This is a competitive renewal of a NIDA-funded P50 Center that serves as a Medication Development Center of Excellence (MDCE). Our MDCE complements Penn's longstanding research program to develop effective addiction treatments. Our MDCE is integrated within the umbrella of the PennA/A Center for the Study of Addiction, allowing us to focus on pharmacotherapy for cocaine alcohol dependence (CAD). Yet, the MDCE benefits greatly from Center integration because it permits access to infrastructure resources not provided by a P50 Center. The MDCE has priority access to important resources: 1) Clinical Translational Research Center - an inpatient/outpatient facility for human laboratory trials;2) Center bio-statistician;3) web-based Data Management Unit;and, 4) a specialty drug screen laboratory. Our theme is testing innovative medication combinations for managing "hard-to-treat" CAD patients. This group responds poorly to existing treatments and is notoriously treatment nonadherent. Our MDCE proposes to continue testing new medications singly and in combination with an emphasis on novel medications not yet approved by the FDA, plus improved treatment adherence procedures. The CORE will coordinate and integrate a "Neuro" Core Pilot Program and three Components. Core functions also identify candidate medications, conduct safety studies of medication combinations and their interactions with cocaine and/or alcohol, and provide a mentoring structure for new investigators. The Neuro Core Pilot Program emphasizes a multidimensional neuroimaging-behavioral-genetic model that identifies individual predictors of response to the medications to be studied in MDCE Components. The Components reflect developing prototypes, which contain descriptions of projects planned over the next 5 years. Projects are arranged to allow for novel medications to be studied from safety through efficacy, singly and in combination, to make more informed selections for clinical trials from among the group of candidates now available. Component 1 proposes to evaluate promising novel compounds in 9-week placebo-controlled trials. Component 2 proposes human lab studies to evaluate the mechanisms by which those compounds may decrease cocaine use, also providing more safety data for these compounds. Component 3 will test the efficacy of specific medication combinations for CAD. By starting with a large number of candidate medications and sequentially testing as described, we hope to more rapidly identify effective medications that justify the next level of development: Multi-site trials.
Co-occurring cocaine and alcohol dependence continues to be common in this country, and represents a public health problem that is well documented as hard to treat. Research has missed opportunities to study this problem due to the complexities of addressing combined dependencies study designs. The goal of this P50 Center is to bridge the gap in our knowledge about how best to treat this patient population.
|Clarke, Toni-Kim; Weiss, Amy R D; Ferarro, Thomas N et al. (2014) The dopamine receptor D2 (DRD2) SNP rs1076560 is associated with opioid addiction. Ann Hum Genet 78:33-9|
|Pettinati, Helen M; Kampman, Kyle M; Lynch, Kevin G et al. (2014) A pilot trial of injectable, extended-release naltrexone for the treatment of co-occurring cocaine and alcohol dependence. Am J Addict 23:591-7|
|Young, Kimberly A; Franklin, Teresa R; Roberts, David C S et al. (2014) Nipping cue reactivity in the bud: baclofen prevents limbic activation elicited by subliminal drug cues. J Neurosci 34:5038-43|
|Kampman, Kyle M; Pettinati, Helen M; Lynch, Kevin G et al. (2013) A double-blind, placebo-controlled trial of topiramate for the treatment of comorbid cocaine and alcohol dependence. Drug Alcohol Depend 133:94-9|
|Pettinati, Helen M; O'Brien, Charles P; Dundon, William D (2013) Current status of co-occurring mood and substance use disorders: a new therapeutic target. Am J Psychiatry 170:23-30|
|Crist, R C; Ambrose-Lanci, L M; Vaswani, M et al. (2013) Case-control association analysis of polymorphisms in the ýý-opioid receptor, OPRD1, with cocaine and opioid addicted populations. Drug Alcohol Depend 127:122-8|
|Lam, Shing Chun Benny; Wang, Ze; Li, Yin et al. (2013) Wavelet-transformed temporal cerebral blood flow signals during attempted inhibition of cue-induced cocaine craving distinguish prognostic phenotypes. Drug Alcohol Depend 128:140-7|
|Plebani, Jennifer G; Lynch, Kevin G; Rennert, Lior et al. (2013) Results from a pilot clinical trial of varenicline for the treatment of alcohol dependence. Drug Alcohol Depend 133:754-8|
|Crist, Richard C; Ambrose-Lanci, Lisa M; Zeng, Angela et al. (2013) Case-control association study of WLS variants in opioid and cocaine addicted populations. Psychiatry Res 208:62-6|
|Clarke, Toni-Kim; Bloch, Paul J; Ambrose-Lanci, Lisa M et al. (2013) Further evidence for association of polymorphisms in the CNR1 gene with cocaine addiction: confirmation in an independent sample and meta-analysis. Addict Biol 18:702-8|
Showing the most recent 10 out of 46 publications