Characterization of the Prosocial and Prosexual Effects of GHB
Condition: Depressive Disorder, Major; Bipolar Disorder; Autistic Disorder
MeSH terms: Depressive Disorder; Bipolar Disorder; Autistic Disorder; Depressive Disorder, Major
Study type: Interventional

Summary: 
      The purpose of this study is to determine whether gamma-Hydroxybutyrate (GHB) has prosocial
      and prosexual effects in healthy male participants, and to characterize these putative
      effects via behavioral tests, functional magnetic resonance imaging (fMRI),
      electroencephalography (EEG), and neuroendocrine parameters. The investigators predict that
      GHB in fact has prosocial and prosexual effects which can be neurobiologically characterized
      using the assessed methods. Such effects would be of high interest for the treatment of
      mental disorders which involve impairments of social interaction and sexual function such as
      major depression or autism.
    

Detailed description: 
      Introduction

      Gammahydroxybutyrate (GHB) is an endogenous short-chain fatty acid and discussed as a
      neurotransmitter (Bessman and Fishbein, 1963) with high affinity to specific GHB (Benavides
      et al., 1982; Snead, 2000) and α4βδ-gamma-Aminobutyric acid (GABA)A receptors (Absalom et
      al., 2012) that also binds with lower affinity to GABAB receptors (Engberg and Nissbrandt,
      1993). It is internationally used as standard treatment for narcolepsy with cataplexy
      (Alshaikh et al., 2012), and in some European countries for alcohol withdrawal and craving
      (Keating, 2014). Additionally, recent randomized controlled studies showed therapeutic
      effects in fibromyalgia (Spaeth et al., 2013). Anecdotal reports from GHB abusers indicate
      mood enhancing, prosocial and prosexual effects of the drug (Sumnall et al., 2008), which
      were not objectively assessed so far. Impaired social decision making is a behavioral finding
      in depression (Pulcu et al., 2014), that is related to social withdrawal symptoms. Moreover,
      sexual dysfunction is both a symptom of depression and an adverse effect of most
      antidepressant medications (Kennedy and Rizvi, 2009), with a deteriorating impact on quality
      of life measures. Due to its unique pharmacologic effects on sleep, daytime vigilance, pain,
      and social interaction, GHB was recently proposed as experimental therapeutic for the
      treatment of depression (Bosch et al., 2012).

      Study Aims

      A) Investigating the putative prosocial effects of GHB in humans B) Investigating the
      putative prosexual effects of GHB in humans C) Investigating the neuroendocrine mechanisms of
      putative prosocial and prosexual effects of GHB in humans D) Investigating
      electrophysiological effects of GHB in decision-making in humans E) Investigating the
      functional neurobiology of GHB and its putative prosexual effects in humans

      Study Design

      A) The effects of GHB on social cognition, sexual arousal, neuroendocrine parameters, and EEG
      measures in healthy subjects: GHB (20 mg/kg p.o.) was tested in 16 healthy males, using a
      randomized, placebo-controlled, cross-over design. Subjective effects on mood were assessed
      by visual analogue scales (VAS) and the GHB Specific Questionnaire (GSQ). Prosocial behavior
      was examined by the Charity Donation Task, the Social Value Orientation test, and the
      Reciprocity Task. We assessed reaction time and motor performance using the Delayed Matching
      to Sample and the Reaction Time tasks from the Cambridge Neuropsychological Test Automated
      Battery (CANTAB). We assessed social cognition using the Multifaceted Empathy Task (MET) and
      the Movie for the Assessment of Social Cognition (MASC). We assessed memory using a German
      version of the Rey Auditory Verbal Learing Task. Sexual arousal was assessed using the Sexual
      Arousal and Desire Inventory (SADI), sexual perception was assessed using a self-designed
      Sexual Arousal Task (SAT). Furthermore, the investigators assessed GHB effects on brain
      electrophysiological activity using electroencephalography (EEG) and a flanker task for the
      assessment of error-related negativity. Blood plasma levels of GHB, oxytocin, testosterone,
      progesterone, dehydroepiandrosterone (DHEA), cortisol, aldosterone, and adrenocorticotropic
      hormone (ACTH) were determined.

      B) The effects of GHB on neuronal networks and sexual arousal in healthy subjects - an fMRI
      study: The investigators performed a characterization of the putative prosexual effects of
      GHB (35 mg/kg vs. placebo p.o.) in 19 healthy participants. Questionnaires (VAS, SADI, GSQ)
      were used to assess subjective aspects. Brain reactivity towards erotic vs. neutral pictures
      of persons, as well as resting state connectivity and arterial spin labelling (ASL) was
      investigated with functional magnetic resonance imaging (fMRI).
    

Intervention name(s): GHB 35 mg/kg p.o.; GHB 20 mg/kg p.o.
Intervention type(s): Drug; Drug
Intervention description(s): GHB 35 mg/kg p.o.; GHB 20 mg/kg p.o.
Other intervention name(s): Sodium Oxybate; Sodium Oxybate
Intervention MeSH terms: Sodium Oxybate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Other
Keywords: Sodium Oxybate, Altruism, Neurostreroids, Liquid Ecstasy