Psychedelic research is progressing at breakneck speed and is creating new challenges for drug developers, regulatory authorities, and legislators. Most “classic” psychedelics undergoing clinical investigation are C-I controlled drugs with perceived high potential for abuse and no medical use. These and next-generation psychedelic drug-candidates require scientific and clinical assessment of...
Clinical response and remission may not fully reflect patient priorities in treatment-resistant depression (TRD). Health-related quality-of-life (HRQoL) outcomes should be assessed to comprehensively capture treatment benefits. ESCAPE-TRD (NCT04338321) was a 32-week randomized, phase IIIb trial comparing esketamine nasal spray (NS) versus quetiapine extended release (XR), both alongside an...
MDMA, 3,4-methylenedioxymethamphetamine (“ecstasy,” “molly”), is a distinctive entactogen that reverses the serotonin (5-HT) transporter to increase synaptic 5-HT, while also engaging catecholaminergic and oxytocinergic pathways. In clinical trials, MDMA-assisted psychotherapy has yielded substantial improvements in treatment-resistant posttraumatic stress disorder (PTSD), although regulatory...
Psychiatric illness, particularly stress-related disorders including depression, anxiety and posttraumatic stress disorder, presents a considerable health burden worldwide with high prevalence, disabling symptoms, and scant efficacy of available treatments. Chronic stress is a major contributor to the origin and development of these conditions, to the detriment of both individual and, by...
A crystalline cocrystal of psilocin and psilocybin enhances exposure, neuroplasticity biomarkers, and functional activity, while adjunctive atypical antipsychotics modulate serotonergic signaling to mitigate 5-HT2B-linked safety concerns. Together, these inventions advance formulation, mechanistic selectivity, and translational biomarkersoffering a chemistry-enabled path to scalable...
Revista fisio&terapiaOctober 8, 2025Maurício Pedro Luciano da Costa, Pedro Bruschi Peiretti, Pedro Vinicius Rodrigues Silveira Silva et al.
A resurgence of scientific and clinical interest in psychedelic-assisted therapies, particularly with Psilocybin, has been observed. This paper presents an integrative literature review aiming to identify the scientific contributions, potential benefits, and limitations of the therapeutic use of psilocybin in mental health. The study followed a rigorous protocol. Searches were conducted in the...
Research SquareOctober 7, 2025Małgorzata Domżalska, Joanna Kwiatkowska, Iwona Cichoń et al.
preprint
Abstract Depression is a debilitating mental disorder affecting millions worldwide, yet current pharmacological treatments, such as selective serotonin reuptake inhibitors (SSRIs), often exhibit delayed onset and limited efficacy. The chronic social defeat (CSD) stress model in mice is a well-established preclinical paradigm for inducing depression-like behaviors and evaluating antidepressants...
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 psychotherapeutic context is associated with...
Journal of PsychopharmacologyOctober 4, 2025Michael G. Palfreyman, Geoffrey B. Varty, Erik M. Stang et al.3 citations
The last decade represented a period of unprecedented interest in, and development of, traditional psychedelic substances for the treatment of a variety of neuropsychiatric disorders. While early clinical trials of classical psychedelics, several of the major ones being tryptamines, have demonstrated robust efficacy in patients with minimal adverse effects, many of these molecules have...
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-like states in adult male and female...