Reductions in circulating endocannabinoid levels in individuals with post-traumatic stress disorder following exposure to the World Trade Center attacks

Abstract

Endocannabinoid (eCB) signaling has been identified as a modulator of adaptation to stress, and is integral to basal and stress-induced glucocorticoid regulation. Furthermore, interactions between eCBs and glucocorticoids have been shown to be necessary for the regulation of emotional memories, suggesting that eCB function may relate to the development of post-traumatic stress disorder (PTSD). To examine this, plasma eCBs were measured in a sample (n=46) drawn from a population-based cohort selected for physical proximity to the World Trade Center (WTC) at the time of the 9/11 attacks. Participants received a structured diagnostic interview and were grouped according to whether they met diagnostic criteria for PTSD (no PTSD, n=22; lifetime diagnosis of PTSD=24). eCB content (2-arachidonoylglycerol (2-AG) and anandamide (AEA)) and cortisol were measured from 8 a.m. plasma samples. Circulating 2-AG content was significantly reduced among individuals meeting diagnostic criteria for PTSD. The effect of reduced 2-AG content in PTSD remained significant after controlling for the stress of exposure to the WTC collapse, gender, depression and alcohol abuse. There were no significant group differences for AEA or cortisol levels; however, across the whole sample AEA levels positively correlated with circulating cortisol, and AEA levels exhibited a negative relationship with the degree of intrusive symptoms within the PTSD sample. This report shows that PTSD is associated with a reduction in circulating levels of the eCB 2-AG. Given the role of 2-AG in the regulation of the stress response, these data support the hypothesis that deficient eCB signaling may be a component of the glucocorticoid dysregulation associated with PTSD. The negative association between AEA levels and intrusive symptoms is consistent with animal data indicating that reductions in AEA promote retention of aversive emotional memories. Future work will aim to replicate these findings and extend their relevance to clinical pathophysiology, as well as to neuroendocrine and molecular markers of PTSD.

Keywords: 2-Arachidonoylglycerol; Anandamide; Anxiety; Cortisol; Endocannabinoid; HPA axis; N-arachidonylethanolamine; PTSD; Stress; Trauma.

Conflict of interest statement

Conflict of Interest

Drs. Hill, Bierer, Makotkine, Golier and Hillard declare no conflicts of interest.

Copyright © 2013 Elsevier Ltd. All rights reserved.

Figures

Figure 1

Plasma 2-arachidonoylglycerol (2-AG), anandamide (AEA), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) concentrations in individuals who were diagnosed with post-traumatic stress disorder (PTSD) or healthy age and gender matched controls (No PTSD). Plasma levels of 2-AG, but not AEA, PEA or OEA, are found to be reduced in PTSD. Data are presented as mean +/− SEM. Significant diferences (p

Figure 2

Correlations between plasma cortisol and 2-arachidonoylglycerol (2-AG), anandamide (AEA), palmitoylethanolamide (PEA) or oleoylethanolamide (OEA). All of AEA, PEA and OEA, but not 2-AG, were found to correlate with cortisol in the entire sample (both healthy control and those with post-traumatic stress disorder). Significant correlations (p