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The human brain is an extraordinarily complex organ responsible for all aspects of cognition and control. Billions of neurons form connections with thousands of other neurons, resulting in trillions of synapses that create a vast and intricate network. This network is subjected to continuous remodeling that adapts to environmental and developmental changes. The resulting neuroplasticity is crucial to both healthy states and many forms of mental illness and neurodegeneration. This narrative review comprehensively examines N,N-dimethyltryptamine (DMT), a naturally occurring hallucinogen and psychedelic compound, focusing on its implications in promoting neuroplasticity via neuritogenesis. We examine DMT’s pharmacology, including its interaction with serotonergic, sigma-1, and trace amine-associated receptors and their associated signaling pathways. The therapeutic potential of DMT in both animal models and clinical trials is discussed with impacts on perception, cognition, emotion, and consciousness. We uniquely focus on current directions centered on unveiling the direct mechanisms of DMT’s therapeutic effects that demonstrate transformative effects on mental well-being, particularly for conditions like depression, anxiety, and post-traumatic stress disorder. We discuss the connection between DMT and neuroplasticity, offering the potential for forming new neural connections, improving learning, memory, and aiding recovery from brain injuries, including neurorehabilitation and neuroregeneration. The ultimate potential of DMT’s therapeutic efficacy to enhance neurogenesis, especially for neurodegenerative conditions, is also discussed.
Colosimo et al. (Mon,) studied this question.