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BDNF gene polymorphisms and substance use disorders: a systematic review

  • Danil Peregud ORCID logo EMAIL logo , Valeria Baronets ORCID logo , Olga Pavlova ORCID logo and Konstantin Pavlov ORCID logo
Published/Copyright: November 5, 2025

Abstract

The development of substance use disorders (SUDs) is partly determined by genetic factors. Brain-derived neurotrophic factor (BDNF) underlies the neurobiological mechanisms of action of psychoactive substances (PASs) and development of SUDs, while genetic markers within the BDNF gene may be associated with a risk of SUDs and accompanied clinical manifestations. This is a systematic review of the relationships between single nucleotide polymorphisms (SNPs) within the BDNF gene locus and various aspects of SUDs. We searched, appraised, and summarized the research evidence of these associations for the main pharmacological groups of PASs (tobacco, cannabis, alcohol, opioids, and stimulants). Most studies have focused on the functional Val66Met (rs6265) polymorphism. They demonstrated that the rs6265 Met (T) allele may be a protective factor for the development of SUDs. In addition to rs6265, other individual BDNF-related SNPs and the corresponding haplotypes were associated with the risk of the development of SUDs, their clinical manifestations, presence of comorbidity, and sensitivity to pharmacotherapy. The identified associations often depended on the studied population and were influenced by sex and ancestry. Established BDNF-related genetic markers or their combinations potentially may be used as objective diagnostic or prognostic criteria in clinical practice.


Corresponding author: Danil Peregud, Federal State Budgetary Institution “V. Serbsky National Medical Research Centre for Psychiatry and Narcology” of the Ministry of Health of the Russian Federation, Kropotkinsky ln. 23, Moscow 119034, Russia; and Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Butlerova st. 5A, Moscow 117485, Russia, E-mail:

  1. Research ethics: Not applicable. This article does not contain any studies with human participants or animals performed by any of the authors.

  2. Informed consent: Not applicable.

  3. Author contributions: Danil Peregud (Conceptualization, Methodology, Data Curation, Formal analysis, Writing –Original Draft, Writing – Review & Editing), Valeria Baronets (Data Curation), Olga Pavlova (Data Curation, Writing – Review & Editing), Konstantin Pavlov (Writing – Review & Editing). All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors report no conflicts of interest.

  6. Research funding: Nothing declared. The study was carried out within the state assignment of Federal State Budgetary Institution “V. Serbsky National Medical Research Centre for Psychiatry and Narcology” of the Ministry of Health of the Russian Federation.

  7. Data availability: No data was used for the research described in the study.

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Received: 2025-08-24
Accepted: 2025-10-18
Published Online: 2025-11-05

© 2025 Walter de Gruyter GmbH, Berlin/Boston

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