Enhanced peripheral levels of BDNF and proBDNF: elucidating neurotrophin dynamics in cocaine use disorder

Mauro Pettorruso, Andrea Miuli, Katia Clemente, Gianluca Mancusi, Giuseppe Migliara, Francesco Di Carlo, Giulia Pernaci, Teresa Di Crosta, Mario Santorelli, Giacomo d’Andrea, Luisa De Risio, Mariaceleste Ciavarella, Valentina Baccolini, Ilenia Di Meo, Ivana Cataldo, Stefano L. Sensi, Giovanni Martinotti

Research output: Contribution to journalArticlepeer-review


Brain-derived neurotrophic factor (BDNF) and its precursor, proBDNF, are known to significantly contribute to brain homeostasis, neuroplasticity, and neuronal remodeling. Although these neurotrophins are thought to have opposing roles, both play a critical part in shaping long-lasting behavioral changes following substance use. In this context, our study sought to explore the implications of these neurotrophins in the pathophysiology of cocaine use disorder (CUD). We conducted a case-control study, which included 28 individuals seeking treatment for CUD and 38 matched healthy participants. We measured peripheral neurotrophin concentrations via an enzyme-linked immunosorbent assay. Additionally, all participants were screened for cocaine-associated pathways (e.g., cocaine intake, craving intensity), along with associated psychopathological data. Our findings highlighted an increased concentration of BDNF and proBDNF in CUD individuals when compared to healthy controls (BDNF: 18092.80 ± 6844.62 vs. 11334.42 ± 5061.85 pg/ml, p < 0.001; proBDNF: 87.03 ± 33.23 vs. 55.70 ± 23.26 ng/ml, p < 0.001). We further corroborated the relationship between neurotrophin levels and CUD using a linear regression model. Nevertheless, there was no significant difference in the proBDNF to BDNF ratio between the two groups. Interestingly, our study also demonstrated the influence of factors like usage of psychotropic medications, history of psychiatric hospitalizations, and psychiatric diagnoses on neurotrophin dynamics. In conclusion, our study underscores the significance of neurotrophin fluctuations in CUD. The observed increase in BDNF and proBDNF levels could play a pivotal role in driving craving and relapse risk. Thus, a nuanced understanding of these neurobiological underpinnings in CUD might contribute to the development of more targeted and effective therapeutic strategies.
Original languageEnglish
Pages (from-to)760-766
Number of pages7
JournalMolecular Psychiatry
Issue number3
Early online date4 Jan 2024
Publication statusPublished - 1 Mar 2024


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