Endocannabinoid system in trauma and psychosis: distant guardian of mental stability

Central endocannabinoid system (eCBS) is a neuromodulatory system that inhibits potentially harmful, excessive synaptic activation. Endocannabinoid receptors are abundant among brain structures pivotal in different mental disorders development (for example, hippocampus, amygdala, medial-prefrontal cortex, hypothalamus). Here, we review eCBS function in etiology of psychosis, emphasizing its role in dealing with environmental pressures such as traumatic life events. Moreover, we explore eCBS as a guard against hypothalamic-pituitary-adrenal axis over-activation, and discuss its possible role in etiology of different psychopathologies. Additionally, we review eCBS function in creating adaptive behavioral patterns, as we explore its involvement in the memory formation process, extinction learning and emotional response. We discuss eCBS in the context of possible biomarkers of trauma, and in preclinical psychiatric conditions, such as at-risk mental states and clinical high risk states for psychosis. Finally, we describe the role of eCBS in the cannabinoid self-medication-theory and extinction learning.