Major depressive disorder (MDD) and treatment-resistant depression (TRD) are prevalent and debilitating conditions. Over 50% of patients have inadequate response to first-line serotonergic antidepressants and are left with suboptimal treatment options. Rapid-acting and individually tailored treatments for MDD remain major unmet needs. This review discusses p...
Background: Treatment-resistant depression (TRD) affects a significant proportion of individuals with major depressive disorder and remains difficult to manage with conventional treatments. Psychedelic-assisted therapies and neuromodulation have emerged as innovative interventions targeting neurobiological mechanisms beyond traditional antidepressant approac...
Major depressive disorder remains a leading cause of disability worldwide, and current antidepressants are limited by delayed onset and incomplete response. Building on advances driven by ketamine research, renewed interest has focused on classical serotonergic psychedelics-particularly psilocybin, N,N-dimethyltryptamine (DMT), 5-methoxy-DMT, and lysergic ac...
psychiatric disorders, beta-carbolines, trace amine, phosphoproteomics, social hierarchy. Scientific interest in psychedelic substances has re-emerged, offering new perspectives on the treatment of neuropsychiatric and neurological disorders.Historically, psychedelics have been associated with a wide spectrum of positive and negative effects, encompassing ri...
Psychedelic compounds, particularly psilocybin, have demonstrated remarkable therapeutic potential for mental health disorders through mechanisms involving structural neural plasticity. This comprehensive review examines recent breakthrough research revealing how psilocybin triggers activity-dependent rewiring of large-scale cortical networks. Using monosyna...
Psilocybin-assisted interventions have shown rapid reductions in depressive symptoms in controlled clinical settings, raising questions about biological mechanisms supporting durability beyond the acute drug effect. [5,7] Mechanistic accounts increasingly focus on neuroplasticity as a candidate pathway linking transient serotonergic receptor activation to lo...
Metastability of BOLD fMRI signals is a commonly used proxy of brain dynamics in behavioral and clinical studies. To date, little has been done to assess the confidence with which we can use estimates of metastability as reliable biomarkers of individual brain state. We analyze whole-brain and network-specific metastability for a highly sampled individual br...
The purpose of this study is to determine the safety and feasibility of sequencing psilocybin therapy with a short-duration, aiTBS protocol (Stanford Accelerated Intelligent Neuromodulation Therapy, or SAINT) in individuals with treatment-resistant major depressive disorder. This will be a phase II 2x2 design (device and dose) clinical trial. 100 participant...
Human neuroimaging studies report that psychedelics induce serotonin-2A receptor-dependent changes in functional brain reorganization, presumably reflecting neuromodulation. However, these studies often overlook the potent vasoactive effects of serotonin. Here we identified psilocybin-induced alterations in hemodynamic response functions during human functio...
The study hypothesis is that the antidepressant effect of psilocybin is mediated by a normalization of the functioning of the positive valence system. Depressive states, especially moderate to severe depressions that associate a certain level of anhedonia, produce an overvaluation of the cost of efforts and an infra-evaluation of the possible rewards derived...
Through its widespread reciprocal connections with the cerebral cortex, the claustrum is implicated in sleep and waking cortical network states. Yet, basic knowledge of neuromodulation in this structure is lacking. The claustrum is richly innervated by serotonergic fibers, expresses serotonin receptors, and is suggested to play a role in the ability of psilo...
Perception of visual contrast depends on the surrounding spatial context. Typically, the salience of a central target is reduced by a high contrast surrounding stimulus, an effect known as surround suppression. Although this phenomenon is well-studied, the role of specific neurotransmitter systems during surround suppression in human vision remains unclear. ...
Anhedonia is a transdiagnostic domain that leads to poor disorder outcome and low remission rates. This narrative review describes a broad range of interventions targeting anhedonia, including pharmacological, neuromodulatory, behavioral, and lifestyle-based approaches. Drugs such as vortioxetine, agomelatine, bupropion, ketamine, and brexpiprazole show prom...
Executive function deficits, common in psychiatric disorders, hinder daily activities and may be linked to diminished neural plasticity, affecting treatment and training responsiveness. In this pioneering study, we evaluated the feasibility and preliminary efficacy of psilocybin-assisted frontal-midline theta neurofeedback (NF), a neuromodulation technique l...
Psilocin, the active metabolite of psilocybin, is a psychedelic and agonist at the serotonin 2A receptor (5-HT2AR) that has shown positive therapeutic effects for brain disorders such as depression. To elucidate the brain effects of psilocybin, we directly compared the acute effects of 5-HT2AR agonist (psilocybin) and antagonist (ketanserin) on cerebral bloo...
One of the main causes of misery and incapacity is chronic pain, which is frequently linked to psychological issues. Psychedelic substances are drugs that can exert a psychological effect on patients. Psychedelic drugs like lysergic acid diethylamide (LSD) and psilocybin, exert their action mainly via activation of the serotonin-2A (5-HT2A).1 In a trial to u...
Serotonergic psychedelics have been identified as promising next-generation therapeutic agents in the treatment of mood and anxiety disorders. While their efficacy has been increasingly validated, the mechanism by which they exert a therapeutic effect is still debated. A popular theoretical account is that excessive 5-HT2a agonism disrupts cortical dynamics,...
Executive function deficits, common in psychiatric disorders, hinder daily activities and may be linked to diminished neural plasticity, affecting treatment and training responsiveness. In this pioneering study, we evaluated the feasibility and preliminary efficacy of psilocybin-assisted frontal-midline theta neurofeedback (NF), a neuromodulation technique l...
Executive function deficits, common in psychiatric disorders, hinder daily activities and may be linked to diminished neural plasticity, affecting treatment and training responsiveness. In this pioneering study, we evaluated the feasibility and preliminary efficacy of psilocybin-assisted frontal-midline theta neurofeedback (NF), a neuromodulation technique l...
Psychedelics hold therapeutic promise for mood disorders due to rapid, sustained results. Human neuroimaging studies have reported dramatic serotonin-2A receptor-(5-HT2AR)-dependent changes in functional brain reorganization that presumably reflect neuromodulation. However, the potent vasoactive effects of serotonin have been overlooked. We found psilocybin-...
