Gamma-hydroxybutyrate enhances mood and prosocial behavior without affecting plasma oxytocin and testosterone

Abstract

Word count main text:4734 Word count abstract: 200 Number of references: 59Number of tables: 2 ABSTRACTGamma-hydroxybutyrate (GHB) is a GHB-/GABA B -receptor agonist. Reports from GHB abusers indicate euphoric, prosocial, and empathogenic effects of the drug. We measured the effects of GHB on mood, prosocial behavior, social and non-social cognition and assessed potential underlying neuroendocrine mechanisms. GHB (20 mg/kg) was tested in 16 healthy males, using a randomized, placebo-controlled, cross-over design. Subjective effects on mood were assessed by visual-analoguescales and the GHB-Specific-Questionnaire. Prosocial behavior was examined by the Charity Donation Task, the Social Value Orientation test, and the Reciprocity Task. Reaction time, memory, empathy, and theory-of-mind were also tested. Blood plasma levels of GHB, oxytocin, testosterone, progesterone, dehydroepiandrosterone (DHEA), cortisol, aldosterone, and adrenocorticotropichormone (ACTH) were determined. GHB showed stimulating and sedating effects, and elicited euphoria, disinhibition, and enhanced vitality. In participants with low prosociality, the drug increased donations and prosocial money distributions. In contrast, social cognitive abilities such as emotion recognition, empathy, and theory-of-mind, and basal cognitive functions were not affected.GHB increased plasma progesterone, while oxytocin and testosterone, cortisol, aldosterone, DHEA, and ACTH levels remained unaffected. GHB has mood-enhancing and prosocial effects without affecting social hormones such as oxytocin and testosterone. These data suggest a potential involvement of GHB-/GABA B -receptors and progesterone in mood and prosocial behavior.

Prohedonic properties of gamma‐hydroxybutyrate are associated with changes in limbic resting‐state functional connectivity

“…Quantitatively, there were two peaks at 55 and 77 min due to visual stimulation, were sexual arousal was increased in both the GHB and the placebo group, resulting in no significant difference between the groups. Both profiles are in line with previous pharmacokinetic and pharmacodynamic studies (Abanades et al, ; Bosch et al, ; Brenneisen et al, ; Liechti et al, ). Depending on dosage and time, GHB frequently exerts biphasic effects such as euphoria in lower doses and in early stages of intoxication and sedation or coma with higher doses and in later stages of intoxication (Abanades et al, ; Madah‐Amiri, Myrmel, & Brattebo, ).…”

“…It is remarkable that a predominant GABA‐B agonist exerts a spectrum of subjective effects that is usually attributed either to tranquilizers (sedation, relaxation, anxiolysis) or stimulants (euphoria, stimulation, sexual arousal; Abanades et al, ; Abanades et al, ; Barker, Harris, & Dyer, ; Bosch et al, ; Bosch, Havranek, et al, ; Kapitany‐Foveny et al, ; Miotto et al, ; Sumnall et al, ). Here, we show that GHB induces euphoria and sexual arousal.…”

“…Both, euphoria and sexual arousal are linked to frontolimbic dopaminergic activity (Drevets et al, ; Wise & Bozarth, ), which is dampened in certain anhedonic states (Argyropoulos & Nutt, ). In fact, although most of the subjective and behavioral actions of GHB are mediated by its GABA‐B agonism (Carter, Koek, & France, ), its specific hedonic properties such as mood enhancement, as well as prosocial and prosexual activation might be mediated by downstream dopaminergic disinhibition of the VTA via GABAergic autoreceptors on GABAergic interneurons (Bosch et al, ; Bosch, Esposito, et al, ; Bosch, Havranek, et al, ; Cruz et al, ; Labouebe et al, ; Maitre, ; Pistis et al, ). Although GHB did not induce significant nausea in our volunteers at 35 mg/kg p.o., this is usually a typical side effect of high doses of GHB (Carter, Richards, Mintzer, & Griffiths, ; Chin, Kreutzer, & Dyer, ; Elsing, Stremmel, Grenda, & Herrmann, ; Russell et al, ), which is probably also related to the drug's capacity to rapidly increase central dopaminergic tone.…”

“…Thus, on the thalamic level, GHB seems to work as a differential regulator of cortical activity. Consequently, the observed increase of rAI‐thalamic rsFC is most likely generated by GABA‐B mediated disinhibition of somatosensory projections, which is the bottom‐up element of an overall activation of the salience and reward networks, corresponding to subjective hedonic effects such as euphoria, sexual arousal, and enhanced body and emotion awareness (Bosch et al, ; Bosch, Esposito, et al, ; Bosch, Havranek, et al, ).…”

Effect of γ-hydroxybutyrate (GHB) on driving as measured by a driving simulator

“…In human studies with lower GHB doses, 1–2 g did not significantly impair psychomotor skills related to driving (Mattila 1978). GHB at 12.5 and 25 mg/kg had no effects on attention, vigilance or psychomotor co-ordination (Ferrara 1999), at 0.32−3.2 g/70kg (4.5−45.7 mg/kg) produced dose-related changes in subjective effects but no changes in psychomotor performance (Oliveto 2010), and at 20 mg/kg had no significant effects on visual working memory, reaction time and verbal recall (Bosch 2015). In studies using higher GHB doses (Carter 2006), 8 g/70kg (114 mg/kg) produced sedation in almost all participants, and in approximately one third painful stimuli were required to elicit a response.…”