Neuroscience & Biobehavioral Reviews
September 1, 2022
Michiel van Elk, David Bryce Yaden
214 citations
This critical review examines multiple levels of mechanisms behind psychedelics' effects and therapeutic potential. At the biochemical level, they primarily act on 5-HT2A receptors, increase neuroplasticity, open a critical period for social reward learning, and have anti-inflammatory properties. At the neural level, they reduce thalamo-cortical filtering efficacy, loosen top-down predictive signaling, increase sensitivity to bottom-up prediction errors, and activate the claustro-cortical circuit. At the psychological level, they induce altered and affective states, affect cognition, change beliefs, exert social effects, and produce lasting behavioral changes. The authors contrast a potential unifying account with pluralistic causation and propose a research agenda for better understanding causal-mechanistic pathways to enable targeted therapies.
Consciousness and Cognition
August 1, 2019
Michael Lifshitz, Michiel van Elk, T M Luhrmann
162 citations
A general tendency called 'absorption'—the capacity to become deeply immersed in sensory and imaginative experiences—underlies a broad proclivity for spiritual experiences. People high in absorption readily sense supernatural presences, receive messages from God, and feel self-transcendence, awe, and wonder. High scorers on the Tellegen Absorption Scale report vivid experiences such as hearing God's voice during prayer, intense mystical states from psychedelics or placebo brain-stimulation, and strong feelings of presence and transcendence when encountering natural beauty, virtual reality, or music. Absorption appears to intensify inner and outer sensory experience, blending prior expectation with novel engagement, making imagined things feel more real.
Therapeutic Advances in Psychopharmacology
January 1, 2023
Michiel van Elk, Eiko I. Fried
126 citations
Despite a decade of optimism about psychedelics for treating mental disorders, psychedelic science faces serious challenges that threaten the validity of core findings. The paper identifies 10 pressing problems grouped into easy, moderate, and hard categories, showing how they undermine internal validity (treatment effects due to unrelated factors), external validity (lack of generalizability), construct validity (unclear working mechanisms), and statistical conclusion validity (conclusions not supported by data). These problems often co-occur, limiting conclusions about safety and efficacy. The authors provide a roadmap and checklist for stakeholders to assess study quality, emphasizing that addressing these issues is necessary to determine whether therapeutic optimism is warranted and to avoid repeating past mistakes.
Human Brain Mapping
May 7, 2019
Michiel van Elk, M. Andrea Arciniegas Gomez, Wietske van der Zwaag et al.
122 citations
Watching awe-inspiring videos reduces activity in brain regions linked to self-focused thinking, such as the frontal pole, angular gyrus, and posterior cingulate cortex, which are part of the default mode network. In contrast, regions of the fronto-parietal network, including the supramarginal gyrus, medial frontal gyrus, and insula, become more active when people analytically count perspective changes while viewing awe videos. These findings suggest that awe diminishes self-referential processing, consistent with participants reporting feeling their self was smaller.
Religion Brain & Behavior
June 5, 2018
Neil Van Leeuwen, Michiel van Elk
91 citations
A new model, the Interactive Religious Experience Model (IREM), proposes that general religious beliefs (e.g., God exists) are mostly acquired from culture, while personal religious beliefs (e.g., God appeared to me last night) arise from agency-detection intuitions and other low-level experiences. IREM inverts the standard Hyperactive Agency-Detection Device Theory: rather than agency-intuitions causing general religious belief, general belief in supernatural agents leads people to seek situations that trigger such intuitions, enabling personal beliefs. The model incorporates philosophical work on indexical belief, addresses empirical and conceptual problems with earlier theories, and suggests future research directions.
Journal of Psychopharmacology
December 17, 2021
Josephine Marschall, George Fejer, Pascal Lempe et al.
69 citations
In a double-blind, placebo-controlled, within-subject crossover study, psilocybin microdosing (a sub-hallucinogenic dose taken every third day) did not alter emotion processing, symptoms of anxiety or depression, or self-reported interoceptive awareness compared with placebo. Exploratory analyses showed that symptoms of depression and stress were significantly reduced in the first block compared with baseline, but participants broke blind in the second block, and there was no effect of expectations. The authors call for further research in a substance-naïve population with clinical-range anxiety and depressive symptoms to substantiate potential beneficial effects.
ACS Pharmacology & Translational Science
July 16, 2021
Joost J. Breeksema, Michiel van Elk
69 citations
The authors argue that the concept of mystical experience should remain central to psychedelic science, countering a recent call to abandon it. They emphasize the need to recognize the diversity and strangeness of psychedelic experiences, drawing on a rich tradition and scientific tools for studying mystical-type experiences. These experiences are relevant for understanding the therapeutic effects of psychedelics. The authors also call for greater diversity in both the types of experiences and the participants included in future research.
Psychopharmacology
September 1, 2020
Valerie van Mulukom, Ruairi E Patterson, Michiel van Elk
61 citations
Classical serotonergic psychedelic (CSP) experiences that induce awe, but not ego dissolution, are linked to lower maladaptive narcissism through increased feelings of connectedness and affective empathetic drive. In a survey of 414 participants describing their most awe-inspiring psychedelic experience, those reporting more awe showed higher connectedness and empathy, which in turn predicted reduced exploitative-entitled narcissism. This relationship persisted after controlling for sensation-seeking. No evidence was found that ego dissolution produced the same effects. The findings suggest CSPs may have therapeutic potential for disorders involving deficits in connectedness and empathy, such as pathological narcissism, with awe-driven connectedness as a key mechanism.
Psychopharmacology
April 30, 2021
Michiel van Elk, George Fejer, Pascal Lempe et al.
53 citations
People who take small, non-hallucinogenic doses of psilocybin (microdosing) report feeling more awe when watching videos of funny animals and moving objects compared to when they take a placebo. However, about two-thirds of participants correctly guessed whether they had received psilocybin or placebo, suggesting that expectancy effects—rather than the drug itself—may explain the subjective benefits of microdosing. The study used a double-blind, placebo-controlled crossover design with a microdosing workshop and lab visits over several weeks.
Frontiers in Psychology
January 1, 2010
Michiel van Elk, Marc Slors, Harold Bekkering
46 citations
The paper argues that criticisms of embodied cognition—such as whether sensorimotor brain activation is necessary for language comprehension and how we understand language for which we lack relevant experiences—stem from interpreting embodiment through a cognitivist lens. Instead, the authors propose an enactivist, non-representationalist model: language comprehension is procedural knowledge (knowing how, not knowing that) that enables interaction with others in a shared physical world. On this view, activation in modality-specific brain areas reflects the use of sensorimotor skills, and comprehension is context-bound. The enactivist approach thus supports an embodied view of language while avoiding the problems faced by cognitivist interpretations.
Religion Brain & Behavior
December 22, 2017
David L. R. Maij, Michiel van Elk, Uffe Schjoedt
32 citations
In a field study at a Dutch festival, 193 participants were led to believe a placebo brain stimulation device (the God Helmet) could induce mystical experiences. Participants reported a range of extraordinary experiences, including out-of-body sensations, involuntary movements, and sensing invisible beings. Self-identified spiritualism predicted these experiences, but neither objective nor subjective alcohol intoxication increased susceptibility to the suggestion. The authors discuss methodological limitations that may explain the lack of an alcohol effect and explore the God Helmet's usefulness for studying extraordinary experiences.
March 10, 2023
Michiel van Elk, Eiko I. Fried
30 citations
preprint
Despite a decade of optimism about psychedelics for treating mental disorders, the field faces ten pressing challenges that threaten the validity of core findings. These problems undermine internal validity (treatment effects from non-treatment factors), external validity (poor generalizability), construct validity (unclear mechanisms), and statistical conclusion validity (conclusions unsupported by data and methods). The challenges co-occur, strongly limiting conclusions about safety and efficacy. A roadmap and checklist are provided for researchers, journalists, funders, and policymakers to assess study quality. Addressing these issues is necessary to determine whether the optimism is warranted and to avoid repeating past mistakes.
Psychoactives
April 16, 2024
Daniel Meling, Rebecca Ehrenkranz, Sandeep M. Nayak et al.
26 citations
Psychedelic research has returned after a period of suppression, but media coverage now often overstates benefits as much as it once overstated risks. The actual evidence is more mixed than commonly portrayed, so conclusions about effectiveness remain preliminary. Poor communication may mislead patients and misinform policy. This article reviews studies on psychedelics for depression, noting that effect sizes for other depression treatments—cognitive behavioral therapy, mindfulness, SSRIs, and ketamine—have decreased over time as trials improved. The authors suggest the same may happen for psychedelics: larger, better-controlled trials will likely show smaller, more realistic benefits. Clear communication is essential to set public expectations and guide policy.
Journal of Psychoactive Drugs
May 28, 2022
Maja Kohek, Genís Ona, Michiel van Elk et al.
25 citations
Regular participation in ayahuasca ceremonies is not linked to relevant health harms. Compared to normative Dutch data, 377 participants (50.1% women, mean age 48.8 years) showed better general well-being, fewer chronic or lifestyle-related diseases, more physical activity, and a more balanced diet. During the COVID-19 pandemic, they used less alcohol. Although they used more illegal drugs than the general population, they did not report associated harms. This evidence could inform drug policymakers in developing evidence-based public policies.
Psychiatr Res Clin Pract
February 11, 2025
Jules Evans, Marc Aixalà, Brian T Anderson et al.
18 citations
Thirty psychedelic researchers identified critical gaps in knowledge about harms from psychedelic use, including how to define those harms, predict them, and treat them effectively. They recommend better online information, peer support groups, affordable therapy, and psychiatric consultation for people experiencing post-psychedelic difficulties. The researchers also call for improved funding for a psychedelic safety net, suggesting that psychedelic philanthropists, investors, and companies commit 1% of their investment to support safety measures such as research and support services. The article outlines practical steps to make the field of psychedelic medicine safer.
Journal of Psychoactive Drugs
June 23, 2025
Annika Wirsching, Erwin Krediet, Martijn H B Koolen et al.
4 citations
Dutch mental health professionals hold generally positive attitudes toward psychedelic-assisted psychotherapy (PAP) for conditions like PTSD and major depression, according to a survey of 198 clinicians. Positive attitudes were associated with clinicians' own prior use of MDMA or psilocybin. Respondents considered psychiatrists and licensed psychologists the most suitable professionals to administer PAP, expressed concerns about maintaining therapeutic connection during patients' altered states, and preferred that PAP be delivered in specialized hospital-based facilities. The findings point to implementation needs, including targeted training and clear clinical guidelines.
Psychology & Neuroscience
May 26, 2022
Evan Lewis-Healey, Ruben Laukkonen, Michiel van Elk
4 citations
Psilocybin-assisted psychotherapy may treat depression by weakening the connections between symptoms in a complex dynamic network, according to a theoretical model called the Relaxed Symptom Network. Drawing on the Network Theory of Mental Disorders, which views depression as an emergent phenomenon from strong symptom interactions, the authors propose that successful therapy reduces these connections, making patients less vulnerable to developing or relapsing into depression. The article summarizes clinical trials showing antidepressant effects of psilocybin when embedded in psychotherapy, reviews contested mechanisms, and offers practical guidance for integrating network theory into future clinical research.
June 14, 2021
Luisa Prochazkova, Michiel van Elk, Josephine Marschall et al.
4 citations
preprint
Microdosing psychedelic truffles increased the quality of divergent thinking, measured as the ratio of original responses to total responses on the Alternative Uses Task, in a pooled analysis of three double-blind placebo-controlled trials with 175 participants. The unadjusted originality score was significantly higher only when relative dosage (dose per body weight) was considered. No effects were found on convergent thinking or other divergent-thinking scores. The effects were subtle and persisted after controlling for expectation and demographic biases. The findings underscore the importance of controlling for placebo effects and prior psychedelic experience in microdosing research.
Philosophical Psychology
November 30, 2025
Julian Kiverstein, Hüseyin Beyköylü, Michiel van Elk
3 citations
Psychedelic experiences are shaped by the interaction of the drug, the user's psychological state (set), and the environment (setting), not just by pharmacology. A causal pluralist theory holds that multiple valid explanations—pharmacological, neural, psychological, social, political, and historical—can account for how set and setting influence the experience. Concepts from enactive cognitive science help clarify how higher-level causes like psychological states and cultural practices work, but enactive science has not yet produced testable models. Predictive processing theory may fill that gap. A pluralist synthesis of enactive cognitive science and predictive processing could provide the best conceptual tools for understanding the psychedelic experience scientifically.
May 19, 2021
Evan Lewis-Healey, Ruben Laukkonen, Michiel van Elk
3 citations
preprint
Psilocybin-assisted psychotherapy (PAP) shows promise for treating depression, but how it works is debated. The authors propose that depression arises from strong interactions among symptoms in a dynamic network, and that successful PAP weakens these connections, making relapse less likely. They call this the Relaxed Symptom Network hypothesis and argue that applying network theory could improve treatment response and reduce relapse. Practical guidance for integrating this framework into future clinical research with psilocybin is provided.
Neuropharmacology
November 2, 2025
Luisa Prochazkova, Josephine Marschall, Michiel van Elk et al.
2 citations
Microdosing psilocybin from truffles modestly improved the quality of divergent thinking—specifically the ratio of original responses to total responses—in a pooled analysis of three double-blind, placebo-controlled trials with 171 participants. The effect on unadjusted originality was significant only when dosage relative to body weight was considered, and it remained after controlling for dose guess and demographic biases. No effects were found on other measures of divergent thinking or on convergent thinking. The findings underscore the need to account for placebo effects and prior psychedelic experience when evaluating microdosing claims.
L. J. Flameling, Jacob S. Aday, Michiel van Elk
1 citation
preprint
A commentary on a phase 3 trial of MDMA-assisted therapy for PTSD raises concerns about expectancy effects. The trial reported positive results, but most participants correctly guessed their treatment assignment, and expectations were not measured. The authors argue these effects were minimal, but the commentary contends that without measuring expectations, it remains possible that placebo or nocebo effects contributed to the observed outcomes.
Psychedelics
June 28, 2026
Joost J. Breeksema, Ulf Bremberg, Jens H van Dalfsen et al.
Psychedelic therapies face layered complexity from interactions between pharmacological and extra-pharmacological factors, and their embeddedness in societal, legal, and regulatory systems. This is compounded by epistemic fragmentation: dominant biomedical paradigms often clash with knowledge from social sciences, humanities, or Indigenous traditions. Though interdisciplinary engagement is increasingly recognized as necessary, existing calls rarely specify structural or pedagogical conditions for operationalizing it. Addressing these complexities requires moving beyond superficial collaboration; genuine interdisciplinary progress needs researchers capable of productive friction across epistemic cultures. The authors propose cultivating T-shaped competencies and intersectoral training as a structural response to these systemic challenges.
Philosophical Psychology
April 27, 2026
Michiel van Elk
Mystical experiences are characterized by ineffability, noetic quality, transiency, and passivity, as outlined by William James. The abstract discusses the long-standing scholarly interest in these experiences within religious studies, noting that they have been a focus of research since James's foundational work. The text describes the key features of such experiences but does not present new empirical findings or a specific argument beyond acknowledging the historical and ongoing academic attention to the topic.
Sci Rep
November 25, 2025
Laura C. Carvalho, Jorge Encantado, Michiel van Elk et al.
Psychedelic experiences may help people adopt healthier behaviors like improved diet, more exercise, and regular meditation, according to a survey of 96 practitioners working in legal and underground settings. Practitioners reported perceived positive changes in clients' contemplative practices (61.4%), time in nature (60.1%), eating patterns (56.9%), and diet and nutrition (56%). The findings suggest that practitioners often see psychedelic experiences as linked to beneficial health behavior changes, though further research is needed to confirm these results and understand their long-term sustainability.