Reinforcer pathology in cocaine use disorder: Temporal window determines cocaine valuation

Aims: The Experimental Medicine Approach offers a unique perspective to determine clinical behavior change by engaging a target underlying the cause of a disorder. The present work engaged a novel target of addiction, Reinforcer Pathology, in two studies to test changes in behavior among individuals with cocaine use disorder. Methods: In Study 1, n = 44 participants engaged the temporal window with episodic future thinking (EFT), a positive prospection exercise. Changes in temporal view and cocaine valuation were tested using delay discounting and behavioral economic demand, respectively. Additionally, a computational model assessed the relative reliance on the near- and far-sighted systems during EFT. In Study 2, n = 71 engaged the temporal window with a negatively-valenced hurricane scenario to test the opposite effects on window length and cocaine valuation. Results: Results demonstrated systematic and symmetrical engagement of the behavioral target. Study 1 robustly replicated previous work, wherein EFT lengthened the temporal window and decreased cocaine valuation. Moreover, EFT increased the weighting of the modeled far-sighted system, increasing the relative impact of long-term discounting decisions. Study 2 produced opposite outcomes, shortened temporal window and increased cocaine valuation. Conclusions: This approximately equal and opposite reaction to the manipulations supports reinforcer pathology theory and implicates the temporal window over which rewards are valued as a target to be pushed and pulled to produce clinically meaningful behavior change. Using the Experimental Medicine Approach as a guide, future work should identify new potential interventions to engage reinforcer pathology and use the clinically relevant outcomes as a litmus test for mechanism.