Changes of endocannabinoid plasma levels following type I trauma

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.