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.
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.
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.
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 Oña, 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.
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.
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.
Open Science Framework
November 6, 2025
Michiel van Elk
In a naturalistic field setting, the dose of psilocybin truffles, along with participants' trait absorption and expectations, shaped their subjective experiences and neurophysiological responses. The study aimed to replicate effects previously observed in lab and clinical environments. Higher doses were associated with more intense subjective effects, and individual differences in absorption and expectations moderated these outcomes. The findings suggest that psilocybin's effects can be reproduced outside controlled settings, highlighting the role of psychological factors in modulating the experience.
March 10, 2020
Valerie van Mulukom, Ruairi Patterson, Michiel van Elk
preprint
Awe experienced during classical serotonergic psychedelic (CSP) use is linked to lower maladaptive narcissism. In a survey of 414 people, those who reported greater awe during recent CSP experiences also reported stronger feelings of social connectedness and affective empathy, which in turn were associated with less exploitative and entitled narcissistic traits. This pattern held even after accounting for sensation-seeking. Ego dissolution during the experience showed no similar effect. The findings suggest that awe-induced connectedness, not ego loss, may underlie the therapeutic potential of psychedelics for conditions involving impaired empathy and connection, such as pathological narcissism.