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...
The integration of psychedelics and music in therapeutic settings is gaining recognition for its potential to enhance mental health outcomes. This review synthesizes current evidence on the neurobiological mechanisms underlying this synergy, focusing on receptor-level pathways (e.g., 5-HT2A receptor agonism, BDNF-TrkB signaling) and neural circuit dynamics (e.g., default mode network...
Psychedelics are undergoing a renaissance as potential therapy for psychiatric disorders, with more than 200 clinical trials being studied across several countries1-3. However, the precise mechanisms by which these drugs bring about benefits and the potential clinical risks are not yet fully understood. The serotonin 2A receptor (5-HT2AR) was reported to be a Gq-coupled receptor and the primary...
Psychedelics, particularly psilocybin, have garnered significant attention as potential therapeutic tools for treating substance use disorders (SUDs), such as those related to alcohol, nicotine, heroin (an opioid), or cocaine. Traditional treatments often fall short, leading to high relapse rates and an urgent need for innovative approaches. This article explores the emerging role of...
Ketamine and electroconvulsive therapy (ECT) achieve rapid remission in treatment-resistant depression. However, their mechanisms of action—the understanding of which is essential for refining therapeutic precision—remain unclear1, 2–3. Here, using mouse models, we identify adenosine signalling as a central pathway that underlies the antidepressant effects of these interventions. Results from...
This viewpoint reconceptualizes mysticism and fundamentalism as brain network disorders, with psychedelics like psilocybin, lysergic acid diethylamide, and N,N-dimethyltryptamine offering potential to modulate these states. By disrupting rigid neural patterns, psychedelics may foster cognitive flexibility, challenge inflexible belief systems, and offer therapeutic value for extremism and mental...
The interplay between psychedelics, such as psilocybin, lysergic acid diethylamide (LSD) and dimethyltryptamine (DMT), and sleep is an emerging area, but their impact on sleep remains relatively underexplored. This viewpoint provides a perspective on how psychedelics may alter sleep phases, dreaming, and their potential therapeutic applications for sleep disorders.
This viewpoint explores the therapeutic potential of psychedelics in treating neuropsychiatric disorders, particularly through the modulation of brain entropy and the experience of ego dissolution. Psychedelics disrupt rigid neural patterns, facilitating enhanced connectivity and fostering profound emotional breakthroughs that may alleviate symptoms of disorders like depression, anxiety, PTSD,...
The surge of new psychoactive substances (NPS) poses significant public health challenges due to their unregulated status and diverse effects. However, existing in vivo models for evaluating their activities are limited. To address this gap, this study utilizes the model organism Caenorhabditis elegans (C. elegans) to evaluate the activity of amphetamine-type stimulants (ATS) and their analogs....
Depression, a pervasive mental health condition, has increasingly been linked to neuroinflammation, as evidenced by elevated levels of pro-inflammatory markers such as TNF-α and IL-1β observed in patients, which underscores the role of inflammation in its pathophysiology. This study investigates the differential effects of S-ketamine (S-KET) and R-ketamine (R-KET) on inflammation-induced...
Anorexia nervosa (AN) is a severe psychiatric disorder characterized by extreme food restriction, an intense fear of weight gain, and a distorted body image, leading to significant morbidity and mortality. Conventional treatments such as cognitive-behavioral therapy (CBT) and pharmacotherapy often prove inadequate, especially in severe cases, highlighting the need for novel therapeutic...
Psychedelics, known for their therapeutic potential in psychiatric disorders, interact with the autonomic nervous system in ways that are not well understood. This viewpoint examines the complex relationships between psychedelics and autonomic functions, focusing on sympathetic and parasympathetic modulation. We propose a research framework to elucidate how these interactions influence...
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...