Jesús Isaac Castillo-Sánchez
preprint
Abstract The COMP006 Phase 3 trial showed that 39% of patients with treatment-resistant depression (TRD) respond to a single 25 mg dose of psilocybin, while 61% do not — at identical dose, protocol, and pharmacological exposure. No mechanistic explanation for this heterogeneity has been established. Here we propose and validate a two-threshold model in which the psilocybin dose-response...
Gabriel P. A. Costa, Christina Riggione, Christopher Pittenger et al.
Supervised psilocybin services are expanding across the United States, yet how individuals accessing these programs compare with those using psilocybin in the general population is unknown. We conducted a cross-sectional descriptive comparison of Oregon Psilocybin Services (OPS) data from licensed service centers in 2025 (5,935 encounters) and the 2024 National Survey on Drug Use and Health...
Juan Sebastián Gómez-Cañón, Carly Leininger, Danielle Mayall et al.
preprint
Abstract Music plays a central role in psilocybin therapy (PT), where playlists are designed to be supportive and stimulating over a 4–6-hour psychedelic experience. The primary design principle underlying PT music programming is that music should be affectively aligned with the onset–peak–return model of pharmacodynamic action. However, in the absence of clear acoustic criteria, this framework...
Ziming Li, Crystal Weber, Francesca Sellitti et al.
Abstract A single dose of psilocybin can induce long-lasting antidepressant effects. The neurobiological mechanisms underlying such sustained antidepressant effect remain insufficiently understood, particularly at the level of synaptic function and drug-target specificity. Here, we aimed to delineate single-dose psilocybin-induced excitatory synaptic plasticity. Synaptic plasticity was assessed...
Michael Sarvi, Aryan Sarparast
preprint
Abstract Background State-regulated psilocybin services have expanded access outside research settings. Patients seeking these services may have medical and psychiatric complexity not represented in clinical trials, while guidance for clinicians advising them remains limited. We introduce the Psilocybin Education and Assessment Collaborative for Excellence (PEACE), a consultation model within a...
Sixtine Fleury, Luke J. Chang, Katherine M. Nautiyal
ABSTRACT Psychedelic drugs offer a potentially promising avenue for novel therapeutics for the treatment of psychiatric conditions, including for mood and anxiety disorders. Emerging clinical studies have prompted increased preclinical research into mechanisms of action. However, post-acute behavioral outcomes in rodents remain inconsistent and difficult to reproduce across laboratories. To...
Poonam Bhadoria, Manish Kumar Tripathi, Ramanathan Venkatnarayan
preprint
Conformational space of the psychedelic molecule psilocybin was explored. A global minimum was identified and among the several local minima, of the conformers matched with the earlier reported literature. The difference in energy between these two conformers is 9.275 kcal/mol and the rotational barrier is 17.620 kcal/mol. Further properties of these conformers were investigated using FMO, AIM,...
Çağrı Özkurt
preprint
A recent living systematic review in Nature Mental Health found psilocybin reduced depression symptoms across 12 randomized controlled trials, with pooled effect g = 0.90. The original analysis assessed publication bias using Egger’s test, non-significant — but this test has limited power with few studies and cannot produce a bias-corrected estimate. We re-analysed the same open dataset using...
Edward S. Adams
preprint
This Article explores the regulation of the cannabis industry, highlighting its origins, history, and shortcomings. The Article then compares the cannabis and psilocybin industries, arguing against the replication of the cannabis regulatory structure for psilocybin. Instead, this Article will propose tailored regulatory solutions designed to address the unique characteristics of psilocybin and...
Christopher P. Albertyn, Jérémie Richard, Ron Joseph Shore et al.
preprint
Demoralization syndrome (DS) - a distinct clinical entity characterized by helplessness, hopelessness, and a persistent loss of meaning - affects approximately one in five Canadians with advanced cancer and is associated with increased desire for hastened death, negative clinical outcomes, and higher economic burden, yet recognition and treatment of DS remains suboptimal in modern oncology....