In internal medicine, relapse or recidivism is a recurrence of a past (typically medical) condition. For example, multiple sclerosis and malaria often exhibit peaks of activity and sometimes very long periods of dormancy, followed by relapse or recrudescence.

In psychiatry, relapse or reinstatement of drug-seeking behavior, is the recurrence of pathological drug use, self harm or other symptoms after a period of recovery. Relapse is often observed in individuals who have developed a drug addiction or a form of drug dependence, as well as those who have a mental disorder.

The availability of the dopamine receptor D2 plays a role in self-administration and the reinforcing effects of cocaine and other stimulants. The D2 receptor availability has an inverse relationship to the vulnerability of reinforcing effects of the drug. With the D2 receptors becoming limited, the user becomes more susceptible to the reinforcing effects of cocaine. It is currently unknown if a predisposition to low D2 receptor availability is possible; however, most studies support the idea that changes in D2 receptor availability are a result, rather than a precursor, of cocaine use. It has also been noted that D2 receptors may return to the level existing prior to drug exposure during long periods of abstinence, a fact which may have implications in relapse treatment.

Social interactions, such as the formation of linear dominance hierarchies, also play a role in vulnerability to substance use. Animal studies suggest that there exists a difference in D2 receptor availability between dominant and subordinate animals within a social hierarchy as well as a difference in the function of cocaine to reinforce self-administration in these animal groups. Socially dominant animals exhibit higher availability of D2 receptors and fail to maintain self-administration.

Drug taking and relapse are heavily influenced by a number of factors including the pharmacokinetics, dose, and neurochemistry of the drug itself as well as the drug taker’s environment and drug-related history. Reinstatement of drug use after a period of non-use or abstinence is typically initiated by one or a combination of the three main triggers: stress, re-exposure to the drug or drug-priming, and environmental cues. These factors may induce a neurochemical response in the drug taker that mimics the drug and thus triggers reinstatement. These cues may lead to a strong desire or intention to use the drug, a feeling termed craving by Abraham Wikler in 1948. The propensity for craving is heavily influenced by all three triggers to relapse and is now an accepted hallmark of substance dependence. Stress is one of the most powerful stimuli for reinstating drug use because stress cues stimulate craving and drug-seeking behavior during abstinence. Stress-induced craving is also predictive of time to relapse. Comparably, addicted individuals show an increased susceptibility to stressors than do non-addicted controls. Examples of stressors that may induce reinstatement include emotions of fear, sadness, or anger, a physical stressor such as a footshock or elevated sound level, or a social event. Drug-priming is exposing the abstinent user to the addictive substances, which will induce reinstatement of the drug-seeking behavior and drug self-administration. Stimuli that have a pre-existing association with a given drug or with use of that drug can trigger both craving and reinstatement. These cues include any items, places, or people associated with the drug.

Relapse treatment is somewhat of a misnomer because relapse itself is a treatment failure; however there exist three main approaches that are currently used to reduce the likelihood of drug relapse. These include pharmacotherapy, cognitive behavioral techniques, and contingency management. The main goals of treating substance dependence and preventing relapse are to identify the needs that were previously met by use of the drug and to develop the skills needed to meet those needs in an alternative way.

Various medications are used to stabilize an addicted user, reduce the initial drug use, and prevent reinstatement of the drug. Medications can normalize the long-term changes that occur in the brain and nervous system as a result of prolonged drug use. This method of therapy is complex and multi-faceted because the brain target for the desire to use the drug may be different from the target induced by the drug itself. The availability of various neurotransmitter receptors, such as the dopamine receptor D2, and changes in the medial prefrontal cortex are prominent targets for pharmacotherapy to prevent relapse because they are heavily linked to drug-induced, stress-induced, and cue-induced relapse. Receptor recovery can be upregulated by administration of receptor antagonists, while pharmacotherapeutic treatments for neruoadaptations in the medial prefrontal cortex are still relatively ineffective due to lacking knowledge of these adaptations on the molecular and cellular level.

The various behavioral approaches to treating relapse focus on the precursors and consequences of drug-taking and reinstatement. Cognitive-behavioral techniques (CBT) incorporate Pavlovian conditioning and operant conditioning, characterized by positive reinforcement and negative reinforcement, in order to alter the cognitions, thoughts, and emotions associated with drug-taking behavior. A main approach of CBT is cue exposure, during which the abstinent user is repeatedly exposed to the most salient triggers without exposure to the substance in hopes that the substance will gradually lose the ability to induce drug-seeking behavior. This approach is likely to reduce the severity of a relapse than to prevent one from occurring altogether. Another method teaches addicts basic coping mechanisms to avoid using the illicit drug. It is important to address any deficits in coping skills, to identify the needs that likely induce drug-seeking, and to develop another way to meet them.