[Craving as a core symptom in substance use disorders: epidemiology, neurobiological substrates and clinical relevance.]

Objective: Observed by physicians and often reported by patients, craving is a core symptom of addiction, although not well defined nor understood completely. In the last several years, functional imaging as well as the measurement of different biological substrates of addiction have greatly evolved, allowing for a better understanding of the underlying neurobiological pathways of craving. Furthermore, with the development of the DSM-V and its inclusion as a diagnostic criterion for substance use disorders, craving has gained a whole new level of interest. Hence, the general objective of this article is to examine findings of studies that have led to a better understanding of craving and its implications. First, we address the definition of craving and its epidemiology in individuals with substance use disorders. We then summarize the results of the research conducted on the neurobiological substrates of craving. Finally, we present the role of craving in the cycle of addiction and its potential as a therapeutic target for pharmacological and non-pharmacological interventions.Methods: Narrative review of the literature.Results: The definition of craving has greatly evolved throughout the years, and it is commonly described as an abnormal desire or need to take a drug. While its conscious aspect is well known, whereas it is expressed subjectively, it is growingly also defined as an unconscious phenomenon illustrated by a physiologic activation that is not perfectly correlated with subjective measures. Available data on craving have also demonstrated the presence of this symptom in all three phases of the addiction cycle, including early and prolonged abstinence, long after the acute physical withdrawal syndrome. Three factors have been identified as potent craving inducers: the drug itself, drug related cues and stress. PET scan studies and fMRI studies confirmed the implication of dopaminergic pathways in craving, and have more recently shed light on the contribution of other neurotransmission systems, such as GABA, norepinephrine as well as the endocannabinoid and opioid systems, but their roles are not yet fully understood. Furthermore, craving-related activations of specific areas of the brain involved in learned habits and behavior as well as memory have been demonstrated by various studies; in contrast, regions associated with regulation and control of emotion have been demonstrated to be hypoactive during craving episodes. Finally, several studies have demonstrated that craving is a valid predictive indicator of relapse, making it an interesting target for pharmacological and non-pharmacological treatment. Several anti-craving medications have been shown to decrease craving, including varenicline for tobacco and naltrexone for alcohol dependence. Studies examining the efficacy of other anti-craving medications for other substances are growing in numbers.Conclusions: Available data on craving support its role as a core symptom of addiction and allow for a better understanding of the underlying neurobiological substrates. Studies tend to show that it is a valid indicator of relapse during early and prolonged abstinence. Further research is needed to truly understand the complexity of the neurobiological substrates involved in craving as well as to develop new anti-craving interventions to facilitate long-term abstinence in individuals with substance use disorders.