Carolina L Haass-Koffler1,2,3, Roberta Perciballi4, Molly Magill4, Antonella Loche5, Roberto Cacciaglia5, Lorenzo Leggio4,6,7,8,9, Robert M Swift10,11. 1. Center for Alcohol and Addiction Studies, Department of Psychiatry and Human Behavior, Brown University, 121 South Main Street, Providence, RI, 02903, USA. carolina_haass-koffler@brown.edu. 2. Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, RI, USA. carolina_haass-koffler@brown.edu. 3. Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, NIDA IRP and NIAAA DICBR, Baltimore and Bethesda, MD, USA. carolina_haass-koffler@brown.edu. 4. Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, RI, USA. 5. Laboratorio CT, San Remo, Italy. 6. Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, NIDA IRP and NIAAA DICBR, Baltimore and Bethesda, MD, USA. 7. Medication Development Program, National Institute On Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, USA. 8. Division of Addiction Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 9. Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. 10. Center for Alcohol and Addiction Studies, Department of Psychiatry and Human Behavior, Brown University, 121 South Main Street, Providence, RI, 02903, USA. 11. Providence Veterans Affairs Medical Center, Providence, RI, USA.
Abstract
RATIONALE: Previous work suggests that GET 73, a novel compound with putative activity on the metabotropic glutamate receptor subtype 5 (mGluR5), may represent a novel pharmacological treatment for alcohol use disorder (AUD). OBJECTIVE: In this study, we investigated the safety, tolerability, pharmacokinetics, and biobehavioral effects of GET 73, when co-administered with alcohol, in individuals with alcohol dependence (AD). METHODS: This was an inpatient, cross-over, randomized, double-blind, placebo-controlled, human laboratory study with non-treatment-seeking, alcohol-dependent individuals. The study used a within-subject design, with two counterbalanced stages, during which participants received GET 73 and then placebo, or vice versa. During each stage, participants underwent an alcohol interaction session and, on a separate day, an alcohol cue reactivity, followed by an alcohol self-administration session. RESULTS: Safety outcomes of GET 73 were excellent with no serious adverse events, nor adverse events of severe grade. The co-administration of alcohol and GET 73 did not affect the pharmacokinetics of GET 73 or alcohol. GET 73, compared to placebo, did not affect the alcohol-related stimulation effects, but increased the subjective sedative effects of alcohol. GET 73 did not affect alcohol cue-induced craving, or alcohol self-administration in the laboratory. CONCLUSIONS: The study confirms the safety and tolerability of GET 73 when co-administered with alcohol. Although, under this experimental condition, we did not detect an effect on alcohol craving and consumption in the laboratory, additional studies should be conducted administering GET 73 for an extended period in an outpatient setting.
RATIONALE: Previous work suggests that GET 73, a novel compound with putative activity on the metabotropic glutamate receptor subtype 5 (mGluR5), may represent a novel pharmacological treatment for alcohol use disorder (AUD). OBJECTIVE: In this study, we investigated the safety, tolerability, pharmacokinetics, and biobehavioral effects of GET 73, when co-administered with alcohol, in individuals with alcohol dependence (AD). METHODS: This was an inpatient, cross-over, randomized, double-blind, placebo-controlled, human laboratory study with non-treatment-seeking, alcohol-dependent individuals. The study used a within-subject design, with two counterbalanced stages, during which participants received GET 73 and then placebo, or vice versa. During each stage, participants underwent an alcohol interaction session and, on a separate day, an alcohol cue reactivity, followed by an alcohol self-administration session. RESULTS: Safety outcomes of GET 73 were excellent with no serious adverse events, nor adverse events of severe grade. The co-administration of alcohol and GET 73 did not affect the pharmacokinetics of GET 73 or alcohol. GET 73, compared to placebo, did not affect the alcohol-related stimulation effects, but increased the subjective sedative effects of alcohol. GET 73 did not affect alcohol cue-induced craving, or alcohol self-administration in the laboratory. CONCLUSIONS: The study confirms the safety and tolerability of GET 73 when co-administered with alcohol. Although, under this experimental condition, we did not detect an effect on alcohol craving and consumption in the laboratory, additional studies should be conducted administering GET 73 for an extended period in an outpatient setting.
Authors: John E McGeary; Peter M Monti; Damaris J Rohsenow; Jennifer Tidey; Robert Swift; Robert Miranda Journal: Alcohol Clin Exp Res Date: 2006-08 Impact factor: 3.455
Authors: George A Kenna; William H Zywiak; Robert M Swift; John E McGeary; James S Clifford; Jessica R Shoaff; Samuel Fricchione; Michael Brickley; Kayla Beaucage; Carolina L Haass-Koffler; Lorenzo Leggio Journal: Alcohol Date: 2014-08-14 Impact factor: 2.405
Authors: Bankole A Johnson; Chamindi Seneviratne; Xin-Qun Wang; Nassima Ait-Daoud; Ming D Li Journal: Am J Psychiatry Date: 2013-09 Impact factor: 18.112