# Associations of cardiorespiratory fitness and muscular fitness with plasma levels of endocannabinoids and their analogues in adults with diagnosed depression: SONRIE study

## TL;DR

The study found that higher physical fitness is linked to lower levels of endocannabinoids in people with depression.

## Contribution

This study is novel in examining how cardiorespiratory and muscular fitness relate to endocannabinoid levels in adults with depression.

## Key findings

- Higher cardiorespiratory fitness and jump performance were inversely associated with plasma levels of anandamide and 2-AG.
- Endocannabinoid analogues also correlated negatively with physical fitness measures after adjusting for lean mass.

## Abstract

Depression is a leading cause of global disability, affecting approximately 280 million individuals worldwide. Emerging evidence suggests that both physical fitness and endocannabinoids system play significant roles in the pathophysiology and management of depressive disorders.

To examine the associations between physical fitness, in terms of cardiorespiratory fitness (CRF) and muscular fitness (MF), with plasma levels of endocannabinoids (eCBs) and their analogues, in adults diagnosed with depression.

The study involved 80 adults (ages 25–65) with a psychiatric diagnosis of mild-to-moderate depression based on the International Classification of Diseases 10th Revision (ICD-10) criteria. Physical fitness was assessed through tests measuring CRF (6-Minute Walk Test) and MF (Handgrip, Arm Curl, Chair Stand, Standing Long Jump Test). Fasting plasma levels of eCBs, such as anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), and their analogues were measured using liquid chromatography-tandem mass spectrometry. Linear regression analyses were conducted or the associations between fitness variables and plasma levels of eCBs and their analogues using three models.

CRF and jump performance were inversely associated with plasma levels of the eCBs AEA (β range: − 0.302 to − 0.237 for CRF, − 0.315 to − 0.370 for jump; All p < 0.05) and 2-AG (β range: − 0.308 to − 0.326 across all models). eCBs analogues correlated negatively with CRF [2-linoleoylglycerol, 2-oleoylglycerol, docosatetraenoylethanolamide (DEA)] and jump (linoleylethanolamine, stearoylethanolamine, DEA); findings persisted after lean mass normalization.

Our findings indicated that higher physical fitness was associated with lower plasma levels of eCBs and their analogues.

The online version contains supplementary material available at 10.1007/s00406-025-02032-w.