Translational Psychiatry
December 14, 2023
Ivan Skorodumov, Rainer Spanagel, Jonathan R Reinwald et al.
25 citations
Psilocybin, a psychedelic compound, may help treat alcohol use disorder (AUD), but its brain effects in AUD are not well understood. In a placebo-controlled crossover study with healthy rats and a rat model of alcohol relapse, psilocybin broadly decreased functional connectivity across the brain while increasing connectivity between serotonin-related core regions and cortical areas. It also reduced connectivity within the default mode network (DMN), mirroring human findings. However, in rats with a history of alcohol relapse, this DMN hypoconnectivity was blunted, and the blunting correlated with relapse intensity. The results suggest that a standard psilocybin dose may be insufficient for severe AUD, a consideration for future clinical trials.
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.
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.
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 R 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.
Der Nervenarzt
March 1, 2022
Gerhard Gründer, Manuela Brand, Laura Kärtner et al.
Psychedelics like psilocybin are among the most promising new treatments for depression, potentially working within one day. A review of clinical studies from before the 1960s prohibition and after the 2000s revival—mostly using psilocybin—shows small sample sizes (total depressed patients <200) and some methodological weaknesses. Nevertheless, the evidence suggests a pronounced, very rapid antidepressant effect within one day for depression, treatment-resistant depression, and depression in life-threatening cancer, often lasting several months. Ongoing studies with hundreds of patients will clarify psilocybin's potential.