Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
January 1, 2023
Abigail E. Calder, Gregor Hasler
303 citations
Classic psychedelics like LSD, psilocybin, and ayahuasca may help treat depression, anxiety, and addiction, with clinical improvements lasting months or years. The leading theory is that these drugs rapidly and persistently stimulate neuroplasticity. This review examines evidence that psychedelics promote neuroplasticity, including dendritogenesis, synaptogenesis, neurogenesis, and plasticity-related gene expression, particularly in the prefrontal cortex and hippocampus. It also considers the doses required—hallucinogenic versus microdoses—and how long neuroplastic changes last. The authors discuss consequences for patients and healthy individuals and identify key research questions for future study.
European Neuropsychopharmacology
June 21, 2023
Seline Mock, Nicole Friedli, Patrick Pasi et al.
46 citations
Eating disorders are serious illnesses with high mortality and comorbidity. Psychedelic-assisted therapy shows promise for common comorbidities like mood disorders, PTSD, and substance use disorders, and may also benefit eating disorders themselves. This review summarizes preliminary data on ketamine, MDMA, psilocybin, and ayahuasca for anorexia nervosa, bulimia nervosa, and binge eating disorder. Preliminary evidence suggests psychedelic-assisted therapy may be effective for anorexia and bulimia, with very little data on binge eating disorder. Potential mechanisms include improving body image beliefs, normalizing reward processing, promoting cognitive flexibility, and facilitating trauma processing, alongside general therapeutic factors. Safety concerns and future research recommendations are discussed.
Journal of Psychopharmacology
January 12, 2024
Antonin Rouaud, Gregor Hasler, Abigail E. Calder
36 citations
Microdosing psychedelics like LSD and psilocybin has become popular, but its long-term effects on heart health are unknown. These drugs share structural similarities with medications that raise the risk of cardiac fibrosis and valvulopathy when taken regularly. This review evaluates the evidence that microdosing for months or more could increase the risk of cardiac fibrosis, discusses the role of the 5-HT2B receptor in drug-induced cardiac fibrosis, and recommends safety evaluations for future studies.
Psychopharmacology
January 15, 2022
Adrian Hase, M Erdmann, Verena Limbach et al.
33 citations
Differences among psychedelic substances in subjective experience can be detected through quantitative linguistic analysis of online experience reports. Analyzing 2947 reports, distinct linguistic profiles emerged: MDMA reports showed high emotional intensity and cognitive process words, while Ayahuasca/DMT reports had little emotional language, few cognitive process words, increased analytical thinking language, and the closest semantic similarity to mystical experience descriptions. LSD, psilocybin, and ketamine reports differed only slightly from each other on these measures. Antidepressant reports featured more negative emotion and cognitive process words and were unlike mystical or psychedelic language. These findings may inform experimental research and clinical trials.
CNS Spectrums
June 19, 2019
Gregor Hasler
31 citations
Around 50% of people with major depression respond to monoaminergic antidepressants, which modulate synapses but do not substantially influence synaptogenesis. They also increase brain-derived neurotrophic factor (BDNF), but for activity-dependent plasticity, BDNF release must work with synaptogenesis. Ketamine, in contrast, leads to fast changes in synaptic function and plasticity beyond classical antidepressants, suggesting it could enhance psychotherapy effects. Since ketamine's purely pharmacological effect is transient, such enhancement may become an important clinical indication. The editorial outlines mechanistic hypotheses for how Behavioral Activation, Trauma-Focused Psychotherapies, and Humanistic Psychotherapy may prolong ketamine's antidepressant effects.
Journal of affective disorders
November 15, 2024
Abigail E. Calder, Gregor Hasler
20 citations
A new standardized tool, the Swiss Psychedelic Side Effects Inventory (SPSI), was developed to systematically record clinically relevant side effects of psychedelics and MDMA, including their severity, duration, impact, and treatment-relatedness. The SPSI was constructed from previous research and pilot tested in 145 participants across three studies, with expert panel feedback improving its validity. The final version contains 32 side effects with standardized follow-up questions, compatible with any study design and administrable as interview or self-report. It omits less important side effects but includes space for additional symptoms. The SPSI is available in English and German to improve clinical decisions, informed consent, and patient safety.
Journal of Psychopharmacology
September 20, 2024
Abigail E Calder, Benjamin Rausch, Matthias E Liechti et al.
17 citations
In Switzerland, where psychedelic-assisted therapy (PAT) is permitted under a limited medical use program, patients receiving PAT and healthy volunteers given LSD or psilocybin reported similar overall drug effects and mystical experiences. However, patients reported lower ratings of ego dissolution. Depressive symptoms, measured by the Montgomery-Åsberg Depression Rating Scale, significantly decreased in patients. The strongest predictor of antidepressant improvement was relaxation during the session, while mystical-type experiences did not predict antidepressant effects. Most patients had mild adverse effects that resolved within 48 hours. Hourly assessments of drug effects may better predict clinical outcomes than retrospective measures of mystical experience.
European Neuropsychopharmacology
February 25, 2022
Gregor Hasler
17 citations
No Summary
Current topics in behavioral neurosciences
April 29, 2025
Abigail E Calder, Vincent J Diehl, Gregor Hasler
14 citations
Psychedelic experiences that involve extreme horror, helplessness, or perceived threats can be traumatizing. Such traumatic psychedelic experiences are rare, extreme, and largely preventable, arising from frightening drug effects, unsafe settings, or the emergence of pre-existing trauma. While some people recover quickly, others develop prolonged anxiety, sleep disturbances, derealization, or other trauma-related symptoms. The chapter covers causes, phenomenology, potential outcomes, prevention, and strategies to minimize negative impact.
JAMA Psychiatry
May 31, 2023
Abigail Calder, Gregor Hasler
14 citations
Optimizing safety for patients and therapists during psychedelic-assisted psychotherapy requires specific methods. The Viewpoint proposes approaches to enhance safety in this therapeutic context.
Molecular Psychiatry
November 29, 2024
Adrian Hase, Gregor Hasler, Abigail E. Calder
12 citations
A meta-analysis of 29 studies found no evidence that psychoplastogens—including ketamine, LSD, psilocybin, and MDMA—elevate peripheral brain-derived neurotrophic factor (BDNF) levels in humans. The overall effect size was negligible (SMD = 0.024) and not statistically significant. This null result held across different drugs, doses, blood fractions, participant ages, and psychiatric diagnoses. Better-controlled studies showed even smaller effects. The findings suggest that peripheral BDNF may not be a useful biomarker for rapid neuroplasticity changes in humans, or that preclinical findings on psychoplastogen-induced neuroplasticity may not translate to humans. More precise methods, such as neuroimaging, are recommended for future translational research.
Biological psychiatry global open science
March 1, 2025
Abigail E Calder, Clifford Qualls, Gregor Hasler et al.
5 citations
The Hallucinogen Rating Scale (HRS) is a widely used questionnaire for measuring subjective effects of psychedelics and other psychoactive drugs. By analyzing 991 questionnaires from 18 studies involving 13 substances, researchers identified 8 factors with good internal consistency that map onto psychedelic effects. The factor model fit the data better than previous models and showed dose responses for most drugs. Patterns on the 8 factors clearly distinguished classic psychedelics (psilocybin, DMT) from dissociatives (ketamine, salvinorin A), empathogens (MDMA), stimulants (methylphenidate, amphetamine), and THC. The meaningfulness factor uniquely differentiated psychedelics from all other substances, supporting the HRS as a psychometrically sound tool for measuring drug-induced altered states.
Frontiers in psychiatry
January 1, 2024
Aleksandra Kupferberg, Gregor Hasler
4 citations
Social cognitive deficits and impaired social behavior are common in major depressive disorder and harm quality of life and recovery. Standard treatments like antidepressants, psychotherapies, and brain stimulation show mixed results for improving social functioning, with some limitations and side effects. Newer treatments such as intranasal oxytocin, mindfulness-based cognitive therapy, and psychedelic-assisted psychotherapy have demonstrated positive effects on social cognition and behavior by modulating self-referential processing, empathy, emotion regulation, and enhancing neuroplasticity. Animal models reveal underlying neurobiological mechanisms. Future research should explore combining treatments and investigate long-term outcomes and individual differences.
The Lancet Psychiatry
February 15, 2023
Gregor Hasler
2 citations
No Summary
June 7, 2024
Abigail Calder, Gregor Hasler
1 citation
preprint
A new standardized tool, the Swiss Psychedelic Side Effects Inventory (SPSI), was developed to systematically record side effects of psychedelics and MDMA in clinical studies. The SPSI includes 32 side effects with follow-up questions on severity, duration, impact, and treatment-relatedness. It was pilot tested in 145 participants from three studies and refined with expert feedback. The tool is designed for any study design and can be used as an interview or self-report at any time after treatment. Its systematic approach aims to improve clinical decisions, informed consent, and patient safety by providing consistent side effect data.
Neuropsychopharmacology
June 18, 2026
Abigail E. Calder, Vincent J Diehl, Morten P. Lietz et al.
A single 100 µg dose of lysergic acid diethylamide (LSD) improved offline motor learning the next day and, one week later, reduced perceived stress and increased aspects of cognitive flexibility in 45 healthy adults. Electroencephalography showed that LSD acutely decreased N1 and P2 auditory event-related potential amplitudes, with P2 still modulated after one week. Transcranial magnetic stimulation revealed increased motor-evoked potential amplitude and faster latency under LSD. Brain-derived neurotrophic factor levels were unchanged. The findings suggest lasting effects of LSD on learning and neural signals, while highlighting challenges in measuring long-term potentiation in humans.
Journal of psychopharmacology (Oxford, England)
May 1, 2026
Vincent J Diehl, Abigail E Calder, Gregor Hasler
A new questionnaire, the Helioscope Questionnaire, measures how psychedelics such as psilocybin and MDMA alter the processing of traumatic memories during an experience, a process called the helioscope effect. In an online survey of 468 people who had used psychedelics or MDMA, the 21-item scale captured three factors: protection, exposure, and avoidant-distress. A composite score from protection and exposure subscales predicted positive changes in mood and attitude afterward, while avoidant-distress predicted negative changes. Having a trip sitter was linked to stronger protection and exposure scores, and MDMA use was linked to less avoidant-distress. The scale adds a new way to assess therapeutic mechanisms beyond existing measures.
Therapeutic advances in psychopharmacology
January 1, 2026
Kristian Beichmann, Polina Catzeflis, Helena D Aicher et al.
In Switzerland, physicians provide psychedelic-assisted therapy (PAT) with psilocybin, LSD, or MDMA under case-by-case exemptions from the Federal Office of Public Health. An anonymous survey of 41 physicians found that PAT is used mainly for depression, anxiety, PTSD, and chronic pain. Most physicians work in private practices (82%) and use body-oriented (61%), psychodynamic (59%), and eclectic (54%) approaches. Psilocybin is the most used substance (85%), followed by MDMA (71%) and LSD (65.9%). Substance choice is linked to diagnosis: psilocybin for depression (54%) and substance use disorder (46%), MDMA for PTSD (86%) and anxiety (54%). Music is played in 90% of sessions. Group therapy is common; 42% provide both individual and group settings. Challenges include legal constraints, high patient expectations, and financial barriers.
Psychedelics
September 2, 2025
Gregor Hasler
Professor Gregor Hasler's research focuses on how psychedelics such as LSD, psilocybin, and MDMA can rapidly enhance neuroplasticity, leading to clinical improvements in depression, PTSD, and addiction that last months or years after treatment. His team discovered that mGluR5 is a biomarker for nicotine dependence, translating molecular research into practical applications. Hasler's work on glutamate and GABA systems has reshaped understanding of mood disorders and opened new treatment pathways for treatment-resistant conditions. His book 'Higher Self: Psychedelics in Psychotherapy' synthesizes decades of research, advocating for safe integration of psychedelic therapies into mainstream medicine.