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.
Psychoactives
April 16, 2024
Daniel Meling, Rebecca Ehrenkranz, Sandeep M. Nayak et al.
26 citations
Psychedelic research has returned after a period of suppression, but media coverage now often overstates benefits as much as it once overstated risks. The actual evidence is more mixed than commonly portrayed, so conclusions about effectiveness remain preliminary. Poor communication may mislead patients and misinform policy. This article reviews studies on psychedelics for depression, noting that effect sizes for other depression treatments—cognitive behavioral therapy, mindfulness, SSRIs, and ketamine—have decreased over time as trials improved. The authors suggest the same may happen for psychedelics: larger, better-controlled trials will likely show smaller, more realistic benefits. Clear communication is essential to set public expectations and guide policy.
Frontiers in Psychology
August 6, 2021
Daniel Meling
20 citations
The enactive approach in cognitive science holds that cognition is sense-making: organisms enact a meaningful world rather than receiving a pre-given one. This sense-making has no fixed, substantial ground; it arises from a dynamic web of relations and is therefore groundless. The article argues that this groundlessness is not merely a theoretical concept but is directly accessible in lived experience. It explores what it means to know groundlessness and how one can come to know it, describing how this knowing fits within enactive theory and can be experienced when certain conditions are met. A reflexive analysis highlights the context-dependency and observer-relativity of these claims.
Frontiers in Psychology
April 3, 2023
Daniel Meling, Milan Scheidegger
17 citations
Psychedelics are psychoactive substances whose effects involve changes in biochemistry, brain activity, and subjective experience, but how these levels relate is debated. Two current views are the integration view and the pluralistic view. This article proposes an enactive perspective that re-evaluates the molecule-brain-experience relationship. It applies the concept of autonomy to the causal link between the drug and brain activity, and dynamic co-emergence to the link between brain activity and experience. This enactive view emphasizes interdependence and circular causality across multiple levels, supporting and enriching the pluralistic view by offering a principled account of how layered processes interact. It has implications for understanding causality in psychedelic therapy and research.
Frontiers in psychology
January 1, 2022
Daniel Meling
17 citations
Non-dual-oriented contemplative practices aim to shift experience into a mode where self-other and subject-object distinctions dissolve, de-reifying the sense of a separate observing witness. Despite the importance of such non-dual insight in traditions like Zen, Mahāmudrā, Dzogchen, and Advaita Vedanta, contemplative science has rarely studied these practices. This article uses an enactive cognitive science framework to model the requirements for a temporary experiential shift free from subject-object structure. It outlines common elements of non-dual practices, presents an enactive model of pure non-dual experience, and compares this model with Mahāmudrā meditation from Tibetan Buddhism to evaluate external coherence. The article concludes with a research agenda for studying non-dual practices.
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.
Scientific reports
March 26, 2024
Berit Singer, Daniel Meling, Matthias Hirsch-Hoffmann et al.
15 citations
Brain activity patterns during meditation shift after a psilocybin-assisted retreat, especially when open-monitoring meditation is practiced. Using functional MRI and a topological data analysis method (Mapper), researchers compared experienced meditators who received psilocybin or placebo over five days. The psilocybin group showed a link between positive derealization—an altered perception that can foster insight—and a greater geometric distance between open-monitoring meditation and resting-state brain activity, as measured by optimal transport distance. This suggests that combining psilocybin with open-monitoring practice enhances meta-awareness and insight. The findings point to possible brain markers for synergistic effects between mindfulness and psychedelics.
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.
The international journal of neuropsychopharmacology
December 28, 2024
Michael J Mueller, Helena D Aicher, Dario A Dornbierer et al.
10 citations
A new pharmaceutical formulation combining pure DMT and harmine produced ayahuasca-like psychological effects lasting 2-3 hours in 31 healthy male volunteers, with consistent drug levels and no serious adverse events. DMT reached peak plasma concentrations of 22.1 ng/mL, while buccal harmine reached 32.5 ng/mL in a sustained-release profile but caused no distinguishable subjective effects on its own. All drug conditions were safe and well tolerated, suggesting the formulation could reduce risks and improve therapeutic outcomes for mental health disorders.
NeuroImage
June 1, 2025
Dila Suay, Helena D Aicher, Micheal Kometer et al.
4 citations
A psychedelic formulation combining DMT and harmine, inspired by ayahuasca, altered brain responses to faces in 30 healthy men. It increased early visual reactivity (P1 wave) and disrupted face-structural encoding (N170 wave) for all face types. Crucially, it reduced the neural distinction between self and other faces in the P300 wave, while familiar-face processing remained stable. Harmine alone did not produce these effects. The findings suggest psychedelics can reorganize self-related neural dynamics, potentially promoting cognitive flexibility and offering therapeutic benefits for conditions involving rigid self-focus, such as depression and social anxiety.
Journal of psychopharmacology (Oxford, England)
June 19, 2025
Helena D Aicher, Ilhui A Wicki, Daniel Meling et al.
2 citations
A single dose of an ayahuasca-inspired DMT/harmine formulation increased mindfulness and compassion in 31 healthy participants one day after administration. The randomized, double-blind, placebo-controlled trial found significant effects on mindfulness, self-compassion, and compassion with others, with larger effects in participants who reported higher sensitivity to the drug. These results suggest the formulation may have therapeutic potential for enhancing traits relevant to mood disorders, though further research in clinical settings is needed.
The Oxford Handbook of Psychedelic, Religious, Spiritual, and Mystical Experiences
May 22, 2024
Daniel Meling, Milan Scheidegger
2 citations
Two competing views on psychedelic experiences—realism, which sees them as revealing a pre-given world, and idealism, which sees them as projections of a pre-given mind—both rely on grasping and representations. An enactive approach offers an alternative that moves beyond these assumptions, emphasizing observer relativity and context dependency without grounding experience in either the world or the self. The chapter argues for this perspective and discusses its implications for understanding the common core of psychedelic experiences, the role of hallucinogens in enactive theory, and the relationship between direct experience and belief.
Scientific Reports
March 18, 2026
Jonas T. T. Schlomberg, Daniel Meling, Robin Grylka et al.
The acute subjective effects of psychedelics are thought to be key to their therapeutic benefits, but conventional measurement methods may be biased. Using natural language processing to analyze phenomenological interviews from a randomized trial of DMT/harmine versus placebo during meditation in experienced meditators, the study found that meditation under DMT/harmine produced different thematic content and greater experiential diversity than meditation under placebo, though semantic overlap existed. The analysis detected well-known primary effects and subtle language patterns, including frequent use of Buddhist concepts and spiritual jargon regardless of condition. Findings suggest shared features between meditative and psychedelic states, a strong drug-context interconnection, and potential synergistic effects.
Scientific Reports
April 23, 2024
Berit Singer, Daniel Meling, Matthias Hirsch-Hoffmann et al.
No Summary
medRxiv
Klemens Egger, Daniel Meling, Firuze Polat et al.
preprint
In a double-blind, placebo-controlled pharmaco-fMRI study, 40 meditation practitioners on a three-day retreat received either placebo or buccal DMT-harmine (120 mg each). Meditation alone increased network segregation across several resting-state networks, while DMT-harmine increased functional connectivity within the visual network and between visual and attention networks. Between-group differences showed increased connectivity between visual and salience networks in the DMT-harmine group. No prolonged cortical gradient disruption was observed, indicating a return to typical brain organization shortly after the experience. Meditation reduced connectivity between networks, whereas DMT-harmine increased within- and between-network connectivity, revealing distinct neural mechanisms.