GHB: Drug of Abuse or Therapeutic Agent?

Gamma-hydroxybutyrate (GHB), first synthesized in the 1960s, is a water-soluble sedative able to cross the blood-brain barrier. Controversy still exists as to whether GHB should be considered a neurotransmitter or, simply, a neuromodulator; there is pharmacologic evidence both for a unique GHB receptor in the brain and for agonism at the G-protein–coupled GABA_B receptor. When administered orally, GHB is characterized by “fast-in, fast-out” pharmacokinetics with a two-compartment model of distribution (rapid decline in blood levels and then a longer period of metabolism).

These authors summarize GHB physiology and pharmacokinetics, as well as its abuse and associated dependency and withdrawal syndromes. The authors also characterize the poten…