The article "Neurotherapeutics: Current Perspectives" by Bryan R. Barksdale, Manoj K. Doss, Gregory A. Fonzo, and Charles B. Nemeroff explores the potential of psychedelics as novel therapeutics for various conditions, particularly severe and treatment-resistant psychiatric disorders. The authors review the current understanding of how psychedelics produce profound alterations in consciousness, focusing on receptor binding and downstream cellular and transcriptional pathways. They highlight the long-term impacts of these compounds on brain structure and function, from single neurons to large-scale circuits. The article discusses the mechanisms of psychedelic action, emphasizing the role of 5-HT2A receptors, which are primarily responsible for the subjective effects of psychedelics. It also addresses the ongoing controversy surrounding the necessity of the "psychedelic experience" for therapeutic effects, comparing the psychoplastogen model (cellular level) with the behavioral catalyst model (psychological/behavioral level). The authors argue that bridging the gap between these levels of inquiry through innovative methods and collaborative efforts is crucial for fully capitalizing on the therapeutic properties of psychedelics. Key findings include the enhancement of neuronal excitability, increased glutamate release, and the activation of neurotrophic factors like BDNF. These changes lead to structural alterations in neural plasticity, such as enhanced synaptogenesis and dendritic growth. Neuroimaging studies have shown inconsistent acute effects on brain activity and connectivity, with some studies indicating decreased connectivity within canonical brain networks and increased connectivity between networks. The article concludes by emphasizing the need for multidisciplinary collaborations to bridge the gap between molecular, cellular, neural circuit, and psychological/behavioral levels of inquiry. This comprehensive understanding is essential for developing effective treatments and further exploring the therapeutic potential of psychedelics.The article "Neurotherapeutics: Current Perspectives" by Bryan R. Barksdale, Manoj K. Doss, Gregory A. Fonzo, and Charles B. Nemeroff explores the potential of psychedelics as novel therapeutics for various conditions, particularly severe and treatment-resistant psychiatric disorders. The authors review the current understanding of how psychedelics produce profound alterations in consciousness, focusing on receptor binding and downstream cellular and transcriptional pathways. They highlight the long-term impacts of these compounds on brain structure and function, from single neurons to large-scale circuits. The article discusses the mechanisms of psychedelic action, emphasizing the role of 5-HT2A receptors, which are primarily responsible for the subjective effects of psychedelics. It also addresses the ongoing controversy surrounding the necessity of the "psychedelic experience" for therapeutic effects, comparing the psychoplastogen model (cellular level) with the behavioral catalyst model (psychological/behavioral level). The authors argue that bridging the gap between these levels of inquiry through innovative methods and collaborative efforts is crucial for fully capitalizing on the therapeutic properties of psychedelics. Key findings include the enhancement of neuronal excitability, increased glutamate release, and the activation of neurotrophic factors like BDNF. These changes lead to structural alterations in neural plasticity, such as enhanced synaptogenesis and dendritic growth. Neuroimaging studies have shown inconsistent acute effects on brain activity and connectivity, with some studies indicating decreased connectivity within canonical brain networks and increased connectivity between networks. The article concludes by emphasizing the need for multidisciplinary collaborations to bridge the gap between molecular, cellular, neural circuit, and psychological/behavioral levels of inquiry. This comprehensive understanding is essential for developing effective treatments and further exploring the therapeutic potential of psychedelics.