Remission from addiction: erasing the wrong circuits or making new ones?

Chronic relapse is a hallmark of substance-use disorders (SUDs), but many people with SUDs do recover and eventually enter remission. Many preclinical studies in this field aim to identify interventions that can precipitate recovery by reversing or erasing the neuronal circuit changes caused by chronic drug use. A better understanding of remission from SUDs can also come from preclinical studies that model factors known to influence recovery in humans, such as the negative consequences of drug use and positive environmental influences. In this Perspective we discuss human neuroimaging studies that have provided information about recovery from SUDs and highlight mechanisms identified in preclinical studies - such as the reconfiguration of neuronal circuits - that could contribute to remission. We also analyse how studies of memory and forgetting can provide insights into the mechanisms of remission. Overall, we propose that remission can be driven by the introduction of new neuronal changes (which outcompete those induced by drugs) as well as by the erasure of drug-induced changes.