{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T16:29:00Z","timestamp":1790440140958,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ume\u00e5 University, Ume\u00e5, Sweden","award":["54762345"],"award-info":[{"award-number":["54762345"]}]},{"name":"the Greek Organization Against Drugs","award":["54762345"],"award-info":[{"award-number":["54762345"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Physical exercise may affect drug use by balancing neurohormonal system mechanisms. Cortisol and \u03b2-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 \u03b2-endorphin levels in patients with an opioid use disorder (OUD) and on a substitution treatment during a short-term, 24\u201336 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 \u00b1 SD): 41.9 \u00b1 6.1 yrs), (b) buprenorphine control (BCON) (n = 25; age: 41.9 \u00b1 5.6 yrs), (c) methadone exercise (MEX) (n = 20; age: 46.7 \u00b1 6.6 yrs), and (d) methadone control (MCON) (n = 19; age: 46.1 \u00b1 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 \u03b2-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 \u03b2-endorphin levels was observed after the completion of the training intervention (24th exercise session) in both exercise groups (BEX before: 63.8 \u00b1 33; BEX after: 185.6 \u00b1 182.8 pg\/mL; MEX before: 115 \u00b1 211; MEX after: 262.3 \u00b1 505.7 pg\/mL), whereas \u03b2-endorphin was decreased in the control groups (BCON before: 34.7 \u00b1 20.1; BCON after: 24.2 \u00b1 8.8 pg\/mL; MCON before: 129.7 \u00b1 185.7; MCON after: 84.9 \u00b1 104.3 pg\/mL) (p &lt; 0.05). Inversely, cortisol decreased in both exercise groups post-intervention (BEX before: 9.5 \u00b1 5.9; BEX after: 2.8 \u00b1 1.5 ng\/mL; MEX before: 9.3 \u00b1 6.6; MEX after: 3.1 \u00b1 1.5 ng\/mL) and increased in control groups (BCON before: 6.3 \u00b1 2.5; BCON after: 10.1 \u00b1 5.4 ng\/mL; MCON before: 7.5 \u00b1 3.2; MCON after: 12.5 \u00b1 4.3 ng\/mL) (p &lt; 0.05). Moderate-intensity aerobic exercise can beneficially influence \u03b2-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 \u03b2-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\u2014and its effects on relapse rates, mental health outcomes, and overall quality of life\u2014would provide further insight into its therapeutic value in addiction recovery.<\/jats:p>","DOI":"10.3390\/ijms26115178","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T08:12:47Z","timestamp":1748419967000},"page":"5178","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cortisol and \u03b2-Endorphin Responses During a Two-Month Exercise Training Program in Patients with an Opioid Use Disorder and on a Substitution Treatment"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0831-1387","authenticated-orcid":false,"given":"Alexandros E.","family":"Psarianos","sequence":"first","affiliation":[{"name":"1st Department of Psychiatry, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece"},{"name":"Greek Organization Against Drugs (OKANA), 10433 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0047-3003","authenticated-orcid":false,"given":"Anastassios","family":"Philippou","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4230-1835","authenticated-orcid":false,"given":"Argyro","family":"Papadopetraki","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8086-3444","authenticated-orcid":false,"given":"Eirini","family":"Chatzinikita","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Costas","family":"Chryssanthopoulos","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8191-6659","authenticated-orcid":false,"given":"Apostolos","family":"Theos","sequence":"additional","affiliation":[{"name":"Section of Sports Medicine, Department of Community Medicine & Rehabilitation, Ume\u00e5 University, 901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios","family":"Theocharis","sequence":"additional","affiliation":[{"name":"Greek Organization Against Drugs (OKANA), 10433 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3242-9066","authenticated-orcid":false,"given":"Chara","family":"Tzavara","sequence":"additional","affiliation":[{"name":"1st Department of Psychiatry, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Paparrigopoulos","sequence":"additional","affiliation":[{"name":"1st Department of Psychiatry, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Maremmani, I., Dematteis, M., Gorzelanczyk, E.J., Mugelli, A., Walcher, S., and Torrens, M. 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