The discovery of
gamma-hydroxybutyrate (GHB) over 40 years ago led to its immediate use as a
general anesthetic agent. Subsequent research demonstrated that GHB is an endogenous compound in the mammalian brain and current research suggests that GHB is a probable
neurotransmitter. In the United States, reports of
anabolic effects lead to its misuse among body builders during the 1980's while the intoxicating properties of the
drug lead to its popularization as a substance of abuse during the 1990's. GHB became associated with reports of
drug-facilitated sexual assault and cases of physical dependence and withdrawal. Efforts to ban GHB caused increased use of GHB analogues and
pro-drugs. Against this backdrop, GHB was being developed for the treatment of
narcolepsy, leading to the approval of
Xyrem (
sodium oxybate) oral
solution in 2002 for the treatment of
cataplexy in patients with
narcolepsy. A risk management program permits the safe handling and distribution of the approved product, minimizes the risk for diversion, provides professional and patient education about the risks and benefits of
sodium oxybate, and includes physician and patient registries. Post-marketing surveillance indicates
sodium oxybate has an acceptable safety profile and presents minimal risk for the development of physical dependence.