Serotonergic psychedelics have revitalized psychiatric research by producing rapid and potentially sustained clinical benefits in selected neuropsychiatric conditions. However, the mechanisms linking receptor activation to neural plasticity, altered conscious experience, and clinical improvement remain incompletely understood, while the evolutionary origins of psychedelic signaling and the...
Amphetamine-type stimulants (ATSs) disrupt the brain monoaminergic system and strongly stimulate motivation, movement, and addiction. Vesicular monoamine transporter 2 (VMAT2) plays a vital role in monoaminergic neurotransmission by sequestering monoamines in presynaptic vesicles. How ATS binds to and regulates VMAT2 remains elusive. Here, we report the cryo-EM structures of human VMAT2 in...
Abstract Precise control over the thermodynamics and kinetics of receptor–ligand interactions is pivotal for manipulating physiological processes and developing targeted therapies. However, conventional pharmacological approaches often lack the spatiotemporal precision required for noninvasive in vivo modulation. Terahertz (THz) technology offers a promising alternative by using nonionizing...
Natural hallucinogenic compounds have arisen independently across plants, fungi, and animals, evolving into a diverse chemical arsenal that includes phenethylamines, indolealkylamines, and terpenoid scaffolds. Beyond clinical and cultural frameworks, their ecological origins and evolutionary trajectories may help explain why such potent modulators of perception, emotion, and cognition persist...
Psychedelics show great promise for treating Central Nervous System (CNS) disorders but are limited by side effects like hallucinations. Molecular dynamics (MD) simulations offer atomic-level insights into receptor interactions, helping to overcome these challenges and guide the development of safer, more effective psychedelic-based therapies. This perspective reviews how MD simulations provide...
Neuropsychiatric disorders reflect disruptions in brain network dynamics along an "order-complexity-chaos" continuum. Psychedelics may therapeutically increase neural entropy, disrupt maladaptive patterns, and promote network reorganization. This system-level framework emphasizes dynamic connectome remodeling over static molecular correction, offering a novel strategy for treating psychiatric...
Yibo Wang, Xiaohui Wang; Entheogen: An Evolutionary Medicine for Neuropsychiatric Disorders, National Science Review, , nwaf168, https://doi.org/10.1093/ns
Recent advancements in the study of mushroom-derived tryptamines, particularly psilocybin and its metabolite psilocin, highlight their unique psychedelic properties and potential therapeutic applications, especially for mental health conditions like depression. This study examines how the position of the hydroxyl group on the indole ring affects the 5-HT2A receptor activity and psychedelic-like...
Psychedelics have long been recognized not only for their profound impact on human consciousness but also for their potential therapeutic applications. This perspective explores the multifaceted relationship between psychedelics and consciousness, emphasizing their capacity to alter sensory perceptions, disrupt self-referential thought processes, and catalyze profound spiritual and existential...