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.
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
January 20, 2025
Joshua Liebnau, Felix Betzler, André Kerber
10 citations
Psilocybin, given in a supportive setting, may relieve depression by promoting openness, cognitive and neural flexibility, and greater acceptance of emotional experiences. A renewed sense of connectedness to self, others, and the world emerged as a key experience. Imaging studies consistently found altered brain dynamics, including reduced connectivity within and across the default mode network and increased connectivity between networks. These changes may create a vulnerable window for change, highlighting the need for a supportive environment and therapeutic guidance. The antidepressant effects appear to arise from an interplay between neurobiological mechanisms and common psychotherapeutic factors, rather than from pharmacology alone.
Current topics in behavioral neurosciences
October 23, 2024
Grace Viljoen, Felix Betzler
5 citations
A systematic review of 39 papers examined whether classic psychedelics can cause anxiety and affective disorders, finding that persistent problems are rare and typically occur in people with multiple risk factors such as overdose, polydrug use, unstructured recreational settings, psychosocial stress, or personal or family psychiatric history. In clinical psychedelic-assisted therapy, enduring anxiety or mood symptoms were uncommon; acute anxiety that arose during sessions usually resolved on its own without extra treatment. The role of emotional catharsis in therapy is discussed. Recommendations to improve safety include strengthening the therapeutic alliance, ensuring adequate mental preparation, acclimating to high doses, and providing ongoing therapeutic support.
Journal of psychopharmacology (Oxford, England)
May 1, 2026
Grace Viljoen, Henrik Walter, Antonia Bendau et al.
3 citations
A systematic review of 54 studies found that the intensity of the acute psychedelic experience, particularly mystical-type experiences, is the most frequently reported predictor of therapeutic response in psychedelic-assisted therapy for mental disorders, though this was not consistent across all disorders or time points. Factors related to set, setting, and dose were associated with the likelihood and intensity of these experiences. The review included adult populations with substance-use disorders, major depressive disorder, anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, and existential distress, as well as naturalistic samples.
Psychopharmakotherapie
January 1, 2026
Antonia Bendau, Felix Betzler, Twyla Michnevich et al.
1 citation
Party drugs are a diverse group of legal and illegal psychoactive substances used in social settings like clubs and festivals to alter mood, perception, and social interaction. Alcohol and cannabis are most common, followed by amphetamine, MDMA, cocaine, and ketamine. These drugs act through various pharmacological mechanisms: alcohol affects GABAergic, glutamatergic, and dopaminergic systems; cannabis acts on the endocannabinoid system; stimulants increase monoaminergic neurotransmitters; MDMA has a strong serotonergic component; ketamine produces dissociative effects via glutamatergic mechanisms; and psychedelics alter sensory processing through serotonergic modulation. Polydrug use is frequent. Acute risks include cardiovascular strain, hyperthermia, and anxiety, while long-term consequences can involve cognitive impairments, dependence, and social complications.
npj Mental Health Research
July 10, 2026
Constantin Volkmann, Michael Seitz, Ricarda Evens et al.
Among Berlin university students followed for one year, first-time psychedelic users showed small increases in Openness and decreases in Conscientiousness compared to never-users. After adjusting for age, sex, income, psychiatric diagnosis, and baseline substance use, the changes were attenuated and not statistically significant after correction for multiple comparisons. Exploratory analyses indicated that first-time users with psychiatric diagnoses experienced larger reductions in Neuroticism. The personality changes were not clearly different from those seen in first-time users of other illicit substances, and the authors caution against causal interpretation.
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.