Robin von Rotz - Mindscape Collective

Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial.

EClinicalMedicine February 1, 2023 Robin von Rotz, Eva M Schindowski, Johannes Jungwirth et al. 345 citations

A single, moderate dose of psilocybin (0.215 mg/kg body weight) significantly reduced depressive symptoms compared to placebo in adults with major depressive disorder. Over two weeks, depression severity scores dropped by 13.0 points on the MADRS and 13.2 points on the BDI in the psilocybin group, with improvements significantly larger than in the placebo group. 54% of participants receiving psilocybin met remission criteria. No serious adverse events occurred. The findings suggest psilocybin offers rapid antidepressant effects, though larger, longer-term trials are needed.

DOI: 10.1016/j.eclinm.2022.101809 Full text Depression Major depressive disorder Psychedelic-assisted therapy Magic mushrooms +8

TMS-EEG and resting-state EEG applied to altered states of consciousness: oscillations, complexity, and phenomenology.

iScience May 19, 2023 Andres Ort, John W Smallridge, Simone Sarasso et al. 47 citations

Classical psychedelic drugs like psilocybin induce profound changes in consciousness, including heightened sensory-emotional awareness and arousal, accompanied by increased spontaneous EEG signal diversity. By combining Transcranial Magnetic Stimulation (TMS) with EEG, this work shows that psilocybin creates a state of increased chaotic brain activity, which is not due to altered complexity in causal interactions between brain regions. The study also maps regional effects of psilocybin on TMS-evoked activity, identifying changes in frontal brain structures that may relate to the phenomenology of psychedelic experiences.

DOI: 10.1016/j.isci.2023.106589 Full text Psilocybin Medical imaging Pharmacology Neuroscience clinical neuroscience +6

Potential therapeutic effects of an ayahuasca-inspired N,N-DMT and harmine formulation: a controlled trial in healthy subjects.

Frontiers in psychiatry January 1, 2023 Helena D Aicher, Michael J Mueller, Dario A Dornbierer et al. 34 citations

A standardized formulation combining the monoamine oxidase inhibitor harmine (100 mg orodispersible tablet) with incremental intranasal N,N-dimethyltryptamine (DMT, up to 100 mg) produced a psychedelic experience in 31 healthy male subjects, as measured by the 5D-ASC rating scale. The experience was characterized by psychological insights, emotional breakthroughs, and low scores on challenging experiences. Participants reported personal and spiritual significance and mainly positive persisting effects at 1- and 4-month follow-ups. No changes in trait personality, psychological flexibility, general well-being, or increases in psychopathology were observed. The formulation appears well tolerated and may support psychotherapy, but further studies in patients are needed.

DOI: 10.3389/fpsyt.2023.1302559 Full text DMT Ayahuasca analog Harmine Psychological processes +7

Overcoming the clinical challenges of traditional ayahuasca: a first-in-human trial exploring novel routes of administration of N,N-Dimethyltryptamine and harmine.

Frontiers in pharmacology January 1, 2023 Dario A Dornbierer, Laurenz Marten, Jovin Mueller et al. 32 citations

Ayahuasca, an Amazonian plant medicine containing DMT and harmine, shows promise for mental health disorders but its oral use causes gastrointestinal side effects and unpredictable drug levels. This study tested new ayahuasca-analogue formulations in 10 healthy men: an oral capsule of purified DMT and harmine versus a combined oromucosal harmine tablet with intranasal DMT spray. The combined buccal/intranasal route significantly reduced variations in systemic exposure and attenuated common side effects like nausea, vomiting, and diarrhea compared to traditional oral ayahuasca. All preparations were well tolerated. This approach may enable safer, patient-friendly DMT/harmine administration for affective disorders.

DOI: 10.3389/fphar.2023.1246892 Full text Psychedelics/entheogens/hallucinogens Drug-delivery/formulations/administration Ayahuasca/DMT/Harmine Pharmaceutical-innovation/drug-development

Examining the pharmacokinetic and pharmacodynamic interaction of N,N-dimethyltryptamine and harmine in healthy volunteers: Α factorial dose-escalation study.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie March 1, 2025 Klemens Egger, Javier Jareño Redondo, Jovin Müller et al. 14 citations

Ayahuasca contains DMT and harmine, but their interactions are not fully understood. In a single-blind, randomized, two-arm, factorial dose-finding study with 16 healthy participants, each received six dose combinations of DMT (0-120 mg) and harmine (0-180 mg) via a transmucosal delivery system. All combinations produced dose-dependent subjective effects lasting 4-5 hours, with peak DMT and harmine levels reaching 33 ng/mL and 49 ng/mL, respectively. The interaction was bidirectional: harmine reduced DMT metabolism, while DMT altered harmine pharmacokinetics. The formulation had a favorable safety profile, supporting further testing for affective disorders.

DOI: 10.1016/j.biopha.2025.117908 Full text DMT Ayahuasca pharmahuasca Harmine Pharmacokinetics +5

Corrigendum to 'Single-dose psilocybin-assisted therapy in major depressive disorder: a placebo-controlled, double-blind, randomised clinical trial'.

EClinicalMedicine February 1, 2023 Robin von Rotz, Eva M Schindowski, Johannes Jungwirth et al. 8 citations correction

A correction was issued for a figure in a clinical trial on psilocybin-assisted therapy for major depressive disorder. The colors representing the Psilocybin and Placebo conditions were swapped in Fig. 2; the correction aligns them with the caption and other figures. The error does not affect the results. The trial found that a single, moderate dose of psilocybin significantly reduces depressive symptoms compared to placebo for at least two weeks, with no serious adverse events. Larger, multi-centric trials with longer follow-up are needed to optimize this treatment.

DOI: 10.1016/j.eclinm.2023.101841 Full text Psilocybin Depression Correction Clinical trials +1

Population pharmacokinetic-pharmacodynamic modeling of co-administered N,N-dimethyltryptamine and harmine in healthy subjects.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie July 9, 2025 Angela Äbelö, John W Smallridge, Robin von Rotz et al. 3 citations

The psychedelic compound DMT is often taken with harmine, a monoamine oxidase inhibitor, as in ayahuasca, but how harmine alters DMT's effects was not well understood. In a study of 16 healthy adults, six combinations of buccal DMT (0-120 mg) and harmine (0-180 mg) were given. Harmine increased DMT's bioavailability and prolonged its absorption, leading to higher and more sustained blood levels. The intensity of subjective psychedelic effects rose with dose, and harmine potentiated these effects at higher DMT doses. A mathematical model captured these relationships and individual variability, offering a foundation for more personalized dosing in psychedelic therapy.

DOI: 10.1016/j.biopha.2025.118329 Full text Pharmacodynamics Pharmacokinetics Psychedelics Harmine-DMT Interaction Alter +10

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