Gamma-Hydroxybutyrate (GHB) Toxicity: From Clandestine Synthesis to Clinical Coma—A Pharmacotoxicological Primer for the Practicing Clinician

Gamma-hydroxybutyrate (GHB) occupies a curious and clinically treacherous position in the landscape of recreational drugs. First synthesized in 1960 as an intravenous anesthetic, GHB was quickly abandoned in mainstream medicine due to a narrow therapeutic window and unpredictable adverse effects, only to re-emerge decades later as a popular agent for sleep enhancement, physical performance, and weight loss. Today, it is a Schedule I substance in the United States—excepting its pharmaceutical formulation sodium oxybate—and is perhaps best known to emergency clinicians as a cause of sudden, profound coma followed by equally abrupt awakening. This review offers a conceptual and practical walk through GHB toxicity: its clandestine manufacturing roots, the peculiar epidemiology that clusters among young white middle-class males and party subcultures, and the dual-receptor (GABA-B and GHB-specific) pathophysiology that explains its paradoxical biphasic effects of euphoria followed by deep sedation. Toxicokinetically, GHB’s rapid absorption, brief half-life (20–60 minutes), and dose-dependent clinical course (from REM sleep at 20–30 mg/kg to coma and respiratory depression at 50 mg/kg) are central to understanding both its abuse pattern and its management. Because GHB is not detected on routine drug screens, diagnosis remains clinical, anchored by the classic history of a sudden comatose patient who awakens fully within hours. Treatment is entirely supportive—airway protection first—with no antidote available. Special attention is given to the rising challenge of GHB withdrawal syndrome, a potentially fatal autonomic storm lasting up to 15 days, and to the interprofessional teamwork required to manage these patients safely. The goal is not merely to recognize GHB overdose but to anticipate its complications, avoid common missteps (like premature extubation or undertreated withdrawal), and appreciate the drug’s strange career from operating room to nightclub.