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Exploring Biological Mechanisms and Therapeutic Strategies for Substance Use Disorders
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Exploring Biological Mechanisms and Therapeutic Strategies for Substance Use Disorders

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 10 July 2025 | Viewed by 1353

Special Issue Editor

Dr. Thomas Paparrigopoulos

E-Mail Website
Guest Editor
First Department of Psychiatry, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece
Interests: addiction medicine; psychoneuroendocrinology; clinical psychopharmacology

Special Issue Information

Dear Colleagues,

Substance use disorders (SUDs) are multifactorial disorders of biopsychosocial etiology associated with structural and functional changes of the human brain leading to an impulsive/compulsive behavior. The neuroendocrine system mediates a wide range of responses and adaptations that help maintain homeostasis in stressful situations. An impaired regulation of this system has been proposed as a major contributing factor to substance abuse and recidivism in a wide range of drugs and substances. Considering the increasing rate of substance use among the global population, a future SUD epidemic might be expected. This provides the rationale for further characterizing the molecular mechanisms and abnormalities of SUDs, including the neuroendocrine dysfunctions and alterations, to help reveal risk factors and consequently develop efficient preventive and therapeutic strategies. In this Special Issue, papers exploring the complex biological mechanisms underlying substance use disorders (SUDs) and the development of innovative therapeutic strategies are included, particularly delving into the neurobiological mechanisms of how physical exercise impacts SUDs.

Dr. Thomas Paparrigopoulos
Guest Editor

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Keywords

  • addiction
  • alcohol use disorder
  • opioid use disorder
  • substance use disorders
  • physical exercise
  • physical activity
  • molecular mechanisms
  • neuroendocrine system

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Published Papers (1 paper)

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Research

14 pages, 621 KiB  
Article
Cortisol and β-Endorphin Responses During a Two-Month Exercise Training Program in Patients with an Opioid Use Disorder and on a Substitution Treatment
by Alexandros E. Psarianos, Anastassios Philippou, Argyro Papadopetraki, Eirini Chatzinikita, Costas Chryssanthopoulos, Apostolos Theos, Athanasios Theocharis, Chara Tzavara and Thomas Paparrigopoulos
Int. J. Mol. Sci. 2025, 26(11), 5178; https://doi.org/10.3390/ijms26115178 - 28 May 2025
Viewed by 939
Abstract
Physical exercise may affect drug use by balancing neurohormonal system mechanisms. Cortisol and β-endorphin, associated with stress, mood, and pleasure feelings, can be affected by exercise and act as regulators of withdrawal symptoms associated with drug use during short-term abstinence. The present study [...] Read more.
Physical exercise may affect drug use by balancing neurohormonal system mechanisms. Cortisol and β-endorphin, associated with stress, mood, and pleasure feelings, can be affected by exercise and act as regulators of withdrawal symptoms associated with drug use during short-term abstinence. The present study investigated the effect of a supervised, two-month moderate-intensity aerobic exercise program on salivary cortisol and β-endorphin levels in patients with an opioid use disorder (OUD) and on a substitution treatment during a short-term, 24–36 h withdrawal phase from methadone/buprenorphine medication. Ninety opioid users (41 females) in methadone and buprenorphine substitution treatment were randomly divided into four groups: (a) buprenorphine exercise (BEX) (n = 26; age (mean ± SD): 41.9 ± 6.1 yrs), (b) buprenorphine control (BCON) (n = 25; age: 41.9 ± 5.6 yrs), (c) methadone exercise (MEX) (n = 20; age: 46.7 ± 6.6 yrs), and (d) methadone control (MCON) (n = 19; age: 46.1 ± 7.5 yrs). The exercise intervention groups (BEX and MEX) followed a training program on a treadmill for 20 min at 70% HRmax, 3 days/week for 8 weeks. The responses of cortisol and β-endorphin were measured before (t0) and immediately after an exercise session (t20) on different days (i.e., the 1st, 12th, and 24th session) corresponding to the beginning, middle, and end of the training program. A significant increase in β-endorphin levels was observed after the completion of the training intervention (24th exercise session) in both exercise groups (BEX before: 63.8 ± 33; BEX after: 185.6 ± 182.8 pg/mL; MEX before: 115 ± 211; MEX after: 262.3 ± 505.7 pg/mL), whereas β-endorphin was decreased in the control groups (BCON before: 34.7 ± 20.1; BCON after: 24.2 ± 8.8 pg/mL; MCON before: 129.7 ± 185.7; MCON after: 84.9 ± 104.3 pg/mL) (p < 0.05). Inversely, cortisol decreased in both exercise groups post-intervention (BEX before: 9.5 ± 5.9; BEX after: 2.8 ± 1.5 ng/mL; MEX before: 9.3 ± 6.6; MEX after: 3.1 ± 1.5 ng/mL) and increased in control groups (BCON before: 6.3 ± 2.5; BCON after: 10.1 ± 5.4 ng/mL; MCON before: 7.5 ± 3.2; MCON after: 12.5 ± 4.3 ng/mL) (p < 0.05). Moderate-intensity aerobic exercise can beneficially influence β-endorphin and cortisol levels in individuals undergoing treatment for OUD. By increasing endogenous opioid levels and reducing stress hormones, exercise emerges as a promising adjunctive strategy for alleviating withdrawal symptoms, enhancing emotional regulation, and potentially reducing the risk of relapse. The inverse relationship between β-endorphin and cortisol highlights the role of physical activity as a long-term modulator of neuroendocrine function in the context of substance use recovery. Future research should prioritize longitudinal studies extending beyond two months and involving larger, more diverse populations. Additionally, investigating the integration of exercise with non-pharmacological interventions—and its effects on relapse rates, mental health outcomes, and overall quality of life—would provide further insight into its therapeutic value in addiction recovery. Full article
(This article belongs to the Special Issue Exploring Biological Mechanisms and Therapeutic Strategies for Substance Use Disorders)
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