John W Smallridge - Mindscape Collective

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

Meditating on psychedelics. A randomized placebo-controlled study of DMT and harmine in a mindfulness retreat

Journal of Psychopharmacology September 27, 2024 Daniel Meling, Klemens Egger, Jovin Mueller et al. 15 citations

In a double-blind, placebo-controlled study over a 3-day meditation retreat, 40 experienced meditators received either DMT-harmine or a placebo. Those who took DMT-harmine reported greater mystical-type experiences, non-dual awareness, and emotional breakthrough during the acute substance effects, and greater psychological insight one day later after adjusting for baseline differences. Mindfulness and compassion did not differ significantly between groups. At one-month follow-up, the DMT-harmine group rated their experience as more personally meaningful, spiritually significant, and well-being-enhancing than the placebo group. The findings suggest specific synergistic effects of DMT-harmine during meditation.

DOI: 10.1177/02698811241282637 Ayahuasca Meditation Mindfulness Psilocybin +5

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

The influence of psilocybin on subconscious and conscious emotional learning

iScience May 19, 2024 Andres Ort, John W Smallridge, Erich Seifritz et al. 1 citation

Psilocybin, a serotonergic psychedelic being studied for psychiatric treatment, preserved reinforcement learning in a probabilistic cue-reward task using emotional faces presented consciously or subconsciously. Across dosages, psilocybin was statistically noninferior to placebo and suggested higher exploratory behavior. The 20 mg group showed significantly better learning rates than placebo. Psilocybin led to inferior learning with subconscious cues compared to placebo, but better results with conscious neutral cues in some conditions. The findings indicate that modulating serotonin signaling with psilocybin sufficiently preserves reinforcement learning.

DOI: 10.1016/j.isci.2024.110034 Psilocybin Neuroscience Subconscious Psychology +2

Global increases in brain glucose metabolism following acute N,N-dimethyltryptamine and harmine administration in healthy volunteers: A randomised [18F]FDG-PET study.

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism June 1, 2026 Klemens Egger, Robert Bozsak, Helena D Aicher et al.

A psychedelic dose of DMT combined with harmine (mimicking ayahuasca) globally increased cerebral glucose metabolism by 12.5% in 14 healthy males, as measured by FDG-PET scans during peak drug effects. Widespread cortical increases appeared in higher-order brain networks. Global glucose metabolism correlated positively with harmine plasma levels but not with DMT levels or subjective intensity. This recapitulates a classic finding for psilocybin, suggesting a potential metabolic signature of the psychedelic state.

DOI: 10.1177/0271678x261454172 Full text DMT Fdg-PET Glucose metabolism Harmine +2

Global increases in brain glucose metabolism following acute N,N-dimethyltryptamine and harmine administration in healthy volunteers: A randomised [ 18 F]FDG-PET study

Universität Zürich, ZORA June 1, 2026 Klemens Egger, Robert Bozsak, Helena D Aicher et al.

A psychedelic dose of DMT combined with the MAO-A inhibitor harmine, mimicking ayahuasca, globally increased cerebral glucose metabolism by 12.5% compared to placebo in 14 healthy males. Scans acquired during peak drug effects using FDG-PET showed widespread cortical increases, particularly in higher-order brain networks. Higher harmine plasma levels correlated with greater global glucose metabolism, while DMT levels and subjective intensity did not. This metabolic signature recapitulates a classic finding for psilocybin, suggesting a potential hallmark of the psychedelic state.

DOI: 10.5167/uzh-434709 Harmine Placebo Neuroimaging Metabolite +12