medRxiv
July 19, 2026
Naama Levy‐Cooperman, Edward M. Sellers, Paul Glue et al.
Low doses of psilocybin (0.5 to 4.0 mg) produce perceptible pharmacological effects without causing hallucinations, cognitive impairment, or increased anxiety. In a Phase 1 randomized, double-blind, placebo-controlled trial, 56 healthy adults received a single oral dose of psilocybin or placebo. No serious adverse events occurred; side effects were comparable to placebo, mainly somnolence. Psilocin appeared rapidly in the blood with dose-proportional exposure and a short half-life. Subjective drug effects were dose-related and distinguishable from placebo at or below 2.5 mg, but hallucination and altered-states scores remained low and not different from placebo.
Zenodo (CERN European Organization for Nuclear Research)
July 17, 2026
Bartosz Niciński, Magdalena Kloc, Ewa Wiench, Natasza Millan, Aleksandra Blicharz, Wojciech Kozdraś, Lidia Kozaczko, Gabriela Szewczyk, Elżbieta Bukowczan, Alicja Zając, Damian Broda, Alicja Benecka
Major depressive disorder is a common and burdensome condition, and many patients do not fully recover after standard antidepressant treatment, prompting interest in rapid-acting interventions that target brain pathways beyond serotonin, norepinephrine, and dopamine. This review examines ketamine, esketamine, and classic psychedelics for depression, especially treatment-resistant depression. Ketamine and esketamine have the strongest evidence, with ketamine showing rapid antidepressant and anti-suicidal effects, and intranasal esketamine being the first NMDA receptor antagonist approved for treatment-resistant depression. Psilocybin-assisted therapy has shown promising results but remains investigational and requires a structured therapeutic framework. Evidence for LSD, DMT, and mescaline is preliminary. These treatments highlight the roles of glutamatergic modulation, serotonergic mechanisms, and neuroplasticity. Key unresolved issues include maintaining effects over time, identifying which patients benefit most, and safe delivery outside specialized settings.
Frontiers in Psychiatry
July 15, 2026
Rafał Marecki, Wiktoria Zaniewska, Adam Hamed et al.
Classic psychedelics such as psilocybin, LSD, DMT, 5-MeO-DMT, mescaline, and DOI work primarily by activating 5-HT2A receptors, causing widespread brain and behavior changes relevant to psychiatric research. Evidence from rodent studies shows that these effects differ by sex across pharmacokinetics, physiology, neuroplasticity, behavior, and disease models. Females often show stronger or qualitatively distinct behavioral responses, including head twitch, locomotor activity, prepulse inhibition, stress reactivity, and social behavior, with ovarian cycle phase further modulating some effects. Disease model studies also find sex-dependent outcomes, such as psilocybin's effects on alcohol consumption and DMT microdosing on mood and neuroplasticity. The review concludes that sex is a critical biological variable shaping psychedelic effects in rodents, and integrating sex-specific analyses is essential for improving translational validity and guiding clinical applications.
Revista de Arqueología Americana
July 10, 2026
Stacy B. Schaefer
Peyote (Lophophora williamsii) is a psychoactive cactus central to religious beliefs, healing practices, and transformative experiences among Indigenous peoples of Mexico and North America. The Wixárika (Huichol) have the longest known continuous use, while the Native American Church's practices in the US and parts of Canada developed more recently. This article reviews peyote's botany, chemistry, medicinal qualities, ecology, archaeology, history, and religious practices, presenting Indigenous knowledge, rituals, and adaptation to change. It concludes by discussing the alarming scarcity of peyote and conservation efforts to protect the plant's future.
Molecular Psychiatry
July 10, 2026
Cong Lin, Xiaohui Wang
Classic psychedelics like LSD, psilocybin, DMT, and mescaline, as well as the antidepressant ketamine, can cause lasting changes in brain function and behavior beyond their immediate effects. This review examines how these substances may influence epigenetic regulation—changes in gene activity that do not alter the DNA sequence itself—through mechanisms such as DNA methylation, histone modifications, and non-coding RNA dynamics. The authors propose that psychedelics also affect metabolic pathways, altering the availability of key molecules like acetyl-CoA and SAM, which in turn may impact gene expression and synaptic connectivity. Understanding these processes could help explain how short-term psychedelic exposure leads to sustained therapeutic benefits and guide the development of new treatments for neuropsychiatric conditions.
Zenodo (CERN European Organization for Nuclear Research)
July 8, 2026
Schüller Thomas
Two works examine the appropriation of Indigenous healing practices. The first, 'Die enteignete Heilerin' (The Expropriated Healer), focuses on the Mazatec shaman Maria Sabina, whose use of psilocybin mushrooms was co-opted by outsiders. The second, 'Vier Enteignungen, ein Muster' (Four Expropriations, One Pattern), compares the appropriation of peyote, ayahuasca, salvia, and iboga, arguing that a common pattern of colonial and capitalist expropriation underlies these cases.
Zenodo (CERN European Organization for Nuclear Research)
July 1, 2026
Schüller Thomas
A transdisciplinary monograph examines the cultivated psychoactive mushroom as a case of access reorganization, comparing it with peyote. The work argues that the regulation and cultural framing of these substances reshape who can access them and under what conditions, thereby reorganizing social and legal boundaries. The analysis draws on psychoanalysis and social critique to explore themes of closure, the fall of man, and therapeutic applications. The author presents this as a theoretical and philosophical paper, not an empirical study, and offers a bilingual (German and English) account funded privately and licensed under Creative Commons.
Zenodo (CERN European Organization for Nuclear Research)
July 1, 2026
Schüller Thomas
DMT is the fourth classical psychedelic in a series and has five distinguishing features: oral inactivity without an MAO inhibitor; ultra-short duration (minutes) when smoked or injected; ayahuasca as a plant combination (DMT source plus β-carboline MAOI); endogenous occurrence in mammals; and the unique religious legal ruling Gonzales v. O Centro (2006). Chemically, DMT is a tryptamine (like psilocybin and LSD), contrasting with the phenethylamine mescaline. This bilingual full work provides a transdisciplinary scientific overview of DMT and ayahuasca across eight disciplines, with explicit labeling of levels of certainty (confirmed / probable / open).
Zenodo (CERN European Organization for Nuclear Research)
July 1, 2026
Schüller Thomas
Mescaline is the only phenethylamine among the classic psychedelics, with the lowest affinity for the 5-HT2A receptor, requiring the highest doses (hundreds of milligrams) and producing a dose-dependent duration of 6.4 to 14 hours. Clinical research is the weakest strand: as of 2026, no adequate randomized controlled trial exists. In the ecologically bound case of peyote, the logic of dispossession reverses compared to synthetic substances like LSD and psilocybin. The work elevates Discipline 8 (Law/Society) to address peyote conservation (IUCN 'vulnerable') and Indigenous rights (Native American Church, AIRFA 1994) as a standalone discipline.
Journal of Psychopharmacology
June 26, 2026
Flavia Giaffone de Paiva Ferreira, João Ariel Bonar Fernandes, Renato Filev et al.
A scoping review categorized psychosocial protocols used in psychedelic research for mental health treatment. Seven categories were defined, reflecting distinct emphases on the substance, participant, research team, and sociocultural context. Although limited reporting and heterogeneity remain methodological challenges, the proposed parameters suggest a shared language to describe, compare, and examine psychosocial protocols across studies, reducing conceptual uncertainty. The review may facilitate research decision-making and support structured, replicable study designs while allowing flexibility for individualized and culturally responsive care. Explicitly defining the intended purpose of psychosocial protocols could improve transparent reporting and evaluation.