Preventing incubation of drug craving to treat drug relapse: from bench to bedside

In 1986, Gawin and Kleber reported a progressive increase in cue-induced drug craving in individuals with cocaine use disorders during prolonged abstinence. After years of controversy, as of 2001, this phenomenon was confirmed in rodent studies using self-administration model, and defined as the incubation of drug craving. The intensification of cue-induced drug craving after withdrawal exposes abstinent individuals to a high risk of relapse, which urged us to develop effective interventions to prevent incubated craving. Substantial achievements have been made in deciphering the neural mechanisms, with potential implications for reducing drug craving and preventing the relapse. The present review discusses promising drug targets that have been well investigated in animal studies, including some neurotransmitters, neuropeptides, neurotrophic factors, and epigenetic markers. We also discuss translational exploitation and challenges in the field of the incubation of drug craving, providing insights into future investigations and highlighting the potential of pharmacological interventions, environment-based interventions, and neuromodulation techniques.

Automated summary

In 1986, Gawin and Kleber reported an increased drug craving in individuals with cocaine use disorders during prolonged abstinence, which was confirmed as the incubation of drug craving in rodent studies in 2001. The intensification of cue-induced drug craving after withdrawal puts abstinent individuals at a high risk of relapse, urging the development of effective interventions. Achievements have been made in deciphering neural mechanisms and identifying potential drug targets, neurotransmitters, neuropeptides, neurotrophic factors, and epigenetic markers, with implications for reducing drug craving and preventing relapse.