n-oleoylethanolamine and Stress-Disorders--Post-Traumatic

The endocannabinoid (eCB) system is a modulatory system that is both altered by stress and mediates the effects of acute stress, including contributing to restoration of homeostasis. Earlier studies suggest that circulating eCBs are dysregulated in adults with post-traumatic stress disorder (PTSD); however, it is not known whether circulating eCBs remain responsive to stress. The purpose of this study was to examine eCB and psychological responses to physical (exercise) and psychosocial (Trier Social Stress Test) stressors, using a randomized, counterbalanced procedure in adults with PTSD and healthy controls (N = 20, mean age = 24, SD = 7 yrs). Results from mixed-design, repeated measures ANOVAs revealed significant increases (p <  .05) in N-arachidonoylethanolamine (AEA) and oleoylethanolamide (OEA) following exercise and psychosocial stress in both groups. However, only the control group exhibited a significant increase (p < .05) in 2-arachidonoylglycerol (2-AG) following exercise and psychosocial stress exposure. These data extend our current understanding of circulating eCB responsiveness in PTSD, and provide preliminary evidence to suggest that the eCB system is hypoactive in PTSD following exposure to physical and psychosocial stressors.

Topics: Adult; Arachidonic Acids; Chronic Disease; Endocannabinoids; Exercise; Glycerides; Humans; Male; Oleic Acids; Polyunsaturated Alkamides; Stress Disorders, Post-Traumatic; Stress, Psychological; Young Adult

Previous reports have shown improvements in mood and increases in endocannabinoids in healthy adults following a session of aerobic exercise, but it is unclear whether adults with posttraumatic stress disorder (PTSD) experience similar responses. The purpose of this study was to examine psychobiological responses (plasma endocannabinoids [eCBs], mood, and pain) to aerobic exercise in a sample of adults with a diagnosis of PTSD (n = 12) and healthy controls (n = 12). Participants engaged in an aerobic exercise session in which they ran on a treadmill for 30 min at a moderate intensity (70 to 75% maximum heart rate [MHR]). Results indicated improvements in mood states and reductions in pain for both groups following exercise, ds = 0.19 to 1.53. Circulating concentrations of N-arachidonylethanolamine (AEA), 2-arachidonoylglycerol (2-AG), and oleoylethanolamide (OEA) significantly increased (ps = .000 to .050) following the aerobic exercise session for both groups. There were no significant time, group, or interaction effects (ps = .062 to .846) for palmitoylethanolamide (PEA) and 2-oleoylglycerol (2-OG). Although eCBs increased significantly for both groups, within-group effect size calculations indicated the healthy controls experienced a greater magnitude of change for AEA when compared with adults with PTSD, d = 1.21 and d = 0.45, respectively; as well as for 2-AG, d = 0.43 and d = 0.21, respectively. The findings from this study indicated that adults with and without PTSD reported significant mood improvements following 30 min of moderate-intensity aerobic exercise. In addition, the endocannabinoid system was activated in adults with and without PTSD, although effect sizes suggest that adults with PTSD may have a blunted endocannabinoid response to exercise.

Topics: Adolescent; Adult; Affect; Arachidonic Acids; Cannabinoids; Case-Control Studies; Endocannabinoids; Exercise; Female; Glycerides; Humans; Male; Oleic Acids; Pain; Pilot Projects; Stress Disorders, Post-Traumatic; Young Adult

The endocannabinoid system has been implicated in the regulation of the stress response, fear memory formation, and inflammatory processes. Posttraumatic stress disorder (PTSD) can result from exposure to extreme stress and is characterized by strong, associative memories for the traumatic events experienced. Furthermore, an elevated physical disease risk has been observed in PTSD, likely to be mediated by inflammatory processes. Therefore, altered endocannabinoid regulation can be expected in individuals with PTSD. However, attempts to assess PTSD-associated differences in the endocannabinoid system from human blood samples have provided inconsistent results, possibly due to fluctuating levels of endocannabinoids. In hair, these neuromodulators are accumulated over time and thus give access to a more stable and reliable assessment. We therefore investigated PTSD-associated differences in hair concentrations of endocannabinoids (N-acyl-ethanolamides palmitoylethanolamide [PEA], oleoylethanolamide [OEA] and stearoylethanolamide [SEA]) in 38 rebel war survivors from Northern Uganda suffering from PTSD and N=38 healthy rebel war survivors without current and lifetime PTSD. PTSD diagnosis and symptom severity were assessed in structured clinical interviews employing the Posttraumatic Diagnostic Scale (PDS). A significant group difference was observed for OEA, with PTSD patients showing reduced hair concentrations. Regression analyses further revealed strong negative relationships between all investigated N-acyl-ethanolamides and symptom severity of PTSD. The observed reductions in endocannabinoids might account for the increased inflammatory state as well as for the failure to extinguish fear memories observed in PTSD. Our findings add to the accumulating evidence suggesting the endocannabinoid system as a target for pharmacological enhancement of exposure-based psychotherapy for PTSD.

Topics: Adult; Amides; Case-Control Studies; Endocannabinoids; Ethanolamines; Female; Hair; Humans; Male; Oleic Acids; Palmitic Acids; Stearic Acids; Stress Disorders, Post-Traumatic; Uganda; Veterans; Young Adult

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.

Topics: Aged; Alcoholism; Amides; Arachidonic Acids; Endocannabinoids; Ethanolamines; Ethnicity; Female; Glycerides; Humans; Hydrocortisone; Male; Middle Aged; Neuropsychological Tests; Oleic Acids; Palmitic Acids; Polyunsaturated Alkamides; Psychiatric Status Rating Scales; Sex Characteristics; Stress Disorders, Post-Traumatic; Terrorism