Using an Experimental Medicine Approach to Identify Novel Determinants of Addiction.

Our understanding and effectiveness in treating addiction is not fully adequate. Therefore, perhaps developing a pragmatic theory for identifying novel determinants and potential interventions is needed. The experimental medicine approach, derived from Claude Bernard, proposes a methodology for inductive theory development and suggests interventions directed at targets closely aligned with the underlying mechanisms of the disorder. The steps of theory development under this approach are intended to (1) identify an intervention target; (2) develop assays to verify target measurement; (3) engage the target via experiment or intervention; and (4) test the degree to which target engagement produces other therapeutically useful changes in the disorder. In this article, we review these steps in detail using an example from our work. That is, shortened temporal windows (target) is frequently observed among those who are addicted. Delay discounting is an assay used to measure that target. We and others have demonstrated manipulation of the target, delay discounting, is associated with changing the drug valuation among those with addiction. We conclude with a culmination of the experimental medicine approach by proposing a recently developed hypothesis of substance use disorder, Reinforcer Pathology 2.0.