Progress in neuro-psychopharmacology & biological psychiatry
February 2, 2018
Simon Reiche, Leo Hermle, Stefan Gutwinski et al.
125 citations
Anxiety and depression are common in people with life-threatening diseases, harming quality of life and prognosis. Serotonergic hallucinogens like LSD and psilocybin were first studied in the 1960s, and interest has recently revived. A systematic review of clinical trials from 1960 to 2017 identified 11 eligible trials with 445 participants: 7 on LSD (323 participants), 3 on psilocybin (92), and 1 on DPT (30). Four more recent randomized controlled trials (104 participants) had higher methodological quality than earlier studies. Evidence supports that these substances reduce anxiety and depression in patients with life-threatening diseases, with anecdotal reports of improved quality of life and reduced fear of death. Side effects were low in studies following safety guidelines.
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.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
October 1, 2023
Tim Hirschfeld, Johanna Prugger, Tomislav Majić et al.
24 citations
LSD produces a sigmoid-like increase in altered states of consciousness that plateaus around 100 micrograms, with the strongest effects on perception and illusory imagination, followed by positive ego-dissolution. Anxiety and dread of ego dissolution show only small effects. Considerable variability in most measures indicates that non-pharmacological factors also shape subjective experiences. These dose-response relationships can serve as general references for future research to compare observed with expected effects and to explore phenomenological differences between psychedelics.
Frontiers in Pharmacology
September 16, 2021
Lukas A. Basedow, Thomas Riemer, Simon Reiche et al.
16 citations
Repeated use of serotonergic psychedelics such as LSD, ayahuasca, and peyote is associated with distinct neuropsychological profiles rather than a uniform pattern of impairment. A systematic review of 13 studies (539 participants) found that LSD users performed worse on executive-functioning tasks, ayahuasca users showed better performance on the Stroop incongruent task, and peyote users showed no differences across domains. However, methodological quality varied widely, and most studies failed to fully control for confounding factors like other substance use. The evidence suggests that different psychedelics may have different long-term cognitive consequences.
Journal of Psychopharmacology
March 4, 2021
Tomislav Majić, Meike Sauter, Felix Bermpohl et al.
14 citations
An online survey of 386 mostly well-educated individuals who had used Kambô, the secretion of the Giant Maki Frog, found that motivations included general healing, detoxification, and spiritual growth. Acute effects involved severe physical reactions and mild psychoactive experiences, with 41.97% reporting a feeling of connection to the frog's spirit. Most participants (87.31%) reported increased well-being or life satisfaction, and 64.26% considered Kambô of high spiritual significance. Few reported lasting physical (2.85%) or mental (1.81%) health problems attributed to Kambô. The authors note that further research is needed to understand how setting and expectations influence reported effects.
Scientific reports
June 26, 2024
Lukas A Basedow, Tomislav Majić, Nicklas Jakob Hafiz et al.
13 citations
A systematic review and meta-analysis examined how psychedelics and MDMA affect cognitive performance during acute drug effects and the sub-acute (afterglow) window. Acute psychedelic use impairs attention and executive function, while MDMA primarily impairs memory, leaving executive functions and attention unaffected. During the sub-acute period (at least 24 hours after acute effects subside), executive functioning and creativity may be increased following psychedelics, but no such effects were observed for MDMA. These findings can inform harm reduction recommendations for recreational use and support differential therapeutic approaches for psychedelics and MDMA.
Scientific Reports
December 9, 2020
Timo Torsten Schmidt, Simon Reiche, Caroline L. C. Hage et al.
12 citations
Kambô, the secretion of the Amazonian Giant Leaf Frog, contains many bioactive peptides and was traditionally used by indigenous Amazonian communities as medicine to improve hunting. In Western urban healing circles, its use has spread over the past 20 years. This retrospective study assessed psychological effects in 22 anonymous users using standardized questionnaires for altered states of consciousness. Acute effects were mild to moderate, with no psychedelic-type perceptual or thinking distortions. Persisting effects were predominantly positive, with high scores on personal and spiritual significance.
Fortschritte der Neurologie · Psychiatrie
July 1, 2017
Tomislav Majić, Henrik Jungaberle, Timo Torsten Schmidt et al.
10 citations
The use of serotonergic hallucinogens (psychedelics) such as LSD and psilocybin, and entactogens such as MDMA, in psychotherapy has recently gained increasing scientific interest. This review summarizes current evidence on substance-assisted psychotherapy with serotonergic psychoactive substances. A selective literature search in PubMed and the Cochrane Library identified studies since 2000 examining these substances in psychotherapy. Indications studied include alcohol dependence (LSD and psilocybin), nicotine dependence (psilocybin), anxiety and depression in life-threatening physical illness (LSD and psilocybin), obsessive-compulsive disorder (psilocybin), treatment-resistant major depression (psilocybin), and post-traumatic stress disorder (MDMA). Dependence disorders, PTSD, and anxiety and depression in life-threatening physical illness are the best-evaluated indications. Evidence suggests efficacy with relatively good tolerability, but further studies are needed to assess these substances as future options for certain treatment-resistant mental disorders.
Progress in neuro-psychopharmacology & biological psychiatry
April 2, 2025
Simon Reiche, Tim Hirschfeld, Anna Lena Gröticke et al.
5 citations
People who have used psychedelics such as psilocybin, LSD, or ayahuasca a mild to moderate number of times over their lives show broadly equivalent neuropsychological performance to non-users, but with a modest advantage in executive functions, particularly cognitive flexibility as measured by the Wisconsin Card Sorting Test (WCST). In matched-pair analyses, users performed better on the WCST, and dose-response analyses within the user group found that greater lifetime use was positively associated with fewer total errors, perseverative responses, perseverative errors, non-perseverative errors, and more conceptual level responses. The study did not find any negative associations between sporadic psychedelic use and cognition.
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.
bioRxiv (Cold Spring Harbor Laboratory)
November 7, 2022
Tim Hirschfeld, Johanna Prugger, Tomislav Majić et al.
4 citations
preprint
Lysergic acid diethylamide (LSD) produces a sigmoid-like increase in altered states of consciousness, with effects plateauing around 100 micrograms. The strongest changes involve perception and illusory imagination, followed by positively experienced ego-dissolution, while anxiety and dread of ego dissolution show only small effects. Considerable variability in responses highlights the importance of non-pharmacological factors. These dose-response relationships can serve as references for future research on LSD.
Scientific Reports
December 31, 2024
Georg Leistenschneider, Tomislav Majić, Simon Reiche et al.
3 citations
Classic psychedelics like LSD and psilocybin show promise for treating psychiatric disorders but can occasionally cause lasting psychological harm, including Hallucinogen Persisting Perception Disorder (HPPD), a rare condition with enduring perceptual symptoms. This study examined the neuropsychological profiles of eight individuals with HPPD using a comprehensive test battery, comparing their performance against normative data and two matched control groups (with and without prior psychedelic use). Some participants with HPPD scored below average on tests of visual memory and executive function. Statistically adjusted comparisons found no significant differences between groups, though unadjusted analyses hinted at impaired executive functions in HPPD patients. These preliminary findings highlight the need for more focused research on the neuropsychological aspects of HPPD.
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.
Current topics in behavioral neurosciences
January 1, 2026
Anna-Lena Bröcker, Tomislav Majić, Christiane Montag
2 citations
Psychotic symptoms are uncommon and non-specific adverse effects of classic psychedelics like LSD, psilocybin, and mescaline. They can occur during the acute drug phase, persist into the subacute period, or rarely develop into long-term psychotic illness. The symptoms can be deeply distressing due to rapid changes, unpredictability, and adverse behavioral consequences. Psychedelics have been used as research models for schizophrenia because of phenomenological overlaps, but this "model psychosis" paradigm has been criticized: etiology and psychodynamic background only partially apply.
Nature Medicine
July 24, 2023
Tomislav Majić, Stefan Ehrlich
2 citations
Psilocybin, a hallucinogen derived from mushrooms, shows promise as a treatment for anorexia nervosa. In a trial involving 50 participants, 70% reported significant reductions in eating disorder symptoms after just three sessions with a trained psychotherapist. The treatment appears to influence neurotransmitter receptors, potentially altering behaviors associated with anorexia. These findings suggest that psychedelics could reshape psychiatry and psychology approaches to eating disorders, offering new avenues for patients struggling with this challenging condition.
Current topics in behavioral neurosciences
January 1, 2026
Marija Franka Žuljević, Tomislav Majić
1 citation
Flashbacks, hallucinogen persisting perception disorder (HPPD), and reactivations are complications linked to classic psychedelic use, all involving perceptual disturbances similar to acute drug effects. HPPD is persistent, while flashbacks and reactivations are typically transient and cause less distress. HPPD has low relative prevalence but can be clinically significant; many patients mistakenly believe they have it, but only a minority meet diagnostic criteria. In very rare cases, HPPD becomes chronic and requires long-term treatment, but most cases resolve within a year or become tolerable. Evidence-based treatments are lacking, so current knowledge relies on case reports and clinical experience.
SUCHT - Zeitschrift für Wissenschaft und Praxis / Journal of Addiction Research and Practice
December 1, 2025
Dario Jalilzadeh Masah, Derin Marbin, Tomislav Majić
1 citation
Symptoms of depersonalization and derealization are common during the acute effects of classic psychedelics and can persist, leading to depersonalization-derealization disorder (DDD) with distress and help-seeking behavior. Three cases of DDD after use of LSD, psilocybin, and 5-methoxy-dimethyltryptamine are presented, all treated at an outpatient clinic for post-psychedelic complications. Symptoms emerged shortly after exposure and lasted months. Psychotherapeutic interventions were helpful, while initial misdiagnoses delayed treatment in some cases. Psychotherapy should be prioritized for psychedelic-related DDD, with pharmacological treatment as a second-line option. Exploring the acute drug experience may validate patients and strengthen the therapeutic relationship, while revealing psychodynamic factors underlying individual pathologies.
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.
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.
medRxiv Preprint Server
May 23, 2026
Lisa Maria Jöbstl, Bente Lubahn, Ebru Kaya et al.
preprint
A subset of individuals who use classic psychedelics outside clinical settings reports persisting adverse effects, including hallucinogen persisting perception disorder, depersonalization/derealization disorder, anxiety, and depression. Despite growing non-clinical use, few medical services are equipped to address these complications. The authors highlight a delay in attention to these persisting adverse effects relative to enthusiasm for therapeutic potential.
Fortschritte der Neurologie · Psychiatrie
April 1, 2024
Stefan Borgwardt, Tomislav Majić, Mihai Avram et al.
Classic psychedelics such as psilocybin, LSD, ayahuasca, and 5-MeO-DMT are attracting renewed psychiatric, psychotherapeutic, and neuroscientific interest, driven by recent clinical trials suggesting therapeutic benefits for treatment-resistant depression, substance use disorders, anxiety disorders, and existential distress in life-threatening physical illness. Despite these promising effects, the substances carry unique risks due to the phenomenology of their central nervous system effects, the temporal dynamics of their psychological impacts, and their biological action profile, distinguishing them from many other psychoactive drugs.
bioRxiv (Cold Spring Harbor Laboratory)
July 24, 2020
Timo Torsten Schmidt, Simon Reiche, Caroline L. C. Hage et al.
preprint
Kambô, the secretion of the Giant Leaf Frog (Phyllomedusa bicolor), is ritually used by Amazonian ethnicities against bad luck in hunting and has spread to Western urban centers, often alongside ayahuasca. A retrospective study of 22 anonymous users (mean age 39 years, 45.5% female) assessed acute and subacute psychological effects with standardized questionnaires. Acutely, participants reported mild to moderate psychological effects without psychedelic-type perceptual or thinking distortions. Persisting effects were predominantly positive and pleasant, with surprisingly high personal and spiritual significance. Subacute and long-term effects overlapped with the 'afterglow' phenomena following serotonergic psychedelics.