- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02342366
Characterization of the Prosocial and Prosexual Effects of GHB
Multimodal Characterization of the Prosocial and Prosexual Effects of GHB Assessing Behavior, fMRI, EEG, and Neuroendocrine Mechanisms
Study Overview
Status
Intervention / Treatment
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).
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
-
Zurich, Switzerland, 8032
- Hospital for Psychiatry, University of Zurich
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
|
GHB 35 mg/kg p.o.
Other Names:
GHB 20 mg/kg p.o.
Other Names:
|
Experimental: GHB
GHB, Gamma-Hydroxybutyrate, two doses (20 and 35 mg/kg p.o.)
|
GHB 35 mg/kg p.o.
Other Names:
GHB 20 mg/kg p.o.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Sexual Arousal
Time Frame: 14 days
|
Changes in sexual arousal after GHB challenge compared to placebo (Sexual Arousal and Desire Inventory [SADI], Sexual Arousal Task [SAT], brain reactivity towards erotic vs. neutral pictures ([fMRI-Task])
|
14 days
|
Social Cognition and Behavior
Time Frame: 14 days
|
Changes in social cognition and behavior after GHB challenge compared to placebo (Charity Donation Task, Social Value Orientation test, Reciprocity Task, Multifaceted Empathy Task [MET], Movie for the Assessment of Social Cognition [MASC])
|
14 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Composite measure of Neuroendocrine Parameters
Time Frame: 14 days
|
Testosterone, DHEA, cortisol, aldosterone, ACTH, progesterone, oxytocin plasma levels after GHB challenge compared to placebo
|
14 days
|
electroencephalography (EEG) activity
Time Frame: 14 days
|
EEG activity during a flanker task after GHB challenge compared to placebo
|
14 days
|
fMRI activity
Time Frame: 14 days
|
Brain activity in fMRI after GHB challenge compared to placebo (Picture-Task, Resting State Connectivity, ASL)
|
14 days
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Erich Seifritz, Professor, University of Zurich
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- BESSMAN SP, FISHBEIN WN. GAMMA-HYDROXYBUTYRATE, A NORMAL BRAIN METABOLITE. Nature. 1963 Dec 21;200:1207-8. doi: 10.1038/2001207a0. No abstract available.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Pathologic Processes
- Mood Disorders
- Bipolar and Related Disorders
- Neurodevelopmental Disorders
- Child Development Disorders, Pervasive
- Autism Spectrum Disorder
- Depressive Disorder
- Disease
- Bipolar Disorder
- Autistic Disorder
- Depressive Disorder, Major
- Physiological Effects of Drugs
- Central Nervous System Depressants
- Anesthetics, Intravenous
- Anesthetics, General
- Anesthetics
- Adjuvants, Anesthesia
- Sodium Oxybate
Other Study ID Numbers
- PUK-GHB01
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Bipolar Disorder
-
ProgenaBiomeRecruitingBipolar Disorder | Bipolar I Disorder | Bipolar II Disorder | Bipolar Type I Disorder | Bipolar Disorder Mild | Bipolar Disorder Moderate | Bipolar Disorder SevereUnited States
-
Rush University Medical CenterThe Ryan Licht Sang Bipolar FoundationCompletedBipolar Disorder | Bipolar Depression | Bipolar I Disorder | Bipolar Disorder I | Bipolar Affective DisorderUnited States
-
University of PittsburghNational Alliance for Research on Schizophrenia and DepressionCompletedBipolar I Disorder | Bipolar II Disorder | Bipolar Disorder NOSUnited States
-
Region StockholmKarolinska InstitutetRecruitingBipolar Disorder | Bipolar Depression | Bipolar I Disorder | Bipolar II Disorder | Bipolar Affective Disorder; Remission in | Bipolar Affective Disorder, Currently Depressed, ModerateSweden
-
Hospital de Clinicas de Porto AlegreFederal University of Rio Grande do Sul; Hospital Moinhos de VentoActive, not recruitingBipolar Disorder | Bipolar Depression | Major Depressive Disorder | Bipolar I Disorder | Affective Disorder | Bipolar II DisorderBrazil
-
Medical University of South CarolinaMilken InstituteCompletedBipolar Disorder | Bipolar I Disorder | Bipolar II DisorderUnited States
-
Mayo ClinicCompletedMajor Depressive Disorder, Bipolar I and Bipolar IIUnited States
-
Joshua RosenblatRecruitingBipolar Disorder | Bipolar Depression | Bipolar I Disorder | Bipolar II DisorderCanada
-
Myriad Genetic Laboratories, Inc.University of MinnesotaCompletedMajor Depressive Disorder, Bipolar I and Bipolar IIUnited States
-
University Hospital, Strasbourg, FranceUnknownBipolar Disorder I | Bipolar Disorder II | Rapid Cycling Bipolar Disorder(DSM-IV-TR)France
Clinical Trials on GHB 35 mg/kg p.o.
-
University Hospital, Basel, SwitzerlandCompletedHyperalgesia | Allodynia | Pain SensationSwitzerland
-
Zhejiang Hisun Pharmaceutical Co. Ltd.Unknown
-
University of Split, School of MedicineClinical Hospital Centre ZagrebUnknownApnea | Obesity | Respiratory Insufficiency | Sedation Complication | Hypoxic Respiratory Failure | Airway Obstruction, NasalCroatia
-
PharmaKingCompletedEfficacy and Safety of MG in the Patients With Alcoholic Fatty Liver Disease and Alcoholic HepatitisAlcoholic Hepatitis | Alcoholic Fatty Liver DiseaseKorea, Republic of
-
Axovant Sciences Ltd.TerminatedDementia With Lewy BodiesUnited States, Canada, France, Italy, Netherlands, Spain, United Kingdom
-
Axovant Sciences Ltd.CompletedAlzheimer's Disease | Dementia With Lewy Bodies | Parkinson's Disease DementiaUnited States
-
Keymed Biosciences Co.LtdNot yet recruitingSystemic Lupus Erythematosus
-
GlaxoSmithKlineCompletedMuscular DystrophiesFrance, United States
-
Healthgen Biotechnology Corp.RecruitingEmphysema Secondary to Congenital AATDUnited States
-
Gangnam Severance HospitalCompleted