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HISTORY AND EPIDEMIOLOGY

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γ-Hydroxybutyric acid (GHB) was discovered in 1960 while searching for an analog for γ-aminobutyric acid (GABA).38 Because of its central nervous system (CNS) depressive and amnestic properties, GHB was initially used as an anesthetic adjunct, especially in Europe, but never gained favor in the United States for this indication. Outside of the United States, GHB is still used for anesthesia or as an adjunct sedative for therapeutic hypothermia and wound care in children.50,61 During the 1970s, a Food and Drug Administration (FDA) investigational new drug application (NDA) was submitted to test the use of GHB as a treatment for sleep disturbances. In the 1980s and 1990s, body builders popularized GHB as an anabolic dietary supplement because of its purported release of growth hormone. Its euphoric effects were recognized at this time, and it rapidly gained favor as a “club drug.” Because it can cause coma and profound amnesia, GHB was reportedly used in drug-facilitated sexual assault, and in 1990, the FDA banned all use of nonprescription GHB because of this concern.70

Following the ban, the analogs γ-butyrolactone (GBL) and 1,4-butanediol (BD) were quickly substituted for GHB in dietary supplements. After the Samantha Reid and Hillory J. Farias Date-Rape Prevention Act of 1999 was passed in 2000, the Drug Enforcement Administration (DEA) classified GHB and its analogs as Schedule I substances, claiming that GHB was a hazard to public safety.54,70 Also in 2000, an NDA was submitted to the FDA for GHB—under the generic name sodium oxybate and the trade name Xyrem—to reduce the incidence of cataplexy and improve the symptoms of daytime sleepiness in patients with narcolepsy.35 This latter indication was approved in 2002 and given a Schedule III designation by the DEA,83 which was expanded, in 2005, to include the treatment of excessive daytime sleepiness in patients with narcolepsy. In 2017, the generic sodium oxybate was approved for the same use. It is now also used “off label” for fibromyalgia, chronic fatigue syndrome, and depressive disorders, and shows promising results in treating spasmodic dysphonia.6,63,65,74 However, in 2010 the FDA declined to approve GHB for fibromyalgia because of a lack of evidence of efficacy and concerns for safety, citing specifically concerns for respiratory depression, abuse or misuse, and potential unintentional exposure and overdose in children. In the case of narcolepsy, these medications are subject to a Risk Evaluation and Mitigation Strategy (REMS). This requires prescribers to be certified and that patients must be enrolled in certified pharmacies. These pharmacies ship the medications directly to the patients.23,36 In Europe, specifically Austria and Italy, sodium oxybate is used both for alcohol withdrawal syndrome and for relapse prevention.10

In 2007, during an epidemic largely in England and Australia, 1,4-BD was identified in the sticky surface material of toy beads marketed under the names ...

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