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Psychedelics and ketamine/esketamine in depressive disorders: biological mechanisms and associated neuroimaging and clinical changes.
BackgroundOver the past ten years, several psychedelic compounds, including tryptamines like lysergic acid diethylamide/LSD, psilocybin, ayahuasca, and dimethyltryptamine/DMT, have been tested in clinical trials for a range of psychiatric conditions, such as anxiety and depression. While these compounds are relatively available for treatment, ketamine and it...
Neurobiological and Therapeutic Potential of Psilocybin in Psychiatric Disorders
Psilocybin, an indoleamine alkaloid derived from various fungal species, is the subject of renewed, rigorous investigation for its therapeutic potential in psychiatry. This compound, a prodrug for the active metabolite psilocin, functions primarily as a partial agonist at the serotonin 2A (5-HT2A) receptor. Its administration within a structured psychotherap...
Single-dose psilocybin rapidly and sustainably relieves allodynia and anxiodepressive-like behaviors in mouse models of chronic pain
Chronic pain and mood disorders co-occur, exacerbate one another and share neurobiological mechanisms, but whether a single intervention could promptly alleviate both conditions remains unclear. Here, in two chronic pain models, we show that a single dose of psilocybin induces a rapid and sustained reversal of both mechanical allodynia and anxiodepression-li...
Temporal dynamics in neuroimaging as correlates of therapeutic response to psilocybin in major depressive disorder: A systematic review and critical appraisal.
BackgroundPsychedelics are emerging as promising treatments for major depressive disorder (MDD) and treatment-resistant depression (TRD). Functional magnetic resonance imaging (fMRI) offers a powerful tool to study neural mechanisms underlying therapeutic response.MethodsThis systematic review (PROSPERO #CRD42024557973) examined neuroimaging studies of psilo...
Evaluation of the Effect of a Single Dose of Psilocybin on Neural Correlates of Cognitive Control in Patients With Psychogenic Nonepileptic Seizures
Psychogenic non-epileptic seizures (PNES) are functional paroxysmal motor disorders that may be clinically suggestive of epilepsy but are not associated with the electroencephysiological and electroencephalographic changes of epilepsy. Thus, hyper-connectivity of the regions of the default mode network (DMN) linked to executive control could be involved in t...
Psilocybin triggers an activity-dependent rewiring of large-scale cortical networks
SUMMARY Psilocybin holds promise as a treatment for mental illnesses. One dose of psilocybin induces structural remodeling of dendritic spines in the medial frontal cortex in mice. The dendritic spines would be innervated by presynaptic neurons, but the sources of these inputs have not been identified. Here, using monosynaptic rabies tracing, we map the brai...
Accurate and Interpretable Prediction of Antidepressant Treatment Response from Receptor-informed Neuroimaging
Conventional antidepressants show moderate efficacy in treating major depressive disorder. Psychedelic-assisted therapy holds promise, yet individual responses vary, underscoring the need for predictive tools to guide treatment selection. Here, we present graphTRIP (graph-based Treatment Response Interpretability and Prediction) - a geometric deep learning a...
What fMRI studies say about the nature of the psychedelic effect: a scoping review.
Research on psychedelic drugs, such as psilocybin, LSD or DMT, is a burgeoning field, with an increasing number of studies showing their promise in treatment of mental disorders as well as examining their mechanism of action. Determining their effect on the brain is crucial from clinical standpoint, but also offers highly promising avenues of advancement in ...
Neurocognitive effects of psilocybin: A systematic and comprehensive review of neuroimaging studies in humans.
Psilocybin is a psychedelic serotonergic compound that is renowned for its potent psychoactive effects. Over the past 15 years, an increasing number of controlled clinical trials showed that it has a fast-acting and sustainable efficacy in treating various psychiatric disorders. Neuroimaging studies have been conducted with the objective of elucidating the n...
Exploring the Role of Psychedelics in Modulating Ego and Treating Neuropsychiatric 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 disor...
PSYCHEDELIC PHARMACOLOGY IN PSYCHIATRY: THE MECHANISMS AND THERAPEUTIC POTENTIAL OF PSILOCYBIN, MDMA, AND LSD IN MENTAL HEALTH DISORDERS
Psilocybin, MDMA, and LSD have recently emerged as popular psychedelic substances for use in psychopharmacology in managing various disorders including treatment-resistant depression, PTSD, and anxiety. These substances mainly affect the serotonergic receptors that involve the regulation of consciousness, perceptions, and cognition. These unique alterations ...
Revealing Changes in Linear and Nonlinear Functional Connectivity After Psilocybin and Escitalopram Treatment in Patients with Depression
Major Depressive Disorder (MDD) is typically characterized by altered linear functional connectivity (FC) across large-scale brain networks. Yet, it is unclear whether similar alterations are observed when nonlinear FC is examined. This study investigated how antidepressant treatment (i.e., psilocybin and escitalopram) modulates both linear FC and nonlinear ...
Psychedelic-assisted Therapy as a Promising Treatment for Irritable Bowel Syndrome.
Irritable bowel syndrome (IBS) is prevalent and can be disabling. Many patients remain symptomatic despite behavioral and medical therapies. Psychedelic-assisted therapy (PAT), in which serotonergic agents like psilocybin are administered in a psychotherapeutic context, has shown promise for refractory psychiatric disorders, including major depressive disord...
Mushrooms, Microdosing, and Mental Illness: The Effect of Psilocybin on Neurotransmitters, Neuroinflammation, and Neuroplasticity.
The incidence of mental health disorders is increasing worldwide. While there are multiple factors contributing to this problem, neuroinflammation underlies a significant subset of psychiatric conditions, particularly major depressive and anxiety disorders. Anti-inflammatory interventions have demonstrated benefit in these conditions. Psilocin, the active in...
Catalyst for change: Psilocybin's antidepressant mechanisms-A systematic review.
BackgroundRecent clinical trials suggest promising antidepressant effects of psilocybin, despite methodological challenges. While various studies have investigated distinct mechanisms and proposed theoretical opinions, a comprehensive understanding of psilocybin's neurobiological and psychological antidepressant mechanisms is lacking.AimsSystematically revie...
Uncovering Psychedelics: From Neural Circuits to Therapeutic Applications.
Psychedelics, historically celebrated for their cultural and spiritual significance, have emerged as potential breakthrough therapeutic agents due to their profound effects on consciousness, emotional processing, mood, and neural plasticity. This review explores the mechanisms underlying psychedelics' effects, focusing on their ability to modulate brain conn...
Single-dose psilocybin alters resting state functional networks in patients with body dysmorphic disorder
Body dysmorphic disorder (BDD) is a severe psychiatric condition characterized by preoccupation with perceived flaws in one's appearance, which the individual views as defective or ugly. Psilocybin, a serotonin 2A receptor agonist with psychedelic properties, has emerged as a potential therapeutic agent for depression and other psychiatric disorders. This st...
CCNP Innovations in Neuropsychopharmacology Award: The psychopharmacology of psychedelics: where the brain meets spirituality.
For 3000 years, psychedelics have been used in religious contexts to enhance spiritual thinking, well-being, and a sense of community. In the last few years, a renaissance in the use of psychedelic drugs for mental disorders has occurred in Western society; consequently, a pressing scientific need to elucidate the intricate mechanisms underlying their action...
Psilocybin alters brain activity related to sensory and cognitive processing in a time-dependent manner
Psilocybin is a classic psychedelic and a novel treatment for mood disorders. Psilocybin induces dose-dependent transient (4-6 hours) usually pleasant changes in perception, cognition, and emotion by non-selectively agonizing the 5-HT2A receptors and negatively regulating serotonin reuptake, and long-term positive antidepressant effect on mood and well-being...