Eva Gallacher, Maria Arnold, Uwe Herwig et al.
preprint
Background: The role, necessity, and relevance of psychotherapy within psychedelic-assisted therapy (PAT) remain contested: some view it principally as safety support, whereas others regard it as essential to safety and efficacy. Patient-centred evidence on how psychotherapy is experienced within real-world PAT is scarce. We examined how patients understood the role of psychotherapy in their...
Devon Christie, Manesh Girn
preprint
Psychedelic-assisted therapy (PAT) has demonstrated transdiagnostic efficacy across a range of psychiatric conditions and is increasingly conceptualized through third-wave cognitive–behavioral frameworks. These frameworks, including Contextual Behavioral Science (CBS) and the psychological flexibility model, emphasize processes such as cognitive insight, belief revision, and narrative...
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...
Amanda E. Downey, Ellen Bradley, Daniel Dickison et al.
preprint
Psychedelic-assisted psychotherapy is generating substantial clinical interest, yet despite growing economic scrutiny, a practical question has received surprisingly little attention: how do specific delivery decisions drive cost? Labor costs—typically the dominant cost component of psychedelic therapy delivery—depend on a tangle of interacting design choices: the number, length, and staffing...
Michael Alvear
preprint
Patients undergoing ketamine-or psychedelic-assisted therapy for cancer-related distress, treatment-resistant depression, or end-of-life existential fear frequently report experiences resembling death or near-death: a sense of leaving the body, encountering something transcendent, or having died and returned. This synthesis reviews peer-reviewed evidence on how often this occurs, why it may...
Vincent Joralemon
preprint
As psychedelic-assisted therapies advance through the FDA approval pipeline, the question of who will pay for them is moving from academic to urgent. Experts project that MDMA-assisted therapy for PTSD will cost upwards of $11,000-$12,000 per course of treatment-a price tag that, absent insurance, places these therapies out of reach for many of the patients most likely to benefit. This essay...
Mark A. Michaels
preprint
This client-authored, autoethnographic case study documents a 10-week course of collaborative therapy integrating EMDR, ketamine, MDMA, psilocybin, creative expression, and AI-assisted reflection and writing. Drawing on affect theory, mentalization, earned secure attachment, and Dabrowski's theory of positive disintegration, the paper analyzes how recognition of core affects, rupture-and-repair...
Michael Palmieri
preprint
Psychedelic-assisted therapy is advancing rapidly toward clinical legitimacy in the United States. The Food and Drug Administration has granted Breakthrough Therapy designations to psilocybin and MDMA, several states have established regulated access frameworks, and major research institutions have invested hundreds of millions of dollars in psychedelic science. Yet the legal infrastructure...
Michael Palmieri
preprint
American informed consent doctrine rests on an unexamined premise: the stable-agent assumption—that the patient who authorizes a medical intervention and the patient who experiences its consequences share a continuous evaluative framework. Materiality doctrine presupposes this continuity; causation doctrine embeds it; capacity doctrine assumes it. For most of modern medical practice, the...
Viviana D. Evans, Alejandro Arenas, Kenneth Shinozuka et al.
preprint
Background: Ketamine, an arylcyclohexylamine dissociative anesthetic agent, has evolved into a versatile therapeutic. It has a rapid onset, well-understood cardiovascular effects, and a favorable safety profile in clinical use. Its enantiomeric compound, esketamine, was approved by the FDA in 2019 for both treatment-resistant depression as well as major depressive disorder (MDD) with suicidal...