Effects of biperiden in the treatment of alcohol use disorder: a randomized, double-blind, placebo-controlled trial

• Grant number: 23/01520-0
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2023
• End date: August 31, 2025
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: José Carlos Fernandes Galduroz
• Grantee: José Carlos Fernandes Galduroz
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Andréia Gomes Bezerra ; Paola Palombo ; Thiago Marques Fidalgo

Abstract

Introduction: According to the World Health Organization (WHO), alcohol dependence ranks second in the list of preventable deaths, second only to smoking. Alcohol, like other drugs of abuse, when administered acutely, activates the mesolimbic dopaminergic system and, after chronic administration, promotes important functional alterations of the brain's reward system. On the other hand, the cholinergic system interacts with the dopaminergic system in the ventral tegmental area, in the nucleus accumbens, in the cortex and also has a very important role in modulating the release of dopamine in different parts of the striatum. In the prefrontal cortex, the cholinergic system contributes to the learning and memory processes involved in cravings and relapses induced by drugs of abuse. Compulsion (craving, craving) is defined as an emotional-motivational state of impulse and the symptoms are triggered by internal and external stimuli that evoke the memory of the euphoric effects of alcohol or the discomfort of withdrawal and is a key element for relapses. Studies carried out in our laboratory have shown that blockade of the cholinergic system by biperiden (M1 and M4 receptor antagonist) decreased alcohol-induced conditioned place preference, Fos expression in the center and shell of the nucleus accumbens, and dopamine turnover . Therefore, biperiden could be acting as an anticraving substance. Objectives: the main objective is to verify the possible decrease in compulsion (craving, craving) in patients with alcohol use disorders who will receive biperiden or placebo. In addition, the effect of biperiden on relapses during outpatient treatment and during follow-ups will be evaluated, in addition to the possible change in the degree of dependence. Methods: this is a double-blind, randomized, placebo-controlled clinical trial. Research participants will be followed up at our service weekly, receiving biperiden or placebo, for 2 months. At the end of this period, the substance will be withdrawn slowly (1 capsule every 10 days). Finally, patients will be reassessed 6 months after the end of biperiden or placebo. Group therapy will be offered to all participants weekly, in total four sessions of brief cognitive-behavioral psychotherapy performed by professionals trained in this type of treatment. The group sessions will consist of an average of 15 patients/group, for 3 months. Study outcomes: the primary outcome is related to the intensity of compulsion (craving, craving) for alcohol and will be evaluated using the OCDS (Obsessive-Compulsive Drinking Scale) and Penn (Penn Alcohol Craving Scale) scales. The secondary outcomes of this study are related to relapses during treatment and in the Follow-up by the Timeline Followback Method Assessment (TLFB) and by qualitative interviews to study the number, intensity, duration, of relapses and changes in the degree of dependence that will be assessed by SADD. (AU)