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.
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.
Therapeutic Advances in Psychopharmacology
January 1, 2023
Ricarda Evens, Tomislav Majić, Timo Torsten Schmidt et al.
49 citations
A systematic review of 48 studies involving 1,774 participants found that classic serotonergic psychedelics (LSD, psilocybin, DMT, 5-MeO-DMT, mescaline, or ayahuasca) produce a characteristic pattern of subacute effects lasting from one day to one month after use. These include reductions in psychopathological symptoms, increases in wellbeing, mood, mindfulness, social measures, spirituality, and positive behavioral changes, along with mixed changes in personality and creativity. Subacute adverse effects included headaches, sleep disturbances, and individual cases of increased psychological distress, but no serious adverse events were reported. The findings support the existence of a 'psychedelic afterglow' phenomenon that may enhance psychotherapeutic interventions.
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.
Journal of Psychopharmacology
October 21, 2025
Abdo Uyar, Linda Forbrich, Ulrike Lueken et al.
4 citations
Psychedelic clinical trials have grown exponentially since 2006, with a sharp acceleration after 2019. Psilocybin is the most studied substance and closest to approval, while short-acting psychedelics like 5-MeO-DMT have recently entered trials with narrower clinical goals. Industry involvement is rising, but university-led research still dominates. Reporting of psychotherapy components increased after 2023 FDA recommendations, yet descriptions of interventions remain inconsistent. The rapid expansion across diverse indications and substances reflects growing clinical interest, though industry prioritizes scalability and approval. Incomplete reporting of psychotherapeutic elements limits cross-study comparisons and understanding of which therapeutic combinations optimize outcomes.
Journal of Psychopharmacology
March 31, 2025
Tomislav Majić, Timo Torsten Schmidt, Anna Gröticke et al.
4 citations
A new questionnaire called the Afterglow Inventory (AGI) reliably measures pleasant psychological effects that can occur days after a psychedelic experience, such as with psilocybin or LSD. The AGI captures five distinct dimensions: vitality, transpersonal aspects, inspiration/creativity, interpersonal relationships, and relationship to nature. In an international online survey of 1,323 people who had recently used a psychedelic and 157 controls, the AGI successfully distinguished between the two groups. Stronger and more positive acute psychedelic experiences were associated with higher afterglow scores. This tool may help researchers understand how short-term afterglow effects connect to longer-term therapeutic outcomes.
Current topics in behavioral neurosciences
January 1, 2026
Tomislav Majić, Euphrosyne Gouzoulis‐mayfrank, Ricarda Evens
2 citations
Classic psychedelics like psilocybin, LSD, and 5-MeO-DMT show promise for treating mental health conditions, but enthusiastic media coverage has led to increased non-clinical use and more complications. While these substances have low toxicity and low addiction potential, their risks are often overlooked by mental health professionals, mirroring historical patterns with other psychoactive drugs. The effects unfold in acute, subacute, and long-term phases, essential for understanding both therapeutic use and risks. This overview classifies complications associated with classic psychedelics, examines causal attribution of disorders to their use, and discusses placement in diagnostic systems, aiming to maximize benefits and minimize harms in research and therapy.
October 22, 2024
Tomislav Majić, Timo Torsten Schmidt, Anna Gröticke et al.
1 citation
preprint
A new questionnaire called the Afterglow Inventory (AGI) was developed and validated to measure the pleasant, temporary psychological effects that sometimes follow the acute phase of a psychedelic experience. An international online survey of 1,323 people who had taken a psychedelic and 157 who had taken a non-psychedelic substance in the past four weeks identified five key factors: vitality, transpersonal aspects, inspiration/creativity, interpersonal relationships, and relationship to nature. The 24-item AGI successfully distinguished psychedelic users from controls, and its overall score was positively correlated with the intensity and positive valence of the acute effects. The AGI may help researchers better understand how acute, subacute, and long-term effects of psychedelics relate to each other.
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.
Psychological Medicine
January 1, 2026
Ricarda Evens, Abdo Uyar, Emily Gosslau et al.
About 31% of people who had a distressing psychedelic experience that lasted beyond the acute phase met diagnostic criteria for post-traumatic stress disorder (PTSD). Avoidance during the acute experience predicted worse PTSD symptoms, while acceptance predicted milder symptoms. Post-traumatic growth was unrelated to the intensity of the challenge or avoidance but was linked to acceptance. Most participants sought help from online resources or friends, though psychotherapy was rated most helpful. The study targeted those with highly challenging experiences, so findings do not reflect prevalence among all psychedelic users.