Journal Article

Nocturnal Gamma-Hydroxybutyrate Reduces Cortisol-Awakening Response and Morning Kynurenine Pathway Metabolites in Healthy Volunteers

Dornbierer, D A, Binz, T M, Bosch, O G, Boxler, M, Quednow, B B, Stucky, B, Voegel, C D, Baur, D M, Seifritz, E, Landolt, H P, Kraemer, T, Steuer, A E, Baumgartner, M R

2019

Overview

Gamma-hydroxybutyrate (GHB; or sodium oxybate) is an endogenous GHB-/gamma-aminobutyric acid B receptor agonist. It is approved for application in narcolepsy and has been proposed for the potential treatment of Alzheimer's disease, Parkinson's disease, fibromyalgia, and depression, all of which involve neuro-immunological processes. Tryptophan catabolites (TRYCATs), the cortisol-awakening response (CAR), and brain-derived neurotrophic factor (BDNF) have been suggested as peripheral biomarkers of neuropsychiatric disorders. GHB has been shown to induce a delayed reduction of T helper and natural killer cell counts and alter basal cortisol levels, but GHB's effects on TRYCATs, CAR, and BDNF are unknown. Therefore, TRYCAT and BDNF serum levels, as well as CAR and the affective state (Positive and Negative Affect Schedule [PANAS]) were measured in the morning after a single nocturnal dose of GHB (50 mg/kg body weight) in 20 healthy male volunteers in a placebo-controlled, balanced, randomized, double-blind, cross-over design. In the morning after nocturnal GHB administration, the TRYCATs indolelactic acid, kynurenine, kynurenic acid, 3-hydroxykynurenine, and quinolinic acid; the 3-hydroxykynurenine to kynurenic acid ratio; and the CAR were significantly reduced (P < 0.05-0.001, Benjamini-Hochberg corrected). The quinolinic acid to kynurenic acid ratio was reduced by trend. Serotonin, tryptophan, and BDNF levels, as well as PANAS scores in the morning, remained unchanged after a nocturnal GHB challenge. GHB has post-acute effects on peripheral biomarkers of neuropsychiatric disorders, which might be a model to explain some of its therapeutic effects in disorders involving neuro-immunological pathologies. This study was registered at ClinicalTrials.gov as NCT02342366.

• Publisher: Oxford University Press
• Subject: Acids / Adolescent / Adult / Affect - drug effects / Alzheimer's disease / Amino acids / Automobiles / Biological markers / Biomarkers / Biomarkers - blood / Body weight / Brain-derived neurotrophic factor / Brain-Derived Neurotrophic Factor - blood / Cross-Over Studies / Darkness / Diseases / Double-Blind Method / Fibromyalgia / GABA / Gamma hydroxybutyrate / Glucocorticoids / Health aspects / Healthy Volunteers / Hormones / Humans / Hydrocortisone - blood / Hydroxybutyrates - administration & dosage / Hydroxybutyrates - pharmacology / Immunology / Killer cells / Kynurenine - blood / Kynurenine - metabolism / Male / Medical research / Metabolites / Narcolepsy / Nervous system diseases / Organic acids / Phenols (Class of compounds) / Regular s / Serotonin - blood / Signal Transduction - drug effects / Time Factors / Tryptophan / Tryptophan - analogs & derivatives / Tryptophan - blood / Wakefulness - drug effects / Young Adult