In 80 adults with diagnosed depression, higher cardiorespiratory fitness and jump performance were associated with lower plasma levels of endocannabinoids anandamide and 2-AG.
People interested in how exercise affects the brain in depression, and researchers studying the endocannabinoid system and mood.
Higher fitness = lower resting endocannabinoid levels in depression
What the researchers found
Among 80 adults with mild-to-moderate depression, better cardiorespiratory fitness and jump performance were inversely associated with plasma levels of both main endocannabinoids: anandamide and 2-AG. These relationships persisted after adjusting for lean mass.
Why it matters
Exercise is known to help depression, and the endocannabinoid system has been proposed as a key mediator. This study provides direct data on the relationship between fitness and endocannabinoid levels in people with depression.
The numbers in context
80 adults with depression. CRF and AEA: beta -0.302 to -0.237. CRF and 2-AG: beta -0.308 to -0.326. Jump and AEA: beta -0.315 to -0.370. All p<0.05.
How the study worked
Cross-sectional study of 80 adults ages 25-65 with mild-to-moderate depression (ICD-10). Physical fitness assessed via 6-Minute Walk Test, handgrip, arm curl, chair stand, and standing long jump. Fasting plasma endocannabinoids measured by LC-MS/MS.
What this study cannot tell us
Cross-sectional; cannot determine causation. Plasma levels may not reflect brain activity. Small sample. No comparison group without depression.
How to read the evidence
Preliminary: small cross-sectional study with novel findings, cannot determine causation.
When this study was published
Published in 2025.
The bigger picture
Lower resting endocannabinoid levels in fitter people may reflect a more efficient or better-regulated endocannabinoid system, similar to how fitter people have lower resting heart rates.
Questions still open
- Do fitter people have more efficient endocannabinoid systems?
- Would exercise interventions change endocannabinoid levels in depression?
- Are endocannabinoid levels a mediator or marker of fitness-related mood improvement?
Common questions
Does exercise affect the endocannabinoid system in people with depression?
Is the runner's high related to endocannabinoids?
Read the original research
Associations of cardiorespiratory fitness and muscular fitness with plasma levels of endocannabinoids and their analogues in adults with diagnosed depression: SONRIE study.
European archives of psychiatry and clinical neuroscience
Citation
Ruiz-Muñoz, Manuel; Ortega-Gómez, Sonia; Espinosa-Nogales, Maria Del Mar; de Lara, Eulalio Valmisa-Gómez; Rosety-Rodríguez, Miguel Ángel; España-Romero, Vanesa. (2025). Associations of cardiorespiratory fitness and muscular fitness with plasma levels of endocannabinoids and their analogues in adults with diagnosed depression: SONRIE study.. European archives of psychiatry and clinical neuroscience. https://doi.org/10.1007/s00406-025-02032-w