Journal de recherche et de thérapie en toxicomanie

Abstrait

Treatment of Alcoholic Patients Using Anticonvulsant Urea Derivative Influences the Metabolism of Neuro-active Steroid Hormones - The System of Stress Markers

Shushpanova TV*, Bokhan NA, Lebedeva VF, Mandel AI, Novozheeva TP, Solonskii AV, Schastnyy ED, Semke AV, Kazennich TV, Udut VV, Arbit GA and Filimonov VD

Objective: Disturbed homeostasis of neuroactive steroid hormones (NAS) may be a risk factor for the development of mental illness and alcohol addiction; psychopharmacological drugs that modulate the activity of NAS can cause clinical effects through their impact on the balance of hormones. We investigated the levels of NAS: cortisol, adrenocorticotropin (ACTH), dehydroepiandrosterone (DHEA) and dehydroepiandrosterone - sulfate (DHEA-S) in the blood serum of male alcoholics and healthy volunteers at baseline and at the background anticonvulsant therapy galodif, showed a positive trend in the reduction of craving for ethanol.
Materials and Method: The study included 68 patients with alcoholism only men and 23 healthy volunteers, standardized to the main group in age. Patients were treated at the Department of addictive states Mental Health Research Institute with the diagnosis according to ICD - 10: F10.232 and F10.302). The studies of the effect of therapy with galodif on the levels of NAS were performed by assigning galodif at dose of 300 mg/day during the ongoing course of treatment 21 days. ACTH, cortisol, DHEA and DHEA-S were determined with use kits for enzyme-linked immunosorbent assay (ELISA).
Results: Our research has shown that increased levels of hormones index ratio cortisol/DHEA in patients with alcoholism during abstinence significantly reduced on the background of the course of therapy with galodif. Reduced levels of cortisol and increasing DHEA levels during therapy with galodif indicates the stimulation of synthesis of DHEA, providing anti-glucocorticoid effect on the background of high levels of cortisol. DHEA and DHEA–S can protect neurons from glucocorticoid-induced neurotoxicity.
Conclusion: The ratio of cortisol/DHEA is of particular importance because the anti-glucocorticoid effect of DHEA underlies the reduction of anxiety and depression in humans. Galodif reduces the ratio of cortisol/DHEA that can enhance GABAergic neurotransmission and provide a positive effect on the therapy.
Graphical Abstract: Anticonvulsant galodif having anti-glucocorticoid effect and reduces the ratio of cortisol/DHEA that can enhance GABAergic neurotransmission in the brain and provide a positive effect of treatment of patients with alcoholism.