二甲基色胺的临床潜力:突破精神疾病、神经变性和意识的另一面

Frankie A. Colosimo, Philip Borsellino, Reese I. Krider, Raul E. Marquez, Thomas A Vida
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摘要

人脑是一个异常复杂的器官,负责认知和控制的各个方面。数十亿个神经元与成千上万个其他神经元形成连接,从而产生数万亿个突触,形成一个庞大而复杂的网络。这一网络不断重塑,以适应环境和发育变化。由此产生的神经可塑性对健康状态以及多种形式的精神疾病和神经变性都至关重要。这篇叙述性综述全面研究了 N,N-二甲基色胺(DMT)这种天然致幻剂和迷幻化合物,重点探讨了它通过神经元发生促进神经可塑性的意义。我们研究了 DMT 的药理学,包括它与血清素能、sigma-1 和微量胺相关受体及其相关信号通路的相互作用。我们讨论了 DMT 在动物模型和临床试验中的治疗潜力,以及对感知、认知、情感和意识的影响。我们特别关注当前的研究方向,其核心是揭示 DMT 治疗效果的直接机制,这些机制对心理健康,尤其是抑郁症、焦虑症和创伤后应激障碍等疾病具有变革性影响。我们讨论了 DMT 与神经可塑性之间的联系,这为形成新的神经连接、改善学习和记忆以及帮助脑损伤恢复(包括神经康复和神经再生)提供了可能性。我们还讨论了 DMT 在增强神经发生(尤其是神经退行性疾病)方面的最终治疗功效潜力。
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The Clinical Potential of Dimethyltryptamine: Breakthroughs into the Other Side of Mental Illness, Neurodegeneration, and Consciousness
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.
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