Cortisol and β-Endorphin Responses During a Two-Month Exercise Training Program in Patients with an Opioid Use Disorder and on a Substitution Treatment
Abstract
1. Introduction
2. Results
2.1. Sociodemographic and Clinical Characteristics of the Participants
2.2. Medical History
2.3. Measurements of β-Endorphin in the Buprenorphine and Methadone Subgroups
2.4. β-Endorphin: Buprenorphine Exercise Group vs. Methadone Exercise Group
2.5. Measurements of Cortisol in the Buprenorphine and Methadone Subgroups
2.6. Cortisol: Buprenorphine Exercise Group vs. Methadone Exercise Group
2.7. Correlation Between β-Endorphin and Cortisol
3. Discussion
3.1. Changes in β-Endorphin and Cortisol Levels
3.2. Stress, β-Endorphin, and Cortisol: A Dynamic Interaction
3.3. Therapeutic Implications of Exercise in OUD
4. Materials and Methods
4.1. Study Design, Participants, Recruitment, and Experimental Procedures
4.2. Ethical Approval
4.3. Analysis of Salivary Cortisol and β-Endorphin
4.4. Aerobic Exercise Training
4.5. Statistical Analysis
5. Limitations of the Study
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Buprenorphine | p 1 | Methadone | p 1 | p 2 | ||||
---|---|---|---|---|---|---|---|---|
Exercise Group | Control Group | Exercise Group | Control Group | |||||
Ν = 26; 28.9% | Ν = 25; 27.8% | Ν = 20; 22.2% | Ν = 19; 21.1% | |||||
Ν (%) | Ν (%) | Ν (%) | Ν (%) | |||||
Age (years), mean (SD) | 41.9 (6.1) | 41.9 (5.6) | 0.983 + | 46.7 (6.6) | 46.1 (7.5) | 0.794 + | 0.014 + | |
Gender | ||||||||
Men | 15 (57.7) | 11 (44.0) | 0.328 ++ | 12 (60.0) | 11 (57.9) | 0.894 ++ | 0.875 ++ | |
Women | 11 (42.3) | 14 (56.0) | 8 (40.0) | 8 (42.1) | ||||
BMI (kg/m2), mean (SD) | 23 (2.4) | 22.9 (2.3) | 0.911 + | 25 (3.4) | 25.3 (1.8) | 0.742 + | 0.019 + | |
BMI (kg/m2) | ||||||||
Normal | 22 (84.6) | 16 (64.0) | 0.091 ++ | 9 (45.0) | 8 (42.1) | 0.855 ++ | 0.004 ++ | |
Overweight/Obese | 4 (15.4) | 9 (36.0) | 11 (55.0) | 11 (57.9) | ||||
Age at first use, mean (SD) | 21 (2.9) | 22.2 (3.3) | 0.175 + | 17.5 (2.5) | 18.2 (3.2) | 0.449 + | <0.001 + | |
Diagnosis | ||||||||
F.19 | 5 (19.2) | 2 (8.0) | - | 10 (50.0) | 7 (36.8) | - | - | |
F.19–F.30 | 0 (0.0) | 0 (0.0) | 1 (5.0) | 0 (0.0) | ||||
F.19–F.32 | 0 (0.0) | 0 (0.0) | 1 (5.0) | 2 (10.5) | ||||
F.19–F.40 | 1 (3.8) | 0 (0.0) | 3 (15.0) | 2 (10.5) | ||||
F.19–F.41.1 | 2 (7.7) | 2 (8.0) | 0 (0.0) | 0 (0.0) | ||||
F.20–7.29 | 0 (0.0) | 0 (0.0) | 1 (5.0) | 2 (10.5) | ||||
F.30–F.39 | 0 (0.0) | 0 (0.0) | 1 (5.0) | 2 (10.5) | ||||
F.40–F.48 | 5 (19.2) | 10 (40.0) | 3 (15.0) | 4 (21.1) | ||||
F.41 | 5 (19.2) | 2 (8.0) | 0 (0.0) | 0 (0.0) | ||||
F.41 | 7 (26.9) | 7 (28.0) | 0 (0.0) | 0 (0.0) | ||||
F.41–F.39 | 1 (3.8) | 2 (8.0) | 0 (0.0) | 0 (0.0) | ||||
HIV | 3 (11.5) | 0 (0.0) | 0.080 ++ | 6 (30.0) | 2 (10.5) | 0.235 ‡‡ | 0.149 ‡‡ | |
Hepatitis | 3 (11.5) | 4 (16.0) | 0.703 ‡‡ | 4 (20.0) | 0 (0.0) | 0.106 ‡‡ | 0.682 ‡‡ | |
Number of relapses during rehabilitation, mean (SD), median (IQR) | 1 (1–2) | 1 (1–2) | 0.802 ‡ | 4 (3–4) | 4 (3–4) | 0.767 ‡ | <0.001 ‡ |
β-Endorphin (pg/mL) | 1st Session | 12th Session | 24th Session | ||||||
---|---|---|---|---|---|---|---|---|---|
Pre | Post | Change | Pre | Post | Change | Pre | Post | Change | |
Buprenorphine | |||||||||
Control | |||||||||
Mean (95% CI) | 16 (14.5–17.5) | 34.7 (26.3–43) | 18.6 (10.7–26.6) | 38.8 (27.4–50.2) | 82.1 (55.1–109.2) | 43.4 (19.5–67.2) | 18.3 (15.7–20.8) | 24.2 (20.5–27.8) | 5.9 (3.5–8.2) |
Median (IQR) | 14.8 (13.4–16.7) | 30.6 (16.1–57.1) | 14 (3.1–40.4) | 26.8 (21.9–45.5) | 73.1 (35–98.2) | 27.6 (2.1–64.6) | 17.1 (13.6–19.2) | 26.8 (17.4–29.3) | 6 (1–10.7) |
Exercise | |||||||||
Mean (95% CI) | 18.4 (13.1–23.7) | 63.8 (50.5–77.1) | 45.4 (34.1–56.7) | 34.1 (25–43.2) | 95.3 (73.2–117.3) | 61.2 (43.4–79) | 55.5 (40.9–70) | 185.6 (111.8–259.5) | 130.2 (57.6–202.7) |
Median (IQR) | 14.5 (7.2–31.3) | 57.2 (42.3–86.2) | 40.6 (26–63) | 26.9 (14.8–53) | 81.1 (55.9–124.5) | 49.4 (28.1–91.4) | 46.7 (25.4–78.5) | 129.8 (89–204.4) | 67.9 (40.6–139.7) |
p + | 0.665 | 0.001 | <0.001 | 0.522 | 0.250 | 0.020 | <0.001 | <0.001 | <0.001 |
r 1 | −0.06 | −0.49 | −0.52 | −0.09 | −0.16 | −0.32 | −0.68 | −0.86 | −0.85 |
Methadone | |||||||||
Control | |||||||||
Mean (95% CI) | 17.4 (14.8–20) | 129.7 (40.2–219.2) | 112.3 (24.6–200) | 54.4 (36.4–72.4) | 187.9 (76.8–299.1) | 133.5 (39.2–227.8) | 20.1 (17.3–22.9) | 84.9 (34.6–135.2) | 64.8 (15.4–114.2) |
Median (IQR) | 15.7 (12.7–19.4) | 59.6 (24.2–160.5) | 43.9 (7.5–132.4) | 44.7 (24.1–81.6) | 77.8 (55.2–247.9) | 41.6 (24.5–166.3) | 18.5 (14.5–24.7) | 53.1 (19.1–108.1) | 32.5 (2.2–76.3) |
Exercise | |||||||||
Mean (95% CI) | 19.4 (9.7–29.2) | 115 (16.2–213.7) | 95.6 (0.6–190.5) | 34.9 (19.6–50.1) | 220.8 (−7–448.5) | 185.9 (−36–407.9) | 67.2 (25.6–108.8) | 262.3 (25.7–499) | 195.1 (−27–417.3) |
Median (IQR) | 13.8 (7.9–19.6) | 37.9 (17.8–96.9) | 22.7 (9.8–76.2) | 23.5 (10.9–51.6) | 66.9 (26.9–165.4) | 48.2 (13.5–123.3) | 31.1 (17.6–81.9) | 111.6 (61.8–216.3) | 62.4 (32.2–132.7) |
p + | 0.185 | 0.448 | 0.749 | 0.056 | 0.399 | 0.555 | 0.033 | 0.013 | 0.025 |
r 1 | −0.21 | −0.12 | −0.05 | −0.31 | −0.14 | −0.09 | −0.34 | −0.40 | −0.36 |
p ++ | 0.877 | 0.215 | 0.268 | 0.520 | 0.506 | 0.756 | 0.352 | 0.506 | 0.723 |
r 1 | −0.02 | −0.18 | −0.16 | −0.09 | −0.10 | −0.05 | −0.14 | −0.10 | −0.05 |
Dependent Variable: β-Endorphin | β + | SE ++ | p | |
---|---|---|---|---|
Buprenorphine subgroup | Measurement (Post vs. Pre) | 1.38 | 0.12 | <0.001 |
Session | ||||
1st vs. 24th | 0.65 | 0.12 | <0.001 | |
12th vs. 24th | 1.16 | 0.13 | <0.001 | |
Measurement ∗ Session interaction | ||||
1st vs. 24th | −0.27 | 0.17 | 0.109 | |
12th vs. 24th | −0.25 | 0.17 | 0.139 | |
Methadone subgroup | Measurement (Post vs. Pre) | 1.25 | 0.15 | <0.001 |
Session | ||||
1st vs. 24th | 0.59 | 0.15 | <0.001 | |
12th vs. 24th | 1.05 | 0.15 | <0.001 | |
Measurement ∗ Session interaction | ||||
1st vs. 24th | −0.09 | 0.21 | 0.687 | |
12th vs. 24th | −0.12 | 0.21 | 0.586 |
Cortisol (ng/mL) | 1st Session | 12th Session | 24th Session | ||||||
---|---|---|---|---|---|---|---|---|---|
Pre | Post | Change | Pre | Post | Change | Pre | Post | Change | |
Buprenorphine | |||||||||
Control | |||||||||
Mean (95% CI) | 7.9 (6.8–9) | 6.3 (5.3–7.3) | −1.6 (−2–−1.3) | 6.3 (5.5–7.1) | 5.4 (4.6–6.2) | −0.9 (−1.2–−0.6) | 11.4 (8.7–14) | 10.1 (7.8–12.3) | −1.3 (−2–−0.6) |
Median (IQR) | 8.8 (6.3–9.5) | 6.4 (4.4–8.4) | −1.7 (−2.1–−1.4) | 6.5 (5.2–7.6) | 6.2 (4.7–6.5) | −0.9 (−1.4–−0.5) | 10.2 (7.2–15) | 9.2 (5.7–13.1) | −1.4 (−2.1–−0.3) |
Exercise | |||||||||
Mean (95% CI) | 7.4 (5.4–9.4) | 9.5 (7.2–11.9) | 2.1 (0.7–3.5) | 3.3 (2.5–4) | 4.2 (3.3–5.1) | 0.9 (0.5–1.3) | 2 (1.6–2.4) | 2.8 (2.2–3.4) | 0.8 (0.5–1.1) |
Median (IQR) | 5.6 (3.6–10.5) | 8.7 (4.3–13.6) | 1.3 (0.3–1.9) | 2.9 (1.8–4.1) | 4 (2.2–5.8) | 0.6 (0.2–1.1) | 1.6 (1.2–2.5) | 2.3 (1.7–3.5) | 0.6 (0.2–1.3) |
p + | 0.258 | 0.083 | <0.001 | <0.001 | 0.040 | <0.001 | <0.001 | <0.001 | <0.001 |
r 1 | −0.16 | −0.24 | −0.86 | −0.66 | −0.29 | −0.86 | −0.84 | −0.77 | −0.73 |
Methadone | |||||||||
Control | |||||||||
Mean (95% CI) | 8.7 (7.3–10.2) | 7.5 (6–9.1) | −1.2 (−2–−0.4) | 7.5 (6.2–8.8) | 5.6 (4.4–6.9) | −1.8 (−2.9–−0.8) | 11.3 (9.3–13.3) | 12.5 (10.4–14.6) | 1.2 (0–2.4) |
Median (IQR) | 8.7 (6.3–10.2) | 6.9 (4.4–9.4) | −0.8 (−1–−0.3) | 7.4 (5.2–9.3) | 5.3 (3.2–7.2) | −1.9 (−2.8–−0.2) | 9.7 (8.3–13.9) | 11.3 (8.9–14) | 1.7 (0.1–2.5) |
Exercise | |||||||||
Mean (95% CI) | 8 (5.2–10.8) | 9.3 (6.2–12.4) | 1.3 (0.9–1.7) | 3.7 (2.9–4.5) | 5.3 (3.6–7) | 1.6 (0.4–2.8) | 2.4 (1.9–2.9) | 3.1 (2.4–3.8) | 0.7 (0.4–1) |
Median (IQR) | 4.9 (3.5–14.7) | 6.5 (4.4–16.2) | 1.2 (0.6–1.8) | 3.5 (2.2–5.1) | 4.8 (2.7–6.1) | 1.1 (0.5–1.5) | 2.1 (1.7–3.1) | 2.8 (1.9–4) | 0.5 (0.3–0.7) |
p + | 0.086 | 0.888 | <0.001 | <0.001 | 0.431 | <0.001 | <0.001 | <0.001 | 0.149 |
r 1 | −0.27 | −0.02 | −0.86 | −0.66 | −0.13 | −0.74 | −0.86 | −0.86 | −0.23 |
p ++ | 0.790 | 0.842 | 0.833 | 0.278 | 0.268 | 0.163 | 0.141 | 0.358 | 0.947 |
r 1 | −0.04 | −0.03 | −0.03 | −0.16 | −0.16 | −0.21 | −0.22 | −0.14 | −0.01 |
Dependent Variable: Cortisol | β + | SE ++ | p | |
---|---|---|---|---|
Buprenorphine subgroup | Measurement (Post vs. Pre) | 0.25 | 0.07 | <0.001 |
Session | ||||
1st vs. 24th | −0.74 | 0.09 | <0.001 | |
12th vs. 24th | −1.21 | 0.13 | <0.001 | |
Measurement ∗ Session interaction | ||||
1st vs. 24th | 0.001 | 0.10 | 0.991 | |
12th vs. 24th | 0.06 | 0.01 | 0.556 | |
Methadone subgroup | Measurement (Post vs. Pre) | 0.19 | 0.07 | 0.012 |
Session | ||||
1st vs. 24th | −0.59 | 0.10 | <0.001 | |
12th vs. 24th | −1.03 | 0.14 | <0.001 | |
Measurement ∗ Session interaction | ||||
1st vs. 24th | 0.12 | 0.10 | 0.268 | |
12th vs. 24th | 0.06 | 0.10 | 0.546 |
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Psarianos, A.E.; Philippou, A.; Papadopetraki, A.; Chatzinikita, E.; Chryssanthopoulos, C.; Theos, A.; Theocharis, A.; Tzavara, C.; Paparrigopoulos, T. Cortisol and β-Endorphin Responses During a Two-Month Exercise Training Program in Patients with an Opioid Use Disorder and on a Substitution Treatment. Int. J. Mol. Sci. 2025, 26, 5178. https://doi.org/10.3390/ijms26115178
Psarianos AE, Philippou A, Papadopetraki A, Chatzinikita E, Chryssanthopoulos C, Theos A, Theocharis A, Tzavara C, Paparrigopoulos T. Cortisol and β-Endorphin Responses During a Two-Month Exercise Training Program in Patients with an Opioid Use Disorder and on a Substitution Treatment. International Journal of Molecular Sciences. 2025; 26(11):5178. https://doi.org/10.3390/ijms26115178
Chicago/Turabian StylePsarianos, Alexandros E., Anastassios Philippou, Argyro Papadopetraki, Eirini Chatzinikita, Costas Chryssanthopoulos, Apostolos Theos, Athanasios Theocharis, Chara Tzavara, and Thomas Paparrigopoulos. 2025. "Cortisol and β-Endorphin Responses During a Two-Month Exercise Training Program in Patients with an Opioid Use Disorder and on a Substitution Treatment" International Journal of Molecular Sciences 26, no. 11: 5178. https://doi.org/10.3390/ijms26115178
APA StylePsarianos, A. E., Philippou, A., Papadopetraki, A., Chatzinikita, E., Chryssanthopoulos, C., Theos, A., Theocharis, A., Tzavara, C., & Paparrigopoulos, T. (2025). Cortisol and β-Endorphin Responses During a Two-Month Exercise Training Program in Patients with an Opioid Use Disorder and on a Substitution Treatment. International Journal of Molecular Sciences, 26(11), 5178. https://doi.org/10.3390/ijms26115178