mimetic effects in several CNS actions. It substitutes the discriminative stimulus effects of alcohol in rats, and has cross tolerance with alcohol. All together, this leads to think of SO as a substitution therapy for alcohol use disorders. SO was initially studied in the prevention of alcohol withdrawal, and it showed similar efficacy to benzodiacepines. The studies on relapse prevention were developed later and the results are mixed and more complex to understand. While open label studies show a positive effect, RCTs have not been able to show a significant effect for the whole sample. Nevertheless, post-hoc analysis show a robust effect in the subsample of patients with high risk drinking levels, that would be the preferred target for a substitution treatment. The potential for abuse of GHB is well documented, which should be no surprise for a substitution treatment. Nevertheless, when correctly prescribed the risk of abuse of SO remains very low, as shown both in clinical trials and in the pharmacovigilance database, with more than 260000 cases documented. SO can be considered a substitution treatment, effective in patients with high risk drinking levels.DisclosureI was investigator in the SMO study on sodium oxybate, funded by D&A Pharma.

Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline.

This guideline establishes clinical practice recommendations for the treatment of central disorders of hypersomnolence in adults and children. The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine to develop recommendations and assign strengths to each recommendation, based on a systematic review of the literature and an assessment of the evidence using the GRADE process. The task force provided a summary of the relevant literature and the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations that support the recommendations. The AASM Board of Directors approved the final recommendations. The following recommendations are intended to guide clinicians in choosing a specific treatment for central disorders of hypersomnolence in adults and children. Each recommendation statement is assigned a strength ("strong" or "conditional"). A "strong" recommendation (ie, "We recommend…") is one that clinicians should follow under most circumstances. A "conditional" recommendation (ie, "We suggest…") is one that requires that the clinician use clinical knowledge and experience and strongly consider the individual patient's values and preferences to determine the best course of action. Under each disorder, strong recommendations are listed in alphabetical order followed by the conditional recommendations in alphabetical order. The section on adult patients with hypersomnia because of medical conditions is categorized based on the clinical and pathological subtypes identified in ICSD-3. The interventions in all the recommendation statements were compared to no treatment. We recommend that clinicians use modafinil for the treatment of narcolepsy in adults. (STRONG). We recommend that clinicians use pitolisant for the treatment of narcolepsy in adults. (STRONG). We recommend that clinicians use sodium oxybate for the treatment of narcolepsy in adults. (STRONG). We recommend that clinicians use solriamfetol for the treatment of narcolepsy in adults. (STRONG). We suggest that clinicians use armodafinil for the treatment of narcolepsy in adults. (CONDITIONAL). We suggest that clinicians use dextroamphetamine for the treatment of narcolepsy in adults. (CONDITIONAL). We suggest that clinicians use methylphenidate for the treatment of narcolepsy in adults. (CONDITIONAL). We recommend that clinicians use modafinil for the treatment of idiopathic hypersomnia in adults. (STRONG). We suggest that clinicians use clarithromycin for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL). We suggest that clinicians use methylphenidate for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL). We suggest that clinicians use pitolisant for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL). We suggest that clinicians use sodium oxybate for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL). We suggest that clinicians use lithium for the treatment of Kleine-Levin syndrome in adults. (CONDITIONAL). We suggest that clinicians use armodafinil for the treatment of hypersomnia secondary to dementia with Lewy bodies in adults. (CONDITIONAL). We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to Parkinson's disease in adults. (CONDITIONAL). We suggest that clinicians use sodium oxybate for the treatment of hypersomnia secondary to Parkinson's disease in adults. (CONDITIONAL). We suggest that clinicians use armodafinil for the treatment of hypersomnia secondary to traumatic brain injury in adults. (CONDITIONAL). We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to traumatic brain injury in adults. (CONDITIONAL). We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to myotonic dystrophy in adults. (CONDITIONAL). We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to multiple sclerosis in adults. (CONDITIONAL). We suggest that clinicians use modafinil for the treatment of narcolepsy in pediatric patients. (CONDITIONAL). We suggest that clinicians use sodium oxybate for the treatment of narcolepsy in pediatric patients. (CONDITIONAL). Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2021;17(9):1881-1893.

Gamma-hydroxybutyrate abuse: pharmacology and poisoning and withdrawal management.

Gamma-hydroxybutyrate (GHB) is a central nervous system depressant primarily used as a recreational drug of abuse, but also for the treatment of narcolepsy with cataplexy in adult patients and as an adjuvant for control of alcohol withdrawal syndrome. The main aim of this review is to summarise updated knowledge about GHB pharmacokinetics and pharmacodynamics, acute poisoning, and clinical features of GHB withdrawal syndrome, its diagnosis and medical treatment. The most common clinical signs and symptoms of acute poisoning include sleepiness to deep coma, bradycardia, hypotension, and respiratory failure. Therapy is essentially supportive and based on continuous monitoring of vital signs. GHB withdrawal syndrome shares patterns with other withdrawal syndromes such as alcohol withdrawal and is sometimes difficult to distinguish, especially if toxicological tests are GHB-negative or cannot be performed. There are no official detoxification protocols for GHB withdrawal syndrome, but its therapy is based on benzodiazepine. When benzodiazepine alone is not effective, it can be combined with barbiturates or antipsychotics. Information about abuse and distribution of GHB and its precursors/analogues among the general population is still limited. Their prompt identification is therefore crucial in conventional and non-conventional biological matrices, the latter in particular, to clarify all the issues around this complex molecule.

Incidence of Gamma-Hydroxybutyrate (GHB) abuse and dependence in a rural crisis resolution team in the Netherlands

IntroductionGHB abuse and dependence are common in the Western region of Northern Brabant, a rural region in the south of the Netherlands.AimThe main goal is to look at the incidence and management of GHB abuse and dependence seen by the CRT in a rural area.MethodThis is a retrospective data analysis based on patient files of all assessments of the Western Northern Brabant crisis resolution team (CRT) from 2013 till 2015. Inclusion criterion was current or recent (<24 hours) use of GHB with or without alcohol and other drugs. Several parameters were studied: frequency, duration and dose of GHB use, reason for referral and treatment/policy, which is used (admission, prescribed medication).ResultsOn a total of 4093 cases 50 persons were included. It shows that the percentage over the years has remained about the same (resp. 1.13%, 1.54% and 1.02%). Of all cases 41.5% used GHB only, 39.6% also used other drugs, and 9.4% GHB with alcohol and other drugs. During the assessment in the emergency department 37.7% was treated with a benzodiazepine, while 43.4% received no psychotropic medication.ConclusionGHB abuse and dependence are not commonly seen in the CRT, but the withdrawal symptoms can be challenging and GHB withdrawal is often accompanied by aggressive outbursts. Therefore, it is very important to make a decision whether outpatient or inpatient treatment is necessary and if psychotropic medication is needed.

Gamma-hydroxybutyrate (GHB) induces cognitive deficits and affects GABAB receptors and IGF-1 receptors in male rats

In recent years, the abuse of the club drug gamma-hydroxybutyrate (GHB) has become increasingly popular among adolescents. The drug induces euphoria but can also result in sedation, anaesthesia as well as short-term amnesia. In addition, the abuse of GHB causes cognitive impairments and the mechanism by which GHB induces these impairments is not clarified. The present study investigates the impact of GHB treatment on spatial learning and memory using a water maze (WM) test in rats. Furthermore, the behavioural data is combined with an autoradiographic analysis of the GABAB and the IGF-1 receptor systems. The results demonstrate that the animals administered with GHB display an impaired performance in the WM test as compared to controls. In addition, significant alterations in GABAB and IGF-1 receptor density as well as GABAB receptor functionality, were observed in several brain regions associated with cognitive functions e.g. hippocampus. To conclude, our findings suggest that GHB treatment can affect spatial learning and memory, and that this outcome at least to some extent is likely to involve both GABAB and IGF-1 receptors.

SAT2 * TREATMENT OF ALCOHOL ADDICTION: HOW TO USE SODIUM OXIBATE? (D&A) * SAT2.2 * NEUROBIOLOGY OF GHB IN RELATION TO ALCOHOL DEPENDENCE

SAT2 * TREATMENT OF ALCOHOL ADDICTION: HOW TO USE SODIUM OXIBATE? (D&A) * SAT2.2 * NEUROBIOLOGY OF GHB IN RELATION TO ALCOHOL DEPENDENCE

The impact of gamma hydroxybutyrate (GHB) legal restrictions on patterns of use: Results from an International Survey

Aims: To conduct an Internet-based survey of gamma hydroxybutyrate (GHB) use and identify differences by respondent residence.Methods: We recruited GHB-knowledgeable persons via ‘social networking Internet sites’. Individuals (n = 314) or groups (n = 66) were approached based on GHB-use testimonials. Data collected: location, use and reason for cessation (if applicable).Findings: We recruited 155 GHB users. The US respondents (53 of the 70; 76%) compared to the non-US respondents (38 of 85; 45%) were older and more highly educated (p < 0.05) but manifest a three-fold greater adjusted odds of GHB cessation (odds ratio [OR] 3.1; 95% confidence interval [CI] 1.4–6.9; p < 0.05). Of the 80 respondents stating reason for cessation, 36 (45%) cited legal risk, price, or access; 44 (55%) cited health or related concerns. The US compared to the non-US respondents more frequently invoked legal and related concerns (OR 2.5; 95% CI 0.99–6.3; p = 0.05). In a nested analysis, narrowly stated legal (n = 4/5 the US) versus health (n = 6/18 the US) reasons differed by location (p = 0.048, one-tailed).Conclusions: In the US, where GHB has stricter legal penalties, GHB cessation is more likely, with legal and related reasons more commonly invoked for cessation. These findings support a link between the declining US GHB abuse and more stringent restrictions, although other un-assessed factors may also explain this association.

Gamma Hydroxybutyrate: An Ethnographic Study of Recreational Use and Abuse

Gamma hydroxybutyrate (GHB) is a psychoactive substance with complex neurophysiological activity and significant potential for abuse, addiction, and dangerous toxicity. In this study, a semistructured interview was administered to 17 subjects to investigate GHB use, including: manner of use; setting; positive and negative consequences; other drug history; and sexual practices. Respondents were overwhelmingly male, but otherwise had a broad demographic background. Settings varied from nightclubs to private use at home. There was significant variability in the drug obtained, which subjects found problematic because of the narrow therapeutic window and ease of accidental overdose. Common positive experiences included increased sexual desire, decreased sexual inhibitions, and decreased anxiety. Common negative consequences included oversedation, loss of consciousness, motor incoordination, and mental confusion. Nine subjects reported that they would use GHB again, some despite severe negative consequences. Although most subjects reported negative experiences, only three felt their use was problematic, and none sought treatment for GHB abuse or addiction. Subjects were highly drug-experienced, most commonly using MDMA, ketamine, cocaine, alcohol, and methamphetamine. Some reported that GHB could cause poor decision making in sexual situations. This effect has significant ramifications for issues such as date rape and control of sexually transmitted diseases, such as HIV.

Chronic intragastric administration of gamma-butyrolactone produces physical dependence in baboons

Abuse of gamma-hydroxybutyrate (GHB) and its precursors is a public health concern. Gamma-butyrolactone (GBL) is found in commercially available products and, when ingested, is metabolized to GHB. The goal was to evaluate the physical dependence potential and behavioral effects of GBL. Vehicle and then GBL were administered continuously (24 h per da y) in baboons (Papio anubis, n=5) via intragastric catheters. GBL dosing was initiated at 100 mg/kg/day and then progressively increased stepwise by increments of 100 mg/kg to a final dose of 600 mg/kg. The number of food pellets earned, fine-motor task performance, and observed behaviors were used as dependent measures. Precipitated withdrawal was evaluated after administration of GABA-B and benzodiazepine receptor antagonists during chronic GBL dosing (400-600 mg/kg). Spontaneous withdrawal was evaluated after discontinuation of chronic GBL 600 mg/kg. Blood GHB levels were determined during chronic dosing of each GBL dose by isotope dilution assay. Chronic GBL dose-dependently decreased food-maintained behavior, disrupted performance on the fine-motor task, and produced signs of sedation and muscle relaxation. The GABA-B antagonist SGS742 [56 mg/kg, intramuscular (IM)] precipitated a withdrawal syndrome, whereas the benzodiazepine antagonist flumazenil (5 mg/kg, IM) produced little or no effect. Signs of physical dependence were also demonstrated when chronic GBL dosing was discontinued. Analysis of plasma indicated GBL was metabolized to GHB; levels were 825 to 1,690 micromol l(-1) GHB and 2,430 to 3,785 micromol l(-1) GHB after week 1 of 400 and 600 mg/kg/day, respectively. These data indicate that, like GHB, chronic GBL dosing produced physical dependence that likely involved the GABA-B receptor.

Gamma-hydroxybutyrate – a drug of abuse

Gamma-hydroxybutyrate (GHB) is a drug of abuse that causes euphoria, anxiolysis, and hypnosis. The recent rise in the recreational intake of GHB, as well as its association with 'drug rape', has turned the attention to GHB in acute hospital settings. Acutely admitted GHB intoxicated patients may display various levels of sedation or coma, but may also show paradoxical agitation, combativeness, or self-injurious behaviors. The symptoms can be nonspecific and the definite diagnosis therefore normally relies on the detection of GHB in blood or body fluids, which is an analysis that may not be promptly available. As a basis for understanding the clinical features of GHB intoxication and abuse, we here review the pharmacological and neurophysiological knowledge about GHB, which stems from decades of clinical and basic GHB research. In addition, we discuss the latest discoveries in the quest for distinct GHB receptors in the brain, and their possible implications for future therapies of GHB abuse.

Unusually High Concentrations in a Fatal GHB Case

The first case in France involving a fatal overdose resulting from the ingestion of gamma-hydroxybutyrate (GHB) is presented. GHB was tested by gas chromatography-mass spectrometry (GC-MS) after precipitation. Briefly, 20 microL of body fluids (blood, bile, urine, gastric contents, or vitreous humor) was pipetted in a glass tube, followed by 20 microL GHB-d6 and 45 microL acetonitrile. After vortex mixing and centrifuging, the supernatant was collected and evaporated to dryness. The residue was derivatized with BSTFA with 1% TMCS for 20 min at 70 degrees C. After injection on a 30-m HP5 MS capillary column, GHB (m/z 233, 204, and 147) and GHB-d6 (m/z 239) were identified by MS. GHB was also tested in pubic hair after incubation in 0.01 N NaOH, neutralization, acidification, extraction in ethyl acetate and derivatization with MTBSTFA, using GC-MS-MS. GHB was positive in all the tested specimens, with the following concentrations 2937, 33,727, 1800, and 2856 mg/L in femoral blood, urine, bile, and vitreous humor, respectively. This seems to be the highest blood concentration ever observed. Postmortem redistribution appears weak, as the concentration in cardiac blood was 3385 mg/L (cardiac blood/femoral blood ratio of 1.15). Oral route was suggested with GHB at 7.08 g in 100 mL of gastric contents. Pubic hair analysis clearly indicated chronic GHB abuse, with concentrations along the shaft in the range 19.4 to 25.0 ng/mg (in comparison with physiological concentrations < 2 ng/mg). Methylenedioxymethamphetamine was present in femoral blood at 144 ng/mL. These results are consistent with an acute fatal overdose of GHB.

Gamma hydroxy butyrate abuse and dependency

The recreational use of gamma hydroxy butyrate (GHB) has gained popularity over the last decade. GHB was initially sold as a safe body building and fat burning compound. It is now also widely abused by body builders and young ravers. GHB attracts young people due the euphoria that it initially produces, and the claimed increase in sociability and sexual function (it is also known as liquid Ecstasy). Over the last few years, there has been an increase in the number of cases of GHB intoxication, dependence and severe withdrawal, as reported in medical literature. The situation is complicated by the use of GHB analogues, other toxic chemicals that are easily converted into GHB. GHB has recently been classified as a class 'C' drug in the UK, but no provisions were made in relation to GHB analogues. GHB has been increasingly used in rape cases due to its capacity to produce intoxication and amnesia. The management of patients dependent on GHB is rather complicated due to the high doses of medication that they require to control withdrawal symptoms.

Nonfatal Instances of Intoxication with γ-Hydroxybutyrate in the United Kingdom

There has been much publicity regarding the use and abuse of gamma-hydroxybutyrate (GHB, "liquid ecstasy," or "GBH"). GHB has been found to be an endogenous compound but has also been used for various therapeutic applications in addition to illicit use, particularly as a dietary supplement, sexual adjunct, and "party drug." Toxicological analysis was performed using urine and/or plasma specimens from 27 nonfatal instances of suspected GHB intoxication in the United Kingdom between May 1998 and May 2003. GHB was detected in the plasma and urine, invariably with the additional presence of ethanol and other drugs of abuse (eg, amphetamines, cocaine, and morphine). GBL was also detected in the majority of urine specimens analyzed but was not detected in the plasma samples (<10 mg/L). The mean plasma and urine concentrations measured as "total GBL" were found to be 245 mg/L (range 86-551 mg/L) and 1732 mg/L (range 5-5581 mg/L), respectively. This is believed to be the largest compilation of nonfatal cases from the United Kingdom.

Club drugs: methylenedioxymethamphetamine, flunitrazepam, ketamine hydrochloride, and gamma-hydroxybutyrate.

The abuse of methylenedioxymethamphetamine (MDMA), flunitrazepam, ketamine hydrochloride, and gamma-hydroxybutyrate (GHB) is discussed. Club drugs are chemical substances used recreationally in social settings. Use is increasingly frequent among young people, especially during all-night dance parties. All four agents have been classified as controlled substances. MDMA ("ecstasy") is available as a tablet, a capsule, and a powder; formulations may contain many adulterants. MDMA increases the release of neurotransmitters. The desired effects are euphoria, a feeling of intimacy, altered visual perception, enhanced libido, and increased energy. The most common adverse effects are agitation, anxiety, tachycardia, and hypertension. More serious adverse effects include arrhythmias, hyperthermia, and rhabdomyolysis. Flunitrazepam is a potent benzodiazepine. At higher doses, the drug can cause lack of muscle control and loss of consciousness. Other adverse effects are hypotension, dizziness, confusion, and occasional aggression. Ketamine is a dissociative anesthetic used primarily in veterinary practice. It may be injected, swallowed, snorted, or smoked. Like phencyclidine, ketamine interacts with the N-methyl-D-aspartate channel. Analgesic effects occur at lower doses and amnestic effects at higher doses. Cardiovascular and respiratory toxicity may occur, as well as confusion, hostility, and delirium. GHB, a naturally occurring fatty acid derivative of gamma-aminobutyric acid, was introduced as a dietary supplement. Increasing doses progressively produce amnesia, drowsiness, dizziness, euphoria, seizures, coma, and death. Flunitrazepam, ketamine, and GHB have been used to facilitate sexual assault. Supportive care is indicated for most cases of club drug intoxication. The increasing abuse of MDMA, flunitrazepam, ketamine hydrochloride, and GHB, particularly by young people in social settings such as clubs, should put health care professionals on guard to recognize and manage serious reactions.

GHB: a new and novel drug of abuse

There has been increasing attention in the United States to problems of abuse of gamma-hydroxybutyrate (GHB), with some evidence for problems in other parts of the world as well. In vitro and animal research show that, while GHB shares some properties with abused central nervous system depressant drugs, it has unique aspects of its pharmacology as well, including actions at a specific neural receptor which probably mediates many of its effects. Abuse potential assessment of GHB using standard animal models has not yielded a picture of a highly abusable substance, but little human testing has yet been done. Very little systematic data exist on tolerance and dependence with GHB, but both have been seen in human users. Quantitative data on the prevalence of GHB abuse is incomplete, but various qualitative measures indicate that a mini-epidemic of abuse began in the late 1980s and continues to the present. GHB is often included with the group of ‘club drugs’, and can be used as an intoxicant. It also has been used as a growth promoter and sleep aid and has been implicated in cases of ‘date rape’, usually in combination with alcohol. Undoubtedly the easy availability of GHB and some of its precursors has contributed to its popularity. Recent changes in the control status of GHB in the US may reduce its availability with as yet unknown consequences for the scope of the public health problem. Drug abuse experts need to familiarize themselves with GHB as possibly representing a new type of drug abuse problem with some unique properties.

Severe gamma-hydroxybutyrate withdrawal: a case report and literature review

We report a case of gamma-hydroxybutyrate (GHB) withdrawal resulting in severe agitation, mental status changes, elevated blood pressure, and tachycardia hours after stopping chronic use of GHB. The patient admitted to substantial GHB abuse on a daily basis for 2.5 years. Previous attempts at cessation reportedly resulted in diaphoresis, tremors, and agitation. The patient’s symptoms, negative polypharmacy history, and negative urine and blood toxicological analysis for alcohol, benzodiazepines, sedative-hypnotics, or other substances suggested the diagnosis of GHB withdrawal. Later analysis of a patient drug sample confirmed the presence of GHB. The patient required 507 mg of lorazepam and 120 mg of diazepam over 90 h to control agitation. This is one of the few reported cases of GHB withdrawal and one of the most severe. Given the increasing use of GHB, more cases of severe GHB withdrawal should be anticipated.

Gamma‐hydroxybutyrate: an emerging drug of abuse that causes physical dependence

Gamma-hydroxybutyrate (GHB) is a compound found in mammalian brain which meets many criteria of a neurotransmitter. GHB has been investigated as a tool for inducing absence (petit mal) seizures, for use as an anesthetic, and for treatment of narcolepsy, alcohol dependence and opiate dependence. Since 1990 GHB has been abused in the United States for euphoric, sedative and anabolic effects. Coma and seizures have been reported following abuse of GHB, but dependence liability has received little attention. The neuropharmacology, potential therapeutic uses and acute adverse effects of GHB are reviewed, followed by a case series of eight people using GHB. Adverse effects of GHB may include prolonged abuse, seizure activity and a withdrawal syndrome. This withdrawal syndrome includes insomnia, anxiety and tremor; withdrawal symptoms resolve in 3-12 days. GHB has the potential to cause a significant incidence of abuse and adverse effects. Prolonged use of high doses may lead to a withdrawal syndrome, which resolves without sequelae. Educational efforts should address the narrow therapeutic index, possible physical dependence and dangers of combining GHB with other drugs of abuse.

Gamma-hydroxybutyrate: an emerging drug of abuse that causes physical dependence

Gamma-hydroxybutyrate (GHB) is a compound found in mammalian brain which meets many criteria of a neurotransmitter. GHB has been investigated as a Tool for inducing absence (petit mal) seizures, for use as an anesthetic, and for treatment of narcolepsy, alcohol dependence and opiate dependence. Since 1990 GHB has been abused in the United States for euphoric, sedative and anabolic effects. Coma and seizures have been reported following abuse of GHB, but dependence liability has received little attention. The neuropharmacology, potential therapeutic uses and acute adverse effects of GHB are reviewed, followed by a case series of eight people using GHB. Adverse effects of GHB may include prolonged abuse, seizure activity and a withdrawal syndrome. This withdrawal syndrome includes insomnia, anxiety and tremor; withdrawal symptoms resolve in 3-12 days. GHB has the potential to cause a significant incidence of abuse and adverse effects. Prolonged use of high doses may lead to a withdrawal syndrome, which resolves without sequelae. Educational efforts should address the narrow therapeutic index, possible physical dependence and dangers of combining GHB with other drugs of abuse.

Sites of action of gamma-hydroxybutyrate (GHB)--a neuroactive drug with abuse potential.

This review highlights the biochemistry, pharmacology, and toxicology of the naturally-occurring fatty acid derivative, gamma-hydroxybutyrate (GHB). GHB is derived from gamma-aminobutyric acid (GABA) and is proposed to function as an inhibitory chemical transmitter in the central nervous system. When administered in pharmacological doses, its powerful central nervous system depressant effects are readily observed. Although some of the neurophysiological actions of GHB could involve alterations in dopaminergic transmission in the basal ganglia, both its physiological and pharmacological actions are probably mediated through specific brain receptors for GHB. In addition, GHB might mediate some of its effects through interaction with the GABA(B) receptor. Experimentally, GHB has been used as a model for petit mal epilepsy; clinically, it has been used as a general anesthetic and as a drug to treat certain sleep disorders and related conditions. Owing to the purported ability of GHB to induce a state of euphoria, recreational use of this substance is popular. Although no deaths or long-term problems have been associated with GHB abuse, symptoms of GHB intoxication can be severe. The continued potential for GHB abuse makes it imperative for clinical toxicologists to be aware of the effects of this agent. Future research on the mechanism of action of GHB is needed to elucidate both its central nervous system depressant properties and its ability to effect a state of well-being.

"Grievous bodily harm:" gamma hydroxybutyrate abuse leading to a Wernicke-Korsakoff syndrome.

Gamma-hydroxybutyrate (GHB) is a naturally occurring GABA-like drug used illicitly by bodybuilders. Although there are reports of several cases of GHB abuse, with a variety of nervous system complications, we present the first case associated with a Wernicke-Korsakoff syndrome.