GHB

We tend to think of GHB as purely a recreational drug, often associated with nightlife and illicit use, but chemically, it's an intriguing compound with legitimate clinical applications. Originally synthesized as an anesthetic in the 1960s, GHB is also a naturally occurring substance in the human central nervous system. This duality makes GHB a paradox: a molecule that is both a neurotransmitter and a controversial drug of abuse.

GHB primarily exerts its effects through agonism of the GABA_B receptor, which is a metabotropic receptor that modulates neurotransmission via a second messenger system. Interestingly, GHB also has a weaker affinity for the GHB-specific receptor, whose function remains less clearly defined but may contribute to its unique effects. Pharmacokinetically, GHB is rapidly absorbed with oral bioavailability ranging from 25% to 65%. It exhibits a short half-life of approximately 30 to 60 minutes due to its rapid metabolism, primarily in the liver where it undergoes conversion to succinic semialdehyde and subsequently to succinic acid, entering the Krebs cycle.

In the clinical realm, GHB is approved under the name sodium oxybate for the treatment of narcolepsy, particularly for cataplexy and excessive daytime sleepiness. Its safety profile is complex; it carries a black box warning due to its potential for abuse, central nervous system depression, and respiratory depression, especially when combined with other depressants like alcohol or benzodiazepines. Despite its efficacy, the narrow therapeutic window demands careful titration and monitoring. Regulatory status varies globally, with strict controls in many regions. Current research explores its effects on alcohol withdrawal and fibromyalgia, highlighting its diverse potential. In research settings, practical deployment requires stringent adherence to ethical guidelines due to its psychoactive properties and abuse potential.