Childhood trauma and being at-risk for psychosis are associated with higher peripheral endocannabinoids

Psychol Med. 2020 Aug;50(11):1862-1871. doi: 10.1017/S0033291719001946. Epub 2019 Aug 19.


Background: Evidence has been accumulating regarding alterations in components of the endocannabinoid system in patients with psychosis. Of all the putative risk factors associated with psychosis, being at clinical high-risk for psychosis (CHR) has the strongest association with the onset of psychosis, and exposure to childhood trauma has been linked to an increased risk of development of psychotic disorder. We aimed to investigate whether being at-risk for psychosis and exposure to childhood trauma were associated with altered endocannabinoid levels.

Method: We compared 33 CHR participants with 58 healthy controls (HC) and collected information about previous exposure to childhood trauma as well as plasma samples to analyse endocannabinoid levels.

Results: Individuals with both CHR and experience of childhood trauma had higher N-palmitoylethanolamine (p < 0.001) and anandamide (p < 0.001) levels in peripheral blood compared to HC and those with no childhood trauma. There was also a significant correlation between N-palmitoylethanolamine levels and symptoms as well as childhood trauma.

Conclusions: Our results suggest an association between CHR and/or childhood maltreatment and elevated endocannabinoid levels in peripheral blood, with a greater alteration in those with both CHR status and history of childhood maltreatment compared to those with either of those risks alone. Furthermore, endocannabinoid levels increased linearly with the number of risk factors and elevated endocannabinoid levels correlated with the severity of CHR symptoms and extent of childhood maltreatment. Further studies in larger cohorts, employing longitudinal designs are needed to confirm these findings and delineate the precise role of endocannabinoid alterations in the pathophysiology of psychosis.

Keywords: Anandamide; childhood trauma; clinical high-risk; endocannabinoid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Adverse Childhood Experiences / psychology*
  • Amides / blood*
  • Arachidonic Acids / blood*
  • Case-Control Studies
  • Endocannabinoids / blood*
  • Ethanolamines / blood*
  • Female
  • Humans
  • Male
  • Palmitic Acids / blood*
  • Polyunsaturated Alkamides / blood*
  • Prodromal Symptoms
  • Psychiatric Status Rating Scales
  • Psychotic Disorders / blood*
  • Psychotic Disorders / etiology
  • Risk Factors
  • Young Adult


  • Amides
  • Arachidonic Acids
  • Endocannabinoids
  • Ethanolamines
  • Palmitic Acids
  • Polyunsaturated Alkamides
  • palmidrol
  • anandamide