Frustration brake failure hypothesis of substance use disorders.

It is common knowledge that individuals with substance use disorders (SUDs) may persist seeking drug despite experiencing large degrees of frustration (i.e., due to loss of supplier, unsurmountable cost increases, etc.), beyond where one without an SUD would quit seeking. While preceding SUD hypotheses study various aspects of persistence of drug seeking in the face of negative consequences, this hypothesis posits a distinct mechanistic failure. We hypothesize that, unlike persons using drugs who do not have an SUD, a subset of persons with SUDs exhibit high motivation for drug specifically due to a failure in the ability for frustration to act as a brake on motivation. Frustration and motivation are intrinsically linked and share a biological interface which, if therapeutically targeted, could restore the ability for frustration to appropriately quell motivation and thus prevent some relapses. This paper outlines the existing and missing evidence required to support this hypothesis, with the hope that formalizing this hypothesis will spur important research in this area and yield new treatment possibilities for SUDs.