Abstract
BackgroundEndocannabinoids (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.MethodsWe 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.ResultsIndividuals 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.ConclusionsPTSD 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.
Highlights
Endocannabinoids (ECs) and related N-acyl-ethanolamides (NAEs) play an essential role in many physiological processes, including energy metabolism, immune function and both central and peripheral nervous system function [1]
Given the fact that post-traumatic stress disorder (PTSD) is an anxiety disorder characterized by an inappropriate persistence and uncontrolled retrieval of traumatic memories, it can be assumed that changes in EC signaling might play a role in either the development or persistence of PTSD
This line of reasoning is corroborated by the observation that patients with PTSD exhibit high rates of cannabis abuse which may represent a form of self-medication [16], and a recent study demonstrated that a stimulation of EC signaling in patients with PTSD by administration of the synthetic cannabinoid nabilone resulted in an improvement of memory-related PTSD symptoms [17]
Summary
Endocannabinoids (ECs) and related N-acyl-ethanolamides (NAEs) play an essential role in many physiological processes, including energy metabolism, immune function and both central and peripheral nervous system function [1]. Despite the abovementioned diversity in central and peripheral functions, recent studies in animals [9] and humans [10] point to a major role of EC signaling in both the periphery [10] and central nervous system [11] in controlling adaptive processes to aversive situations and regulating and limiting stress reactions As part of this protective role under aversive conditions, elevated EC signaling during stress has been shown to dampen the development of anxiety [12] and to regulate the encoding [13], retrieval [14] and extinction [15] of 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
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