Methadone maintenance patients show a selective deficit to reverse positive outcomes in drug-related conditions compared to medication free prolonged opiate abstinence

Background: Drug addiction is a chronic relapsing disease. Most users will relapse back to using drugs over and over again throughout their life. These relapses may become more frequent in the presence of contextual reminders. We aimed to examine associations between the ability to maintain a medication-free life-style and the capability to learn and reverse positive and negative stimulus-outcome associations in the presence of neutral and drug-related contextual reminders. Methods: We conducted a highly unique comparison of former opiate-dependent individuals who are either medication free or methadone maintenance patients for the last ten years. Groups were matched for age, gender and education. Participants were tested on a novel partial reversal paradigm, which tests the ability to acquire and reverse stimulus-outcome associations in neutral and drug-related context. Results: Both groups were equally able to acquire and reverse positive and negative outcomes in conditions of neutral context. However, methadone maintenance patients showed a selective deficit in reversing the outcomes of positive stimulus in drug-related context. Hence, after learning a positive stimulus-outcome association in one drug-related context, methadone maintenance patients struggled to learn that the same stimulus predicts negative outcome when presented later in a different drug-related context. Conclusions: Methadone maintenance patients demonstrate a selective difficulty to learn negative outcomes when exposed to a drug, but not neutral, related environment. The results may reflect the core mechanisms of addiction and provide a possible explanation for the inability of methadone maintenance patients to illicit drug abuse without the need of agonist treatment.