PROJECTS


STUDY 1 (OSCO)

This study is randomized controlled trial (RCT) testing intranasal oxytocin in patients with opioid use disorder stable on opioid replacement therapy (ORT). In this RCT, we are testing and validating the combination of pharmacological stress-induced activation paired to an opioid cue reactivity paradigm to prevent opioid relapse. Funding: P20 GM130414 (PI: Monti; PLL: Haass-Koffler) COBRE/CADRE; Clinical trial: NCT04051619


STUDY 2 (DOXY)

This study focuses on the identification of endophenotypes that guide the application of personalized approaches (precision medicine) in the pharmacological treatment of AUD in order to better understand responses (or lack thereof) to pharmacological treatment. This study stemmed from a proof-of-concept RCT with AUD patients in which we demonstrated that blood pressure (clinical marker) (Drug Alcohol Depend, 2017, NEJM Journal Watch 2017) and family history of alcoholism (genetic marker) (Addict Biol, 2016) are independent moderators of doxazosin’s (α-1 inverse agonist) effect on alcohol consumption. Funding: R01 AA027760 (PI: Haass-Koffler) Clinical trial: NCT04135846


STUDY 3 (MIF)

This work translates a validated rodent neuroscience paradigm (Neuropsychopharmacology, 2012; Translational Psychiatry, 2016) to a human laboratory study by designing a 6-week, within-subjects, double-blind randomized controlled trial for the prevention of stress-induced alcohol relapse using mifepristone, a glucocorticoid receptor blocker. This study is the development of a translational research model that integrates administration of pharmacological stressors and environment cues with alcohol laboratory study methods (stress x cues). Funding: K01 AA023867; Research Excellent Award (PI: Haass-Koffler) Clinical Trial: NCT02243709


STUDY 4 (PROB)

This is an exploratory clinical trial that aims to test the hypothesis that proposes a potential relationship between the pannexin 1 channel and alcohol. The goal of this proposal is to evaluate the safety and tolerability of potential new therapeutic targets for the treatment of AUD. The premise prompting this human laboratory study is based on the direct evidence from our preliminary work in collaboration with Dr. Pietro Paolo Sanna at The Scripps Research Institute work with probenecid in a preclinical model of AUD. This work demonstrated that probenecid is able to reduce alcohol consumption in alcohol-dependent rats (Alcohol and Alcoholism, 2020). The scientific rationale for testing probenecid in AUD was derived by the mechanism of action of probenecid as a pannexin 1 channel inhibitor, its role in alcohol-induced extracellular adenosine release, and that this process is promoted by a history of exposure to excessive alcohol. Funding: R21 AA027614 (PI: Haass-Koffler) Clinical Trial:NCT04218357


STUDY 5 (CRFBP)

This is an innovative in vitro chimeric work that, in combination with human genetic variations, has discovered the role of corticotropin releasing factor binding protein (CRFBP) in alcohol use disorder (AUD) (Translational Psychiatry, 2016; Alcohol, 2018). We transferred this chimeric biological assay to a robotic facility at Sanford Burnham Prebys Medical Discovery Institute. We screened >350,000 compounds, selected 2 allosteric modulators and tested them in an ex vivo preclinical alcohol model (electrophysiology). Funding: R01 AA026589 (PI: Shefler; Subaward: Haass-Koffler)


STUDY 6 (FLY-HUMAN)

This is a 3-year MPI translational award between CAAS, Psychiatry, Public Health and Neuroscience at Brown. This foundation grant is an add-on to the STUDY 2 (DOXY). Patients with AUD, stable at the maximum tolerated dose of doxazosin will undergo neuroimaging procedures in Dr. Tara White’s (Public Health) Laboratory. The neuroimaging protocol is comprised of structural MRI (sMRI) and functional/ pharmacological MRI (f/pharmMRI) in order to evaluate the brain mechanisms resulting from doxazosin treatment on pharmacological stress-induced alcohol cue reactivity. In parallel, in Dr. Karla Kaun’s (Neuroscience) Laboratory, we will evaluate the octopamine in Drosophila brain in vivo using two-photon imaging while flies undergo cue-induced alcohol memory retrieval under stressed conditions. Funding: Halon Award (MPI: Haass-Koffler, Kaun, McGeary, White)  Clinical Trial: NCT04135846


STUDY 7 (V1-V2)

This is a secondary analysis that evaluates the motivation of behavioral changes in treatment seeking compared to non-treatment seeking individuals when they are enrolled in randomized controlled trials (RCTs) at the Center of alcohol and Addiction Studies (CAAS) for the development of pharmacotherapies to treat alcohol use disorder (AUD). Funding: Multiple NIAAA Awards.


STUDY 8 (COVID-19)

This is a longitudinal study that evaluates the effects of COVID-19 (isolation, stress, risk) specifically in the AUD population that have previously participated in human lab studies. We created larger database of individuals with AUD diagnosis and vital pre-COVID data (physical exam/psychiatric assessments/blood work). Funding: Rohsenow Pilot Award (PI: Haass-Koffler).


STUDY 9 (THC-CYTO)

This study is a collaboration with Dr. Jane Metrik (School of Public Health) Laboratory and Dr. Lorenzo Leggio (NIH/NIDA) We are examining the role of pro- and anti-inflammatory response and appetite hormones in a human laboratory study that evaluate the effect of tetrahydrocannabinol (THC) and alcohol consumption.