Effect of 3 4-methylenedioxymethamphetamine (MDMA) on the toxicokinetics and sedative effects of the drug of abuse γ-hydroxybutyric acid

摘要

γ-hydroxybutyric acid (GHB) is widely abused in combination with other club drugs such as 3,4-methylenedioxy methamphetamine (MDMA). The objectives of this study were to characterize the effects of MDMA on GHB toxicokinetics/toxicodynamics (TK/TD) and evaluate the use of monocarboxylate transporter (MCT) inhibition as a potential treatment strategy for GHB overdose when GHB is abused with MDMA. Rats were administered GHB 400 mg/kg i.v. alone or with MDMA (5 mg/kg i.v). Effects of MDMA and of the monocarboxylate transporter (MCT) inhibitor, L-lactate, on GHB TK and sedative effects were evaluated. The results of this study demonstrated no significant effect of MDMA on GHB TK or TD. GHB plasma concentrations were unchanged, and GHB concentration-effect relationships, based on plasma and brain concentrations and the return to righting reflex (RRR), were similar in the presence and absence of MDMA. L-lactate administration resulted in a significant decrease in the sedative effect (RRR) of GHB when it was co-administered with MDMA. Our results indicate that MDMA does not affect the TK/TD of GHB at the doses used in this study, and MCT inhibition using L-lactate, an effective overdose treatment strategy for GHB alone, is also effective for GHB overdose when GHB is co-ingested with MDMA.