Frontiers in Psychiatry
February 21, 2020
Max Wolff, Ricarda Evens, Lea J. Mertens et al.
188 citations
A conceptual model proposes that psychedelic-assisted therapies reduce experiential avoidance and increase acceptance through mechanisms similar to those in cognitive behavioral therapy. In controlled clinical settings, psychedelics relax avoidance-related beliefs, boosting motivation for acceptance via operant conditioning. This allows relatively avoidance-free exposure to intensified private events, where relaxed beliefs encounter corrective information and become revised. Such belief revision may explain lasting increases in acceptance and decreases in psychopathology. The article outlines open research questions and clinical implications.
The Lancet Psychiatry
December 12, 2023
Gerhard Gründer, Manuela Brand, Lea J. Mertens et al.
103 citations
Treatment of psychiatric disorders with psychedelic substances is promising, but there is debate over whether therapeutic effects come solely from the drug or require psychotherapy. Some recent studies suggest the substance alone may be responsible, with therapists providing only safety support. This Personal View argues that viewing psychedelic treatment as a purely biological intervention with psychological support for safety reflects an outdated, reductionistic dualism that has long dominated psychiatry. The discussion has important implications for how these compounds are studied and regulated.
Journal of Psychopharmacology
March 1, 2022
Max Wolff, Lea J. Mertens, Marie Walter et al.
57 citations
Psychedelic experiences can promote either acceptance or avoidance, and these two tendencies are relatively independent—they can alternate but do not occur simultaneously. A bilingual online survey of 997 English- and 836 German-speaking participants who used LSD, psilocybin, mescaline, or ayahuasca found that acceptance-related experiences and avoidance-related experiences were distinct and not strongly correlated. Subaspects within each type were closely linked. Therapeutic, escapist, and hedonic motives for use related differently to acceptance and avoidance, and these experiences were associated with later changes in psychological flexibility. The link between acceptance and increased flexibility was weaker when avoidance was high, suggesting an interplay between the two.
Neuroscience Applied
January 1, 2022
Lea J. Mertens, Michael Koslowski, Felix Betzler et al.
40 citations
Clinical trials with psychedelics like psilocybin face unique methodological challenges, particularly the difficulty of maintaining blinding due to the substances' pronounced subjective effects, which raises risks of expectation bias and nocebo effects. A phase II randomized, double-blind, active placebo-controlled parallel group trial with 144 patients is underway to evaluate psilocybin's efficacy and safety in treatment-resistant major depression. The trial, called EPIsoDE, is funded by the German Federal Ministry of Education and Research and addresses these challenges in its design.
Journal of Psychopharmacology
May 1, 2024
Max Wolff, Ricarda Evens, Lea J. Mertens et al.
34 citations
A new questionnaire, the General Change Mechanisms Questionnaire (GCMQ), reliably measures five psychotherapy processes—resource activation, therapeutic relationship, problem actuation, clarification, and mastery—during psychedelic experiences. Validated in 1153 English-speaking and 714 German-speaking users, the GCMQ showed good internal consistency and convergent validity. Experiences varied with setting and use motives (therapeutic, hedonic, escapist). Resource activation, clarification, and mastery moderated the link between stressful life events and well-being, suggesting potential therapeutic benefits. Five distinct user profiles emerged, which may inform clinical use and harm reduction.
International review of psychiatry (Abingdon, England)
December 1, 2024
Helena D Aicher, Max Wolff, Uwe Herwig
10 citations
The renewed interest in psychedelics for treating mental health disorders is often called the "Psychedelic Renaissance," but this article argues it does not represent a true paradigm shift in psychiatry. Instead, the authors contend that current developments are better understood as enhancements to existing therapeutic frameworks, building on extensive mid-20th-century research. They emphasize integrating psychedelics within a broader bio-psycho-social model, combining pharmacological, psychological, and contextual factors. The therapeutic potential is described as working as "nonspecific amplifiers" of psychological processes rather than introducing entirely new mechanisms. The article cautions against "psychedelic exceptionalism" and overselling psychedelics as a revolutionary treatment, advocating for a balanced, integrative approach.
JAMA Psychiatry
March 18, 2026
Lea J. Mertens, Michael Koslowski, Felix Betzler et al.
9 citations
A phase 2b randomized clinical trial tested 25 mg of psilocybin with psychotherapy against a 5 mg dose and a placebo (nicotinamide) in 144 adults aged 25 to 65 with treatment-resistant depression who had stopped antidepressants. The primary outcome—a 50% or greater reduction in depression scores at six weeks—was not statistically significant: 17.0% of those receiving 25 mg responded, versus 12.5% on 5 mg and 10.6% on placebo. Exploratory analyses suggested a clinically meaningful reduction in depressive symptoms with the 25 mg dose. The treatment was generally well tolerated, but safety signals included higher reports of suicidal ideation on dosing days and two serious adverse reactions, one case of hallucinogen persisting perception disorder.
Psychedelic Medicine
January 20, 2025
Marianna Graziosi, Gabrielle Agin-Liebes, Mary P Cosimano et al.
9 citations
Psilocybin and other serotonergic psychedelics are used in research settings with safety measures including controlled environments, staff presence, screening, and psychoeducation. An analysis of study materials from psilocybin trials over the past two decades found that psychoeducation documents varied but commonly emphasized biological and physical safety, psychological safety and well-being, aspects of setting, and the potential for expectancies. The materials prioritized biological and psychological safety across all sites. The authors also identified elements unrelated to safety that may contribute to participant expectancies and suggest these extrapharmacological factors be studied systematically to maximize safety while minimizing extraneous expectancies.
General hospital psychiatry
January 1, 2025
Max Wolff, Hans Rutrecht, Gerhard Gründer et al.
9 citations
As psychedelic treatments move from research settings into hospitals, clinics, and community practices, a new competencies framework outlines the skills needed for safe, effective, and ethically sound therapy. The framework is substance-unspecific and transtheoretical, covering foundational domains including psychotherapy, biomedicine, philosophy, socio-cultural awareness, existential concerns, legal issues, and self-experience. It translates these into practical competencies for multi-professional cooperation, screening, preparation, dosing, integration, and harm-reduction. Developed within the MIND Foundation's Augmented Psychotherapy Training program, the framework awaits systematic evaluation but offers an initial blueprint for future accredited certification and clinician training as these treatments enter mainstream care.
Therapeutic Advances in Psychopharmacology
September 1, 2025
Suresh Muthukumaraswamy, Matthew J. Baggott, Eduardo Ekman Schenberg et al.
8 citations
Psychedelic-assisted therapy (PAT) is a complex intervention combining pharmacological, psychotherapeutic, and contextual elements that interact dynamically with patient experiences and healthcare settings. Conventional randomized controlled trials may fail to capture these complexities. This position paper advocates applying the UK Medical Research Council's framework for complex interventions to PAT development and evaluation, emphasizing the need to articulate the theory of therapeutic change, structure intervention development into phases, account for contextual interactions, and incorporate stakeholder perspectives.
Drug Science Policy and Law
June 16, 2025
Max Wolff, Natalie Gukasyan, Leor Roseman et al.
5 citations
Current drug regulations are ill-suited for psychedelic therapy, which combines pharmacological and psychotherapeutic elements. The authors propose regulating psychedelic drugs as therapeutic tools or adjuncts to psychotherapy, analogous to anesthetics that facilitate medical procedures without being treatments themselves. This reframing would allow regulators to focus on acute drug effects rather than therapeutic outcomes arising from complex interactions with psychotherapy. It could counter the trend in psychedelic drug development that views psychotherapy as a liability and seeks to minimize or remove it, potentially compromising safe and durable clinical outcomes.
Fortschritte der Neurologie · Psychiatrie
June 20, 2022
Christopher W. Schmidt, Max Wolff, Gerhard Gründer et al.
5 citations
A survey of 530 psychiatrists and psychotherapists found divided opinions about psilocybin and psilocybin-assisted therapies. Many respondents considered psilocybin promising for treating mental disorders, with a majority viewing it as promising for depression. Greater knowledge about psilocybin was linked to more optimistic views about its therapeutic use. Providing additional scientific information about current research partly led to more favorable attitudes. As scientific and public discourse on psilocybin grows, shifts in psychotherapists' and psychiatrists' attitudes are expected.
PsyArXiv
February 23, 2025
Suresh Muthukumaraswamy, Matthew Baggott, Eduardo Ekman Schenberg et al.
3 citations
preprint
Psychedelic-assisted therapy (PAT) is a complex, multi-component intervention, yet most clinical trials evaluate it as a simple pharmaceutical treatment, limiting real-world validity. This position piece advocates applying the UK Medical Research Council's complex intervention framework to PAT, emphasizing theory of change, structured development, context, and stakeholder input. Pragmatic randomized controlled trials, informed by the PRECIS-2 tool, are proposed to align trial designs with real-world healthcare settings. The authors contrast drug-centric and psychotherapy-augmented views of PAT's efficacy, and recommend integrating qualitative data, adaptive designs, and comparative effectiveness research. A pluralistic evidentiary model is suggested to advance psychedelic medicine while avoiding past developmental pitfalls.
Journal of Eating Disorders
December 4, 2025
Samuli Kangaslampi, Max Wolff, Manoj K. Doss et al.
1 citation
Psychedelics like psilocybin can trigger vivid memory-like experiences, but a recent case report claiming that two patients recovered dissociated traumatic memories during psilocybin treatment for anorexia nervosa may not have adequately considered alternative explanations. The cases do not necessarily show that psilocybin induces recovery of dissociated traumatic memories or could treat dissociative amnesia. The authors also caution against explicitly preparing patients for the emergence of forgotten material, as such suggestions warrant scrutiny.
Journal of Contextual Behavioral Science
July 1, 2025
Oscar Soto-Angona, Amanda Rodríguez‐Urrutia, Josep Antoni Ramos‐quiroga et al.
1 citation
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Der Nervenarzt
February 12, 2025
Nina Hartter, Marvin Däumichen, Christopher Schmidt et al.
1 citation
An online survey of 1,456 mental health experts, patients, and the general public found that greater knowledge about psilocybin-assisted therapy (PAT), self-assessed knowledge, personal treatment experience, and prior experience with psychedelics predicted more positive attitudes toward introducing PAT. Providing information about PAT's potential only increased acceptance when combined with information about its risks. Participants were generally optimistic about implementing PAT. The link between knowledge and acceptance was confirmed, suggesting that balanced education and reporting on PAT can foster higher acceptance.
Psychedelic Medicine
June 16, 2026
Max Wolff, Samuli Kangaslampi, Richard J. Zeifman et al.
Therapeutic alliance likely plays a meaningful role in shaping both the psychedelic experience and clinical outcomes, contrary to a recent analysis that concluded it did not. This commentary argues that the reported results actually support a meaningful role for alliance when contextualized properly, and that methodological decisions obscured relevant effects. Unexplained deviations from the study protocol also warrant scrutiny. The findings underscore the importance of accurately characterizing psychological and contextual factors in psychedelic treatment research and call for more transparent analyses of psychotherapeutic processes.
Psychotherapy and psychosomatics
May 27, 2026
Lea J Mertens, Felix Betzler, Manuela Brand et al.
A single 25 mg dose of psilocybin, or two such doses given six weeks apart, combined with psychotherapy produced a stable and clinically meaningful reduction in depression symptoms for up to twelve months in people with treatment-resistant depression. The average improvement on the Hamilton Rating Scale for Depression was about 7.9 points at six months and 7.7 points at twelve months, with no significant difference between dosing groups. Restarting standard antidepressant medication during follow-up was strongly linked to higher depression scores. This naturalistic follow-up of a phase 2b trial is the largest and most complete long-term assessment of psilocybin for depression to date.
Psychological Medicine
January 1, 2026
Ricarda Evens, Abdo Uyar, Emily Gosslau et al.
About 31% of people who had a distressing psychedelic experience that lasted beyond the acute phase met diagnostic criteria for post-traumatic stress disorder (PTSD). Avoidance during the acute experience predicted worse PTSD symptoms, while acceptance predicted milder symptoms. Post-traumatic growth was unrelated to the intensity of the challenge or avoidance but was linked to acceptance. Most participants sought help from online resources or friends, though psychotherapy was rated most helpful. The study targeted those with highly challenging experiences, so findings do not reflect prevalence among all psychedelic users.