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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.

Manuel Ruiz-Muñoz·David Jiménez-Pavón·Inmaculada Garrido-Palomino·Juan Manuel Escudier-Vázquez·Eulalio Juan Valmisa Gómez de Lara·Vanesa España-Romero
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Abstract

BACKGROUND: This SONRIE randomized controlled trial (NCT05849792) examined the effects of a 12-week combined physical exercise and internet-based cognitive-behavioral therapy (iCBT) intervention on endocannabinoid system (ES) biomarkers and physical fitness in adults with mild-to-moderate depression. METHODS: Eighty adults were randomly assigned 1:1 to an intervention (IG) or control (CG) group. 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 × 3 repeated-measures ANOVA on completers; mixed-effects intention-to-treat model as sensitivity analysis. RESULTS: No significant time × group interaction was detected for any ES biomarker, including 2-AG (F(2,88) = 0.17, p = 0.844) and AEA (F(2,88) = 1.20, p = 0.306); both groups showed comparable within-group decreases in 2-AG, 2-LG and 2-OG. The intervention significantly improved CRF [between-group difference + 81.6 m at 12 weeks (F(2,78) = 7.88, p = 0.001)], 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) = 2.83, p = 0.065). CONCLUSION: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT05849792 (registered 6 May 2023).

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HumansCognitive Behavioral TherapyFemaleAdultMaleEndocannabinoidsExercise TherapyMiddle AgedBiomarkersInternet-Based InterventionDepressionPhysical FitnessOutcome Assessment, Health CareCombined Modality TherapyDepressive DisorderGlyceridesCardiorespiratory FitnessMuscle StrengthArachidonic Acids2-ArachidonoylglycerolAnandamideCardiorespiratory fitnessCognitive behavioral therapyEndocannabinoid systemInternet-based interventionsMuscular strengthPhysical exerciseRandomized controlled trialJournal ArticleRandomized Controlled Trial

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Manuel Ruiz-Muñoz, David Jiménez-Pavón, Inmaculada Garrido-Palomino, Juan Manuel Escudier-Vázquez, Eulalio Juan Valmisa Gómez de Lara, Vanesa España-Romero. 2026-08-04. 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.. https://doi.org/10.1007/s00406-026-02330-x

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Journal Article; Randomized Controlled Trial resourceAdult subjectBiomarkers subjectCardiorespiratory Fitness subjectCognitive Behavioral Therapy subjectCombined Modality Therapy subjectDepression subjectDepressive Disorder subjectExercise Therapy subjectFemale subjectHumans subjectInternet-Based Intervention subjectJournal Article subjectMale subjectMiddle Aged subjectMuscle Strength subject

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