Circulating endocannabinoid concentrations in grieving adults

Psychoneuroendocrinology. 2020 Oct;120:104801. doi: 10.1016/j.psyneuen.2020.104801. Epub 2020 Jul 10.


Bereavement is one of the most intense, distressing, and traumatic events an elderly person will experience. The symptom responses to bereavement vary, particularly during the first year. However, the neurobiology underlying the symptom variance in grief is poorly understood. The endocannabinoid signaling (ECS) system is stress-responsive; mounting evidence implicates the central ECS in psychopathology. The current study aimed to investigate the hypothesis that the ECS is abnormal in grief, using circulating eCB concentrations as a biomarker of central ECS. A predominantly older sample of grief participants, within 13 months following the death of a loved one, and healthy comparison (HC) participants were studied. Associations of circulating eCBs with symptom variance in grievers were also examined. A total of 61 (grief: n = 44; HC: n = 17) adults completed cross-sectional clinical assessments and a fasting blood draw. Assessments included the Inventory of Complicated Grief scale; the 17-item Hamilton Depression Rating Scale; and the Hamilton Anxiety scale. Serum eCB concentrations (i.e., N-arachidonoylethanolamine [AEA] and 2-arachidonoylglycerol [2-AG]) were quantified using isotope dilution, liquid chromatography-mass spectrometry. Relative to HC participants, grievers had significantly elevated serum AEA but similar 2-AG concentrations. In grievers, serum AEA concentrations were positively associated with depressive and anxiety symptoms, but only in those with low grief symptoms. These novel findings indicate that elevated circulating eCB concentrations are found following bereavement. The eCB signaling response varies based on the degree of grief severity. Circulating eCB measures may have the potential to serve as biomarkers of prolonged grief disorder.

Keywords: Bereavement; Endocannabinoid signaling system; Endocannabinoids; Grief; Older adults; Prolonged grief disorder.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anxiety / metabolism
  • Anxiety / physiopathology
  • Arachidonic Acids / analysis
  • Arachidonic Acids / blood
  • Bereavement
  • Biomarkers / blood
  • Cross-Sectional Studies
  • Depression / metabolism
  • Depression / physiopathology
  • Endocannabinoids / analysis*
  • Endocannabinoids / blood
  • Female
  • Grief*
  • Humans
  • Male
  • Middle Aged
  • Polyunsaturated Alkamides / analysis
  • Polyunsaturated Alkamides / blood


  • Arachidonic Acids
  • Biomarkers
  • Endocannabinoids
  • Polyunsaturated Alkamides
  • anandamide