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viewing psychedelic treatment as a purely biological intervention with psychological support for safety reflects an outdated, reductionistic dualism that has long dominated psychiatry.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.
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.
Pharmacopsychiatry
May 12, 2021
Gerhard Gründer, Henrik Jungaberle
32 citations
Serotonergic psychedelics like psilocybin, LSD, and DMT, along with MDMA and ketamine, are among the most promising new treatments in psychiatry. Psychedelic-assisted psychotherapy requires redefining psychotherapeutic processes and embedding drug interventions in a new treatment infrastructure. Key challenges for practice and research include informed patient referral, screening, dosing preparation, assisted dosing sessions, psychological integration, and supporting patient communities. Defining treatment delivery infrastructures and therapist training requirements are further challenges. Implementation in routine mental health care must include public communication about the potential and risks. This paper provides a synopsis of challenges for practitioners, researchers, and regulators in the approval processes.
The Journal of Clinical Psychiatry
September 30, 2008
Michael Paulzen, Gerhard Gründer
32 citations
The hallucinogenic sage Salvia divinorum, known by many names including ska Maria and ska Pastora, was first identified in 1962 by Wasson and Hofmann among the Mazatec people of Oaxaca, Mexico, who recognized its psychoactive properties. In recent years, the plant has become widely available globally through internet suppliers, sold as leaves or concentrated extracts.
Neurosci Appl
January 11, 2024
Drummond E-Wen McCulloch, Matthias E. Liechti, Kim PC. Kuypers et al.
10 citations
Psychedelic drugs like psilocybin and LSD are being tested in clinical trials for psychiatric and neurological conditions, with phase 2 studies showing particular promise for depression. At a 2023 European College of Neuropsychopharmacology meeting, experts identified key knowledge gaps that need addressing for successful medical implementation. These include understanding how these drugs work in the body (pharmacokinetics and pharmacodynamics), comparing different psychedelics, exploring the link between the duration of subjective effects and therapeutic outcomes, studying polypharmacology, and assessing the role of psychological support. The article also presents perspectives from the European Medicines Agency and Health Technology Assessors on what is most needed for medical adoption in Europe.
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.
Pharmacopsychiatry
June 24, 2021
Gerhard Gründer
9 citations
Public press coverage, exemplified by a New York Times front-page article, declares that a psychedelic revolution is approaching and that psychiatry may be transformed. The abstract notes that this renaissance has accelerated over the past year, reflecting growing public and media attention to psychedelics and their potential impact on mental health treatment.
Frontiers in psychiatry
January 1, 2024
Bruno Pedraz-Petrozzi, Moritz Spangemacher, Anton Deicher et al.
6 citations
Higher baseline absolute monocyte count (AMC) predicts greater symptom improvement during intravenous ketamine therapy for treatment-resistant depression. In 27 participants receiving six ketamine infusions over three weeks, baseline AMC showed a strong negative correlation with depression severity change after the first infusion and before the last infusion, meaning higher monocyte levels were associated with more symptom reduction. Baseline AMC distinguished responders and partial responders from non-responders but not between partial and full responders. Absolute neutrophil count correlated weakly with early improvement, while C-reactive protein showed no correlation. AMC may serve as a simple clinical marker for predicting ketamine treatment response.
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.
Deutsches Ärzteblatt international
December 16, 2024
Moritz Spangemacher, Andrea Jungaberle, Henrik Jungaberle et al.
3 citations
Psilocybin treatment works differently from standard psychiatric medication, potentially offering rapid and lasting benefits across multiple diagnoses. It may improve not just symptoms but broader aspects of mental health, suggesting it could modify the underlying disease process and promote well-being. Psychedelic-assisted psychotherapy might become the first disease-modifying treatment in psychiatry.
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.
Nervenheilkunde
April 1, 2024
Manuela Brand, Luca V. Faerber, Laura Kaertner et al.
1 citation
This article examines the treatment of mental illnesses with psychedelic substances from a psychotherapeutic perspective, focusing on the role of integrating psychedelic experiences. It asks how extraordinary experiences under the influence of psychedelics can be harnessed for psychotherapeutic progress. After an introductory overview of phases of psychedelic-assisted therapy (PAT), it describes a possibility for psychotherapeutically guided integration of psychedelic experiences using the example of treating treatment-resistant depressed patients with psilocybin in a clinical trial (EudraCT: 2019–003984–24; NCT04670081). The integration of psychedelic experiences into daily life is a scientifically little-studied but essential part of PAT. Evidence-based protocols should be developed to increase the efficacy and safety of therapy through integration methods. With the introduction of PAT into established healthcare systems, integration of psychedelic experiences is expected to become increasingly important.
Brain, behavior, and immunity
July 5, 2026
Bruno Pedraz-Petrozzi, Marta Marszalek-Grabska, Emilia Fornal et al.
In adults with treatment-resistant depression receiving six intravenous ketamine infusions over three weeks, higher baseline levels of the neuroprotective metabolite kynurenic acid (KYNA) in the kynurenine pathway were associated with greater symptom improvement by day 18. KYNA remained stable over time and did not track with symptom changes, suggesting it acts as a trait-like marker rather than a state-dependent one. Early shifts toward the neurotoxic branch of the pathway (kynurenine and 3-hydroxykynurenine) were linked to reductions in hopelessness and suicidality scores after the first infusion. These exploratory findings indicate that a kynurenine pathway profile biased toward neuroprotective metabolites may inform future biomarker studies of ketamine response, but require validation in larger samples.
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.
Der Nervenarzt
March 1, 2025
Moritz Spangemacher, Jonathan Reinwald, Hana Adolphi et al.
Classical and novel antidepressants may share a common mechanism: promoting long-term neuroplasticity and improving negative bias in emotional processing. Extrapharmacological factors—body, environment, and social interaction—appear necessary for these biological changes to produce an antidepressant effect. Rather than dismissing such factors as placebo, the authors argue they should be tested as essential components of treatment and integrated into clinical practice.