Comprehensive Monograph on Gamma-Hydroxybutyric Acid (GHB)

Section 1: Executive Summary

Gamma-Hydroxybutyric acid (GHB) is a substance of profound duality, existing as an endogenous neurotransmitter, a highly regulated therapeutic agent, and a potent, dangerous drug of abuse.[1] This report provides a comprehensive analysis of GHB, synthesizing information across chemistry, pharmacology, clinical medicine, toxicology, and regulatory affairs to present a complete profile of this complex molecule.

GHB's core pharmacological activity is defined by its dose-dependent, biphasic effects on the central nervous system (CNS). It acts as an agonist at two distinct receptor sites: a high-affinity, excitatory GHB receptor and a low-affinity, inhibitory GABA-B receptor.[3] This dual mechanism explains its paradoxical profile, capable of producing euphoria and stimulation at low doses while inducing profound sedation, anesthesia, and respiratory depression at higher therapeutic or recreational doses.[3]

The pharmacokinetic properties of GHB are critical to understanding both its therapeutic utility and its significant risk profile. It is characterized by rapid absorption and a very short elimination half-life of 30-60 minutes.[1] Crucially, at high doses, its metabolism becomes saturated and shifts from first-order to zero-order kinetics. This non-linear elimination dramatically increases the risk of drug accumulation and unintentional overdose, narrowing its therapeutic window to a perilous degree.[4]