This secondary analysis of an RCT fMRI study (n=40) of meditation practitioners during a 3-day retreat found that DMT-harmine (‘pharmahuasca’, 120mg/120mg buccal) increased functional connectivity within the visual network and between visual and attention networks, whilst meditation alone reduced between-network connectivity, with no evidence of prolonged cortical gradient disruption characteristic of acute psychedelic effects, suggesting distinct neural mechanisms for meditation versus psychedelic-augmented meditation.
Abstract of Meditation, psychedelics, and brain connectivity
“Both meditation and psychedelics are widely studied for their therapeutic potential in mental health. Recent research suggests potential synergies between mindfulness practice and psychedelics, though empirical studies have primarily focused on psilocybin. This study investigates the distinct and combined effects of mindfulness practice and an ayahuasca-inspired formulation containing N,N-dimethyltryptamine (DMT) and harmine on brain functional connectivity (FC), with implications for advancing clinical interventions. In this double-blind, placebo-controlled pharmaco-functional magnetic resonance imaging (fMRI) study, 40 meditation practitioners participated in a 3-day meditation retreat. They were randomized to receive either placebo or buccal DMT-harmine (120 mg each) and underwent fMRI scans 2 days before and after administration. Neural changes were assessed using multiple connectivity metrics, including within- and between-network connectivity, network and global connectivity, and cortical gradient analyses. Within-group changes showed that meditators in the placebo group exhibited increased network segregation across several resting-state networks, while the DMT-harmine group showed increased FC within the visual network (VIS) and between VIS and attention networks. Between-group differences similarly showed increased FC between VIS and the salience network (SAL) in the DMT-harmine group compared with placebo post-retreat. No evidence of prolonged cortical gradient disruption, which is characteristic of acute psychedelic action, was observed. This suggests a return to typical brain organization shortly after the experience. These findings reveal distinct neural mechanisms underlying meditation and psychedelic-augmented meditation. While meditation alone reduced FC between networks, DMT-harmine increased within- and between-network connectivity. Given the potential of meditation and psychedelics for improving mental health, further exploration of their synergistic potential in clinical contexts is warranted. This study advances the understanding of how psychedelics and mindfulness practice shape brain function, offering insights into their complementary roles in emotional and psychological well-being.”
Authors: Klemens Egger, Daniel Meling, Firuze Polat, Erich Seifritz, Mihai Avram & Milan Scheidegger
Summary of Meditation, psychedelics, and brain connectivity
Egger and colleagues set out to disentangle how meditation and a psychedelic intervention interact to shape large-scale brain connectivity, asking whether their effects are distinct, additive, or synergistic in the days after a combined retreat experience. The study focused on a modern, ayahuasca-inspired combination of N,N-dimethyltryptamine (DMT) and the monoamine oxidase-A inhibitor harmine, delivered during a structured mindfulness retreat, and examined subacute (two-day) changes in resting-state functional connectivity (FC). The introduction contrasts two literatures: acute psychedelic neuroimaging (often showing greater between-network coupling, reduced within-network integrity in systems such as the default mode network (DMN) and visual network (VIS), and increased signal diversity) and meditation research (often showing reductions in VIS–DMN coupling and shifts that support attentional control). The authors also note limited prior work directly combining psychedelics with meditation and emphasise that most prior synergy work has used psilocybin; it remains unclear whether findings generalise to DMT–harmine.
The authors pre-registered four analysis foci spanning multiple spatial scales: (1) within- and between-network connectivity among canonical resting-state networks (RSNs), (2) RSN-to-whole-brain connectivity maps, (3) parcel-wise “global connectivity” (mean correlation of each region with the rest of cortex), and (4) cortical gradient structure and “dispersion”—a manifold-learning characterisation of how unimodal (sensorimotor/visual) areas are differentiated from transmodal association cortex. They hypothesised that, relative to placebo, DMT–harmine would increase integrity and coupling of salience network (SAL) circuits and alter VIS–DMN/SAL–DMN relations, while meditation under placebo would preferentially decouple VIS from DMN and strengthen SAL–DMN.
Subjects and Methods
Participants and study design
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https://doi.org/10.1162/imag.a.907
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Cite this paper (APA)
Egger, K., Meling, D., Polat, F., Seifritz, E., Avram, M., & Scheidegger, M. (2025). Meditation, Psychedelics, and Brain Connectivity: A Randomised Controlled Resting-State fMRI Study of N, N-Dimethyltryptamine and Harmine in a Meditation Retreat. Imaging Neuroscience.
Study details
Compounds studied
Ayahuasca
Topics studied
Healthy Subjects
Study characteristics
Original Re-analysis
Placebo-Controlled
Double-Blind
Participants
40
Humans
Institutes
Institutes associated with this publication
University of ZurichWithin the Department of Psychiatry, Psychotherapy and Psychosomatics at the University of Zurich, Dr Mialn Scheidegger is leading team conducting psychedelic research and therapy development.
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