Cocaine (COC) and methamphetamine (MTH) dependence have profound adverse medical, social and societal consequences. Medications development for these disorders is complicated by the fact that characteristics of COC and MTH addicts differ;the pharmacology of COC and MTH is similar, but not identical;and several agents demonstrating preliminary efficacy in COC users do not appear to be effective in MTH users. Because methodological issues may also be a factor in differential outcome, of importance is to examine medications in both COC and MTH dependent individuals in the same context. Thus, given that recent evidence suggests agents that decrease adrenergic activity may be effective in treating drug dependence, this proposal will examine the efficacy ofthe alphai- and beta-adrenergic antagonist carvedilol in delaying time to relapse in recently abstinent COC- and MTH-dependent individuals. This 12-wk, randomized, double blind, placebo-controlled clinical trial will provide treatment for 60 COC-dependent and 60 MTH-dependent (18-65 yrs) individuals over a five-year period. Participants first will reside at a residential facility (Recovery Centers of Arkansas) to initiate initial drug abstinence and be inducted on the study medication. They will be randomized by sex, severity of dependence, depressive/anxiety symptom severity and race to receive either placebo (N=30COC;N=30MTH), or carvedilol (50 mg/day;N=30COC; N=30MTH). Then participants transfer to the Outpatient Treatment Research Program and continue to receive study medication for weeks 3-12. During the outpatient portion ofthe trial, subjects participate in weekly individual cognitive behavioral therapy. During the trial, participants are given monetary incentives for complying with study requirements. At the end of 12 weeks, patients will be tapered off the study medication and referred to an appropriate treatment program. Efficacy will be determined by length of time in treatment, alleviation of withdrawal symptoms, length of time to lapse/relapse by self-report and urine toxicology, and psychosocial functioning. Prognostic relevance of factors such as sex, withdrawal symptoms, mood, genetic polymorphisms at the, e.g., alpha 1 receptor subtypes, and cognitive measures will be explored.
This project will examine whether carvedilol prevents relapse relative to placebo in cocaine and/or methamphetamine dependent individuals. Findings of this study will not only shed light on whether carvedilol may improve upon treatment for psychostimulant dependence but also inform future medication development strategies for improving treatment for drug dependence disorders.
|Zhang, Xuefeng; Nielsen, David A; Domingo, Coreen B et al. (2018) Pharmacogenetics of Dopamine ?-Hydroxylase in cocaine dependence therapy with doxazosin. Addict Biol :|
|Patriquin, Michelle A; Hamon, Sara C; Harding, Mark J et al. (2017) Genetic moderation of cocaine subjective effects by variation in the TPH1, TPH2, and SLC6A4 serotonin genes. Psychiatr Genet 27:178-186|
|Mahoney, James J; Kalechstein, Ari D; De Marco, Anthony P et al. (2017) The relationship between premorbid IQ and neurocognitive functioning in individuals with cocaine use disorders. Neuropsychology 31:311-318|
|Azadeh, Shabnam; Hobbs, Brian P; Ma, Liangsuo et al. (2016) Integrative Bayesian analysis of neuroimaging-genetic data with application to cocaine dependence. Neuroimage 125:813-824|
|Li, Xiaofan; Shorter, Daryl; Kosten, Thomas R (2016) Buprenorphine Prescribing: To Expand or Not to Expand. J Psychiatr Pract 22:183-92|
|Ayanga, Daniel; Shorter, Daryl; Kosten, Thomas R (2016) Update on pharmacotherapy for treatment of opioid use disorder. Expert Opin Pharmacother 17:2307-2318|
|Cao, Bo; Bauer, Isabelle E; Sharma, Ajaykumar N et al. (2016) Reduced hippocampus volume and memory performance in bipolar disorder patients carrying the BDNF val66met met allele. J Affect Disord 198:198-205|
|Shorter, Daryl; Nielsen, David A; Hamon, Sara C et al. (2016) The ?-1 adrenoceptor (ADRA1A) genotype moderates the magnitude of acute cocaine-induced subjective effects in cocaine-dependent individuals. Pharmacogenet Genomics 26:428-35|
|Ma, Liangsuo; Steinberg, Joel L; Cunningham, Kathryn A et al. (2015) Inhibitory behavioral control: A stochastic dynamic causal modeling study comparing cocaine dependent subjects and controls. Neuroimage Clin 7:837-47|
|Shorter, Daryl; Domingo, Coreen B; Kosten, Thomas R (2015) Emerging drugs for the treatment of cocaine use disorder: a review of neurobiological targets and pharmacotherapy. Expert Opin Emerg Drugs 20:15-29|
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