sodium-oxybate and Substance-Withdrawal-Syndrome

γ-hydroxybutyrate (GHB) is synthesized endogenously from γ-aminobutyric acid (GABA) or exogenously from 1,4-butanediol (butane-1,4-diol; 1,4-BD) or γ-butyrolactone (GBL). GBL, and 1,4-BD are rapidly converted to GHB. The gastric absorption time, volume of distribution, and half-life of GHB are between 5 and 45 min, 0.49 ± 0.9 L/kg, and between 20 and 60 min, respectively. GHB and its analogues have a dose-dependent effect on the activation of GHB receptor, GABA-B, and GABA localized to the central nervous system. After ingestion, most patients present transient neurological disorders (lethal dose: 60 mg/kg). Chronic GHB consumption is associated with disorders of use and a withdrawal syndrome when the consumption is discontinued. GHB, GBL, and 1,4-BD are classified as narcotics but only the use of GHB is controlled internationally. They are used for drug facilitated (sexual) assault, recreational purposes, slamsex, and chemsex. To confirm an exogenous intake or administration of GHB, GBL, or 1-4-BD, the pre-analytical conservation is crucial. The antemortem cutoff doses for detection are 5 and 5-15 mg/L, with detection windows of 6 and 10 h in the blood and urine, respectively Control of GHB is essential to limit the number of users, abuse, associated risks, and death related to their consumption.

Topics: 4-Butyrolactone; gamma-Aminobutyric Acid; Humans; Sodium Oxybate; Substance Withdrawal Syndrome

GHB (gamma-hydroxybutyric acid; sodium oxybate) is a general anaesthetic that is clinically used for the treatment of narcolepsy, cataplexy, alcohol withdrawal and alcohol relapse prevention. In addition, GHB is recreationally used. Most clinical and recreational users regard GHB as an innocent drug devoid of adverse effects, despite its high dependence potential and possible neurotoxic effects. At high doses, GHB may lead to a comatose state. This paper systematically reviews possible cognitive impairments due to clinical and recreational GHB use.. PubMed and PsychINFO were searched for literature data about the acute and residual cognitive deficits following GHB use. This review is conducted using the PRISMA protocol.. A total of 43 reports covering human and animal data on GHB-induced cognitive impairments were eligible and reviewed. This systematic review found no indication for cognitive impairments after clinical GHB use. However, it supports the view that moderate GHB use may result in acute short-term cognitive impairments, whereas regular high-dose GHB use and/or multiple GHB-induced comas are probably neurotoxic resulting in long-term residual cognitive impairments.. These results emphasize the need for awareness among clinicians and recreational users to minimize negative health consequences of recreational GHB use, particularly when high doses are used and GHB-induced comas occur.

Topics: Alcoholism; Animals; Cognitive Dysfunction; Coma; Humans; Hydroxybutyrates; Illicit Drugs; Neurotoxicity Syndromes; Sodium Oxybate; Substance Withdrawal Syndrome

Topics: Alcoholism; Humans; Randomized Controlled Trials as Topic; Sodium Oxybate; Substance Withdrawal Syndrome

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.

Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Illicit Drugs; Male; Middle Aged; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

Gamma-hydroxybutyrate (GHB) withdrawal is a life-threatening condition that does not always respond to standard treatment with benzodiazepines. Baclofen has potential utility as a pharmacological adjunct and anecdotal reports suggest that it is being used by drug users to self-manage GHB withdrawal symptoms. Here, we investigate current patterns of use and the online availably of baclofen.. Data triangulation techniques were applied to published scientific literature and publicly accessible Internet resources (grey literature) to assess the use of baclofen in GHB withdrawal. An Internet snapshot survey was performed to identify the availability of baclofen for online purchase and the compliance of retailers with the UK regulations. Data were collected according to pre-defined criteria.. A total of 37 cases of baclofen use in GHB withdrawal were identified in the scientific literature, as well as 51 relevant discussion threads across eight Internet forums in the grey literature. Baclofen was available to purchase from 38 online pharmacies, of which only one conformed to the UK regulations.. There is limited published evidence on the use of baclofen in GHB withdrawal, but both scientific and grey literature suggests clinical utility. Online pharmacies are readily offering prescription-only-medication without prescription and due to inadequate regulation, pose a danger to the public.

Topics: Animals; Baclofen; Biomedical Research; Drug Trafficking; GABA-B Receptor Agonists; Humans; Internet; Pharmaceutical Services, Online; Practice Patterns, Physicians'; Prescription Drugs; Psychotropic Drugs; Social Media; Sodium Oxybate; Substance Withdrawal Syndrome; United Kingdom

Gamma-hydroxybutyrate (GHB or sodium oxybate) is both an exogenous and endogenous molecule with neuromodulator properties. In the United States, GHB is an approved drug for the treatment of narcolepsy and narcolepsy with cataplexy in adults. In some European Union countries, sodium oxybate is applied for the treatment of opioid and alcohol withdrawal.. The aim of the present review was to describe the state of art of the pre-clinical research and the clinical evidence related to GHB used alone or in combination with other treatments in alcohol withdrawal syndrome and alcohol abstinence maintenance.. Internationally published pre-clinical findings and clinical studies investigating the effects of GHB on alcohol withdrawal syndrome and alcohol abstinence maintenance were collected and described considering seven clinical studies involving GHB in the treatment of alcohol withdrawal abstinence and five clinical studies involving GHB in the treatment of alcohol abstinence maintenance. Furthermore, GHB pharmacology and characteristics of abuse were briefly detailed.. Clinical evidence indicates that GHB is effective in reducing symptoms of alcohol withdrawal syndrome and produces beneficial effects comparable to those of benzodiazepines or chlometiazole. GHB proved effective in increasing alcohol abstinence maintenance and in reducing alcohol craving, but it did not show any influence in relapses of heavy drinkers when given alone. Conversely, it seems to be effective in reducing relapses in alcohol dependent patients when given in combination with naltrexone and escitalopram.. Despite this bunch of evidence, studies are still limited and investigations including a larger number of patients are needed. In addition, some safety concerns, such as insufficiency against hallucinations in alcohol withdrawal and potential development of GHB dependence have to be more investigated.

Topics: Alcohol Abstinence; Alcohol-Related Disorders; Central Nervous System Agents; Humans; Sodium Oxybate; Substance Withdrawal Syndrome

Gamma-hydroxybutyrate (GHB) is a drug of abuse, for which physical addiction develops quickly. GHB withdrawal can develop into a life-threatening condition and has previously been treated mainly with benzodiazepines. These have not always proven effective, leading to long hospitalizations in intensive care units. Based on successful Dutch treatment results for using GHB to treat GHB withdrawal symptoms, we propose to implement a similar method in Denmark. The method requires an interdisciplinary effort for which The Danish Poison Information Centre should be consulted for expertise.

Topics: Algorithms; Benzodiazepines; Drug Administration Schedule; Humans; Sodium Oxybate; Substance Withdrawal Syndrome

γ-Hydroxybutyrate (GHB) is a common drug of abuse and poses important health risks to users in the form of respiratory, cardiovascular, mental, or traumatic adverse events. GHB has non-dose-proportional effects and pharmacologic effects such as sedation and retrograde amnesia, which can incapacitate people targeted for assault. It has Krebs cycle metabolism, rapid clearance, relative hydrophilicity, and unique drug interactions. Promptly seeking medical attention during intentional or inadvertent overdose is critical to survival, as is prompt supportive care once medical personnel are alerted. People drugged before assault also need to promptly notify authorities because the period to detect the drug in the urine or blood is brief and the ultimate metabolites are carbon dioxide and water. After acute treatment has passed, withdrawal could be severe in chronic abusers that could harm the patient directly or drive them back into reuse.

Topics: Anesthetics, Intravenous; Animals; Drug Overdose; Humans; Illicit Drugs; Rape; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

The misuse of γ-hydroxybutyrate (GHB) for recreational purposes has resulted in an increase in GHB-related problems such as intoxications, dependence and withdrawal in several countries in Europe, Australia and the US over the last decade. However, prevalence rates of misuse of GHB and its precursor, γ-butyrolactone (GBL), are still relatively low. In this qualitative review paper, after a short introduction on the pharmacology of GHB/GBL, followed by a summary of the epidemiology of GHB abuse, an overview of GHB dependence syndrome and GHB/GBL withdrawal syndrome is provided. Finally, the existing literature on management of GHB detoxification, both planned and unplanned, as well as the available management of GHB withdrawal syndrome, is summarized. Although no systematic studies on detoxification and management of withdrawal have been performed to date, general recommendations are given on pharmacological treatment and preferred treatment setting.

Topics: 4-Butyrolactone; Animals; Humans; Inactivation, Metabolic; Secondary Prevention; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

Gamma-hydroxybutyrate (GHB) is a putative neurotransmitter, a drug of abuse, and a medical treatment for narcolepsy and other neuropsychiatric disorders. Its precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are endogenously converted to GHB and thereby exert their psychobehavioural effects. In humans, GHB has a wide spectrum of properties ranging from stimulation and euphoria in lower doses, to sedation, deep sleep, and coma after ingestion of high doses. However, behavioural studies in healthy volunteers remain scarce and are usually limited to psychomotor performance testing. Most available data arise from either qualitative studies with illicit users or clinical trials examining therapeutic properties of GHB (then usually termed sodium oxybate). Here, we present an overview of the behavioural effects of GHB, GBL, and 1,4-BD in these three populations. GHB and its precursors strongly influence behaviours related to core human autonomic functions such as control of food intake, sexual behaviour, and sleep-wake regulation. These effects are instrumentalised by illicit users and clinically utilised in neuropsychiatric disorders such as narcolepsy, fibromyalgia, and binge-eating syndrome. Considering the industry withdrawal from psychopharmacology development, repurposing of drugs according to their behavioural and clinical profiles has gained increasing relevance. As such, GHB seems to be an attractive candidate as an experimental therapeutic in depression.

Topics: 4-Butyrolactone; Animals; Butylene Glycols; Central Nervous System Depressants; Circadian Rhythm; Eating; Humans; Sexual Behavior; Social Behavior; Sodium Oxybate; Substance Withdrawal Syndrome

The treatment of alcohol use disorder (AUD) with sodium oxybate (SMO) or gamma-hydroxybutyric acid (GHB) was introduced in Italy and Austria more than 20 years and 15 years ago, respectively, and it is now widely employed to treat alcohol withdrawal syndrome (AWS) and to maintain alcohol abstinence. These indications derive from its similar structure to the inhibitory neurotransmitter γ-amino-butyric acid (GABA), exerting an ethanol-mimicking effect, because it binds to GABAB receptors. Craving for, and abuse of, SMO remain a controversial issue; even though these unfavorable effects are evident in poly-drug addicted patients and in those with psychiatric diagnosis of borderline personality disorder. In addition, despite cases of severe intoxication and deaths being widely documented when GHB is used as "street drug"; its clinical use remains safe. Thus, the aim of the present review is to examine the role of SMO in the treatment of AUD, its possible implications in reducing alcohol consumption, and cases of abuse, and severe intoxication due to SMO during its clinical use in the treatment of AUD.

Topics: Adult; Aged; Aged, 80 and over; Alcohol Drinking; Alcohol-Related Disorders; Alcoholism; Austria; Female; Humans; Hydroxybutyrates; Italy; Male; Middle Aged; Sodium Oxybate; Substance Withdrawal Syndrome; Young Adult

x03B3;-Hydroxybutyrate (GHB) has gained popularity as a drug of abuse. In the Netherlands the number of patients in treatment for GHB dependence has increased sharply. Clinical presentation of GHB withdrawal can be life threatening. We aim, through this overview, to explore the neurobiological pathways causing GHB dependency and withdrawal, and their implications for treatment choices.. In this work we review the literature discussing the findings from animal models to clinical studies focused on the neurobiological pathways of endogenous but mainly exogenous GHB.. Chronic abuse of GHB exerts multifarious neurotransmitter and neuromodulator effects on x03B3;-aminobutyric acid (GABA), glutamate, dopamine, serotonin, norepinephrine and cholinergic systems. Moreover, important effects on neurosteroidogenesis and oxytocin release are wielded. GHB acts mainly via a bidirectional effect on GABAB receptors (GABABR; subunits GABAB1 and GABAB2), depending on the subunit of the GIRK (G-protein-dependent ion inwardly rectifying potassium) channel involved, and an indirect effect of the cortical and limbic inputs outside the nucleus accumbens. GHB also activates a specific GHB receptor and β1-subunits of α4-GABAAR. Reversing this complex interaction of neurobiological mechanisms by the abrupt cessation of GHB use results in a withdrawal syndrome with a diversity of symptoms of different intensity, depending on the pattern of GHB abuse.. The GHB withdrawal symptoms cannot be related to a single mechanism or neurological pathway, which implies that different medication combinations are needed for treatment. A single drug class, such as benzodiazepines, gabapentin or antipsychotics, is unlikely to be sufficient to avoid life-threatening complications. Detoxification by means of titration and tapering of pharmaceutical GHB can be considered as a promising treatment that could make polypharmacy redundant.

Topics: Animals; Brain; Humans; Neurons; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

The illicit recreational drug of abuse, γ-hydroxybutyrate (GHB) is a potent central nervous system depressant and is often encountered during forensic investigations of living and deceased persons. The sodium salt of GHB is registered as a therapeutic agent (Xyrem®), approved in some countries for the treatment of narcolepsy-associated cataplexy and (Alcover®) is an adjuvant medication for detoxification and withdrawal in alcoholics. Trace amounts of GHB are produced endogenously (0.5-1.0 mg/L) in various tissues, including the brain, where it functions as both a precursor and a metabolite of the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). Available information indicates that GHB serves as a neurotransmitter or neuromodulator in the GABAergic system, especially via binding to the GABA-B receptor subtype. Although GHB is listed as a controlled substance in many countries abuse still continues, owing to the availability of precursor drugs, γ-butyrolactone (GBL) and 1,4-butanediol (BD), which are not regulated. After ingestion both GBL and BD are rapidly converted into GHB (t½ ~1 min). The Cmax occurs after 20-40 min and GHB is then eliminated from plasma with a half-life of 30-50 min. Only about 1-5% of the dose of GHB is recoverable in urine and the window of detection is relatively short (3-10 h). This calls for expeditious sampling when evidence of drug use and/or abuse is required in forensic casework. The recreational dose of GHB is not easy to estimate and a concentration in plasma of ~100 mg/L produces euphoria and disinhibition, whereas 500 mg/L might cause death from cardiorespiratory depression. Effective antidotes to reverse the sedative and intoxicating effects of GHB do not exist. The poisoned patients require supportive care, vital signs should be monitored and the airways kept clear in case of emesis. After prolonged regular use of GHB tolerance and dependence develop and abrupt cessation of drug use leads to unpleasant withdrawal symptoms. There is no evidence-based protocol available to deal with GHB withdrawal, apart from administering benzodiazepines.

Topics: Animals; Drug Interactions; Humans; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

Sodium oxybate (SMO) has been shown to be safe and effective in the treatment of patients with alcohol use disorders (AUDs); it was approved in Italy and Austria for the treatment of alcohol withdrawal syndrome and for relapse prevention. The focus of this review is to discuss the clinical evidence on the therapeutic potential of SMO for AUDs.. This review covers the studies in patients with alcohol withdrawal syndrome who received SMO for the treatment of withdrawal symptoms and the studies in patients with AUDs who received SMO to achieve total alcohol abstinence, reduction of alcohol intake, and relapse prevention. Relevant medical literature on SMO was identified by searching databases including MEDLINE and EMBASE (searches last updated 20 September 2013), bibliographies from published literature, clinical trial registries/databases, and websites.. SMO has proved safe and effective in the treatment of alcohol withdrawal syndrome and in the prevention of relapses. Craving for and abuse of SMO have been reported, in particular in some subtypes of alcoholic patients, e.g., those affected by co-addiction and/or psychiatric comorbidity. Future multicenter, multinational, randomized clinical trials should be useful to optimize the treatments in relation with patients' characteristics, for example, pharmacogenetic, neurobiological, and psychological.

Topics: Alcohol Drinking; Alcoholism; Animals; Drug Approval; Humans; Secondary Prevention; Sodium Oxybate; Substance Withdrawal Syndrome; Temperance; Treatment Outcome

A liquid formulation of sodium oxybate (Alcover(®)), the sodium salt of γ-hydroxybutyric acid (GHB), is approved in Italy and Austria for use in alcohol withdrawal syndrome and for the maintenance of abstinence in alcohol dependence. This article reviews the efficacy and tolerability of sodium oxybate in alcohol withdrawal syndrome and in the maintenance of abstinence in alcohol dependence, as well as summarizing its pharmacological properties. Results of randomized controlled trials indicate that sodium oxybate was at least as effective as diazepam and clomethiazole in patients with alcohol withdrawal syndrome, rapidly alleviating symptoms, and was at least as effective as naltrexone or disulfiram in the maintenance of abstinence in alcohol-dependent patients. Sodium oxybate was generally well tolerated. The risk of sodium oxybate abuse is generally low when it is administered to alcohol-dependent patients at its approved dosage, under the supervision of a designated family member and with continuous strict medical surveillance. However, certain patient groups, such as patients with alcohol dependence and borderline personality disorder or who are in remission from heroin or cocaine addiction, may not be suitable candidates for sodium oxybate therapy because of an increased risk of abuse. In conclusion, sodium oxybate is a useful option for the treatment of alcohol withdrawal syndrome and for the maintenance of abstinence in alcohol dependence.

Topics: Alcohol Abstinence; Alcohol Deterrents; Alcohol Drinking; Alcoholism; Animals; Behavior, Addictive; Disease Models, Animal; Drug Interactions; Humans; Sodium Oxybate; Substance Withdrawal Syndrome

In several countries, including the Netherlands, the use of GHB seems to be rising. GHB is regarded by recreational users as an innocent drug without any side effects. Recently, the number of patients in treatment due to GHB addiction sharply increased. In addition, various studies report incidents following risky GHB use or GHB overdosing. Other sedative drugs, like ketamine and alcohol have been shown to result in unintended neurotoxic harm at the level of memory and cognitive function. As outlined in the present review, GHB and ketamine have a common mode of action, which suggests that GHB may also lead to similar neurotoxicity as ketamine. GHB overdosing, as well as binge drinking (and high ketamine doses), induce profound coma which is probably neurotoxic for the brain especially in the maturing brain of young adults. It is therefore advocated to investigate possible long-term neurotoxic effects in recreational GHB users e.g. by studying the residual effects on cognition and memory.

Topics: Alcoholism; Anesthetics; Anesthetics, Dissociative; Animals; Central Nervous System Depressants; Cognition Disorders; Coma; Drug Overdose; Ethanol; Glutamic Acid; Humans; Illicit Drugs; Ketamine; Neurotoxicity Syndromes; Oxidative Stress; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders; Succinate-Semialdehyde Dehydrogenase

Gamma-hydroxybutyrate (GHB) and its precursors, gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), are drugs of abuse which act primarily as central nervous system (CNS) depressants. In recent years, the rising recreational use of these drugs has led to an increasing burden upon health care providers. Understanding their toxicity is therefore essential for the successful management of intoxicated patients. We review the epidemiology, mechanisms of toxicity, toxicokinetics, clinical features, diagnosis, and management of poisoning due to GHB and its analogs and discuss the features and management of GHB withdrawal.. OVID MEDLINE and ISI Web of Science databases were searched using the terms "GHB," "gamma-hydroxybutyrate," "gamma-hydroxybutyric acid," "4-hydroxybutanoic acid," "sodium oxybate," "gamma-butyrolactone," "GBL," "1,4-butanediol," and "1,4-BD" alone and in combination with the keywords "pharmacokinetics," "kinetics," "poisoning," "poison," "toxicity," "ingestion," "adverse effects," "overdose," and "intoxication." In addition, bibliographies of identified articles were screened for additional relevant studies including nonindexed reports. Non-peer-reviewed sources were also included: books, relevant newspaper reports, and applicable Internet resources. These searches produced 2059 nonduplicate citations of which 219 were considered relevant.. There is limited information regarding statistical trends on world-wide use of GHB and its analogs. European data suggests that the use of GHB is generally low; however, there is some evidence of higher use among some sub-populations, settings, and geographical areas. In the United States of America, poison control center data have shown that enquiries regarding GHB have decreased between 2002 and 2010 suggesting a decline in use over this timeframe.. GHB is an endogenous neurotransmitter synthesized from glutamate with a high affinity for GHB-receptors, present on both on pre- and postsynaptic neurons, thereby inhibiting GABA release. In overdose, GHB acts both directly as a partial GABA(b) receptor agonist and indirectly through its metabolism to form GABA.. GHB is rapidly absorbed by the oral route with peak blood concentrations typically occurring within 1 hour. It has a relatively small volume of distribution and is rapidly distributed across the blood-brain barrier. GHB is metabolized primarily in the liver and is eliminated rapidly with a reported 20-60 minute half-life. The majority of a dose is eliminated completely within 4-8 hours. The related chemicals, 1,4-butanediol and gamma butyrolactone, are metabolized endogenously to GHB. CLINICAL FEATURES OF POISONING: GHB produces CNS and respiratory depression of relatively short duration. Other commonly reported features include gastrointestinal upset, bradycardia, myoclonus, and hypothermia. Fatalities have been reported. MANAGEMENT OF POISONING: Supportive care is the mainstay of management with primary emphasis on respiratory and cardiovascular support. Airway protection, intubation, and/or assisted ventilation may be indicated for severe respiratory depression. Gastrointestinal decontamination is unlikely to be beneficial. Pharmacological intervention is rarely required for bradycardia; however, atropine administration may occasionally be warranted. WITHDRAWAL SYNDROME: Abstinence after chronic use may result in a withdrawal syndrome, which may persist for days in severe cases. Features include auditory and visual hallucinations, tremors, tachycardia, hypertension, sweating, anxiety, agitation, paranoia, insomnia, disorientation, confusion, and aggression/combativeness. Benzodiazepine administration appears to be the treatment of choice, with barbiturates, baclofen, or propofol as second line management options.. GHB poisoning can cause potentially life-threatening CNS and respiratory depression, requiring appropriate, symptom-directed supportive care to ensure complete recovery. Withdrawal from GHB may continue for up to 21 days and can be life-threatening, though treatment with benzodiazepines is usually effective.

Topics: 4-Butyrolactone; Antidotes; Butylene Glycols; Charcoal; Humans; Sodium Oxybate; Substance Withdrawal Syndrome; Therapeutic Irrigation; Tissue Distribution

Gamma-hydroxybutyric acid (GHB, "liquid ecstasy") and its legal prodrugs gamma-butyrolactone and 1,4-butanediol are gaining importance as recreational drugs in Germany. Because of the wide availability of GHB and its prodrugs physicians are increasingly being confronted with cases of intoxication. The effect of GHB intoxication is comparable with those of alcohol and/or benzodiazepines. Likewise, symptoms of withdrawal may occur. In this review, we summarise current data regarding the history, pharmacodynamics and pharmacokinetics of the drug as well as the relevant symptoms of intoxication or withdrawal as they pertain to neurology and psychiatry.

Topics: Adolescent; Germany; Humans; Illicit Drugs; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders; Young Adult

Gamma-hydroxybutyrate (GHB) is naturally present in the human body, but may also be used as an intoxicating drug. Information from several sources has suggested its increased availability and use in Norway. There have also been reports of an increasing use of the chemical precursor gamma-butyrolactone (GBL).There is currently a need for knowledge on symptoms, addictiveness and overdoses, as well as targeted preventive measures.. The article is based on a discretionary selection of articles resulting from a literature search in PubMed, as well as reports from Norwegian and European authorities and research institutions.. An intake of small amounts of GHB produces an intoxicating effect, whereas higher doses can result in poisoning. Deaths have been reported. The effect may be variable, due to a steep dose-response curve and interaction with alcohol and other intoxicants. Treatment of poisoning is symptomatic and supportive. Treatment of abstinence is also supportive, while delirium may be treated as delirium tremens.. Preventive measures should be tailored specifically to potential user-groups.

Topics: 4-Butyrolactone; Citric Acid Cycle; Drug Overdose; Europe; Humans; Illicit Drugs; Norway; Sodium Oxybate; Solvents; Substance Withdrawal Syndrome; Substance-Related Disorders

Chronic excessive alcohol consumption may lead to dependence, and to alcohol withdrawal syndrome (AWS) in case of abrupt drinking cessation. Gamma-hydroxybutyric acid (GHB) can prevent and suppress withdrawal symptoms, and improve the medium-term abstinence rate. A clear balance between effectiveness and harmfulness has not been yet established.. To evaluate the efficacy and safety of GHB for treatment of AWS and prevention of relapse. We searched Cochrane Drugs and Alcohol Group' Register of Trials (October 2008), PubMed, EMBASE, CINAHL (January 2005 - October 2008), EconLIT (1969 to February 2008), reference list of retrieved articles. Randomized controlled trials (RCTs) and Controlled Prospective Studies (CPS) evaluating the efficacy and the safety of GHB vs placebo or other pharmacological treatments.. Three authors independently extracted data and assessed the methodological quality of studies.. Thirteen RCTs were included. Eleven studies were conducted in Italy.For withdrawal syndrome, comparing GHB 50mg with placebo, results from 1 study, 23 participants favour GHB for withdrawal symptoms: WMD -12.1 (95% CI, -15.9 to -8.29) and side effects were more frequent in the placebo group: RR 16.2 (95% CI, 1.04 to 254.9).In the comparison with Chlormetiazole, for GHB 50mg, results from 1 study, 21 participants favour GHB for withdrawal symptoms: MD -3.40 (95% CI -5.09 to -1.71), for GHB 100mg, results from 1 study, 98 participants favour anticonvulsants for side effects: RR 1.84 (95% CI 1.19 to 2.85).At mid-term, comparing GHB with placebo, results favour GHB for abstinence rate (RR 5.35; 1.28-22.4), controlled drinking (RR 2.13; 1.07-5.54), relapses (RR 0.36; 0.21-0.63), and number of daily drinks (WMD -4.60; -6.18 to -3.02). GHB performed better than NTX and Disulfiram on abstinence (RR 2.59; 1.35-4.98, RR 1.66; 0.99-2.80 respectively). The association of GHB and NTX was better than NTX on abstinence (RR 12.2; 1.79-83.9), as well was the association of NTX, GHB and Escitalopram versus Escitalopram alone (RR 4.58; 1.28-16.5). For Alcohol Craving Scale results favour GHB versus placebo (WMD -1.90; -2.45 to 1.35) and Disulfiram (WMD -1.40; -1.86 to-0.94).. GHB 50mg is effective compared to placebo in the treatment of AWS, and in preventing relapses in previously detoxified alcoholics at 3 months follow-up, but the results of this review do not provide sufficient evidence in favour of GHB compared to benzodiazepines and Chlormethiazole for AWS prevention. GHB is better than NTX and Disulfiram in maintaining abstinence and it has a better effect on craving than placebo and Disulfiram. Side effects of GHB are not statistically different from those with BZD, NTX or Disulfiram. However, concern has been raised regarding the risk of developing addiction, misuse or abuse, especially in polydrug abusers.

Topics: Alcoholism; Ethanol; Humans; Randomized Controlled Trials as Topic; Secondary Prevention; Sodium Oxybate; Substance Withdrawal Syndrome

Gamma-hydroxybutyric acid (GHB) is a neurotransmitter that occurs naturally in the brain and is increasingly being used as a 'party drug' because of its relaxing and euphoria-inducing effects. GHB has a limited medical use in the treatment of narcolepsy. GHB-intoxications occur often in non-medical use, and generally result in a coma of short duration. GHB use several times a day can lead to tolerance and dependence. After sudden cessation or reduction of intensive GHB use, a severe withdrawal syndrome may occur with symptoms varying from tremor, anxiety and agitation to autonomic instability, hallucinations and delirium. Treatment of the GHB withdrawal syndrome consists of supportive care and benzodiazepines, often in high doses. The controlled detoxification of GHB using pharmaceutical GHB in an adjusted dose is currently being investigated in the Netherlands. There is no literature concerning the treatment of patients following GHB intoxication or after detoxification.

Topics: Adjuvants, Anesthesia; Coma; Drug Tolerance; Humans; Narcolepsy; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

The chronic abuse of Gamma-Hydroxybutyrate (GHB) as a designer drug as well as it's physiological precursors Gamma-Butyrolactone (GBL) and 1,4-Butandiole (1,4-BD) confronts child and adolescent psychiatrists with new challenges. The acute withdrawal of GHB with its cardiovascular and delirant symptoms is of particular importance for child and adolescent psychiatrists.. In the present paper theoretical and biological aspects of acute GHB-/GBL-/1,4-BD-withdrawal syndrome are presented, and selected cases are discussed as regards potential treatment.. High dose treatment with benzodiazepines was successful in some cases of acute GHB-/GBL-/1,4-BD-withdrawal syndrome. Complications were severe dystonia under neuroleptic treatment, and also side-effects of treatment with benzodiazepines. Further problems were vegetative symptoms, electrocardiographic changes, rhabdomyolysis, acute renal failure, and death.. Acute GHB-withdrawal syndrome is a life-threatening condition which requires immediate intensive care treatment along with continuous monitoring of vital parameters. As acute GHB-withdrawal syndrome can present with symptoms close to psychotic episodes or acute alcohol withdrawal this condition is relevant for child and adolescent psychiatrists.

Topics: 4-Butyrolactone; Acute Disease; Adolescent; Anesthetics, Intravenous; Antipsychotic Agents; Benzodiazepines; Butylene Glycols; Child; Critical Care; Delusions; Diagnosis, Differential; Drug Interactions; Humans; Psychoses, Substance-Induced; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

1,4-butanediol (1,4-BD) is an industrial solvent that is metabolized to gamma-hydroxybutyrate (GHB), a gamma-aminobutyric acid agonist and central nervous system depressant. GHB and its analogues are popular drugs of abuse. Withdrawal from these agents is characterized by autonomic instability and altered mental status. We report a case of withdrawal from 1,4-BD lasting 6 days and complicated by new onset of seizures and rhabdomyolysis. In addition, we conducted a systematic review of the English literature pertaining to withdrawal from GHB, 1,4-BD and gamma-butyrolactone (GBL). Data collected from source articles included last use prior to symptom onset, clinical features on presentation, duration of symptoms and outcome. Twenty-seven studies with 57 episodes of withdrawal were included. Thirty-six cases (63%) involved GHB, 3 cases (5%) involved 1,4-BD and 18 (32%) involved GBL. The most common patient symptoms were tremor (67%), hallucinations (63%), tachycardia (63%) and insomnia (58%). Seizures and rhabdomyolysis each occurred in 7% of cases, but only 1 death occurred. Emergency physicians must consider withdrawal from these agents when patients present with clinical features suggestive of a sedative-hypnotic withdrawal syndrome.

Topics: 4-Butyrolactone; Adult; Butylene Glycols; Humans; Illicit Drugs; Male; Rhabdomyolysis; Seizures; Sodium Oxybate; Substance Withdrawal Syndrome

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.

Topics: Adult; Anabolic Agents; Anesthetics, Intravenous; Humans; Male; Rage; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Cataplexy; Humans; Retrospective Studies; Sodium Oxybate; Substance Withdrawal Syndrome

To examine the clinical course of gamma-hydroxybutyrate (GHB) withdrawal and generate management guidelines.. Review and analysis of all published reports of GHB or GHB precursor withdrawal identified from electronic searches.. In total, 38 cases of GHB (n = 28) or GHB precursor (n = 10) withdrawal were identified, 36 of which were from the US. A rapidly deteriorating course into delirium (53% of cases) was typical for heavily dependent users. Symptoms were broadly similar to alcohol withdrawal but often occurred earlier in usage with delirium being associated with severe dependence as determined by more frequent ingestion. High dose benzodiazepines were effective in pharmacological management of GHB withdrawal. In benzodiazepine refractory cases withdrawal responded to other sedative agents, mainly pentobarbital or chloral hydrate. No withdrawal seizures but one death was recorded.. GHB withdrawal is potentially life threatening and requires vigorous clinical management, preferably as an inpatient for severe cases. A management algorithm is proposed.

Topics: Female; Humans; Male; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

gamma-Hydroxybutyrate (GHB) is a GABA-active CNS depressant, commonly used as a drug of abuse. In the early 1990s, the US Drug Enforcement Administration (DEA) warned against the use of GHB and restricted its sale. This diminished availability of GHB caused a shift toward GHB analogues such as gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) as precursors and surrogates. Both GBL and 1,4-BD are metabolically converted to GHB. Furthermore, GBL is commonly used as a starting material for chemical conversion to GHB. As such, the clinical presentation and management of GBL and 1,4-BD intoxication shares a great deal of common ground with that for GHB. This similarity exists not only for acute intoxication but also for withdrawal in those patients with a history of extended high-dose abuse. This review examines the history of GHB analogue abuse as well as the clinical presentation and management of acute intoxication and withdrawal associated with abuse of these compounds.

Topics: 4-Butyrolactone; Body Temperature Regulation; Butylene Glycols; GABA Modulators; Humans; Illicit Drugs; Seizures; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

gamma-Hydroxybutyrate (GHB) is endogenous inhibitory transmitter that, when administered in pharmacological doses, has sedative-hypnotic properties. It is used in anaesthesia for the treatment of narcolepsy/catalepsy and in alcohol/opioid detoxification treatment regimens. Based on its purported anabolic effects, GHB use became established among bodybuilders. As the euphorigenic effects of GHB became publicised, attendees at dance clubs and rave parties began to use it alone or in combination with other psychoactive drugs. Following the ban of GHB in 1990, several precursor products (e.g. gamma-butyrolactone, butanediol) became widely used as replacement drugs until their ultimate proscription from lawful use in 2000. GHB and its precursors, like most sedative-hypnotic agents, can induce tolerance and produce dependence. Although many GHB users will experience a mild withdrawal syndrome upon drug discontinuation, those with chronic heavy GHB use can experience severe withdrawal. This syndrome clinically resembles the withdrawal syndrome noted from alcohol and other sedative-hypnotic drugs (e.g. benzodiazepines). Distinct clinical features of GHB withdrawal are its relatively mild and brief autonomic instability with prolonged psychotic symptoms. Patients with fulminant GHB withdrawal require aggressive treatment with cross-tolerant sedative hypnotics, such as benzodiazepines.

Topics: 4-Butyrolactone; Humans; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

Gamma hydroxybutyric acid (GHB) is a naturally occurring analog of gamma-aminobutyric acid (GABA) that has been used in research and clinical medicine for many years. In the past decade it has become very popular as a dietary supplement and recreational drug. Acute overdose leads to profound alteration of mental status and variable amounts of respiratory depression. With proper management, most patients recover fully within six hours. However, respiratory arrest and death have been reported in severe GHB intoxication. In addition to acute overdose, there is a GHB withdrawal syndrome that is similar to sedative/hypnotic and ethanol withdrawal. Recently several congeners of GHB, gamma butyrolactone and 1,4-butanediol, have emerged as drugs of abuse and show toxidromes similar to GHB. Emergency physicians should be familiar with the presentation and management of GHB-related emergencies.

Topics: Anesthetics; Animals; Antidotes; Drug Interactions; Humans; Prodrugs; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

Neuroscientific underpinnings and pharmacotherapeutic treatments of substance use disorders are rapidly developing areas of study. In particular, there have been exciting new developments in our understanding of the involvement of excitatory amino acid neurotransmitter systems and the opiate and serotonin systems in the pathophysiology of alcohol withdrawal, alcohol dependence, and in subtypes of individuals with alcoholism. In this article, new developments in the pharmacotherapy of alcohol dependence will be reviewed. In particular, the use of anticonvulsants in alcohol withdrawal and protracted abstinence syndromes will be discussed. New data on opiate antagonists and acamprosate, an agent that exerts actions through excitatory amino acid systems in relapse prevention, will be reviewed. Finally, there will be a review of new data concerning the use of serotonin reuptake inhibitors in subtypes of alcoholism and the use of combination pharmacotherapy.

Topics: Acamprosate; Adjuvants, Anesthesia; Alcohol Deterrents; Alcoholism; Anticonvulsants; Buspirone; Carbamazepine; Drug Therapy; Ethanol; Humans; Naltrexone; Narcotic Antagonists; Randomized Controlled Trials as Topic; Ritanserin; Serotonin Agents; Sodium Oxybate; Substance Withdrawal Syndrome; Taurine; Valproic Acid; Vigabatrin

The pathophysiology of substance withdrawal is elucidated by a review of classic and cutting-edge research. The manifestation and evaluation of the associated withdrawal syndromes from ethanol, sedative-hypnotics, opioids, and baclofen, are compared. The general management of and pharmacotherapy for these patients are discussed.

Topics: Alcohol Withdrawal Delirium; Analgesics, Opioid; Baclofen; Emergencies; Emergency Treatment; Ethanol; Humans; Hypnotics and Sedatives; Muscle Relaxants, Central; Sodium Oxybate; Substance Withdrawal Syndrome

Topics: Acetaldehyde; Alcohol Withdrawal Delirium; Anesthesia, General; Blood Proteins; Carbon Dioxide; Catecholamines; Ethanol; Hemoperfusion; Humans; Opioid-Related Disorders; Oxygen; Pregnanediones; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

γ-Hydroxybutyrate (GHB) is used as a treatment for narcolepsy and alcohol withdrawal and as a recreational substance. Nevertheless, there are limited data on the pharmacokinetics and pharmacokinetic-pharmacodynamic relationships of GHB in humans. We characterized the pharmacokinetic profile and exposure-psychotropic effect relationship of GHB in humans.. Two oral doses of GHB (25 and 35 mg kg(-1) ) were administered to 32 healthy male subjects (16 for each dose) using a randomized, placebo-controlled, cross-over design.. Maximal concentrations of GHB were (geometric mean and 95% CI): 218 (176-270) nmol ml(-1) and 453 (374-549) nmol ml(-1) for the 25 and 35 mg kg(-1) GHB doses, respectively. The elimination half-lives (mean ± SD) were 36 ± 9 and 39 ± 7 min and the AUC∞ values (geometric mean and 95% CI) were 15 747 (12 854-19 290) and 40 113 (33 093-48 622) nmol∙min ml(-1) for the 20 and 35 mg kg(-1) GHB doses, respectively. Thus, plasma GHB exposure (AUC0-∞ ) rose disproportionally (+40%) with the higher dose. γ-Hydroxybutyrate produced mixed stimulant-sedative effects, with a dose-dependent increase in sedation and dizziness. It did not alter heart rate or blood pressure. A close relationship between plasma GHB exposure and its psychotropic effects was found, with higher GHB concentrations associated with higher subjective stimulation, sedation, and dizziness. No clockwise hysteresis was observed in the GHB concentration effect plot over time (i.e., no acute pharmacological tolerance).. Evidence was found of a nonlinear dose-exposure relationship (i.e., no dose proportionality) at moderate doses of GHB. The effects of GHB on consciousness were closely linked to its plasma exposure and exhibited no acute tolerance.

Topics: Administration, Oral; Adult; Blood Pressure; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Tolerance; GABA Agonists; Healthy Volunteers; Heart Rate; Humans; Hypnotics and Sedatives; Male; Narcolepsy; Psychotropic Drugs; Sodium Oxybate; Substance Withdrawal Syndrome; Young Adult

Benzodiazepines (BDZs) are the gold standard in the treatment of alcohol withdrawal syndrome (AWS). Sodium oxybate (SMO) has been tested as a treatment for AWS with encouraging results. The aim of this phase IV, multicenter, randomized, double-blind, double-dummy study was to evaluate the efficacy of SMO in comparison with oxazepam in the treatment of uncomplicated AWS.. Alcohol-dependent outpatients (n = 126) affected by uncomplicated AWS according to the Clinical Institute Withdrawal Assessment for Alcohol-revised (CIWA-Ar) scale were enrolled in the study and randomized in two groups: 61 patients received SMO and 65 patients received oxazepam for 10 days. The primary endpoint was the reduction of symptoms of AWS measured by the change in the total CIWA-Ar score from baseline (day 1) to the end of the study (day 10). This study is registered with ClinicalTrials.gov, number: NCT02090504 RESULTS: A significant decrease of the mean total CIWA-Ar score from baseline to the end of the study was found in both the SMO (p < 0.0001) and the oxazepam group (p < 0.0001), with no significant differences between the two treatments (p = 0.21). Treatment with SMO and oxazepam resulted in a marked decrease in the severity of the mean CIWA subscales, i.e. sweating, tremor, and anxiety, with no significant differences between the two treatments. Both drugs were well tolerated and no severe side effects were reported.. SMO is as effective as oxazepam, one of the gold standard BDZs, in the treatment of uncomplicated AWS. Due to its tolerability and absence of significant side effects, SMO may be considered a valid alternative choice in the treatment of AWS.

Topics: Adult; Alcoholism; Anxiety; Craving; Double-Blind Method; Female; Humans; Male; Oxazepam; Severity of Illness Index; Sodium Oxybate; Substance Withdrawal Syndrome; Surveys and Questionnaires; Sweating; Treatment Outcome; Tremor

Sodium oxybate (SMO) is a GABA-ergic drug currently used for the treatment of alcohol-dependence in some European countries. In particular, clinical studies have shown a role of SMO in promoting alcohol abstinence, as well as in relieving withdrawal symptoms. The aim of this study was to describe alcohol abstinence and the onset of craving for and abuse of SMO in alcohol-dependent subjects with and without psychiatric co-morbidity. Forty-eight patients were enrolled and classified into two groups: group A (20 alcoholics without any psychiatric co-morbidity) and group B (28 alcoholics with a psychiatric co-morbidity). All patients were treated with oral SMO (50 mg/kg of body weight t.i.d.) for 12 weeks. Alcohol abstinence as well as alcohol drinking during the 12 weeks of treatment did not differ between the two groups at the end of treatment (p=0.9). In addition, a reduction of alcohol intake in both groups has been observed (p<0.0001). On the other hand, craving for SMO was significantly more frequent in group B than group A (p=0.001). Cases of SMO abuse were observed in almost 10% of group B patients. In conclusion, alcohol abstinence achieved through SMO administration does not differ in patients with and without psychiatric co-morbidity. However, alcoholics with co-morbid borderline disorders appear to be at high risk of developing craving for and abuse of the drug; therefore, SMO may not be indicated in these patients.

Topics: Alcohol Deterrents; Alcoholics; Alcoholism; Biomarkers, Pharmacological; Comorbidity; Ethanol; Female; GABA Agents; Humans; Male; Mental Disorders; Recurrence; Sodium Oxybate; Substance Withdrawal Syndrome; Temperance; Treatment Outcome

A double-blind, placebo-controlled sodium oxybate trial provided a unique opportunity to compare changes in cataplexy following gradual withdrawal from antidepressants in narcolepsy patients.. Of 228 enrolled patients, 71 discontinued antidepressant therapy. Data from 57 patients were available for analysis: 37 patients discontinued tricyclic antidepressants (TCAs) and 20 discontinued selective serotonin reuptake inhibitors (SSRIs). The trial included a 21-day withdrawal phase followed by 18-day washout and 14-day single-blind treatment phases. Two additional weeks were permitted for withdrawal from fluoxetine due to its long half-life. Weekly cataplexy attacks were recorded throughout the trial. No historical data on the frequency of cataplexy prior to treatment with antidepressants was available.. Among the patients who were and were not withdrawn from antidepressants treatment, the median frequency of baseline weekly cataplexy was similar (17.5 vs. 14.0, respectively). As expected, significant between-group differences emerged by the end of the washout period (52.04 vs. 15.25, respectively; p<0.05); however, the frequency of cataplexy events became similar again by the end of the trial (16.5 vs. 17.5, respectively).. Patients gradually withdrawn from antidepressants experienced a significant increase in cataplexy, but eventually returned to their baseline frequency, comparable to previously untreated control patients. Compared to SSRIs, discontinuation from TCAs was associated with a greater increase in cataplexy attacks.

Topics: Adult; Antidepressive Agents, Tricyclic; Cataplexy; Cohort Studies; Dose-Response Relationship, Drug; Humans; Narcolepsy; Retrospective Studies; Risk Factors; Selective Serotonin Reuptake Inhibitors; Sodium Oxybate; Substance Withdrawal Syndrome

Sodium oxybate (gamma-hydroxybutyrate; GHB) has demonstrated efficacy for the treatment of narcolepsy. However, there are reports of withdrawal following chronic abuse of illicit GHB which involve escalating both doses and dosing frequency. The present trial afforded an opportunity to test the hypothesis that chronic daily therapeutic dosing of sodium oxybate in narcoleptics does not cause withdrawal following abrupt cessation. Fifty-five narcoleptic patients, taking sodium oxybate (dose range 3-9 gm/night) for 7-44 months (mean 21 months), were randomized into a 2-week double-blind period: 29 patients received placebo and 26 continued to receive sodium oxybate. During this 2-week trial period, the following symptoms were reported in patients receiving placebo (N): anxiety (2), dizziness (1), insomnia (1) and somnolence (1). While these symptoms may represent possible symptoms of mild GHB withdrawal, they are also highly consistent with the returning symptoms of narcolepsy. We conclude there is minimal evidence of withdrawal symptoms following abrupt cessation of chronic sodium oxybate dosing in the therapeutic range.

Topics: Adult; Cataplexy; Double-Blind Method; Female; Humans; Male; Middle Aged; Narcolepsy; Sodium Oxybate; Substance Withdrawal Syndrome

Seeing as gamma-hydroxybutyrate (GHB) and benzodiazepines interact with the GABA-transmitter system, we investigated whether GHB can replace the conventional therapy, which uses benzodiazepines in the treatment of alcohol withdrawal syndrome in ICU settings.. 42 chronic alcoholics were included in this prospective and randomized study. Following the development of alcohol withdrawal syndrome, the patients were randomly allocated to the GHB or to the flunitrazepam group. In addition to this, clonidine was administered in order to treat autonomic signs of withdrawal. In cases were hallucinations occurred, haloperidol was administered.. There was no significant difference in the efficacy of treatment used in the duration of mechanical ventilation and intensive care unit stay between groups. The patients in the GHB-group required significantly higher dosages of haloperidol and significantly lower dosages of clonidine. 14 out of 21 patients from the GHB-group developed hypernatriaemia and 15 out of 21 developed a metabolic alkalosis.. Symptoms of the autonomic nervous system were more effectively prevented by GHB as evident in the lower dosage requirement of clonidine. However, GHB may not sufficiently block the hyperactivity of the dopaminergic system or may have an hallucinogenic effect itself. This may be evident from the higher dosages of haloperidol which were necessary. Due to the latter fact, the administration of GHB cannot be recommended in all patients suffering from AWS in ICU settings.

Topics: Adrenergic alpha-Agonists; Aged; Alkalosis, Respiratory; Anti-Anxiety Agents; Antipsychotic Agents; Clonidine; Critical Care; Ethanol; Female; Flunitrazepam; Haloperidol; Humans; Hypernatremia; Male; Middle Aged; Prospective Studies; Sodium Oxybate; Substance Withdrawal Syndrome

In a double-blind placebo-controlled trial, gamma-hydroxybutyric acid (GHB) (25 mg/kg orally) suppressed most of the withdrawal symptomatology in 14 heroin addicts and 13 methadone-maintained subjects. The GHB effect was prompt (within 15 minutes) and persisted for between 2 and 3 hours. Subsequently, the same patients received GHB in an open study every 2 to 4 hours for the first 2 days and 4 to 6 hours for the following 6 days: most abstinence signs and symptoms remained suppressed and patients reported felling well. Urine analysis failed to detect any presence of opiate metabolites. No withdrawal symptomatology recurred after 8 days of treatment when GHB was suspended, and patients were challenged with an intravenous injection of 0.4 mg naloxone. The results indicate that GHB may be useful in the management of opiate withdrawal.

Topics: Adult; Double-Blind Method; Heroin Dependence; Humans; Male; Methadone; Naloxone; Sodium Oxybate; Substance Withdrawal Syndrome

The effect of gamma-hydroxybutyric acid on alcohol consumption and alcohol craving in alcoholics was investigated in a randomized double-blind study versus placebo. Patients were treated as outpatients during a three month period either with gamma-hydroxybutyric acid (50 mg/kg/day, divided into three daily doses) or with placebo. Of the 82 alcoholics that entered the study, 71 completed it, 36 in the gamma-hydroxybutyric acid and 35 in the placebo group. Alcohol consumption was assessed by the subject's self report. At the 3rd month of treatment, 11 patients in the gamma-hydroxybutyric acid group referred to be abstinent and 15 referred controlled drinking; while in the placebo group only two and six patients referred abstinence and controlled drinking, respectively. Serum-gammaglutamyl-transferase activity correlated with the admitted alcohol consumption. Gamma-hydroxybutyric acid treatment decreased alcohol craving during the 3 months of treatment. Transient side effects were noted by six patients on gamma-hydroxybutyric acid and two on placebo. The results suggest that gamma-hydroxybutyric acid may be useful in the treatment of alcohol dependence.

Topics: Adult; Alcoholism; Double-Blind Method; Female; Follow-Up Studies; Humans; Liver Function Tests; Male; Sodium Oxybate; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome

The effect of gamma-hydroxybutyric acid (GHB) on ethanol withdrawal syndrome in alcoholics was investigated in a randomised double-blind study. Patients with withdrawal symptoms were treated either with GHB (orally in a syrup preparation) (11 patients) or with the syrup alone (12). GHB treatment (50 mg/kg) led to a prompt reduction in withdrawal symptoms, such as tremors, sweating, nausea, depression, anxiety, and restlessness. The only side-effect was dizziness. GHB may be useful in the management of alcohol withdrawal syndrome in man.

Topics: Administration, Oral; Adult; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Ethanol; Female; Humans; Hydroxybutyrates; Male; Middle Aged; Random Allocation; Severity of Illness Index; Sodium Oxybate; Substance Withdrawal Syndrome; Time Factors

Management of a withdrawal syndrome following cessation of regular gamma-hydroxybutyrate (GHB) use, and its precursors, can represent a clinical challenge due to rapid onset delirium and/or seizures. Severe GHB withdrawal can be characterised by persistent or worsening features despite increasing benzodiazepine doses and regular baclofen. Barbiturates, such as phenobarbital, are an appealing option in this context due to their unique GABA-A receptor action.. This series describes the use of phenobarbital in 13 cases, 12 patients, across two hospitals in Sydney, Australia, with persistent or progressive GHB withdrawal despite benzodiazepine-based management. A median cumulative dose of oral diazepam prior to commencing phenobarbital was 120 mg (range 80-255 mg). The median time from the last GHB use to the first dose of phenobarbital was 24 h (range 7-57 h). Eight cases received phenobarbital orally on a general ward and 5 intravenously in intensive care units. An improvement in GHB withdrawal symptoms was observed after phenobarbital in all cases and there were no adverse events related to phenobarbital.. This case series suggests that phenobarbital for the management of benzodiazepine-resistant GHB withdrawal can be safe, even in general inpatient settings, and may avert the progression of delirium. Most data on the management of GHB withdrawal comes from case reports or series, such as this one. This highlights the need for prospective trials to establish an evidence base for therapeutic approaches, including validated measures of withdrawal severity and more information relating to the safe and effective dosing of phenobarbital.

Topics: Benzodiazepines; Delirium; Humans; Phenobarbital; Prospective Studies; Sodium Oxybate; Substance Withdrawal Syndrome

Regular consumption of gamma-hydroxybutyrate (GHB) may result in a dependence syndrome that can lead to withdrawal symptoms. There are limited data on medications to manage GHB withdrawal.. To examine characteristics associated with delirium and discharge against medical advice (DAMA), in the context of implementing a GHB withdrawal management protocol at an inner-city hospital in 2020.. We retrospectively reviewed records (01 January 2017-31 March 2021), and included admissions that were ≥ 18 years of age, admitted for GHB withdrawal, and with documented recent GHB use. Admissions were assessed for demographics, medications administered, features of delirium, ICU admission, and DAMA. Exploratory analyses were conducted to examine factors associated (p < 0.2) with features of delirium and DAMA.. We identified 135 admissions amongst 91 patients. Medications administered included diazepam (133 admissions, 98.5%), antipsychotics (olanzapine [70 admissions, 51.9%]), baclofen (114 admissions, 84%), and phenobarbital (8 admissions, 5.9%). Features of delirium were diagnosed in 21 (16%) admissions. Delirium was associated with higher daily GHB consumption prior to admission, while duration of GHB use, time from presentation to first dose of diazepam, and concomitant methamphetamine use were inversely associated with delirium. DAMA occurred amongst 41 (30%) admissions, and was associated with a longer time from presentation to first dose of baclofen, while being female and receiving a loading dose of diazepam were inversely associated.. This study adds to the literature in support of the safety and feasibility of diazepam and baclofen for the management of GHB withdrawal. Prospective, randomised trials are required.

Topics: 4-Butyrolactone; Baclofen; Delirium; Diazepam; Female; Hospitals, Urban; Humans; Inpatients; Male; Medical Records; Prospective Studies; Retrospective Studies; Sodium Oxybate; Substance Withdrawal Syndrome

Topics: Humans; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

Gamma-hydroxybutyric acid (GHB), both a metabolic precursor and product of gamma-aminobutyric acid (GABA), is a central nervous system depressant used for the treatment of narcolepsy-associated cataplexy and alcohol withdrawal. However, administration of GHB with alcohol (ethanol) is a major cause of hospitalizations related to GHB intoxication. In this study, we investigated locomotor behavior as well as metabolic and pharmacokinetic interactions following co-administration of GHB and ethanol in rats. The locomotor behavior of rats was evaluated following the intraperitoneal administration of GHB (sodium salt, 500 mg/kg) and/or ethanol (2 g/kg). Further, time-course urinary metabolic profiling of GHB and its biomarker metabolites glutamic acid, GABA, succinic acid, 2,4-dihydroxybutyric acid (OH-BA), 3,4-OH-BA, and glycolic acid as well as pharmacokinetic analysis were performed. GHB/ethanol co-administration significantly reduced locomotor activity, compared to the individual administration of GHB or ethanol. The urinary and plasma concentrations of GHB and other target compounds, except for 2,4-OH-BA, were significantly higher in the GHB/ethanol co-administration group than the group administered only GHB. The pharmacokinetic analysis results showed that the co-administration of GHB and ethanol significantly increased the half-life of GHB while the total clearance decreased. Moreover, a comparison of the metabolite-to-parent drug area under the curve ratios demonstrated that the metabolic pathways of GHB, such α- and β-oxidation, were inhibited by ethanol. Consequently, the co-administration of GHB and ethanol aggravated the metabolism and elimination of GHB and enhanced its sedative effect. These findings will contribute to clinical interpretation of GHB intoxication.

Topics: Alcoholism; Animals; Ethanol; gamma-Aminobutyric Acid; Rats; Sodium Oxybate; Substance Withdrawal Syndrome

Chronic use of gamma-hydroxybutyric acid (GHB) and its precursors can rapidly lead to physical dependence with the emergence of a withdrawal syndrome. This complication is similar to the one linked to alcohol or benzodiazepines. The onset of symptoms and specially neuro-psychiatric symptoms is, however, more rapid in the case of the GHB and precursors. There is currently no consensus on the therapeutic management of GHB withdrawal syndrome. High-dose benzodiazepines are the most commonly used treatment. The use of GHB by titration and tapering could show fewer side effects and withdrawal symptoms. It appears necessary to reflect on and pursue research on the use of GHB and its precursors, which remains poorly understood, on the management of withdrawal syndrome due to the lack of protocol and on its probably underestimated impact on public health.. La consommation chronique d’acide gamma-hydroxybutyrique (GHB) et de ses précurseurs peut rapidement entraîner une dépendance physique avec l’émergence d’un syndrome de sevrage à l’arrêt des consommations. Ce syndrome de sevrage présente des similitudes avec celui lié à l’alcool ou aux benzodiazépines. On retrouvera, cependant, une apparition et une évolution plus brutales ainsi que l’émergence, plus précoce, de symptômes neuropsychiatriques. Il n’y a actuellement pas de consensus concernant la prise en charge thérapeutique de ce syndrome de sevrage. Dès lors, le recours aux benzodiazépines à hautes doses constitue le traitement le plus régulièrement utilisé. L’utilisation de GHB médical, titré et avec une posologie progressivement diminuée, pourrait démontrer moins d’effets secondaires et de symptômes de sevrage. Il apparaît nécessaire de réfléchir et de poursuivre les recherches sur la consommation du GHB et ses précurseurs, qui reste largement méconnue, ainsi que sur la prise en charge du sevrage, au vu de l’absence de protocole et de son impact en santé publique, probablement sous-estimé.

Topics: Benzodiazepines; Humans; Hydroxybutyrates; Sodium Oxybate; Substance Withdrawal Syndrome

GHB (gammahydroxybutyrate) and its precursors are popular recreational drugs due to their sedative, anxiolytic and sexually stimulating effects. Their use has been steadily increasing in recent years. The detoxification process is complex and prone to high rates of complications while little is known about the pathophysiology. This study aims to elucidate the characteristics of GHB-addicted patients and to evaluate the risks and complications of GHB withdrawal treatment.. This observational study describes prospectively the socioeconomic status, clinical history and course of inpatient detoxification treatment of a group of 39 patients suffering from GHB substance use disorder. Detoxification treatment took place in a highly specialized psychiatric inpatient unit for substance use disorders.. GHB patients were characterised by being young, well-educated and by living alone. More than 50% of the patients had no regular income. The patients were male and female in equal numbers. Detoxification treatment was complicated, with high rates of delirium (30.8%) and high need for intensive care (20.5%).. In our sample, GHB users were young, well-educated people and male and female in equal number. Detoxification proved to be dangerous for GHB-addicted patients. The presence of delirium and the need for transfer to an intensive care unit during detoxification treatment was extraordinarily high, even with appropriate clinical treatment. The reasons for this remain unknown. Therefore an intensive care unit should be available for GHB detoxification treatment. Further studies are needed to evaluate the options for prophylactic treatment of delirium during detoxification.

Topics: Delirium; Female; Humans; Inpatients; Male; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

The dual nature and the double use of γ-hydroxybutyric acid (GHB) are the fundamentals of its spread as recreational drug. Endo-genously, GHB acts as inhibitory neurotransmitter while exogenously it is administered in the form of sodium oxybate to treat cataplexy and to menage alcohol withdrawal. Illicit GHB is extensively used along with prescribed drugs and drugs of abuse for its euphoric and anabolic effects. Since it has been used as incapacitating agent to perpetrate rapes and commit robberies, GHB represents a social and public health issues. The tight window of detectability in biological matrices and the difficultly to read symptoms of polydrug overdose represent the modern challenges in forensic and clinical toxicology.

Topics: Humans; Hydroxybutyrates; Illicit Drugs; Sodium Oxybate; Substance Withdrawal Syndrome

GHB is a small molecule and is present in the human CNS. Exogenously, GHB is administered orally in the form of sodium oxybate to treat cataplexy and excessive daytime sleepiness in patients with narcolepsy, and to manage alcohol withdrawal and detoxification in alcoholics. GHB shows a biphasic effect and dose-dependent pharmacokinetics and may interact with neuronal systems different from GABAergic one. The compound is also highly abused among bodybuilders and is associated with drugs of abuse.. This article provides an overview of the risks associated with the recreational consumption of GHB and its analogues, including pharmaceuticals mostly encountered in GHB-related emergency department admissions and postmortem investigations. A literature search was performed using PubMed, Scopus, Google Scholar, and Web of Science databases to identify scientific reports concerning the recreational use of GHB and analogs with prescribed drugs. Further articles were retrieved after consulting international health and regulatory authorities' reports.. Due to its dual nature, interpreting and distinguishing GHB concentrations in biological fluid represents a challenge in forensic toxicology. To demonstrate recent exposure, a quick collection of samples is necessary to maximize the chance of detecting an exogenous GHB intake, especially in cases of GHB-facilitated sexual assaults.

Topics: Alcoholism; Drug Interactions; Humans; Sodium Oxybate; Substance Withdrawal Syndrome

In patients with gamma-hydroxybutyrate (GHB) use disorder (GUD), withdrawal can have a fulminant course with rapid progression of severe, potentially life-threatening complications.

Topics: Benzodiazepines; Coma; Humans; Male; Middle Aged; Sodium Oxybate; Substance Withdrawal Syndrome; Thiopental

Topics: Adult; Delirium; Diagnosis, Differential; Humans; Male; Prisoners; Sodium Oxybate; Substance Withdrawal Syndrome

The management of benzodiazepine-resistant GHB withdrawal requires careful consideration of GHB pharmacodynamics.. A young woman was admitted with tachycardia, confusion, agitation and delusions the day after attempting to quit a daily, high-dose GHB habit. A total of 225 mg of diazepam had no effect. She was sedated with propofol and intubated. An extubation attempt after 24 hours was followed by recurrence of delirium. After reintubation she required high doses of propofol, alfentanil and dexmedetomidine to maintain sedation for two days. Baclofen and diazepam were introduced on the third day, allowing dose reductions in anaesthetic agents the fourth day and extubation on the fifth day with resolution of the delirium.. GHB targets the GABAB receptor and downregulates it with abuse. Most anaesthetic agents affect the GABAA receptor. Our report suggests that baclofen, a GABAB receptor agonist, may reduce the need for anaesthetic agents and facilitate recovery.

Topics: Baclofen; Delirium; Female; Humans; Propofol; Sodium Oxybate; Substance Withdrawal Syndrome

Gamma-hydroxybutyrate (GHB) is a controlled substance that is often abused due to its euphoric, sexual and sedative effects. Both acute intoxication with and withdrawal from GHB are potentially lethal, and need to be treated in an in-patient environment. We report the case of a female patient who used GHB regularly during the first trimester of pregnancy. We subsequently describe available evidence on the impact of GHB on fetal development, and how existing guidelines for GHB detoxification differ in pregnant patients.

Topics: Adult; Antisocial Personality Disorder; Female; Humans; Hypnotics and Sedatives; Pregnancy; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

Gamma-hydroxybutyrate (GHB) and its precursor gamma-butyrolactone (GBL) are popular drugs of abuse used for their euphoric, (potential) anabolic, sedative, and amnestic properties. Daily use of GHB/GBL can lead to addiction and the possibility of withdrawal syndrome on cessation which results in tremor, tachycardia, insomnia, anxiety, hypertension, delirium, coma.. To describe the baseline characteristics, treatment and retention in patients admitted for GHB/GBL withdrawal management.. A retrospective review of 4 consecutive cases of patients reporting GHB/GBL addiction who were admitted for inpatient management of withdrawal syndrome.. All patients were using GHB/GBL daily, 1-1.5 ml per hour. One of them was using cannabis additionally, others were using alcohol, cocaine and amphetamine type stimulants. Psychiatric comorbidities as personality disorders, depression, anxiety and bigorexia were recognized. Patients were treated with benzodiazepines and/or clomethiazole, atypical and typical antipsychotics and beta-blockers. Delirium was developed in two patients. One patient completed detoxification and finished the treatment program. One patient completed detoxification but stopped his treatment earlier, two patients did not completed detoxification and left the program.. GHB/GBL withdrawal can be severe and retention in program is poor. Polysubstance use, psychiatric co-morbidities and heavier GHB/GBL use as possible predictors of poor treatment outcome need consideration in treatment planning.

Topics: 4-Butyrolactone; Humans; Inpatients; Retrospective Studies; Sodium Oxybate; Substance Withdrawal Syndrome

Topics: Adult; Humans; Male; Serotonin Syndrome; Sodium Oxybate; Substance Withdrawal Syndrome

The chronic use of alcohol can lead to the onset of an alcohol use disorder (AUD). About 50% of subjects with an AUD may develop alcohol withdrawal syndrome (AWS) when they reduce or discontinue their alcohol consumption and, in 3-5% of them, convulsions and delirium tremens (DTs), representing life-threatening complications, may occur. Unfortunately, few physicians are adequately trained in identifying and treating AWS. The Italian Society on Alcohol has, therefore, implemented a task force of specialists to draw up recommendations for the treatment of AWS with the following main results: (1) while mild AWS may not require treatment, moderate and severe AWS need to be pharmacologically treated; (2) out-patient treatment is appropriate in patients with mild or moderate AWS, while patients with severe AWS need to be treated as in-patients; (3) benzodiazepines, BDZs are the "gold standard" for the treatment of AWS and DTs; (4) alpha-2-agonists, beta-blockers, and neuroleptics may be used in association when BDZs do not completely resolve specific persisting symptoms of AWS; (5) in the case of a refractory form of DTs, the use of anaesthetic drugs (propofol and phenobarbital) in an intensive care unit is appropriate; (6) alternatively to BDZs, sodium oxybate, clomethiazole, and tiapride approved in some European Countries for the treatment of AWS may be employed for the treatment of moderate AWS; (7) anti-convulsants are not sufficient to suppress AWS, and they may be used only in association with BDZs for the treatment of refractory forms of convulsions in the course of AWS.

Topics: Alcoholic Intoxication; Anticonvulsants; Benzodiazepines; Chlormethiazole; Humans; Phenobarbital; Propofol; Sodium Oxybate; Substance Withdrawal Syndrome; Tiapride Hydrochloride

Gamma-hydroxybutyrate (GHB) and its precursors have gained popularity over the last decade as a drug in the party and club scene; however, the clinical knowledge of these substances is low. In the literature there have been case reports of severe dependence and withdrawal but there is a lack of systematic knowledge about the clinical course and complications of detoxification treatment.. The aim of this article is to evaluate the prevalence, treatment course, complications and compliance of GHB patients seeking inpatient qualified detoxification treatment (QDT).. A retrospective evaluation of the hospital charts of all patients admitted to this clinic in 2017 for QDT of GHB. The Jewish Hospital in Berlin (Jüdisches Krankenhaus Berlin) provides specialized inpatient units for addictive diseases and a general intensive care unit. The control population came from a prospective study of all patients with addictive diseases who were treated in the same hospital in 2012.. In 2017 a total of 18 patients with GHB addiction were treated in this hospital. This corresponds to a 1‑year prevalence of 2.28% of all addictive diseases in this year. During detoxification treatment 52% of the GHB patients had to be temporarily transferred to the intensive care unit, 5% had to be temporarily mechanically ventilated and 26% suffered from withdrawal delirium. Of the patients 42% terminated treatment prematurely against medical advice.. Withdrawal treatment from GHB is a severe and potentially dangerous condition, the prevalence of complications was higher than for most other drugs and the rate of intensive care and withdrawal delirium was very high. Further studies are urgently needed with the aim of reducing the complication rates of GHB withdrawal and enhancing therapy adherence.

Topics: Berlin; Humans; Prospective Studies; Retrospective Studies; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

To describe the baseline characteristics, treatment and retention in patients electively admitted for gamma-hydroxybutyrate (GHB) withdrawal management.. All patients admitted between July 2010 to June 2016 who used GHB two or more times per week with a minimum duration of 3 months were identified and data extracted by file review.. Twelve cases satisfied the inclusion criteria, of whom 50% were female; 75% were using GHB daily, with an average daily amount of 16 ml. Average duration of use was 60 months. All subjects were using amphetamine type stimulants and nicotine. Psychiatric comorbidity and unintentional overdose were common; 50% completed treatment. Medications used included diazepam and neuroleptic. Two patients completed withdrawal with no medications. No subject using greater than 90 ml GHB in the preceding week completed treatment. Pattern of GHB use did not predict medication requirements during withdrawal management.. There were low numbers attending for elective treatment for GHB use. Heavier GHB use predicted poor treatment retention. Polysubstance use and psychiatric co-morbidities need consideration in treatment planning.

Topics: Adult; Female; Humans; Inpatients; Male; Middle Aged; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders; Young Adult

We describe a case of a 51-year old man who used GHB only in the afternoon and evening during 10 consecutive days in a recreational way: 20 ml a day in 4 ml per 2-3 hrs. He developed an excited delirium syndrome at the second day after stopping. Apparently even after relatively short recreational use severe disruptive behavior can develop. This is a unique case in literature. References are provided.

Topics: Delirium; Humans; Male; Middle Aged; Sodium Oxybate; Substance Withdrawal Syndrome

Gamma-hydroxybutyrate (GHB) is a synthetic drug used mainly for recreational purpose. Although the prevalence of GHB abuse is low in Taiwan, GHB has become increasingly popular in certain subpopulations such as clubbers and men who have sex with men (MSM). GHB dependence could be associated with severe withdrawal syndrome including hallucinations and delirium. Despite systematic studies on detoxification and management of GHB withdrawal have been performed, no validated measurement for severity of GHB withdrawal syndrome is available. Here we present a case of GHB withdrawal delirium that was treated successfully with fixed and symptom-triggered benzodiazepine dosing regimen based on Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scale. The utilization of CIWA-Ar in such cases could offer useful guidance for benzodiazepine dosing. To the best of our knowledge, this is the first case report of GHB withdrawal delirium in Taiwan.

Topics: Adult; Benzodiazepines; Delirium; Disease Management; Drug Administration Schedule; Humans; Male; Severity of Illness Index; Sodium Oxybate; Substance Withdrawal Syndrome; Taiwan

Gamma-hydroxybutyrate (GHB) detoxification procedures have been insufficiently studied for effectiveness and safety. Based on case reports, benzodiazepines are generally regarded as first-choice agents in GHB detoxification. Detoxification by titration and tapering (DeTiTap) with pharmaceutical GHB in an open-label consecutive case series of 23 GHB-dependent patients showed to be feasible, effective and safe. This study further explored the feasibility, effectiveness and safety of this detoxification procedure in a large group of patients.. A large observational multicenter study was carried out in six addiction treatment centers in the Netherlands. GHB-dependent inpatients (229 unique patients, 274 admissions) were titrated on and tapered off with pharmaceutical GHB.. Successful detoxification was achieved in 85% of cases. Detoxification was carried out in 12.5days in most patients. The DeTiTap procedure proved to be feasible and significantly reduced the experienced withdrawal symptoms and craving (p≤0.001). Several symptoms were found to influence the course of subjective withdrawal symptoms. During detoxification, psychological symptoms such as depression, anxiety, and stress decreased (p≤0.05). The main complications were hypertension and anxiety. Six patients were sent to the general hospital for observation, but all six were able to continue detoxification in the addiction treatment centers. Most patients (69%) relapsed within three months after detoxification.. The DeTiTap procedure using pharmaceutical GHB seems a safe alternative to benzodiazepines as a GHB detoxification procedure. However, the high relapse rates warrant further investigation.

Topics: Adult; Benzodiazepines; Craving; Dose-Response Relationship, Drug; Female; Humans; Male; Netherlands; Psychotherapy; Recurrence; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders; Treatment Outcome; Young Adult

Topics: Delirium; Dexmedetomidine; Female; Humans; Hypnotics and Sedatives; Sodium Oxybate; Substance Withdrawal Syndrome; Young Adult

Topics: Adult; Depression; Humans; Male; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

In emergency medicine and anesthaesiology liquid ecstasy (LE), the street name for GHB, GBL or 1,4-B, has become infamous for causing severe intoxications and withdrawal. In general psychiatry, however, it is little known. Therefore, we set out to gather data about the role of LE in general psychiatry, typical users and common clinical problems associated with the use of LE.. We retrospectively identified and studied all patients with a reported the use of LE seen at the Department of Psychiatry, University of Ulm, Germany, between 1998 and 2011.. In 14 years, 19 users of LE were identified, the first dating from 2005. The majority reported a use of GBL (63 %), GHB was less common, and 1,4-B was not reported. Patients were predominantly young men (median age 25 years, 79 % men) with a history of multiple substance abuse. Ten patients had only a former use of LE, the other nine patients used it at the time of presentation. Of these, every third patient had to be transiently treated in an intermediate care unit, usually because of very severe and sudden withdrawal symptoms. Otherwise, detoxification was possible in psychiatry, but often required high doses of benzodiazepines. Three patients met the criteria for dependence from GBL.. In recent years, a small number of users of LE is seen also in general psychiatry, The problem is rather the severity of withdrawal than the number of cases. Close cooperation with intermediate care units is needed. In any case of coma of unknown origin or delirium with sudden onset LE use or withdrawal has to be taken into consideration, respectively. Many clinical problems result from the fact that LE cannot be detected in routine drug screenings. According to our experience, withdrawal from LE can be controlled with benzodiazepines.

Topics: Adult; Delirium; Emergency Medical Services; Female; Humans; Legislation, Drug; Male; Retrospective Studies; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders; Young Adult

The objective of this study was to describe the psychiatric symptoms, management and outcomes in a consecutive series of patients being managed medically for symptoms of withdrawal from gamma-hydroxybutyrate (GHB) and its analogue gamma-butyrolactone (GBL) in a general hospital setting.. A toxicology database was used to identify patients presenting with a history suggestive of withdrawal from GHB and analogues. Electronic and paper medical records were searched for demographic features, neuropsychiatric symptoms, psychiatric management while in hospital and overall outcome.. There were 31 presentations with withdrawal from the drugs involving 20 patients. Of these 17 (54%) were referred to and seen by the liaison psychiatry team. Anxiety (61.3%) and agitation (48.4%) were the most common symptoms. Of the 17 cases seen by the liaison psychiatry team, 52.9% required close constant observation by a mental health nurse and 29.4% required to be detained in hospital under mental health legislation.. The significant proportion of patients presenting with neuropsychiatric symptoms and requiring intensive input from the liaison psychiatry team during withdrawal from GHB and its analogues points to the importance of close liaison between medical and psychiatric teams in managing these patients in the general hospital.

Topics: 4-Butyrolactone; Adult; Anxiety; Disease Management; Emergency Service, Hospital; Female; Hospitals, General; Humans; Male; Mental Health Services; Psychomotor Agitation; Sodium Oxybate; Substance Withdrawal Syndrome; Symptom Assessment

1,4-Butanediol (1,4-BD) is a gamma-hydroxybutyrate (GHB) pro-drug, with multiple commercial uses, and a drug of abuse. Although there are case reports of a withdrawal syndrome following 1,4-BD use, no studies have evaluated the physical dependence potential of 1,4-BD and characterized the time course of withdrawal.. Vehicle and then 1,4-BD were administered continuously 24 h/day via intragastric catheters in male baboons (Papio anubis, n=3). Dosing was initiated at 100 mg/kg and increased by 100mg/kg/day to 400mg/kg. After a stabilization period, doses of 500 and then 600 mg/kg/day were each maintained for 3-4 weeks. Plasma levels of 1,4-BD and GHB were determined for each dose condition. Physical dependence was assessed via administration of a GABA-B antagonist (precipitated withdrawal test) during administration of the 600 mg/kg dose and via abrupt termination of chronic 1,4-BD administration (spontaneous withdrawal test). Outcome measures included the number of food pellets earned, performance on a fine-motor task, observed behaviors, and plasma levels of GHB and 1,4-BD.. Following maintenance of 1,4-BD 600 mg/kg for 3 weeks, the number of food pellets earned was significantly decreased. At the end of chronic 1,4-BD dosing, the levels of GHB in plasma ranged from 1290 to 2300 μmol/L and levels of 1,4-BD in plasma ranged from 13.1 to 37.9 μmol/L. Signs of physical dependence were observed following precipitated and spontaneous withdrawal tests. Seizures were not observed.. These data indicate chronic 1,4-BD produced physical dependence in baboons and the withdrawal syndrome can be characterized as mild to intermediate.

Topics: Animals; Butylene Glycols; Conditioning, Operant; Infusions, Parenteral; Male; Papio anubis; Prodrugs; Severity of Illness Index; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

A new detoxification method for GHB dependence was developed recently in the Netherlands. The method involves the use of pharmaceutical GHB.. To describe the characteristics of GHB dependent inpatients, the course of the detoxification process and patients' progress in the three months following inpatient detoxification.. 229 GHB dependent patients were monitored during and after inpatient detoxification. Records were kept of the psychiatric symptoms, withdrawal symptoms and relapses.. The average age of the patients was 29 years; 69% of the patients were male. They reported severe symptoms of co-occurring depression and anxiety. Detoxification was successful in 86% of the patients and, on a whole, the procedure ran smoothly, without complications. However, within three months following detoxification two-thirds of the patients had relapsed and were again taking GHB.. Pharmaceutical GHB can be used as an alternative to the benzodiazepine method for detoxifying patients with GHB dependence. However, the high relapse rates following detoxification are of great concern.

Topics: Adult; Female; Humans; Male; Recurrence; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Alcoholism; Central Nervous System Depressants; Clinical Trials as Topic; Humans; Italy; Secondary Prevention; Sodium Oxybate; Substance Withdrawal Syndrome; Treatment Outcome

To determine the effectiveness and safety of a new detoxification procedure in γ-hydroxybutyrate (GHB)-dependent patients. GHB is an endogenous inhibitory neurotransmitter and anesthetic agent that is being abused as a club drug. In many GHB-dependent patients a severe withdrawal syndrome develops that does not respond to treatment with high dosages of benzodiazepines and often requires an admission to an intensive care unit.. Based on the knowledge of detoxification procedures in opioid and benzodiazepine dependence, we developed a titration and tapering procedure. A consecutive series of 23 GHB-dependent inpatients were transferred from illegal GHB (mostly self-produced) in various concentrations to pharmaceutical GHB. They were given initial doses that resulted in a balance between sedation and withdrawal symptoms. After this titration period, patients were placed on a 1-week taper.. We have found that after titration the patients experienced a low level of withdrawal symptoms. During tapering these symptoms decreased significantly and no patient developed a delirium or a psychosis. None of the patients had to be transferred to a medium or intensive care unit.. This detoxification procedure proved to be safe and convenient in patients with moderate to severe GHB dependence.

Topics: Adult; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Neurotransmitter Agents; Pilot Projects; Sodium Oxybate; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome; Substance-Related Disorders; Treatment Outcome; Young Adult

Much of what is understood regarding gamma hydroxybutyrate (GHB) treatment is based on hospital case studies for overdose and withdrawal, and there are currently no measures developed specifically for GHB or its analogs (e.g., gamma butyrolactone and 1,4-butanediol) to assess drug effect expectancies, reasons for starting use, withdrawal effects, and knowledge and opinions about use.. This pilot study (N = 61) was conducted to begin measures development to assess experiences, functions of use, and opinions regarding use as indicated by respondents taking a Web-based survey.. Minimum average partial correlation and parallel analysis procedures are employed to create scales.. Scales were developed to assess expectancies, reasons for use, withdrawal, and knowledge/opinions of use with median α = .79 and that account for 8.69-24.17% of the variance.. Scales have relatively good psychometric properties and replication is needed.. GHB-specific measures may greatly assist in furthering our understanding of protective and risk factors for use, and withdrawal phenomena.

Topics: Adult; Anxiety; Delirium; Drug Users; Female; Hallucinations; Humans; Illicit Drugs; Male; Pilot Projects; Psychiatric Status Rating Scales; Sodium Oxybate; Substance Withdrawal Syndrome; Surveys and Questionnaires

Topics: Alcoholism; Hospitalization; Humans; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Sodium Oxybate; Substance Withdrawal Syndrome; Temperance; Treatment Outcome

Sodium oxybate (brand name Xyrem) is a sodium salt of gamma-hydroxybutyric acid (GHB), an endogenous CNS depressant, which is an effective treatment of narcolepsy. As a drug of abuse, GHB produces severe psychiatric side effects and withdrawal. However, there are no reports of these effects when using clinically recommended doses. This paper presents a case of a patient who developed altered mental status while taking the recommended dose of sodium oxybate and subsequently became psychotic upon abrupt discontinuation of the medication. It is important for prescribers of sodium oxybate to be aware of the possibility of significant psychiatric side effects of this medication, as well as withdrawal symptoms, even at clinical doses.

Topics: Adult; Central Nervous System Depressants; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Narcolepsy; Psychotic Disorders; Risk Assessment; Severity of Illness Index; Sodium Oxybate; Substance Withdrawal Syndrome

A 35-year-old man had been using high doses of gamma-hydroxybutyrate (GHB) for many years. He had been trying to cut down on use of this drug for 2 months. He was admitted to the hospital suffering from a withdrawal delirium accompanied by hallucinations and agitation. Use of GHB is increasing in the Netherlands. Along with serious intoxication and dependency, the possibility of withdrawal symptoms should also be taken into consideration. Administration of high doses of benzodiazepines is an effective treatment for these withdrawal symptoms.

Topics: Adult; Benzodiazepines; Delirium; Hallucinations; Humans; Male; Psychoses, Substance-Induced; Sodium Oxybate; Substance Withdrawal Syndrome

Acute psychosis and extreme agitation brought about by gamma-hydroxybutyrate GHB withdrawal can be life-threatening. In order to prevent states of excitement accompanied by aggression and somatic complications it is advisable to intervene by administering strong sedatives. It is argued that GHB should be tapered off as an alternative treatment for fixation and high doses of benzodiazepines.

Topics: Adult; Anesthetics, Intravenous; Humans; Male; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

There has been little investigation of the possible lasting adverse effects of γ-hydroxybutyrate (GHB).. This study aims to study whether GHB produces residual adverse effects on memory and social behaviour in rats and lasting changes in brain monoamines and oxytocin-related gene expression.. Rats received daily intraperitoneal injections of GHB (500 mg/kg), methylenedioxymethamphetamine (MDMA; 5 mg/kg) or their combination (GHB/MDMA) over ten consecutive days. Locomotor activity and body weight were assessed during the dosing period and withdrawal-related anxiety was assessed 24 h after drug cessation. After a washout of 4 weeks, rats were tested on the emergence, social interaction, and object recognition tasks over a 2-week period. Monoamine levels in cortex and striatum, and hypothalamic oxytocin and oxytocin receptor mRNA, were then assessed.. MDMA and GHB/MDMA caused modest sensitization of locomotor activity over time, while sedative effects of GHB diminished with repeated exposure. GHB-treated rats showed reduced social interaction 24 h after the final dose, indicating GHB withdrawal-induced anxiety. All drug-treated groups displayed residual deficits in social interaction and object recognition. No changes in monoamine levels were detected 8 weeks post-drug. However, MDMA pre-exposure increased hypothalamic oxytocin mRNA while GHB pre-exposure upregulated oxytocin receptor mRNA. GHB/MDMA pre-exposure caused intermediate changes in both of these measures.. GHB treatment caused residual impairments in memory and social behaviour and increases in anxiety, paralleling the lasting adverse effects of MDMA. Both drugs caused lasting neuroadaptations in brain oxytocin systems and this may be related to the long-term social interaction deficiencies caused by both drugs.

Topics: Animals; Anxiety; Behavior, Animal; Biogenic Monoamines; Body Weight; Brain; Chromatography, High Pressure Liquid; Emotions; Gene Expression Regulation; Injections, Intraperitoneal; Male; Memory; Motor Activity; N-Methyl-3,4-methylenedioxyamphetamine; Oxytocin; Polymerase Chain Reaction; Rats; Rats, Wistar; Receptors, Oxytocin; Recognition, Psychology; RNA, Messenger; Social Behavior; Sodium Oxybate; Substance Withdrawal Syndrome; Time Factors

gamma-Hydroxybutyrat (GHB) is used medically for narcolepsy and as a narcotic. It is also a rare illegal drug. In this case report the development of a GHB-dependency against the background of a primary alcohol dependency is described.. Based on established alcohol withdrawal scales (AWSS by Wetterling, CIWA) and neuropsychological testing procedures (CGI, GAF, SKID-II, PISQ, analog-scale for Craving), the initial situation, the development of psychopathological findings, and the course of detoxification were shown.. The combined detoxication of GHB and alcohol was successfully finished by a reduction schedule of diazepam. Withdrawal-assessment scales for alcohol were helpful, but show limitations for GHB-withdrawal symptoms. The patient suffers, according to ICD-10, from a multiple drug dependence (alcohol, GHB, abstinence from amphetamines). Symptoms of insomnia, major depression, and generalized anxiety disorder can be associated with the use of GHB.

Topics: Adjuvants, Anesthesia; Adult; Alcoholism; Comorbidity; Drug Tolerance; Humans; Illicit Drugs; Male; Neuropsychological Tests; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders; Treatment Outcome

Topics: Adult; Delirium; Female; Humans; Sodium Oxybate; Substance Withdrawal Syndrome

Benzodiazepine treatment of life-threatening gamma-hydroxybutyrate (GHB) withdrawal is frequently unsatisfactory. Animal studies suggest strongly that treatment with GABA(B) agonists, such as baclofen, will be a more effective strategy.. A case report from the medical intensive care unit (ICU) of the university tertiary care hospital.. A 61-year-old woman was admitted to the medical ICU for severe withdrawal symptoms from chronic GHB use. This manifested as delirium, tremor, and seizures despite only small decreases in GHB dose and treatment with benzodiazepines. The addition of baclofen allowed the rapid sequential decreases in the GHB dose without seizure or delirium and resulted in long-term improvement of her tremor.. Baclofen, a GABA(B) agonist, may be a useful agent in the treatment of severe GHB withdrawal.

Topics: Adjuvants, Anesthesia; Baclofen; Benzodiazepines; Delirium; Epilepsy; Female; GABA Agonists; Humans; Middle Aged; Sodium Oxybate; Substance Withdrawal Syndrome; Tremor

Topics: Adult; Female; Humans; Sodium Oxybate; Substance Withdrawal Syndrome; Time Factors

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.

Topics: 4-Butyrolactone; Animals; Behavior, Animal; Catheters, Indwelling; Conditioning, Operant; Dose-Response Relationship, Drug; Flumazenil; Food; GABA Antagonists; GABA-A Receptor Antagonists; GABA-B Receptor Antagonists; Male; Motor Skills; Muscle Relaxation; Organophosphorus Compounds; Papio anubis; Receptors, GABA-A; Receptors, GABA-B; Sleep; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

gamma-Hydroxybuyrate (GHB) is a current drug of abuse that may produce physical dependence.. The present study characterized the behavioral effects of chronic GHB in baboons (n = 4), and evaluated whether signs of withdrawal occurred (1) after administration of the GABA-B antagonist CGP36742 during chronic GHB administration (precipitated withdrawal) and (2) following discontinuation of chronic GHB administration (spontaneous withdrawal).. Water (vehicle) and then GHB was continuously infused via intragastric (IG) catheters. GHB administration was initiated at 350 mg/kg per day, and the dose was increased by 100 mg/kg over 4 days to 750 mg/kg per day. Food pellets were available 20 h/day under a fixed ratio (FR5 or 10) schedule of reinforcement. Observation sessions and a 2-min fine motor task were conducted during vehicle and GHB administration. CGP36742 (32 and 56 mg/kg, IM) was administered during vehicle and chronic GHB administration. After a total of 32-36 days GHB administration was abruptly discontinued. Blood samples were collected during all interventions and analyzed for GHB content.. Chronic GHB decreased food-maintained behavior, disrupted performance of the fine motor task, and produced ataxia, muscle relaxation, tremors and jerks. At the end of GHB administration, plasma levels of GHB ranged from 486 to 2080 micromol/L. Administration of CGP36742 during chronic GHB administration produced increases in aggression, self-directed behaviors, vomit/retch, tremors and/or jerks, which is consistent with a precipitated withdrawal syndrome. Similar signs were observed when GHB administration was discontinued. Seizures were not observed.. These data indicate that chronic GHB administration produced physical dependence and that activation of the GABA-B receptor may be important for GHB physical dependence.

Topics: Animals; Feeding Behavior; GABA-B Receptor Antagonists; Infusions, Parenteral; Male; Organophosphorus Compounds; Papio anubis; Receptors, GABA-B; Sodium Oxybate; Substance Withdrawal Syndrome

Topics: Humans; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

The emergence of gamma-hydroxybutyrate (GHB) dependence in the UK is described, with specific reference to a case study of serial episodes of GHB withdrawal. Symptoms are broadly similar to those for alcohol withdrawal, and rapid deterioration into delirium is common in severe dependence. This case report reflects the variability in clinical presentation of GHB withdrawal and response to treatment, even within the same patient. It is concluded that GHB withdrawal requires vigorous clinical management, preferably on an elective basis, in an inpatient setting if dependence is severe.

Topics: Adult; Female; Humans; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

The gamma-aminobutyric acid type A (GABA(A)) receptor is an important pharmacological target of ethanol. The effect of ethanol withdrawal on the expression of the alpha(2) subunit of this receptor was examined with rat cerebellar granule cells in primary culture. Long-term exposure of these cells to ethanol (100 mM, 5 days) did not affect the abundance of the mRNA for the alpha(2) subunit, as revealed by an RNase protection assay. In contrast, subsequent ethanol withdrawal for 3 h induced a marked increase in the amount of this mRNA (2.6-fold) as well as in that of the encoded polypeptide (2.2-fold), the latter revealed by immunoblot analysis. Exposure of the cells to gamma-hydroxybutyric acid (100 mM) during ethanol withdrawal prevented the increase in the amounts of both the alpha(2) mRNA and polypeptide, whereas similar treatment with diazepam (10 microM) blocked the increase in the abundance of the alpha(2) polypeptide but not that in the amount of the alpha(2) mRNA. The effect of gamma-hydroxybutyric acid was not blocked by the competitive GABA(B) receptor antagonist SCH 50911(10 microM). Given that the alpha(2) subunit of the GABA(A) receptor mediates the anxiolytic action of benzodiazepines, its up-regulation during discontinuation of long-term ethanol exposure might be relevant to the therapeutic efficacy of these drugs in the treatment of anxiety associated with ethanol withdrawal.

Topics: Animals; Animals, Newborn; Cells, Cultured; Central Nervous System Depressants; Cerebellum; Cyclophilins; Diazepam; Dose-Response Relationship, Drug; Drug Interactions; Ethanol; GABA Antagonists; GABA Modulators; Gene Expression Regulation; Morpholines; Neurons; Polymerase Chain Reaction; Protein Subunits; Rats; Receptors, GABA-A; RNA, Messenger; Sodium Oxybate; Substance Withdrawal Syndrome; Up-Regulation

Topics: Drug Tolerance; History, Medieval; Humans; Illicit Drugs; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders; United Kingdom

Gamma-hydroxybutyric acid (GHB) is a naturally occurring substance in the brain, the administration of which has proved useful in the treatment of the opiate withdrawal symptoms in humans.. The aim of the present work was to validate this beneficial effect on the physical and motivational aspects of morphine withdrawal in mice.. In a first experiment, animals rendered morphine-dependent were conditioned to develop a place aversion (CPA) to the compartment paired with naloxone administration in a two-chamber apparatus. The conditioning phase consisted of three pairings of either naloxone (0.250 mg/kg) or vehicle in one compartment, both with similar time allotments during the preconditioning test. During the testing phase, mice were again allowed to explore the entire apparatus. GHB (6, 12.5, 25, and 50 mg/kg) was administered during either the acquisition or expression phase of this conditioning. In a second experiment, the capacity of GHB to ameliorate the intensity of physical signs of morphine withdrawal was evaluated.. GHB blocked CPA in both phases: administered during acquisition (from 12.5 mg/kg and higher) as well as in the expression phase (from 6 mg/kg, except for 25 mg/kg). It also decreased the intensity of physical signs of morphine withdrawal to near control levels measured by the modified Gellert-Holtzman scale (25 mg/kg and higher). Decreases in jumping, body shakes, and paw tremor were also observed.. Our results support the idea that GHB ameliorates both aspects of morphine withdrawal, physical as well as motivational signs.

Topics: Animals; Avoidance Learning; Conditioning, Psychological; Dose-Response Relationship, Drug; Male; Mice; Morphine; Naloxone; Sodium Oxybate; Substance Withdrawal Syndrome

Topics: Adult; Aggression; Dose-Response Relationship, Drug; Drug Administration Schedule; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Humans; Illicit Drugs; Male; Methamphetamine; Sodium Oxybate; Substance Withdrawal Syndrome; Violence

Topics: Adjuvants, Anesthesia; Adult; Fractures, Bone; Humans; Male; Pain; Pelvic Bones; Sodium Oxybate; Substance Withdrawal Syndrome

Many psychiatric professionals are unfamiliar with gamma-hydroxybutyrate (GHB), an increasingly popular drug of abuse. GHB withdrawal can lead to psychosis and agitation, and patients may present to psychiatric facilities for treatment. Withdrawal may progress to delirium, with the potential for severe or even fatal medical complications. Therefore, it is imperative for psychiatric professionals to understand how to treat these patients. In this article, we describe two cases of severe GHB withdrawal syndrome that were treated in our inpatient psychiatric unit. These are among the most severe cases reported. Pertinent literature is reviewed and suggestions for treatment are discussed.

Topics: Adult; Anticonvulsants; Antihypertensive Agents; Clonazepam; Clonidine; Delirium; Hospitalization; Humans; Lorazepam; Male; Phenobarbital; Practice Guidelines as Topic; Psychoses, Substance-Induced; Sodium Oxybate; Substance Withdrawal Syndrome

Long-term daily use of gamma-hydroxybutyrate (GHB) and related compounds has recently been associated with a withdrawal syndrome. To the best of the authors' knowledge, there are currently no animal models of GHB withdrawal.. The authors studied and described the effect of chronic dosing of GHB (3-6 days) on tolerance and withdrawal in a rat model.. Rats were administered GHB every three hours via intraperitoneal catheter. Groups of rats (2 per group) were dosed with GHB for either 3 (24 doses), 4 (32 doses), 5 (40 doses), or 6 (48 doses) days. The GHB dose was 0.25 g/kg for doses 1-8, 0.75 g/kg for doses 9-12, 1 g/kg for doses 13-16, 1.25 g/kg for doses 17-24, 1.5 g/kg for doses 25-32, 1.75 g/kg for doses 33-40, and 2 g/kg for doses 41-48. Following the last dose of GHB, the rats were scored using a 16-point ethanol intoxication-withdrawal scale rating spontaneous behaviors, response to handling, grooming, and neurological signs. Lower scores indicate intoxication, while higher scores indicate withdrawal. Scores were recorded at hours 0, 1, 2, 3, 4, 5, 6, 9, 12, and 24.. Tolerance: Rats dosed with GHB for more days were less intoxicated one hour after their last GHB dose despite receiving higher doses. WITHDRAWAL: The scores for all rats dosed with GHB increased at hours 4 (p = 0.028), 5 (p = 0.037), 6 (p = 0.007), and 9 (p = 0.024) after the last dose, indicating withdrawal. The scores demonstrated a linear increase dependent upon the number of days of GHB dosing at hours 3 (p < 0.000), 4 (p = 0.004), 5 (p = 0.002), and 12 (p = 0.039) as well as prior to the last dose at hour 0 (p = 0.000). No rats developed seizures.. Tolerance and mild withdrawal in rats can be induced by administering intraperitoneal GHB every three hours for 3-6 days. More prolonged dosing and higher doses of GHB may be necessary to induce severe withdrawal.

Topics: Animals; Dose-Response Relationship, Drug; Drug Administration Schedule; Male; Maximum Tolerated Dose; Models, Animal; Probability; Random Allocation; Rats; Rats, Sprague-Dawley; Risk Assessment; Severity of Illness Index; Sodium Oxybate; Substance Withdrawal Syndrome

We describe a 52-year-old man who self-medicated with gamma-hydroxybutyrate (GHB), a widely available illicit substance, to obtain a decrease in ethanol consumption. He successfully reduced his ethanol intake over a 3-month period, but he was unable to sustain abstinence. Although case reports on the use of GHB to induce euphoria have been published, this is the first report of GHB self-medication to facilitate ethanol abstinence. This report highlights the importance of considering GHB self-medication not only for euphoric and mood altering effects, but also as a potential treatment for ethanol intake reduction.

Topics: Adjuvants, Anesthesia; Alcoholism; Humans; Male; Middle Aged; Self Medication; Sodium Oxybate; Substance Withdrawal Syndrome

Gammahydroxybutyrate (GHB) is an endogenous chemical found in the human brain that when administered systemically readily crosses the blood-brain barrier and produces behavioral effects. Some previously reported observations, including reports of specific antagonism by NCS382 (6,7,8,9-tetrahydro-5-[H]-benzocycloheptene-5- ol-4-ylidene acetic acid), support the hypothesis that GHB is a neurotransmitter with its own receptor system. In addition to its uncertain physiological role, the recent interest in GHB has been engendered by its illicit use and abuse.. To further characterize the behavioral effects of GHB and to evaluate NCS382 for its potential antagonistic effects.. Following the administration of GHB alone and in combination with NCS382, mice were tested in a Functional Observational Battery (FOB) and for their effects on locomotor activity and on schedule-maintained behavior. Additionally, spontaneous and NCS382-precipitated withdrawal in rats chronically treated with GHB was examined.. In the FOB, GHB generally produced depressant-like effects that were generally not reversed by NCS382. GHB also dose dependently reduced locomotor activity and rates of operant behavior, which were generally not reversed by co-administrations with NCS382. Neither spontaneous nor NCS382-precipitated signs of physical dependence were observed following chronic GHB administration.. GHB dose dependently produced depressant-like effects on learned and unlearned behavior. The putative GHB antagonist NCS382 failed to convincingly antagonize these effects. Physical dependence was not evident following spontaneous withdrawal or NCS382 challenge. Taken together, these results suggest that NCS382's ability to antagonize GHB's effects may be very limited.

Topics: Anesthetics, Intravenous; Animals; Behavior, Animal; Benzocycloheptenes; Body Weight; Conditioning, Operant; Dose-Response Relationship, Drug; Male; Mice; Motor Activity; Reinforcement Schedule; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

1,4-Butanediol is an industrial solvent that, when ingested, is converted to gamma-hydroxybutyrate, a drug of abuse with depressant effects, primarily on the central nervous system. After reports of toxic effects of gamma-hydroxybutyrate and its resultant regulation by the federal government, 1,4-butanediol and gamma-butyrolactone, another precursor of gamma-hydroxybutyrate and an industrial solvent, began to be marketed as dietary supplements. We investigated reports of toxic effects due to the ingestion of 1,4-butanediol and reviewed the related health risks.. From June 1999 through December 1999, we identified cases of toxic effects of 1,4-butanediol involving patients who presented to our emergency departments with a clinical syndrome suggesting toxic effects of gamma-hydroxybutyrate and a history of ingesting 1,4-butanediol and patients discovered through public health officials and family members. We used gas chromatography-mass spectrometry to measure 1,4-butanediol or its metabolite, gamma-hydroxybutyrate, in urine, serum, or blood.. We identified nine episodes of toxic effects in eight patients who had ingested 1,4-butanediol recreationally, to enhance bodybuilding, or to treat depression or insomnia. One patient presented twice with toxic effects and had withdrawal symptoms after her second presentation. Clinical findings and adverse events included vomiting, urinary and fecal incontinence, agitation, combativeness, a labile level of consciousness, respiratory depression, and death. No additional intoxicants were identified in six patients, including the two who died. The doses of 1,4-butanediol ingested ranged from 5.4 to 20 g in the patients who died and ranged from 1 to 14 g in the nonfatal cases.. The health risks of 1,4-butanediol are similar to those of its counterparts, gamma-hydroxybutyrate and gamma-butyrolactone. These include acute toxic effects, which may be fatal, and addiction and withdrawal.

Topics: Adult; Butylene Glycols; Dietary Supplements; Fatal Outcome; Female; Humans; Male; Psychomotor Agitation; Pulmonary Edema; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders; Unconsciousness; Vomiting

Topics: Anti-Anxiety Agents; Diazepam; Humans; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

Gamma-hydroxybutyrate (GHB) withdrawal syndrome is increasingly encountered in emergency departments among patients presenting for health care after discontinuing frequent GHB use. This report describes the characteristics, course, and symptoms of this syndrome.. A retrospective review of poison center records identified 7 consecutive cases in which patients reporting excessive GHB use were admitted for symptoms consistent with a sedative withdrawal syndrome. One additional case identified by a medical examiner was brought to our attention. These medical records were reviewed extracting demographic information, reason for presentation and use, concurrent drug use, toxicology screenings, and the onset and duration of clinical signs and symptoms.. Eight patients had a prolonged withdrawal course after discontinuing chronic use of GHB. All patients in this series were psychotic and severely agitated, requiring physical restraint and sedation. Cardiovascular effects included mild tachycardia and hypertension. Neurologic effects of prolonged delirium with auditory and visual hallucinations became episodic as the syndrome waned. Diaphoresis, nausea, and vomiting occurred less frequently. The onset of withdrawal symptoms in these patients was rapid (1 to 6 hours after the last dose) and symptoms were prolonged (5 to 15 days). One death occurred on hospital day 13 as withdrawal symptoms were resolving.. In our patients, severe GHB dependence followed frequent ingestion every 1 to 3 hours around-the-clock. The withdrawal syndrome was accompanied initially by symptoms of anxiety, insomnia, and tremor that developed soon after GHB discontinuation. These initial symptoms may progress to severe delirium with autonomic instability.

Topics: Adult; Autonomic Nervous System Diseases; Delirium; Diagnosis, Differential; Doping in Sports; Emergency Treatment; Fatal Outcome; Female; Humans; Hypertension; Male; Psychoses, Substance-Induced; Retrospective Studies; Sodium Oxybate; Substance Abuse Detection; Substance Withdrawal Syndrome; Tachycardia; Time Factors

A 27-year-old man was admitted with tremulousness, diaphoresis, tachypnea (28 breaths/min), full-body rigidity, irritability, paranoia, and auditory and visual hallucinations 2 days after stopping long-term gamma-hydroxybutyrate (GHB) and 8 hours after stopping alcohol intake. He received intravenous fluids and tapering dosages of lorazepam to control agitation and rigidity, and recovered with no significant sequelae after 8 days. Abrupt cessation of GHB after high-dosage abuse can precipitate a clinically significant withdrawal syndrome. Lorazepam should be considered for treatment of GHB withdrawal. Concomitant alcohol abuse may mask early GHB withdrawal symptoms and exacerbate withdrawal.

Topics: Adult; Anesthetics, Intravenous; Anticonvulsants; Central Nervous System Depressants; Ethanol; Fluid Therapy; Hallucinations; Humans; Lorazepam; Male; Muscle Rigidity; Sodium Oxybate; Substance Withdrawal Syndrome

Topics: Adjuvants, Anesthesia; Ethanol; Humans; Narcolepsy; Sodium Oxybate; Substance Withdrawal Syndrome

Topics: Adult; Conscious Sedation; Emergency Treatment; Hallucinations; HIV Seropositivity; Humans; Male; Respiration, Artificial; Sleep Initiation and Maintenance Disorders; Sodium Oxybate; Substance Withdrawal Syndrome; Tremor

Topics: Adult; Anti-Anxiety Agents; Antipsychotic Agents; Haloperidol; Humans; Lorazepam; Male; Sodium Oxybate; Substance Withdrawal Syndrome

Topics: Adult; Butylene Glycols; Emergencies; Female; Humans; Male; Sodium Oxybate; Substance Withdrawal Syndrome

Gamma-hydroxybutyric acid (GHB) is gaining popularity as a drug of abuse. Reports of toxicity and lethality associated with GHB use have increased. This survey study was designed to identify patterns of GHB use, its effects, and withdrawal syndrome. A survey inquiring about the effects of GHB was administered to 42 users. The results showed that GHB was used to increased feelings of euphoria, relaxation, and sexuality. Adverse effects occurred more frequently in daily users and polydrug users than in occasional GHB users. Loss of consciousness was reported by 66%, overdose by 28%, and amnesia by 13% of participants during GHB use and by 45% after GHB use. Three daily users developed a withdrawal syndrome that presented with anxiety, agitation, tremor, and delirium. Participants described GHB intoxication as having similarities to sedative-hypnotic or alcohol intoxication. Regular use has been shown to produce tolerance and dependence. Participants dependent on GHB reported using multiple daily doses around the clock. High frequency users appeared at the greatest risk for developing withdrawal delirium and psychosis after abrupt discontinuation of GHB use.

Topics: Adult; Drug Tolerance; Female; Humans; Male; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders; Surveys and Questionnaires

Topics: Emergency Service, Hospital; Haloperidol; Humans; Sodium Oxybate; Substance Withdrawal Syndrome

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.

Topics: Adult; Akathisia, Drug-Induced; Anti-Anxiety Agents; Autonomic Nervous System Diseases; Emergencies; GABA Modulators; Hallucinations; Humans; Hypertension; Lorazepam; Male; Sodium Oxybate; Substance Withdrawal Syndrome; Tachycardia; Tremor

Topics: Adult; Chloral Hydrate; Delirium; Female; Humans; Psychoses, Substance-Induced; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adjuvants, Anesthesia; Adult; Hospitalization; Humans; Inactivation, Metabolic; Male; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

We describe what we believe is the first psychiatric hospitalization due to GHB-induced delirium reported in the medical literature. We examine the use of the substance gamma hydroxybutyric acid (GHB) and describe the clinical findings in a patient who presented to an acute inpatient psychiatric unit with a chief complaint of feeling suicidal and a 1-year history of GHB use. A review of the literature and GHB's availability through the Internet are discussed.

Topics: Adjuvants, Anesthesia; Adult; Delirium; Female; Hallucinations; Humans; Mental Status Schedule; Psychoses, Substance-Induced; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders; Suicide; Suicide Prevention

Topics: Ethanol; Humans; Sodium Oxybate; Substance Withdrawal Syndrome

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.

Topics: Adult; Anesthetics, Intravenous; Anxiety; Coma; Female; Humans; Male; Sleep Initiation and Maintenance Disorders; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders; Tremor

The first case of fatal intoxication due to ingestion of gamma-hydroxybutyric acid (GHB) and intravenous use of heroin is reported. A 42-year-old man, known to have been a heroin addict and to have taken other psychoactive substances, who had been in treatment with GHB for several months, was found dead. Anatomohistopathologic examination showed generalized visceral congestion, edema and pulmonary anthracosis, chronic bronchitis and chronic active hepatitis. Toxicological findings included fluid and tissue distributions of GHB, morphine and 6-monoacetylmorphine. GHB and morphine concentrations were respectively 11.5 and 0.77 micrograms/mL (blood), 84.3 and 0.3 micrograms/mL (vitreous humor), 258.3 and 1.35 micrograms/mL (urine), 57.0 and 14.3 micrograms/mL (bile), 40.0 and 0.43 micrograms/g (brain), 43.0 and 0.60 micrograms/g (liver), 47.0 and 0.68 micrograms/g (kidney). Blood and urine levels of 6-monoacetylmorphine were 28.5 and 12.1 ng/mL respectively. The presumed mechanism of action and pharmacokinetics of GHB are briefly reviewed, with reference to its therapeutic use and to reports of non-fatal GHB intoxication.

Topics: Adult; Fatal Outcome; Heroin; Heroin Dependence; Humans; Male; Sodium Oxybate; Substance Withdrawal Syndrome

This paper describes the role of gamma-hydroxybutyric acid (GHB) in the treatment of opiate withdrawal syndrome. In the two patients described, after having abruptly withdrawn from long-term methadone treatment, GHB was orally administered (each dose given every 4-6 h) for 8-9 days. The GHB showed both a high efficacy (some mild and transient symptoms attributable to opiate withdrawal were observed, but only in the first days of therapy) and a good tolerability (no clinical phenomena interpreted as GHB side effects were found). These results could be of interest in improving the pharmacological treatment of drug addiction.

Topics: Adult; Female; Follow-Up Studies; Heroin Dependence; Humans; Male; Methadone; Neurologic Examination; Sodium Oxybate; Substance Abuse Detection; Substance Abuse, Intravenous; Substance Withdrawal Syndrome

Topics: Adult; Female; Humans; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders

A gas chromatographic-mass spectrometric (GC-MS) method for the determination of therapeutic levels of gamma-hydroxybutyric acid (GHB) in plasma and urine samples is described. GHB is converted to its lactonic form gamma-butyrolactone (GBL) which is extracted from biological fluids after the addition of the internal standard delta-valerolactone. Final GC-MS analysis is obtained under electron impact selected ion monitoring (SIM) conditions. Mean relative recoveries of GHB from plasma and urine are 75.5% (RSD% = 2.2) and 76.4% (RSD% = 2.4), respectively. The assay is linear over a plasma GHB range of 2-200 micrograms ml-1 (r = 0.999) and a urine GHB range of 2-150 micrograms ml-1 (r = 0.998). Intra- and inter-assay relative standard deviations (n = 5) determined at 10 and 100 micrograms ml-1 are below 5%. The method is simple, specific and accurate, and may be applied for analytical purposes related to pharmacokinetic studies and therapeutic drug monitoring.

Topics: 4-Butyrolactone; Alcoholism; Drug Monitoring; Ethanol; Gas Chromatography-Mass Spectrometry; Humans; Regression Analysis; Sensitivity and Specificity; Sodium Oxybate; Substance Withdrawal Syndrome

The ability of gamma-hydroxybutyric acid to suppress ethanol withdrawal syndrome was tested in male rats rendered physically dependent on ethanol by several intragastric administrations of ethanol (9-15 g/kg daily for 7 days). Gamma-hydroxybutyrate (0.25, 0.50 and 1.00 g/kg i.p.), administered 8 hr after the last ethanol dose, produced a dose-dependent inhibition of withdrawal signs such as tremors and audiogenically-induced seizures; the highest dose tested suppressed all ethanol withdrawal symptoms.

Topics: Animals; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Ethanol; Hydroxybutyrates; Male; Rats; Rats, Inbred Strains; Sodium Oxybate; Substance Withdrawal Syndrome

The effects of sodium hydroxybutyrate (100 mg/kg); phenazepam (1 mg/kg), apomorphine (0.1 mg/kg and haloperidol (1 mg/kg) on the electrophysiological sleep pattern were studied in rats during 7-day alcohol withdrawal after its voluntary consumption for 13 months. It was shown that alcohol withdrawal led to profound disorders in the sleep-waking cycle. Sodium hydroxybutyrate prevented these disturbances and brought sleep to normal. Phenazepam exerted a powerful sedative and hypnotic effects but did not improve the balance of sleep phases. Apomorphine displayed a tendency to sleep normalization. However, this effect was short-term. Haloperidol did not eliminate abstinence manifestations in the sleep pattern.

Topics: Alcoholism; Animals; Anti-Anxiety Agents; Apomorphine; Benzodiazepines; Benzodiazepinones; Haloperidol; Humans; Male; Psychotropic Drugs; Rats; Sleep Wake Disorders; Sodium Oxybate; Substance Withdrawal Syndrome