Abstract

5-Methoxy-N,N-dimethyltryptamine (acronymized as 5-MeO-DMT) is sui generis among the numerous naturally occurring psychoactive substances due to its unparalleled ego-dissolving effects which can culminate in a state of nondual consciousness that is phenomenologically similar to transformative peak experiences described in various ancient contemplative traditions (e.g., Advaita Vedānta, Mahāyāna Buddhism, inter alia). The enigmatic molecule is endogenous to the human brain and has profound psychological effects which are hitherto only very poorly understood due to the absence of scientifically controlled human experimental trials. Its exact neuronal receptor binding profile is a matter of ongoing research; however, empirical evidence indicates that its remarkable psychoactivity is partially mediated via agonism of the 5-HT1A/2A (serotonin) receptor subtypes. Anthropological/ethnopharmacological evidence indicates that various cultures utilized 5-MeO-DMT containing plants for medicinal, psychological, and spiritual purposes for millennia. We propose that this naturally occurring serotonergic compound could be fruitfully utilized as a neurochemical research tool with the potential to significantly advance our understanding of the psychological and neuronal processes which underpin cognition and creativity (e.g., downregulation of the default mode network, increased global functional connectivity, neuroplasticity, σ1 receptor interactions, etc.). An eclectic interdisciplinary perspective is adopted, and we present converging evidence from a plurality of sources in support of our conjecture. Specifically, we argue that 5-MeO-DMT has significant neuropsychopharmacological potential due to its incommensurable capacity to completely disintegrate self-referential cognitive/neuronal processes (viz., ego death). The importance of unbiased systematic scientific research on naturally occurring endogenous psychoactive compounds is discussed from a Jamesian radical empiricism perspective, and potential scenarios of abuse are addressed, particularly in the context of neuroethics, cybernetic manipulation, and military research on torture.

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