From a cycle to a period: the potential role of BDNF as plasticity and phase-specific biomarker in cocaine use disorder

Cocaine Use Disorder (CUD) is one of the diseases with the greatest social and health impact, due to the high cost of rehabilitation management and the high risk of dangerous behavior and relapse. This pathology frequently leads to unsuccessful attempts to interrupt the consumption, resulting in relapses and a vicious circle binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation (craving). The alternation of these phases in addictions was well illustrated by Koob and colleagues in the so-called “addictive cycle”, which nowadays represents a landmark in the addiction field. Recently, there has been an increased interest in the international literature for biomarkers able to explain the several phases of addiction, and one of the most studied biomarkers is undoubtedly Brain-derived Neurotrophic Factor (BDNF). In this perspective article, we discuss the potential role of BDNF as biomarker of the CUD phases described in the “Addictive Cycle”, speculating about the close relationship between BDNF fluctuations and the clinical course of CUD. Furthermore, we discuss BDNF potential role as “staging” biomarker, able to predict disease worsening. Finding valuable biomarkers of CUD severity and disease stage could shift clinicians' attention from the perspective of behavioral symptomatic treatment to a novel brain-based approach, allowing more effective and targeted therapeutic strategies to be developed, thus determining major benefits for CUD patients.