Serum Endocannabinoid and Mood Changes after Exercise in Major Depressive Disorder

Med Sci Sports Exerc. 2019 Sep;51(9):1909-1917. doi: 10.1249/MSS.0000000000002006.


The endocannabinoid (eCB) system is implicated in the pathophysiology of depression and is responsive to acute exercise in healthy adults.

Purpose: We aimed to describe acute changes in serum eCB across a prescribed moderate (MOD) and a self-selected/preferred (PREF) intensity exercise session in women with major depressive disorder (MDD) and determine relationships between changes in eCB and mood states.

Methods: Women with MDD (n = 17) exercised in separate sessions for 20 min on a cycle ergometer at both MOD or PREF in a within-subjects design. Blood was drawn before and within 10 min after exercise. Serum concentrations of eCB (anandamide [AEA], 2-arachidonoylglycerol) and related lipids (palmitoylethanolamine, oleoylethanolamine, 2-oleoylglycerol) were quantified using stable isotope-dilution, liquid chromatography/mass spectrometry/mass spectrometry. The profile of mood states and state-trait anxiety inventory (state only) were completed before, 10 min and 30 min postexercise.

Results: Significant elevations in AEA (P = 0.013) and oleoylethanolamine (P = 0.024) occurred for MOD (moderate effect sizes: Cohen's d = 0.58 and 0.41, respectively). Significant (P < 0.05) moderate negative associations existed between changes in AEA and mood states for MOD at 10 min (depression, confusion, fatigue, total mood disturbance [TMD] and state anxiety) and 30 min postexercise (confusion, TMD and state anxiety). Significant (P < 0.05) moderate negative associations existed between 2-arachidonoylglycerol and mood states at 10 min (depression and confusion) and 30 min postexercise (confusion and TMD). Changes in eCB or related lipids or eCB-mood relationships were not found for PREF.

Conclusion: Given the broad, moderate-strength relationships between improvements in mood states and eCB increases after MOD, it is plausible that the eCB system contributes to the mood-enhancing effects of prescribed acute exercise in MDD. Alternative mechanisms are likely involved in the positive mood state effects of preferred exercise.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Affect / physiology*
  • Amides
  • Arachidonic Acids / blood*
  • Depressive Disorder, Major / blood*
  • Endocannabinoids / blood*
  • Ethanolamines / blood
  • Exercise / physiology*
  • Female
  • Glycerides / blood*
  • Humans
  • Middle Aged
  • Oleic Acids / blood
  • Palmitic Acids / blood
  • Polyunsaturated Alkamides / blood*


  • Amides
  • Arachidonic Acids
  • Endocannabinoids
  • Ethanolamines
  • Glycerides
  • Oleic Acids
  • Palmitic Acids
  • Polyunsaturated Alkamides
  • oleoylethanolamide
  • palmidrol
  • glyceryl 2-arachidonate
  • 2-oleoylglycerol
  • anandamide