Effects of N,N-Dimethyltryptamine on the Phenotype and Diathesis of Depression: A Laboratory Longitudinal Study using C57BL6 Mice
DMT, Neurogenesis, Depression, DCX.
Depression is a neurological disorder that affected 4.4% of the global population in 2017. It is characterized by apathy and anhedonia, which significantly impact the social and professional life of those afflicted. The etiology of depression has not been fully elucidated, although genetic, humoral, environmental, and behavioral factors have been correlated with its development. The conventional treatment typically involves slow-acting serotonergic drugs that often have side effects more detrimental to the clinical condition than the symptoms themselves. In the past two decades, the Neurogenic Hypothesis of Depression has linked the production of new neurons in the adult hippocampus to the neurobiological mechanism essential for alleviating symptoms by classical antidepressants. Concurrently, psychedelic drugs have reemerged as a category of molecules capable of enhancing neuronal plasticity. Unfortunately, the hallucinogenic properties of these compounds, despite their clinical utility, have hindered their widespread assimilation. At this stage of psychedelic research, it is necessary to understand the involvement of the subjective experience, the psychedelic experience, in the therapeutic potential of these compounds. This understanding will enable us to focus on delineating more effective, accessible, and comprehensive ways of applying these compounds to populations. In this study, we induced depression in mice using the Unpredictable Chronic Mild Stress model. We evaluated how a single dose of the psychedelic N,N-Dimethyltryptamine (DMT) affects the symptoms and humoral biomarkers of depression. Additionally, we examined whether being conscious during the hallucinogenic phase is necessary for DMT to exert its neurotrophic effect by administering the drug to anesthetized animals.