Treatment with psychedelics is psychotherapy: beyond reductionism
The Lancet Psychiatry December 12, 2023 Gerhard Gründer, Manuela Brand, Lea J. Mertens et al. 103 citations
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Moritz Spangemacher
Department for Molecular Neuroimaging, Central Institute of Mental Health, Mannheim Medical Faculty, Heidelberg University, Mannheim, Germany; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim Medical Faculty, Heidelberg University, Mannheim, Germany; German Institute for Mental Health (DZPG), partner sites Mannheim-Heidelberg-Ulm; MIND Foundation, Berlin; OVID Clinic, Berlin.
8 papers in the library · 113 citations · publishing 2023-2026
Papers
Baseline monocyte count predicts symptom improvement during intravenous ketamine therapy in treatment-resistant depression: a single-arm open-label observational study.
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.
Psilocybin as a disease-modifying drug—a salutogenic approach in psychiatry
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.
Psychotherapeutisches Setting und Integration bei psychedelikaassistierter Therapie
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.
Kynurenine pathway profiles as markers of ketamine response in treatment-resistant depression.
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.
Strong Alliance, Weak Conclusions: Comment on Goodwin et al. (2026) “The Role of Therapeutic Alliance in Psilocybin Treatment for Treatment-Resistant Depression”
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.
Long-Term Efficacy of Psilocybin with Adjunct Psychotherapy in Treatment-Resistant Major Depression (EPIsoDE): 6- and 12-Month Naturalistic Follow-Up of a Phase 2b Trial.
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.
[Mechanisms of action of antidepressive pharmacotherapy: brain and mind-body and environment].
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.