Memory encoding depends on the joint convergence of substrate readiness, internal drive, environmental input, and a permissive temporal-physiological state. The same logic recurs across vertebrate learning systems: hippocampal-dependent spatial and schema-modulated memory (the Navigia substrate in the Systema Behavorum taxonomy), filial imprinting in the chi...
Introduction This computational modeling study introduces a novel Explainable Artificial Intelligence (XAI) framework for optimizing single-dose psilocybin treatment protocols through personalized intervention modeling using publicly available mental health datasets. All results presented are derived from novel simulated data and predictive modeling only, no...
Abstract Large language models (LLMs) are increasingly consulted by individuals for support during psychedelic experiences ("trip sitting"), yet no framework exists to evaluate whether these models can accurately simulate or safely respond to altered states of consciousness. We aimed to determine if LLMs can be induced to generate narratives resembling human...
Psychedelics are a group of substances within the heterogeneous class of hallucinogenic drugs. Via binding to the serotonin (5-HT) 2A receptor, psychedelics exert profound alterations in various mental domains, including sensation, cognition, emotions, and self-perception. Psychedelics comprise phenethylamines (e.g., mescaline), tryptamines (e.g., psilocybin...
Humphry Osmond coined the term ‘psychedelic’ in 1956, conjoining ‘psyche’ for ‘soul’ and ‘delic’ from ‘dêlos’ for ‘to manifest’ or ‘illuminate.’ Soul-illumination is an adjective that describes a psychological state or process. However, Osmond’s intention was to use the adjective to name- not just a state- but a category of drug that can induce the subjectiv...
Serotonergic psychedelics, such as LSD, psilocybin, and DMT, have strong effects on human brain activity, yet their mechanisms of action at the whole-brain level are only partially understood. Here, we present a biophysically-based mean-field model that integrates cellular and network-level details to simulate the effects of these compounds at different spat...
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...
BACKGROUND: Psychedelic treatment is a rapidly emerging therapeutic approach for a host of chronic, difficult to treat psychiatric disorders, including anorexia nervosa (AN). Trauma and its sequelae, such as dissociation, often contribute to comorbidity and treatment refractoriness. AIMS: In this report, we describe the therapeutic emergence of previously di...
Ketamine and its enantiomers, esketamine and arketamine, have emerged as promising treatments for treatment-resistant depression (TRD). This cross-sectional study evaluates the regulatory alignment of 40 clinical trials listed on ClinicalTrials.gov, focusing on the methodological challenges. The study highlights methodological inconsistencies, particularly a...
Background: Functional neurological disorder (FND) is a common cause of neurological symptoms including seizures and movement disorders. It can be debilitating, is associated with high health and social care costs, and can have a poor prognosis. Functional magnetic resonance imaging (fMRI) has suggested FND is a multi-network disorder. Converging evidence su...
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 r...
There is some evidence that the subjective effects of ketamine and other psychedelics like psilocybin are crucial for their therapeutic outcomes, such as treatment of depression or substance use disorder (SUD). We performed a meta-analysis and systematic review on the correlation of subjective symptoms and dissociation versus ketamine-induced therapeutic out...
Protonation is the most frequent adduct found in positive electrospray ionization collision-induced mass spectra (CID-MS/MS). In a parallel report Lee, J. J. Chem. Inf. Model. 2024, 10.1021/acs.jcim.4c00760, we developed a quantum chemistry framework to predict mass spectra by collision-induced dissociation molecular dynamics (CIDMD). As different protonatio...
Threatening events and stressful experiences can lead to maladaptive memories and related behaviors. Existing treatments often fail to address these issues linked to anxiety/stress-related disorders effectively. This review identifies dose ranges associated with specific actions across various psychedelics. We examined psilocybin/psilocin, lysergic acid diet...
Background: Functional neurological disorder (FND) is a common cause of neurological symptoms including paralysis, seizures, and movement disorders. It is often debilitating, is associated with high health and social care costs, and can have a poor prognosis. Functional magnetic resonance imaging (fMRI) has suggested FND is a multi-network disorder; the defa...
BackgroundInadequate outcomes with monoamine-based treatments in depressive disorders are common and provide the impetus for mechanistically-novel treatments. Esketamine is a proven treatment recently approved for adults with Treatment-Resistant Depression (TRD) while psilocybin is an investigational treatment. Translation of the clinical meaningfulness for ...
Borderline personality disorder (BPD) and post-traumatic stress disorder (PTSD) share overlapping neurobiological mechanisms particularly reward deficiency and stress-like anti-reward processes. And so, BPD may be reclassified as a "traumatic personality stress disorder" (TPSD) with ensuing common therapeutic strategies that may stabilize dopaminergic reward...
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-...
