Abstract

Background and AimsThe regular use of gamma-hydroxybutyrate acid (GHB) can induce GHB-induced comas. Other substance use disorders are associated with alterations in brain structure and impulsivity. Here we aim to investigate if these are also modulated by either regular GHB use or GHB-induced comas.MethodsIn a sample of human males, structural and diffusion neuroimaging data were collected for 27 GHB users with ≥4 GHB-induced comas (GHB-Coma), 27 GHB users without GHB-induced comas (GHB-NoComa), and 27 polydrug users who never used GHB (No-GHB). The structural brain parameters were analyzed macroscopically using voxel-based morphometry and microscopically using tract-based spatial statistics (TBSS) and tractography. Impulsivity was assessed with the Barrat Impulsivity Scale.ResultsIn comparison to the other two groups, the GHB-Coma group showed a higher fractional anisotropy in the body of the corpus callosum and a lower mean diffusivity in the forceps minor (i.e., whole-brain TBSS analysis). No macrostructural differences nor microstructural differences, as assessed with tractography, were observed. The GHB-Coma group also reported higher impulsivity, which was more strongly associated with white matter volume and fractional anisotropy in tracts involved in impulse control (post-hoc analysis). GHB use per se was associated neither with differences in brain structure nor with impulsivity.ConclusionsThe results suggest that multiple GHB-induced comas, but not GHB use per se, are associated with microstructural alterations in white matter and with higher self-reported impulsivity, which in turn was associated with white matter tracts involved in impulse control.

Highlights

  • Since it was first synthesized in the 1960s, gamma-hydroxybutyrate acid (GHB) has been regularly used for different therapeutic purposes [1,2,3,4]

  • The overall exclusion criteria were a history of epilepsy, general anesthesia within the 2 years preceding the study, a contra-indication for functional magnetic resonance imaging scanning, any coma unrelated to GHB use, and currently under treatment for narcolepsy with cataplexy

  • There were no significant group differences in age and education level in any of the different sample sizes that had to be considered for each neuroimaging method of analysis

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Summary

Introduction

Since it was first synthesized in the 1960s, gamma-hydroxybutyrate acid (GHB) has been regularly used for different therapeutic purposes [1,2,3,4]. The appealing effects of the drug start with euphoria, relaxation, and sexual arousal, readily evolving into a state of sedation and altered consciousness when higher doses are used [1,2,3,4,5,6]. This intangible stimulant–sedative shift is dangerously associated with poor control of dosage and effect duration, which creates a high risk for overdosing (including GHB-induced coma), and can lead to tolerance and addiction [2,3,4,5]. We aim to investigate if these are modulated by either regular GHB use or GHB-induced comas

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