ABSTRACT Promoting reductions in problem behaviors is common in medical practice wherein at-risk individuals are counseled to make moderate, sustainable changes in lifestyle. Reducing the percentage of heavy drinking days in individuals with alcohol use disorder is an accepted intervention target in alcohol addiction treatment, yet for other drug use disorders, complete abstinence remains the standard for demonstrating treatment efficacy. Interventions that promote reductions in drug use should improve biopsychosocial outcomes. Little research has been conducted to demonstrate benefits of reduced drug use, however. Demonstrating the benefits of reduced cocaine (COC) use would significantly advance treatment development by challenging expectations for outcomes from possible interventions. COC use produces a number of biopsychosocial detriments (e.g., cardiovascular toxicity, disrupted immune function, increased psychiatric comorbidities) that could be ameliorated by COC use reduction. No studies have prospectively or comprehensively evaluated this possibility to date, although preliminary data support this hypothesis. To fill this critical knowledge gap, we propose a randomized, controlled 12-week trial in which financial incentives will be used to reduce COC use. Subjects will be randomly assigned to one of three groups (n=66 completers/ group): 1) high value financial incentives for COC abstinence in which frequency of COC use is expected to be substantially reduced or completely eliminated, 2) low value financial incentives for COC abstinence in which frequency of COC use is expected to be reduced or 3) a non-contingent control group, in which frequency of COC use is expected to remain stable. This study aims to demonstrate that reduced COC use improves physiological and biochemical indicators of cardiovascular and immune fitness, as well as psychosocial function. The overarching hypothesis is that individuals assigned to the active treatment conditions will display improvements in biopsychosocial domains compared to individuals assigned to the non-contingent control group. A “dose-response” is also expected whereby individuals assigned to the high value condition will display greater reductions in COC use, and consequently greater improvements, relative to the low value condition. This research will advance the field by: 1) using multifaceted health outcomes to provide prospective evidence supporting reduced drug use as a viable endpoint for COC treatment development, 2) identifying biochemical indicators of health improvements associated with reduced COC use and 3) laying the foundation for a paradigm-shifting definition of COC treatment success, thereby challenging expectations for outcomes in behavioral and pharmacological intervention development. These innovations will accelerate identification of promising treatments for cocaine use disorder, resulting in a sustained and powerful impact on scientific and clinical practice.

PROJECT NARRATIVE Reduced drug use is a clinically meaningful target for treatment development, but few studies have evaluated the positive impacts produced by this behavioral change, preventing adoption of this endpoint in clinical trials. The proposed research will fill that critical knowledge gap by demonstrating the biopsychosocial benefits of reduced cocaine use. These data will be used to change current accepted cocaine treatment endpoints and accelerate identification of therapies for cocaine use disorder.