Molecular psychiatry
April 1, 2025
Mihai Avram, Lydia Fortea, Lea Wollner et al.
26 citations
Lysergic acid diethylamide (LSD), d-amphetamine, and MDMA each reduce the integrity (within-network connectivity) of several brain networks, with LSD uniquely reducing integrity in the default-mode network. Contrary to expectations, amphetamines reduced integrity in more networks than LSD. LSD produced more pronounced decreases in between-network segregation, while amphetamines also induced increases. Seed-based connectivity mostly increased between networks across all substances, with LSD showing stronger effects than both amphetamines. All substances decreased global connectivity in visual areas, but LSD specifically increased global connectivity in the basal ganglia and thalamus. These findings clarify distinctive neurobiological effects of psychedelics and support further investigation of their therapeutic potential.
Neuroscience Applied
January 1, 2024
Isabelle Straumann, Friederike Holze, Laura Ley et al.
24 citations
A pooled analysis of three randomized crossover studies with 85 healthy participants and 113 single-dose administrations of psilocybin (15, 20, 25, and 30 mg) examined safety. The 20, 25, and 30 mg doses produced stronger subjective effects than 15 mg, and all doses induced higher 'good drug effects' than 'bad drug effects.' Only 25 and 30 mg increased anxiety. Autonomic effects were moderate: tachycardia occurred with 7% of administrations, and body temperature above 38°C rose with dose, reaching 32% at 30 mg. Kidney and liver function remained unchanged. Five participants (6%) reported transient flashbacks, and no serious adverse reactions occurred. The findings indicate that a single psilocybin dose is safe regarding acute psychological and physical harm in healthy participants under controlled conditions.
Journal of Psychopharmacology
October 31, 2023
Kurt Stocker, Matthias Hartmann, Laura Ley et al.
22 citations
A questionnaire that measures psychedelic experiences, the Psychedelic Experience Scale (PES), contains more useful subscales than the well-known Mystical Experience Questionnaire (MEQ30). Analyzing 239 measurements from 140 healthy participants given LSD or psilocybin, researchers identified four additional factors beyond the original four: paradoxicality, connectedness, visual experience, and distressing experience. Paradoxicality and connectedness correlated strongly with the mystical subscale. Adding these new subscales to the MEQ30 increased the variance explained alongside another measure, the 5D-ASC. A cluster analysis supported these findings. The results provide a validated 6-factor structure (MEQ40) covering mystical experience more comprehensively and a broader 48-item version (PES48), with the full 100-item PES available for future research.
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.
JAMA network open
November 4, 2024
Cihan Atila, Isabelle Straumann, Patrick Vizeli et al.
15 citations
A single dose of MDMA (ecstasy) caused acute hyponatremia (low blood sodium) in 31% of 96 healthy participants across four placebo-controlled trials. Hyponatremia occurred in 37% of those with unrestricted fluid intake but in none of the 15 participants whose fluid intake was restricted, suggesting fluid restriction may prevent this complication. The drop in sodium levels correlated with a sharp rise in oxytocin (433% increase) but not with copeptin, a marker of vasopressin. This challenges the long-held belief that MDMA-induced hyponatremia is caused by vasopressin release and instead points to oxytocin mimicking vasopressin's water-retaining effect in the kidneys due to structural similarity.
Translational psychiatry
September 4, 2024
Patrick Vizeli, Erich Studerus, Friederike Holze et al.
15 citations
LSD dose is the strongest predictor of the drug's subjective and autonomic effects, but non-pharmacological factors also play a significant role. Pre-drug mood states—such as well-being, emotional excitability, and anxiety—predict subjective effects, heart rate, and body temperature. The personality trait openness to experiences correlates with stronger mystical-type effects and oceanic boundlessness. Prior hallucinogen use is linked to less anxious ego dissolution and a less intense overall altered state. Acute anxiety relates negatively to the functionality of the Cytochrome 2D6 enzyme. Sex and body weight do not significantly influence the drug experience.
Biological psychiatry. Cognitive neuroscience and neuroimaging
May 1, 2024
Mihai Avram, Felix Müller, Katrin H Preller et al.
13 citations
In a double-blind, placebo-controlled, crossover study with 25 healthy participants, LSD, MDMA, and d-amphetamine all increased effective connectivity from the thalamus to specific unimodal cortices while reducing the influence of those cortices back onto the thalamus, indicating stronger bottom-up and weaker top-down information flow. For transmodal cortices, including parts of the salience network, amphetamines showed opposite effects. LSD uniquely increased effective connectivity from the thalamus to both unimodal and transmodal cortices, suggesting a breakdown in the hierarchical organization of brain activity. These findings refine models of how psychedelics alter brain connectivity.
British journal of clinical pharmacology
January 1, 2024
Friederike Holze, Livio Erne, Urs Duthaler et al.
12 citations
After oral doses of 85 and 170 μg, LSD reaches peak blood concentrations of 1.8 and 3.4 ng/mL at about 1.7 hours, with elimination half-lives of 3.7 and 4.0 hours. Only 1% of the dose is excreted unchanged in urine within 24 hours, while 16% is eliminated as the metabolite 2-oxo-3-hydroxy-LSD. Subjective drug effects last 9.3 to 11 hours, with maximal intensity reaching 77% to 87%. LSD shows dose-proportional pharmacokinetics and first-order elimination, and its effects are dose-dependent. The findings confirm earlier work on LSD's metabolism and time course.
Psychedelic Medicine
January 20, 2025
Marianna Graziosi, Gabrielle Agin-Liebes, Mary P Cosimano et al.
9 citations
Psilocybin and other serotonergic psychedelics are used in research settings with safety measures including controlled environments, staff presence, screening, and psychoeducation. An analysis of study materials from psilocybin trials over the past two decades found that psychoeducation documents varied but commonly emphasized biological and physical safety, psychological safety and well-being, aspects of setting, and the potential for expectancies. The materials prioritized biological and psychological safety across all sites. The authors also identified elements unrelated to safety that may contribute to participant expectancies and suggest these extrapharmacological factors be studied systematically to maximize safety while minimizing extraneous expectancies.
Clinical pharmacology and therapeutics
May 26, 2025
Denis Arikci, Friederike Holze, Lorenz Mueller et al.
6 citations
LSD base and tartrate formulations taken orally are bioequivalent, meaning they produce the same drug levels in the body. The absolute oral bioavailability of LSD is 80%, and all tested oral forms—ethanolic base solution, watery tartrate solution, and rapid-dissolving tablet—show similar pharmacokinetics. Intravenous LSD causes stronger subjective effects like ego dissolution and anxiety compared to oral forms. These findings support interchangeable oral dosing in research and clinical use.
Journal of psychopharmacology (Oxford, England)
December 26, 2025
Kurt Stocker, Matthias Hartmann, Yasmin Schmid et al.
5 citations
A psychometric revalidation of the Altered States of Consciousness Scale (ASC) using data from 901 questionnaires across 16 psychedelic studies (with LSD, psilocybin, mescaline, and DMT) shows that ten of the eleven subscales can be grouped into three higher-order dimensions—Positive Effects, Distressing Effects, and Perceptual Effects—mirroring the original three-dimensional model but with improved statistical fit. The Anxiety subscale could not be integrated due to floor effects (low anxiety in the sample) but is retained for clinical relevance. The revised scale, 3D-ASCr, is recommended for use with classic serotonergic psychedelics.
Drug metabolism and disposition: the biological fate of chemicals
April 28, 2025
Jan Thomann, Deborah Rudin, Selina Kraus et al.
4 citations
A liquid chromatography-tandem mass spectrometry method was developed and validated to measure the recreational psychedelic 2C-B and two of its metabolites (BDMPAA and B-2-HMPAA) in human plasma. The method achieved linear ranges of 0.5–100 ng/mL for 2C-B, 2.5–1000 ng/mL for BDMPAA, and 0.5–1000 ng/mL for B-2-HMPAA with high accuracy and precision. Pharmacokinetic analysis used samples from clinical participants who received 30 mg of 2C-B. Key metabolic enzymes included MAO-A, MAO-B, cytosolic enzymes, and CYP2D6. Unlike 2C-B, the metabolites did not activate the serotonin 2A receptor, indicating they do not contribute to the psychedelic effect. The method provides a reliable tool for future clinical studies.
Current topics in behavioral neurosciences
July 31, 2024
Friederike Holze, Matthias E. Liechti, Felix Müller
4 citations
Psychedelics, including phenethylamines (e.g., mescaline), tryptamines (e.g., psilocybin), and ergolines (e.g., LSD), bind to the serotonin 5-HT2A receptor, causing profound alterations in sensation, cognition, emotions, and self-perception. While generally considered physiologically safe compared to other recreational drugs, they carry risks of lasting psychological adverse reactions such as persisting anxiety, dissociation, or flashbacks. This chapter provides a comprehensive overview of their pharmacology, origins, psychological and autonomic effects, interactions, risks, dosing, and consumption methods, distinguishing them from other psychoactive drugs like MDMA and ketamine based on distinct receptor profiles.
Psychopharmacology
March 26, 2025
Laura Ley, Matthias E Liechti, Anna M Becker et al.
3 citations
Healthy volunteers enroll in psychedelic trials primarily out of interest in the substances and the appeal of the study setting, hoping for personal development and transformative experiences. In a series of six double-blind, placebo-controlled trials involving 151 participants, positive experiences were promoted by music, access to nature, and a trusting relationship with the investigator. A sterile hospital environment, lack of investigator support, and investigator-induced discomfort were criticized. Most volunteers felt their expectations were exceeded and would take the substances again, ideally in a natural setting with friends. Four key factors for positive study experiences are a secure interpersonal relationship, an aesthetically pleasing environment, access to nature, and music.
Neuroscience Applied
January 1, 2022
Friederike Holze, A. Becker, Karolina E. Kolaczynska et al.
3 citations
No Summary
Frontiers in psychiatry
January 1, 2025
Peter Gasser, Matthias E Liechti, Friederike Holze
2 citations
A 64-year-old man with traumatic life experiences and neuropathic pain from chemotherapy was treated with LSD and MDMA. Initial 200 µg LSD doses produced no acute effects, but 400 µg doses led to subjective effects and lasting therapeutic benefits. Switching to MDMA—both high doses (150-175 mg) and repeated low doses (12.5-25 mg)—resulted in marked improvements in neuropathic pain that persisted after treatment stopped. MDMA mini/microdosing has not been widely studied; this case documents benefits of low-dose MDMA for pain disorders, though further research is needed.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
July 1, 2026
Denis Arikci, Joran Borgulya, Isabelle Straumann et al.
1 citation
In a double-blind, randomized, placebo-controlled crossover trial, 24 healthy adults received three doses of 2C-B (10, 20, and 30 mg), 125 mg MDMA, and 25 mg psilocybin. The 30 mg dose of 2C-B produced subjective effects comparable to MDMA but weaker than psilocybin, and increased emotional empathy similarly to MDMA. Only psilocybin caused bad drug effects and anxiety. MDMA produced the greatest cardiovascular stimulation, followed by psilocybin and then 2C-B. Only MDMA raised plasma oxytocin and neurophysin I. The average subjective effect duration of 30 mg 2C-B was 4.9 hours, similar to MDMA (4.8 h) and shorter than psilocybin (6.1 h). 2C-B had a plasma elimination half-life of about 1.3 hours.
International journal of methods in psychiatric research
June 1, 2026
Kurt Stocker, Matthias Hartmann, Frederick S Barrett et al.
The eight-factor structure of the Psychedelic Experience Scale (PES48), which includes the Mystical Experience Questionnaire (MEQ30) and additional factors for paradoxicality, connectedness, visual experience, and distressing experience, is valid for use in English. Analysis of 280 measurements from 145 healthy participants in four placebo-controlled psilocybin studies found that six subscales have high internal consistency, one good, and one acceptable. Both the MEQ30 and MEQ40 models show acceptable to good model fits, with better fits in English than in German. All six MEQ40 scale means were higher in English data, suggesting that the PES48 provides a broader conceptualization of mystical and non-mystical psychedelic experiences, and that setting may influence mystical experience.
Religion Brain & Behavior
March 31, 2026
Kurt Stocker, Matthias Hartmann, Frederick S. Barrett et al.
After administration of LSD, psilocybin, mescaline, or DMT, mystical oneness—the core of mystical experience—showed dose-sensitive strong correlations with luminous light and renewal, and a moderate-to-strong correlation with ego disintegration. These findings from 386 healthy participants across 15 studies support a broader, dynamic model of mystical experience, where mystical oneness unfolds with ego disintegration, renewal, and luminous light. The results offer insights for psychedelic-assisted therapy.