Characterization of the Prosocial and Prosexual Effects of GHB

NCT ID: NCT02342366

Last Updated: 2019-07-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

19 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-02-29

Study Completion Date

2014-12-31

Brief Summary

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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

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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).

Conditions

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Depressive Disorder, Major Bipolar Disorder Autistic Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

OTHER

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Placebo

Placebo

Group Type PLACEBO_COMPARATOR

GHB 35 mg/kg p.o.

Intervention Type DRUG

GHB 35 mg/kg p.o.

GHB 20 mg/kg p.o.

Intervention Type DRUG

GHB 20 mg/kg p.o.

GHB

GHB, Gamma-Hydroxybutyrate, two doses (20 and 35 mg/kg p.o.)

Group Type EXPERIMENTAL

GHB 35 mg/kg p.o.

Intervention Type DRUG

GHB 35 mg/kg p.o.

GHB 20 mg/kg p.o.

Intervention Type DRUG

GHB 20 mg/kg p.o.

Interventions

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GHB 35 mg/kg p.o.

GHB 35 mg/kg p.o.

Intervention Type DRUG

GHB 20 mg/kg p.o.

GHB 20 mg/kg p.o.

Intervention Type DRUG

Other Intervention Names

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Sodium Oxybate Sodium Oxybate

Eligibility Criteria

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Inclusion Criteria

* Healthy male subjects.

Exclusion Criteria

* Any Axis-I DSM-IV psychiatric disorder, any form of addiction or regular illegal drug use (lifetime use \>5 occasions) with exception of occasional cannabis use, a lifetime history of GHB use, a neurological disorder or head injury, clinically relevant medical diseases, a family history of schizophrenia or bipolar disorder, and any use of prescription drugs.
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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University of Regensburg

OTHER

Sponsor Role collaborator

University of Salerno

OTHER

Sponsor Role collaborator

University of Vienna

OTHER

Sponsor Role collaborator

University of Freiburg

OTHER

Sponsor Role collaborator

University of Zurich

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Erich Seifritz, Professor

Role: PRINCIPAL_INVESTIGATOR

University of Zurich

Locations

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Hospital for Psychiatry, University of Zurich

Zurich, , Switzerland

Site Status

Countries

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Switzerland

References

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Absalom N, Eghorn LF, Villumsen IS, Karim N, Bay T, Olsen JV, Knudsen GM, Brauner-Osborne H, Frolund B, Clausen RP, Chebib M, Wellendorph P. alpha4betadelta GABA(A) receptors are high-affinity targets for gamma-hydroxybutyric acid (GHB). Proc Natl Acad Sci U S A. 2012 Aug 14;109(33):13404-9. doi: 10.1073/pnas.1204376109. Epub 2012 Jul 2.

Reference Type BACKGROUND
PMID: 22753476 (View on PubMed)

Alshaikh MK, Tricco AC, Tashkandi M, Mamdani M, Straus SE, BaHammam AS. Sodium oxybate for narcolepsy with cataplexy: systematic review and meta-analysis. J Clin Sleep Med. 2012 Aug 15;8(4):451-8. doi: 10.5664/jcsm.2048.

Reference Type BACKGROUND
PMID: 22893778 (View on PubMed)

Benavides J, Rumigny JF, Bourguignon JJ, Cash C, Wermuth CG, Mandel P, Vincendon G, Maitre M. High affinity binding sites for gamma-hydroxybutyric acid in rat brain. Life Sci. 1982 Mar 15;30(11):953-61. doi: 10.1016/0024-3205(82)90624-5.

Reference Type BACKGROUND
PMID: 7070203 (View on PubMed)

BESSMAN SP, FISHBEIN WN. GAMMA-HYDROXYBUTYRATE, A NORMAL BRAIN METABOLITE. Nature. 1963 Dec 21;200:1207-8. doi: 10.1038/2001207a0. No abstract available.

Reference Type BACKGROUND
PMID: 14089913 (View on PubMed)

Bosch OG, Quednow BB, Seifritz E, Wetter TC. Reconsidering GHB: orphan drug or new model antidepressant? J Psychopharmacol. 2012 May;26(5):618-28. doi: 10.1177/0269881111421975. Epub 2011 Sep 17.

Reference Type BACKGROUND
PMID: 21926421 (View on PubMed)

Engberg G, Nissbrandt H. gamma-Hydroxybutyric acid (GHBA) induces pacemaker activity and inhibition of substantia nigra dopamine neurons by activating GABAB-receptors. Naunyn Schmiedebergs Arch Pharmacol. 1993 Nov;348(5):491-7. doi: 10.1007/BF00173208.

Reference Type BACKGROUND
PMID: 8114948 (View on PubMed)

Keating GM. Sodium oxybate: a review of its use in alcohol withdrawal syndrome and in the maintenance of abstinence in alcohol dependence. Clin Drug Investig. 2014 Jan;34(1):63-80. doi: 10.1007/s40261-013-0158-x.

Reference Type BACKGROUND
PMID: 24307430 (View on PubMed)

Kennedy SH, Rizvi S. Sexual dysfunction, depression, and the impact of antidepressants. J Clin Psychopharmacol. 2009 Apr;29(2):157-64. doi: 10.1097/JCP.0b013e31819c76e9.

Reference Type BACKGROUND
PMID: 19512977 (View on PubMed)

Pulcu E, Thomas EJ, Trotter PD, McFarquhar M, Juhasz G, Sahakian BJ, Deakin JF, Anderson IM, Zahn R, Elliott R. Social-economical decision making in current and remitted major depression. Psychol Med. 2015 Apr;45(6):1301-13. doi: 10.1017/S0033291714002414. Epub 2014 Oct 10.

Reference Type BACKGROUND
PMID: 25300570 (View on PubMed)

Snead OC 3rd. Evidence for a G protein-coupled gamma-hydroxybutyric acid receptor. J Neurochem. 2000 Nov;75(5):1986-96. doi: 10.1046/j.1471-4159.2000.0751986.x.

Reference Type BACKGROUND
PMID: 11032888 (View on PubMed)

Spaeth M, Alegre C, Perrot S, Wang Y, Guinta DR, Alvarez-Horine S, Russell I; Sodium Oxybate Fibromyalgia Study Group. Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia. Arthritis Res Ther. 2013 Nov 11;15(6):R185. doi: 10.1186/ar4375.

Reference Type BACKGROUND
PMID: 24286114 (View on PubMed)

Sumnall HR, Woolfall K, Edwards S, Cole JC, Beynon CM. Use, function, and subjective experiences of gamma-hydroxybutyrate (GHB). Drug Alcohol Depend. 2008 Jan 1;92(1-3):286-90. doi: 10.1016/j.drugalcdep.2007.07.009. Epub 2007 Sep 4.

Reference Type BACKGROUND
PMID: 17766059 (View on PubMed)

Dornbierer DA, Boxler M, Voegel CD, Stucky B, Steuer AE, Binz TM, Baumgartner MR, Baur DM, Quednow BB, Kraemer T, Seifritz E, Landolt HP, Bosch OG. Nocturnal Gamma-Hydroxybutyrate Reduces Cortisol-Awakening Response and Morning Kynurenine Pathway Metabolites in Healthy Volunteers. Int J Neuropsychopharmacol. 2019 Oct 1;22(10):631-639. doi: 10.1093/ijnp/pyz047.

Reference Type DERIVED
PMID: 31504554 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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PUK-GHB01

Identifier Type: -

Identifier Source: org_study_id

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