The Lost Foundations of Psychedelic Science:
Special Issue of Psychedelic Medicine

Authors: Nathan H. Heller, Jason Samaha, Renaud Jardri, and Frederick S. Barrett

Type: Historical Translation with Commentary

Language: French to English

Source Title: Étude de l’électrencéphalogramme humain dans un cas d’intoxication mescalinique (Chweitzer, Geblewicz, & Liberson, 1936)

English Title: Study of Human Electroencephalogram in a Case of Mescalin Intoxication

Abstract: This contribution presents the first English translation of a groundbreaking yet nearly forgotten study, Étude de l’électrencéphalogramme humain dans un cas d’intoxication mescalinique (1936), authored by A. Chweitzer, E. Geblewicz, and W. Liberson. The study likely represents the earliest attempt to measure brain activity following psychedelic administration. Using EEG, the authors monitored a single subject participant during the acute effects ofunder mescaline, capturing fluctuations in alpha (Berger) rhythms and linking them in real time to hallucinatory episodes. Their approach, observing ‘a-wave silences’ alongside vivid perceptual distortions, anticipates what is now known as the ‘hallucination capture’ paradigm, the real-time tracking of hallucinatory phenomena with neural signals. In our accompanying commentary, we pursue two aims. First, we situate this study within the early history of psychedelic science, when researchers were beginning to link hallucinogenic experience with neural oscillations. Second, to we connect that early framework to both modern hallucination capture approaches and contemporary efforts to understand the role of spectral dynamics in visual perception. By revisiting Chweitzer et al., we aim to restore this study to its rightful place in the lineage of psychedelic neuroscience, and to rekindle interest in using psychedelics as a tool for investigating hallucinogenesis.

Authors: Matthew Company

Type: Narrative Review

Abstract: Beginning in the mid-20th century, behavioral neuroscientists studied psychedelics’ effects on the brain’s reward system. Early LSD-focused work reported paradoxical interactions with dopamine signaling across brain regions. At the same time, other studies probed misuse potential through catecholamine assays and behavioral reward paradigms, raising tantalizing questions about serotonin–dopamine cross-talk. Despite this momentum, research collapsed after the U.S. Controlled Substances Act (1970), the 1975 withdrawal of the National Institute of Mental Health hallucinogen funding, and the creation of the National Institute on Drug Abuse, which redirected pharmacology research toward psychostimulant-abuse studies. Nearly all psychedelics, ketamine, a dissociative exception aside, were placed in Schedule I, the category reserved for drugs with “no accepted medical use,” leaving key questions unanswered. Although constraints were severe, a handful of papers published during the “psychedelic dark ages” (late 1970s – early 2000s) showed that classic psychedelics are non-habit forming and may reduce alcohol, opioid, and stimulant self-administration in preclinical models, hinting at utility for substance-use disorders. These findings quietly laid the groundwork for demonstrated safety and low abuse liability, paving the way for the modern psychedelic renaissance. Today, multidisciplinary teams armed with modern pharmacology, optogenetics, chemogenetics, and multimodal neural recording techniques are dissecting circuit-level mechanisms by which psychedelics recalibrate reward-prediction errors and drive enduring behavioral change. Re-examining the dormant literature through the lens of these technologies, this review maps actionable experiments that can finally test and extend the questions first posed more than half a century ago.

Authors: Lucas Dwiel

Type: Narrative Review

Abstract: Multiple frameworks in psychiatry—from biomedical and biopsychosocial to phenomenological and existential—share a fundamental belief that the treatment of psychiatric illness relies upon influencing neural processes. Neuroplastic mechanisms create long-lasting changes in brain structure and function, thereby producing enduring changes in psychiatric symptoms. Psychedelic drugs engage these neuroplastic mechanisms to reshape neural circuits through alteration of synapses, dendrites, and axons. However, the effects of psychedelics are broadly distributed across the brain rather than specifically targeting the circuit(s) underlying a given symptom or illness. Combining psychedelics with targeted brain stimulation may engage and guide psychedelic-induced neuroplasticity in precise neural circuits, promoting durable alterations in circuit organization and the associated psychological processes. Historically, the serotonergic psychedelic LSD has been paired with brain stimulation, specifically electroconvulsive therapy (ECT), for a variety of purposes. In trying to treat patients with schizophrenia, some used LSD to provoke psychosis before applying ECT, others used ECT to treat LSD-induced psychosis in otherwise healthy individuals. At the same time, LSD and mescaline were used as tools to elucidate the neurophysiological effects of ECT. Last, there is evidence that LSD and ECT were combined as a part of MKULTRA to break down and then reconstruct thoughts and behavior patterns through “depatterning” and “psychic driving”. Each of these lines of inquiry saw some reported success, but most were eventually discontinued—due to a lack of replication, a broader shift away from administering psychedelics to patients with psychotic tendencies, and a growing recognition of patients’ rights. As we begin to study the combination of psychedelics and brain stimulation today, it is important that we keep in mind both the successes and failures of the past. Engaging critically with that history allows us to better understand our own motivations and interrogate the frameworks and assumptions we bring to this research.

Authors: Antoine Bellemare-Pepin, Philipp Thölke, and Karim Jerbi

Type: Historical Translation with Commentary

Language: German to English

Source Title: Malerei aus Bereichen des Unbewussten: Künstler experimentieren unter LSD (Richard P. Hartmann, 1974)

English Title: Painting from realms of the unconscious: Artists experiment under LSD

Abstract: Historical research into psychedelics and creativity often remains underappreciated, especially with regard to altered perception and its influence on artistic processes. Here, we present an English translation and commentary on the core theoretical section (pages 11–55) of ""Malerei aus Bereichen des Unbewußten: Künstler experimentieren unter LSD"" (Painting from Realms of the Unconscious: Artists Experimenting Under LSD), a seminal yet neglected German text documenting early systematic experiments with visual artists under LSD. This book uniquely combines detailed phenomenological reports with theoretical reflections, highlighting how altered perception—ranging from synesthesia and illusions to complex inner imagery—shapes artistic creativity. More specifically, the authors catalogue a graduated series of visual alterations that together form an early taxonomy of psychedelic perception. They show how such shifts heighten pareidolia in ambiguous or multistable images and culminate in new creative affordances through Gestaltungszerfall—a disruption in the formation of stable perception leading to symbol-laden fragments. Our commentary situates these historical findings within the framework of embodied cognition and participatory sense-making, highlighting how creative expression is shaped and enhanced by expanded perceptual affordances. We further contextualize this historical perspective within contemporary research on psychedelic creativity, which has predominantly focused on therapeutic or emotional outcomes, and has largely overlooked the participatory and embodied nature of perceptual transformation. Additionally, we explore how the frameworks and methodologies introduced in this work can be revitalized with modern scientific tools, opening new empirical avenues for investigating perceptual processes such as pareidolia and their implications for creative sense-making. This translation aims not only to enrich current dialogues between neuroscience, creativity, and psychedelic studies, but also to catalyze novel interdisciplinary research directions that bridge historical insights with contemporary embodied and participatory approaches to creative cognition.