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Objective:
This study aims to provide an overview of pharmacological trials that examine the neurocognitive effects of psychedelics among healthy individuals and patients with post-traumatic stress disorder (PTSD) or major depressive disorder (MDD).
Methods:
The Preferred Reporting Items for Systematic Reviews (PRISMA) was used as a guide to str...
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Citations
Mental disorders are a representative type of brain disorder, including anxiety, major depressive depression (MDD), and autism spectrum disorder (ASD), that are caused by multiple etiologies, including genetic heterogeneity, epigenetic dysregulation, and aberrant morphological and biochemical conditions. Psychedelic drugs such as psilocybin and lysergic acid diethylamide (LSD) have been renewed as fascinating treatment options and have gradually demonstrated potential therapeutic effects in mental disorders. However, the multifaceted conditions of psychiatric disorders resulting from individuality, complex genetic interplay, and intricate neural circuits impact the systemic pharmacology of psychedelics, which disturbs the integration of mechanisms that may result in dissimilar medicinal efficiency. The precise prescription of psychedelic drugs remains unclear, and advanced approaches are needed to optimize drug development. Here, recent studies demonstrating the diverse pharmacological effects of psychedelics in mental disorders are reviewed, and emerging perspectives on structural function, the microbiota‐gut‐brain axis, and the transcriptome are discussed. Moreover, the applicability of deep learning is highlighted for the development of drugs on the basis of big data. These approaches may provide insight into pharmacological mechanisms and interindividual factors to enhance drug discovery and development for advanced precision medicine.
Major Depressive Disorder (MDD) is a complex, heterogeneous condition affecting millions worldwide. Computational neuropsychiatry offers potential breakthroughs through the mechanistic modeling of this disorder. Using the Kolmogorov theory (KT) of consciousness, we developed a foundational model where algorithmic agents interact with the world to maximize an Objective Function evaluating affective valence. Depression, defined in this context by a state of persistently low valence, may arise from various factors—including inaccurate world models (cognitive biases), a dysfunctional Objective Function (anhedonia, anxiety), deficient planning (executive deficits), or unfavorable environments. Integrating algorithmic, dynamical systems, and neurobiological concepts, we map the agent model to brain circuits and functional networks, framing potential etiological routes and linking with depression biotypes. Finally, we explore how brain stimulation, psychotherapy, and plasticity-enhancing compounds such as psychedelics can synergistically repair neural circuits and optimize therapies using personalized computational models.
