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Outcomes included nine ES biomarkers (2-arachidonoylglycerol, 2-AG; anandamide, AEA; seven analogues) and physical fitness, including cardiorespiratory fitness (CRF; 6-minute walking test) and muscular strength. Measurements were taken at baseline, post-intervention and 8-week follow-up. Primary analysis performed 2\u2009\u00d7\u20093 repeated-measures ANOVA on completers; mixed-effects intention-to-treat model as sensitivity analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      No significant time \u00d7 group interaction was detected for any ES biomarker, including 2-AG (F(2,88)\u2009=\u20090.17,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.844) and AEA (F(2,88)\u2009=\u20091.20,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.306); both groups showed comparable within-group decreases in 2-AG, 2-LG and 2-OG. The intervention significantly improved CRF [between-group difference\u2009+\u200981.6\u00a0m at 12 weeks (F(2,78)\u2009=\u20097.88,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001)], exceeding the established minimal clinically important difference. None of the exploratory muscular fitness outcomes reached statistical significance; the arm curl test showed a borderline non-significant interaction (F(2,78)\u2009=\u20092.83,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.065).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A 12-week internet-based combined exercise and iCBT intervention significantly improved CRF in adults with mild-to-moderate depression. We did not find evidence of an intervention-specific effect on plasma ES biomarkers. These findings support the inclusion of internet-delivered exercise and psychological interventions in comprehensive treatment strategies for depression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT05849792 (registered 6 May 2023).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00406-026-02330-x","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:41:55Z","timestamp":1785818515000},"page":"3701-3714","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of an internet-based combined exercise and cognitive-behavioral therapy intervention on endocannabinoid system biomarkers and physical fitness in adults with mild-to-moderate depression: a SONRIE randomized controlled trial"],"prefix":"10.1007","volume":"276","author":[{"given":"Manuel","family":"Ruiz-Mu\u00f1oz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Jim\u00e9nez-Pav\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inmaculada","family":"Garrido-Palomino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Manuel","family":"Escudier-V\u00e1zquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eulalio Juan Valmisa","family":"G\u00f3mez de Lara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanesa","family":"Espa\u00f1a-Romero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"issue":"9","key":"2330_CR1","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1037\/a0035001","volume":"68","author":"APA","year":"2013","unstructured":"APA (2013) Guidelines for the practice of telepsychology. 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