Novel Opipramol-Baclofen Combination Alleviates Depression and Craving and Facilitates Recovery From Substance Use Disorder—An Animal Model and a Human Study

Abstract

Substance use disorders (SUDs) are associated with depression and anxiety, with the latter being one of the major factors in substance-seeking and relapse. Due to dose-dependent sedative side effects there is limited efficacy of baclofen treatment for SUDs. Here we suggest the use of a novel combination of opipramol and baclofen (O/B) which is known to attenuate anxiety and depression, for the facilitation of recovery from SUDs. Since both opipramol and baclofen have a common downstream signal transduction, their individual doses could be reduced while still maintaining the benefits of the combination. We tested the O/B combination in both animals and patients. Rats treated with O/B showed significant attenuation in craving behavior and in relapse rate during withdrawal from cocaine. In a double-blind, placebo-controlled pilot study, conducted in a residential detoxification center, 14 males and 3 females, aged 28–60 years were assigned to a study (n = 6) and a placebo (n = 11) group (placebo group: 40 ± 10.5 years; O/B group 40 ± 10.8 years). The participants completed scales measuring depression, anxiety and craving symptoms and provided saliva samples for stress hormone examination [cortisol and dehydroepiandrosterone-sulfate (DHEA-S)]. Participants with polysubstance use disorder (PsUD) treated with O/B showed a reduction in cravings and depression and an increase in DHEA-S and in the DHEA-S/cortisol ratio. Our findings indicate a beneficial effect of O/B treatment. This study suggests a novel candidate for pharmacological treatment of patients with SUD and comorbid mood/anxiety disorders that may facilitate their rehabilitation.

The potential therapeutic roles of Rho GTPases in substance dependence

“…Opipramol combined with baclofen significantly reduced cravings and depressive symptoms in substance abusers, according to a preliminary, double-blind, controlled clinical investigation. These findings suggest that opipramol and baclofen could be candidates for treatment in patients with substance abuse and comorbidities for mood/anxiety disorders, which may help improve their addiction status and promote rehabilitation ( Bareli et al, 2021a ).…”

Overtime Histological Changes in the Lungs after Intoxication with Baclofen Alone or in Combination with Ethanol (Experimental Study)

“…Баклофен в пероральной форме показан для лечения тяжелой мышечной спастичности, при рассеянном склерозе, опухолях, травмах, инфек-ционных заболеваниях спинного мозга, острые нарушениях мозгового кровообращения и менингите. Изучалась эффективность баклофена у пациентов с алкоголизмом [10][11][12][13][14] и наркоманией [14]; в ряде исследований показана эффективность баклофена при церебральном параличе [15,16].…”