3. The endocannabinoid system as a potential buffer against the development of a substance use disorder following childhood trauma exposure

Exposure to trauma in childhood or adolescence is associated with an increased susceptibility to the development of a substance use disorder (SUD) in adulthood. One potential contributing factor is disruption of the endocannabinoid system, a neuromodulatory system involved in stress and emotion processing. The endocannabinoid system undergoes extensive reorganization during adolescence and perturbations of this process, such as trauma expsoure, can last into adulthood. Thus, childhood trauma may impact endocannabinoid system function, imparing stress and emotion processing and potentially contributing to SUD development later in life.

We recruited individuals (N=101) with or without documented histories of childhood trauma and/or a substance use disorder. All participants provided blood samples at baseline and following exposure to a laboratory stressor. Emotion processing was assessed using facial electromyography before and have stress exposure

Individuals exposed to trauma (trauma only) had higher baseline levels of the endocannabinoid ligand anandamide (p = 0.003), which remained elevated even after stress exposure (p=0.005). This effect was absent in trauma-exposed individuals who went on to develop an SUD. There were no differences in cortisol reactivity to stress (p=0.60), though the SUD groups showed blunted autonomic stress reactivity (p = 0.031).

For individuals exposed to childhood trauma, elevated anandamide may serve as a protective factor, mitigating the negative consequences of stress exposure. This data supports the notion that pharmacologically enhancing anandamide may serve as a novel therapeutic target for the treatment of trauma-related disorders, in support of ongoing clinical trials targeting this mechanism.

Disclosure of interest statement: NARSAD Young Investigator Award by the Brain & Behavior Foundation (BBRF; Grant nr.: 27094) to Leah Mayo. ALF Regional Clinical Research Funding (ALF2020 LIO-888021; ALF201 LIO-791581) to Andrea Capusan. Systembolaget Alcohol Research Council (FO2017-0048; FO2018-0030; FO2019- 0007) to Markus Heilig. No pharmaceutical grants were received in the development of this study.