Background: Recently, Gamma-hydroxybutyrate (GHB) consumption in the recreational setting has been
replaced by that of its prodrug Gamma-butyrolactone (GBL), cheaper and easier to obtain due to several legal industrial
Objective: The aim of the present paper was to report the most authoritative literature on the pharmacology and toxicology
of GBL, dependence and abuse potential and the related public health issues together with the results of the
analyses of several illicit liquid preparations containing GHB/GBL generally sold as “G”.
Method: International literature concerning “Gamma-butyrolactone”, “GBL” “toxicology”, “pharmacology”,
“abuse”, “dependence” and “GHB has been reviewed and liquid preparations containing GHB/GBL analysed by
ultra-high performance liquid chromatography coupled to the tandem mass spectrometry validated methodology.
Results: GBL for recreational purposes is orally administered in liquid form and rapidly transformed into GHB by
lactonase enzymes present in the blood. As GBL shows a higher lipophilicity than GHB, it is absorbed more quickly,
its bioavailability is higher and its effects are faster than those of GHB. Studies on rodents have shown that GBL has
a low acute toxicity and only central nervous system depression has been highlighted. GBL abuse potential broadly
mimics that of GHB, taking into account that it exerts its effects on the only after conversion into GHB. The analysis
of 30 illicit preparations generally sold as “G” highlighted the presence of GBL in all of them at a mean concentration
of 760.7 ±91.46 mg/mL (range: 588.5 - 899.3 mg/mL).
Conclusion: GBL currently represents a growing public health issue since the substance is relatively cheaper and easier
to obtain than GHB. Improvement and implementation of laws and policies to place GBL under control are needed to
limit its diffusion, the eventual health threat for users and its non -negligible abuse liability and dependence risk.