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Official websites use. Share sensitive information only on official, secure websites. Gamma-hydroxybutyric acid GHB, 'liquid ecstasy' and its legal pro-drugs gamma-butyrolactone and 1,4-butanediol are gaining in importance as recreational drugs in Germany. The effects of these substances are comparable with those of alcohol or benzodiazepines. Because of the wide availability of GHB physicians are increasingly being confronted with cases of intoxication. Consumption of a high dose of GHB or its prodrugs leads to severe intoxication with respiratory depression and coma. Only supportive therapy can be offered; no antidote is available. In any patient with impaired consciousness of unknown cause, the possibility of intoxication with GHB must be considered. Because of the short half-life of GHB, intoxications treated in intensive care units rarely show any complications. However, a number of fatalities have occurred. The potential abuse of GHB as a date rape drug must be borne in mind. Keywords: liquid ecstasy, gamma-hydroxybutyric acid, drug abuse, designer drugs, diagnosis. Gamma-hydroxybutyric acid GHB is gaining in importance as an illegal drug in Germany 1. In spite of its popular name, 'liquid ecstasy,' the substance is neither chemically nor pharmacologically related to ecstasy substances such as methylenedioxyamphetamine or methylenedioxymethamphetamine MDA or MDMA. Rather, its effects are comparable to those of alcohol or benzodiazepines. Because of its wide availability, clinicians are increasingly confronted with cases of GHB intoxication 1 , 2. This article provides information about the substance and legal regulations. Especially bodybuilders used GHB because of its renowned muscle building effects by increased release of growth hormones and its aphrodisiac effect 3 , 4. After numerous cases of intoxication occurred over the following years, the US Food and Drug Administration FDA reclassified the drug as prescription-only in 5 , 6. However, this did not put a stop to misuse of the drug. It gained in popularity; its users consumed 'liquid ecstasy' or 'soap' on the club scene as a party drug or at private events, as an alternative to, or in combination with, alcohol. Since the beginning of the 21 st century, GHB has also been produced in Germany. However, there are also signs of increased consumption in certain population subgroups, certain social environments, or geographical areas, and consumption in the private arena seems to be becoming more common 1. In spite of the comparatively low popularity of GHB, cases of intoxication — some with a lethal result — have been increasing 6 , 7 , 8. Exact numbers of deaths in Germany or other countries are currently not available. Gamma-hydroxybutyric acid is a derivative of the endogenous neurotransmitter gamma-aminobutyric acid GABA figure. It can pass the blood-brain barrier. GHB was first synthesized in and licensed in Europe as an intravenous narcotic 9. Although it is still commercially available in Germany, it is rarely used, mainly because of:. Narrow therapeutic spectrum and therefore greater occurrence of adverse effects, such as seizures or vomiting;. Insufficiently calculable duration of effect 3. These therapies have many side effects 10 , GHB is administered intravenously for the purpose of sedation and orally for most other indications table 1. Misuse is mostly done by oral administration in liquid form — neat or diluted in drinks. Occasionally, capsules are ingested, which often contain GHB as a sodium salt. GHB has a narrow therapeutic spectrum. The effects are dose dependent and range from a slight state of intoxication, similar to alcohol intoxication, to coma, cardiovascular arrest, and respiratory arrest table 2 4 , 12 , Owing to the extremely fast metabolism of GHB, the desired or undesirable side effects last only one to four hours, depending on the dose. A typical patient is admitted with severely impaired consciousness and suddenly wakes up, usually after a very short time. As a rule GHB does not have longer term side effects, so the patients feel fit and want to leave the hospital — also thanks to the mnemic effect — to 'return to the party. In spite of numerous studies, the mechanism of action of GHB is still not known. According to the literature, several factors seem to influence the neurotransmitter balance. It was found shortly after introduction of the drug to the market that GHB is present as an endogenous substance in the brain. Here it is present as a breakdown product but also most probably as a precursor of GABA A possible mechanism of action that is under discussion is that in the context of the GABA metabolism, GHB functions as a neuromodulator in the brain. Further, studies have shown that GHB leads to a rise or fall in dopamine concentrations in the brain — depending on the dose — and influences the cholinergic system and the serotonergic system like neurosteroids and opioids. Further the possible presence of a G-protein coupled GHB receptor in the brain is under discussion. This is said to be stimulated by endogenous concentrations in the micromolar range. After oral administration, GHB is absorbed very rapidly; maximum plasma concentrations are reached after 25 to 45 minutes. The distribution throughout the body is rapid and follows a two-compartment model 7. The distribution volume is smaller than that of ethanol, at 0. Via the enzyme GHB dehydrogenase, GHB can be oxidated back into succinsemialdehyde and then reaches the citrate cycle, after a further oxidation step, mainly as succinate. The half-life of GHB is about 20 to 40 minutes, but there are indications that the elimination kinetics of GHB is not linear after administration of therapeutic doses GHB was put under the narcotics law in the US since and is subject to the strictest categorization schedule I. As a ready-made preparation, GHB can be prescribed and traded. These substances are metabolized into GHB after oral administration, or they are transformed by means of a simple chemical reaction into GHB by the dealers or users themselves. Instructions on how to synthesize these substances and even whole 'building sets' are available from the internet in a 'customer friendly' format. Since the actual effective substance is GHB, and from a pharmacological perspective GBL and 1,4-BD are therefore pro-drugs, their consumption may result in the same effects, side effects, and symptoms of intoxication 17 , For this reason, the FDA warned the public as early as in not to consume GBL containing products and called for a voluntary stop to the trade of the products. The GHB substitutes have thus far not been included in the German Narcotics Act, owing to their widespread use as solvents and the associated consequences for the chemical industry. They can therefore be traded and consumed without penalty. However, a voluntary monitoring system of the German Federal Criminal Office has been in force since Since not all traders of the chemicals are participating, however, it is still easy for potential consumers to buy GBL or 1,4-BD. The symptoms of gamma-hydrobutyric acid poisoning are partly similar to those of alcohol poisoning. Headaches, nausea, vomiting, vertigo, and speech impairment may be present. Higher concentrations may lead to bradycardia, seizures, respiratory depression to the point of respiratory arrest and impaired consciousness to the point of coma table 2. In contrast to opioid intoxication, patients usually do not have miosis. A further diagnostic pointer may be non-responsiveness to ex juvantibus administration of naloxone or flumenazil. Because of the rapid absorption and the rapid onset of effect, no precise data about the development of symptoms over time can be given. A typical characteristic is a rapid-onset and sudden clinical picture that then develops in a dose dependent fashion. Patients usually recover within six to eight hours after receiving symptom oriented treatment In severe intoxication, myoclonus or seizures followed by loss of consciousness have often been described. It is important to bear in mind possible GBH intoxication in certain risk groups. For a long time, very few cases of GHB intoxication were seen in Hamburg, but since the end of , severe cases of intoxication requiring intensive medical care have been seen regularly. This does not affect a particular clientele since GHB and its analogues can be acquired and consumed not only as prepared medications but also as chemicals. Most of the consumers are aged between 20 and 40 and have prior experience with other drugs 1. From the end of to April , 18 clinically relevant cases of intoxication occurred in the investigated samples that incurred toxicological questions at the institute for forensic medicine at the University Hospital in Hamburg-Eppendorf, in which analysis confirmed ingestion of GHB or GBL. Further, within the area of the institute, three young women and one man died and GHB or GBL intoxication was confirmed. Since samples are sent to the forensic laboratory not in all cases of intoxication in the Hamburg region, a much larger number can be assumed. The treatment of GHB intoxication relies mainly on monitoring in the intensive care setting and stabilizing vital functions. Depending on the clinical picture, protective reflexes, frequency of breathing, and blood gas controls, the indication for endotracheal intubation and temporary ventilator treatment need to be assessed Particular attention is required for the tendency to vomit even in patients with severely impaired consciousness and therefore a clearly increased risk of aspiration. Emergency physicians should be prepared to intubate. Symptomatic cardiac arrhythmias should initially be treated with atropine. If the patient does not respond, the indication for temporary pacemaker therapy should be assessed. Administering active charcoal is mostly not beneficial because of the rapid resorption and metabolization, but this may be discussed in the context of a mixed indication. Although its mechanism of action resembles that of benzodiazepines, the benzodiazepine antagonist flumazenil is equally ineffective as an antidote as the opioid antagonist naloxone 4. However, according to specialist information about GHB as an anesthetic, the symptoms of intoxication can be antagonized by giving physostigmine. However, studies have not shown conclusive results Especially in patients with bradycardic arrhythmias, the risk is so overwhelming that administration of physostigmine is regarded as unadvisable 2. Initial studies after clinical administration of GHB in patients with narcolepsy have not shown any cases of misuse or of tolerance developing. More recent studies, however, indicate the potential for the drug being psychologically and physically addictive 21 , Withdrawal symptoms resemble those of alcohol withdrawal and occur about one to six hours after the most recent administration. Treatment is difficult. GHB and its pro-drugs are colorless liquids, transparent and almost entirely flavorless. They can thus be mixed with drinks and administered to unsuspecting victims without their noticing. Especially in combination with alcohol, GHB can result in impaired consciousness including coma with anterograde amnesia. Studies have shown that GHB is one of the substances most often used for this purpose in the US 6 , Similar cases have also been reported from Germany and other European countries GHB can be confirmed in human blood or urine specimens or in remnants of drinks via tests such as gas chromatography combined with mass spectrometry Thus far, no immunological rapid test for GHB has been developed, which constitutes a problem. Rapid diagnosis in hospital or less well equipped laboratories is therefore impossible. If a patient is admitted with suspected GHB intoxication, the specimen can be sent to a specialist laboratory. The substance can then usually be confirmed within two to three hours. Information about laboratories with the required spectrum of analytic tests, which also provide emergency services, can be obtained from the Poisons Centres. Because of the extremely short half-life of GHB in the body, the currently assumed maximum time span during which GHB can be confirmed in blood samples is five to eight hours and in urine samples, about 12 hours It is therefore important that the specimens — serum or urine — are obtained as early as possible. This should be borne in mind especially in cases of possibly concealed administration 'Someone put something into my beer' , because after a longer time period has passed, GHB — by contrast to other substances — cannot be confirmed any longer. In a forensic scenario — for example, a suspected involuntary ingestion of centrally effective substances — the specimen should be frozen as early on as possible because an increase in GHB concentrations — owing to higher temperatures and subsequent bacterial activity — cannot be excluded. If an acute intoxication is suspected, it is sufficient to keep specimens in the fridge, at temperatures of 2 to 8 degrees Celsius. The authors declare that no conflict of interest exists according to the guidelines of the International Committee of Medical Journal Editors. As a library, NLM provides access to scientific literature. Dtsch Arztebl Int. Find articles by Hilke Andresen. Thomas Stimpfl , Dr. Find articles by Thomas Stimpfl. Nadine Sprys , Dipl. Find articles by Nadine Sprys. Tino Schnitgerhans , Dr. Find articles by Tino Schnitgerhans. PMC Copyright notice. Open in a new tab. Dosage Effect 1. Alleviates withdrawal symptoms in heroin addiction 3. Alleviates withdrawal symptoms in alcohol addiction 4. Treatment of narcolepsy with cataplexy. Individual dose Effect 1. Relaxation, anxiolysis, euphoria, sedation 2. Nausea, vomiting, myoclonic seizures, bradycardia, amnesia 3. Conflict of interest statement The authors declare that no conflict of interest exists according to the guidelines of the International Committee of Medical Journal Editors. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel.
Liquid Ecstasy – A Significant Drug Problem
Stuttgart buying MDMA pills
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Stuttgart buying MDMA pills
How to order prescription and over-the-counter medications online in Germany
Stuttgart buying MDMA pills
Stuttgart buying MDMA pills
Liquid Ecstasy – A Significant Drug Problem
Stuttgart buying MDMA pills
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Stuttgart buying MDMA pills
Stuttgart buying MDMA pills