title: Plasma concentrations of endocannabinoids and related primary fatty acid amides in patients with post-traumatic stress disorder.
abstract: BACKGROUND
  Endocannabinoids (ECs) and related N-acyl-ethanolamides (NAEs) play important roles in stress response regulation, anxiety and traumatic memories. In view of the evidence that circulating EC levels are elevated under acute mild stressful conditions in humans, we hypothesized that individuals with traumatic stress exposure and post-traumatic stress disorder (PTSD), an anxiety disorder characterized by the inappropriate persistence and uncontrolled retrieval of traumatic memories, show measurable alterations in plasma EC and NAE concentrations.
  
  
  METHODS
  We determined plasma concentrations of the ECs anandamide (ANA) and 2-arachidonoylglycerol (2-AG) and the NAEs palmitoylethanolamide (PEA), oleoylethanolamide (OEA), stearoylethanolamine (SEA), and N-oleoyldopamine (OLDA) by HPLC-MS-MS in patients with PTSD (n = 10), trauma-exposed individuals without evidence of PTSD (n = 9) and in healthy control subjects (n = 29). PTSD was diagnosed according to DSM-IV criteria by administering the Clinician Administered PTSD Scale (CAPS), which also assesses traumatic events.
  
  
  RESULTS
  Individuals with PTSD showed significantly higher plasma concentrations of ANA (0.48 ± 0.11 vs. 0.36 ± 0.14 ng/ml, p = 0.01), 2-AG (8.93 ± 3.20 vs. 6.26±2.10 ng/ml, p<0.01), OEA (5.90 ± 2.10 vs. 3.88 ± 1.85 ng/ml, p<0.01), SEA (2.70 ± 3.37 vs. 0.83 ± 0.47, ng/ml, p<0.05) and significantly lower plasma levels of OLDA (0.12 ± 0.05 vs. 0.45 ± 0.59 ng/ml, p<0.05) than healthy controls. Moreover, PTSD patients had higher 2-AG plasma levels (8.93 ± 3.20 vs. 6.01 ± 1.32 ng/ml, p = 0.03) and also higher plasma concentrations of PEA (4.06 ± 1.87 vs. 2.63±1.34 ng/ml, p<0.05) than trauma-exposed individuals without evidence of PTSD. CAPS scores in trauma-exposed individuals with and without PTSD (n = 19) correlated positively with PEA (r = 0.55, p = 0.02) and negatively with OLDA plasma levels (r = -0.68, p<0.01). CAPS subscores for intrusions (r = -0.65, p<0.01), avoidance (r = -0.60, p<0.01) and hyperarousal (r = -0.66, p<0.01) were all negatively related to OLDA plasma concentrations.
  
  
  CONCLUSIONS
  PTSD appears to be associated with changes in plasma EC/NAE concentrations. This may have pathophysiological and diagnostic consequences but will need to be reproduced in larger cohorts.
authors.affiliation: Department of Anaesthesiology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Hauer
authors.forename: Gustav
authors.initials: G
authors.lastname: Schelling
authors.forename: Hannah
authors.initials: H
authors.lastname: Gola
authors.forename: Patrizia
authors.initials: P
authors.lastname: Campolongo
authors.forename: Julia
authors.initials: J
authors.lastname: Morath
authors.forename: Benno
authors.initials: B
authors.lastname: Roozendaal
authors.forename: Gilava
authors.initials: G
authors.lastname: Hamuni
authors.forename: Alexander
authors.initials: A
authors.lastname: Karabatsiakis
authors.forename: Piray
authors.initials: P
authors.lastname: Atsak
authors.forename: Michael
authors.initials: M
authors.lastname: Vogeser
authors.forename: Iris-Tatjana
authors.initials: IT
authors.lastname: Kolassa
mesh_terms: D000328:Adult; D000577:Amides / Q000097:blood* / Q000737:chemistry*; D016022:Case-Control Studies; D015331:Cohort Studies; D063388:Endocannabinoids / Q000097:blood*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D013313:Stress Disorders, Post-Traumatic / Q000097:blood* / Q000209:etiology / Q000523:psychology; D013315:Stress, Psychological / Q000097:blood; D014104:Torture; D014857:Warfare
chemical_list: D000577:Amides; D063388:Endocannabinoids; D006854:Hydrocortisone