This paper follows 8 scientists who ventured into the world of psychedelics on a quest to find transformational pathways forward. Each have worked on aspects of global environmental change for decades, and observing environmental crises converging into a global polycrisis/metacrisis with genuine potential for collapse, we have all carried psychological burdens, including fatigue, anxiety,...
Abstract Psilocybin, a serotonergic psychedelic, can produce rapid and enduring antidepressant effects in patients with major depressive disorder (MDD)[1, 2], yet the neural mechanisms underlying these effects remain unclear. Negative affective biases are an important neuropsychological mechanism central to the development and perpetuation of MDD[3]. Using a translational rodent model, we...
To support ongoing clinical trials, the major human metabolites of psilocybin were synthesized on a preparative scale, specifically psilocin-O-glucuronide and 4-hydroxyindole-3-acetic acid (4-HIAA), along with putative minor metabolites and several deuterium-labeled derivatives. Psilocybin, psilocin, psilocin-O-glucuronide, and 4-HIAA were assayed for engagement at seven serotonin receptor...
Background: Psilocybin-assisted psychotherapy (PAP) may be an effective intervention for a range of mental disorders. However, there appears to be a relative lack of qualitative evidence to complement emerging quantitative findings. To our knowledge, no reviews have systematically mapped the literature on qualitative studies on PAP for the treatment of mental disorders with the intent to...
BACKGROUND: Treatment-resistant depression (TRD) imposes a substantial public health and economic burden. Although psilocybin-assisted therapy (PAT) has shown clinical promise, its economic value remains uncertain. This study evaluated the cost-effectiveness of PAT compared with the standard of care for TRD. METHODS: A Markov model adopting a US healthcare perspective simulated patient...
Psilocybin is an emerging investigational compound with therapeutic potential in neuropsychiatric disorders, creating a need for flexible and scalable dosage forms suitable for early clinical development. This study aimed to develop and evaluate psilocybin-loaded oral thin film (OTF) formulations as a dose-proportional platform for early-phase clinical use. OTFs were prepared using a solvent...
Intestinal inflammation is a complex gastrointestinal condition, arising from immune dysfunction, epithelial cell abnormalities, and gut microbiota imbalances. Intestinal inflammation contributes to many pathological conditions, including irritable bowel disease and depression. This study seeks to find the potential anti-inflammatory properties of psilocybin and eugenol in systemic intestinal...
Psychedelics have emerged as potential therapeutics for substance use disorders, yet preclinical data validating their efficacy remain limited. Here, we investigated the effects of a clinically inspired dose-escalation protocol of psilocybin and ibogaine on extinction and cue-induced reinstatement in Wistar male rats following intravenous cocaine self-administration (IVSA). Rats were trained on...
Background: Major depressive disorder (MDD) is a highly prevalent and disabling psychiatric condition associated with substantial clinical, social, and economic burden [1,2]. Despite the availability of conventional antidepressants, their limited effectiveness, delayed onset of action, and high relapse rates have renewed interest in innovative therapeutic approaches [3,4,5]. Psilocybin-assisted...
Psilocybin, a classic psychedelic compound, has garnered renewed interest as a potential treatment for various psychiatric disorders. This review provides a comprehensive overview of psilocybin's history, recent clinical evidence, ongoing clinical trials, neuroimaging findings, and regulations. Historically used in spiritual and healing rituals, psilocybin was in the early 1970s subjected to...