Journal of Psychopharmacology
January 16, 2020
Lea J. Mertens, Matthew B. Wall, Leor Roseman et al.
211 citations
After a single 25 mg dose of psilocybin, patients with treatment-resistant depression showed decreased functional connectivity between the ventromedial prefrontal cortex and the right amygdala while viewing faces, particularly fearful and neutral ones. This decrease was linked to lower rumination levels one week later. Increased connectivity between these regions and occipital-parietal cortices also emerged. The findings suggest psilocybin therapy may revive emotional responsiveness at both neural and psychological levels, offering a potential treatment mechanism. Placebo-controlled studies are needed to confirm these results.
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.
Frontiers in Psychiatry
August 7, 2020
Richard J. Zeifman, Anne Catherine Wagner, Ros Watts et al.
104 citations
In two prospective studies with convenience samples of people planning to use a psychedelic (total N=358), participants completed questionnaires before use and at 2 and 4 weeks afterward. Across both studies, significant decreases occurred in experiential avoidance, depression severity, and suicidal ideation after psychedelic use. Decreases in experiential avoidance were significantly associated with decreases in depression severity and suicidal ideation. These results suggest that psychedelics may reduce experiential avoidance, depression severity, and suicidal ideation, and that reduced experiential avoidance may be a transdiagnostic mechanism in psychedelic therapy. Integrating psychedelics with therapies targeting experiential avoidance, such as acceptance and commitment therapy, may enhance outcomes.
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.
Neuropsychopharmacology
May 5, 2020
Marcus W. Meinhardt, Cansu Güngör, Ivan Skorodumov et al.
66 citations
Psychedelic-assisted psychotherapy is hypothesized to restore normal brain function in people with alcohol use disorder (AUD) and reduce relapse risk after a single session. In this study, three treatment schedules with psilocybin or LSD were tested in male and female rats using the alcohol deprivation effect (ADE) model of relapse-like drinking. Neither high doses comparable to clinical studies nor chronic microdosing produced long-lasting reductions in relapse-like drinking. Only sub-chronic psilocybin had a short-lasting anti-relapse effect, but this regimen is not considered a translatable treatment. The findings do not support the hypothesis that microdosing or high-dose psychedelics reduce relapse behavior in this model, though the authors note that animal models may not fully capture psychedelics' therapeutic potential.
Pharmacopsychiatry
January 20, 2021
Lea J. Mertens, Katrin H. Preller
63 citations
Classical psychedelics such as psilocybin and LSD were studied in the 1950s and 1960s for substance-assisted psychotherapy and are now being reexamined. Modern clinical research provides new evidence for their safety and efficacy in treating substance use disorders and unipolar depression. This review outlines shared pathological mechanisms of these conditions, summarizes current literature on psychedelics' effects, and discusses clinical trials since 2011. Results are promising, but most trials lack methodological rigor for firm conclusions. Larger, blinded, randomized controlled trials with clear patient groups and endpoints are needed. Therapeutic mechanisms remain unknown, and hypotheses from preclinical and human studies require testing.
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.
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.
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.
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.
InFo Neurologie + Psychiatrie
February 1, 2023
Lea J. Mertens
No Summary