Abstract

The endocannabinoid system has emerged as one of the most important facilitators of stress adaptation in the body. So far, little to no research took place concerning the endocannabinoid response to stress in humans. In this study, we investigated the influence of a type I trauma on endocannabinoid plasma levels in humans over a period of 6 months, compared with non-traumatized controls. We measured endocannabinoid plasma levels (using high performance liquid chromatography-tandem mass spectrometry) as well as hippocampal and amygdala volumes in fourteen participants who had experienced a psychic trauma and developed an acute stress disorder. Fourteen healthy non-traumatized age- and gender-matched controls were studied in comparison over a 6 months period. Data were collected at three points of time: within 48 hours after the traumatic event, after one month and after six months. At each point of time a psychiatric interview was conducted and the Clinician Administered PTSD Scale (CAPS), HAMD and BDI were rated. When 2-Arachidonoylglycerol (2-AG) levels were compared between traumatized subjects and non-traumatized controls, there was a statistical significant difference one month after trauma (p=0.046). Regarding endocannabinoid levels over the course of time, 2-AG decreased in the trauma group between one month and six months after the initial trauma. This finding was in line with the hypothesis that endocannabinoids act on-demand as protective mechanism, being released after a stressful stimulus to inhibit the development of posttraumatic sequelae. In traumatized subjects, anandamide levels after six months showed a strong negative correlation with hippocampal volumes at this time point. A statistically significant negative correlation between left amygdala volume at six months and anandamide level at this time point in traumatized subjects was found. In non-traumatized controls, remarkably, there were positive correlations of 2-AG levels and amygdala volumes one month after trauma, which were not detected at the other time points. In contrast, endocannabinoid levels were neither correlated with any demographic and clinical variable, nor with volumes of cingulate regions. In conclusion, the results of our study point to a delayed and possibly regulatory response of the endocannabinoid system after a single psychic trauma over the course of six months in humans. Moreover, the data point to a genuine relation of peripheral endocannabinoid levels possibly reflecting central endocannabinoid activity and neuroplasticity in brain key regions involved in the generation of traumatic memories, i.e. hippocampus and amygdale.