CRACK-TARGET

Context: Paris region and the French west indies face a specific epidemic of crack-cocaine use, mostly by socially deprived subjects, highly visible in open drug scenes, with little access to the care system. Patients who suffer from crack-cocaine dependence experiment a high rate of medical complications and a high mortality rate, because this type of cocaine is a short-acting form, used through rapid route of administration (usually smoked or injected). Nevertheless, despite important uncovered medical needs, they are not often included in clinical trials and there is to date no pharmacological treatment for this severe condition. We identified behavioral disturbances as a key problem in crack-cocaine dependence, as it is the second cause for emergency visits for those patients and a reason to be excluded from addiction care facilities. Hypothesis: Based on preliminary results already gathered by our group, we suggest that behavioral sensitization (BS), an increase of motor response to cocaine after repetitive intermittent use, could be assessed in Humans and specifically antagonized in preclinical models. Thus, it could constitute a key target for clinical trials in this specific population. Aims and proposed methodology: Our consortium is composed of preclinical and Humans (clinical and sociological) studies experts in research conducted in substance use disorders, and we will benefit from the help of the research network FHU NOR-SUD, combining several research units and care and harm reduction facilities that are familiar with the outreach of this specific population. With the translational project CRACK-TARGET, we aim at demonstrating the existence of BS in patients with crack dependent subjects. Furthermore, we aim at developing specific, repeatable, easy to access measure of BS using questionnaires and objective actigraphy biomarkers to be used as surrogate endpoints in clinical trials (Task 1). We want to use a rapid, valid, reproducible preclinical model of crack-induced BS to select the best candidate treatment among several pharmacological probes (Task 2). We will immediately translate those results in a proof-of-concept trial in affected subjects aiming at reducing the chosen endpoints with the chosen pharmacological probes (Task 3). We also want to better understand the needs of crack dependent patients towards treatments and their expectations for recovery, by conducting a qualitative study where patients will participate in the definition of treatment aims to increase the efficiency of care (Task 4). Expected results: This research program will pave the road for well-dimensioned clinical trial aiming at reducing BS and other behavioral disturbances in subjects with crack cocaine dependence. This program will have a strong impact on patients’ health and meets a high social demand.