Effects of N, N-Dimethyltryptamine on the phenotype and diathesis of a mice model of depression

Abstract

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. 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 work, I induced depression in mice using the Unpredictable Chronic Mild Stress model, applied a single dose of DMT and mitigated depression-like symptoms, anhedonia and anxiety-like behavior, with remarkable efficiency, once it surpassed even the treatment with a classical antidepressant. Our data suggests that DMT is a valuable tool for psychiatry, and the subjective experience can help professionals to have more control over the outcome, as we provide data that points to the importance of considering the set and setting for a positive endpoint.