Dark Times: The Role of Negative Reinforcement in Methamphetamine Addiction

Methamphetamine use is associated with substantial adverse outcomes including poor mental and physical health, financial difficulties, and societal costs. Despite deleterious long-term consequences associated with methamphetamine, many people use drugs for short-term reduction of unpleasant physical or emotional sensations. By removing these aversive states, drug use behaviors are negatively reinforced. Abstinence from methamphetamine can then result in a return to previous aversive emotional states linked to withdrawal and craving, often contributing to an increased likelihood for relapse. This negative reinforcement cycle is hypothesized to be a motivating and maintaining factor for addiction. Thus, this review highlights the current evidence for negative reinforcement mechanisms in methamphetamine use disorder by integrating studies of subjective experience, behavior, functional magnetic resonance imaging, positron emission tomography, and event-related potentials and examining the efficacy of treatments targeting aspects of negative reinforcement. Overall, the literature demonstrates that individuals who use methamphetamine have diminished cognitive control and process emotions, loss of reward, and interoceptive information differently than non-using individuals. These differences are reflected in behavioral and subjective experiments as well as brain-based experiments which report significant differences in various frontal regions, insula, anterior cingulate cortex, and striatum. Together, the results suggest methamphetamine users have an altered experience of negative outcomes, difficulties employing effective emotion regulation, and difficulty engaging in adaptive or goal-directed decision-making. Suggestions for future research to improve our understanding of how negative reinforcement contributes to methamphetamine addiction and to develop effective interventions are provided.