Combined DMT-harmine formulation reduces negative self-referential emotions during social self-evaluation: a randomized placebo-controlled trial in healthy volunteers.
Helena Aicher, Joëlle Dornbierer, Luzia Caflisch, Dila Suay, Michael J Mueller, Hans-Peter Landolt, Boris B. Quednow, Milan Scheidegger, Dario Dornbierer
Psychopharmacology July 14, 2026 DOI: 10.1007/s00213-026-07118-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind, placebo-controlled crossover trial Peer reviewed |
|---|---|
| Sample size | 28 |
| Population | Healthy males |
| Interventions | combined 100mg harmine and 100mg DMT harmine alone placebo |
| Dose | 100mg harmine and 100mg DMT |
| Topics | DMT |
| Keywords | Embarrassment Hallucinogens Harmine N,N-Dimethyltryptamine Self-concept Shame Social cognition |
| Key findings | A combination of harmine and DMT, but not harmine alone, significantly reduced embarrassment and shame compared to placebo in healthy males. |
Abstract
Negative self-referential emotions such as embarrassment and shame play a key role in the psychopathology of psychiatric disorders but are often insufficiently addressed by standard treatments. Psychedelics such as ayahuasca - an Amazonian plant decoction containing the psychedelic N,N-dimethyltryptamine (DMT) and harmala alkaloids, have been proposed to positively modulate self-referential processing. The aim of this study was to investigate the effects of an ayahuasca-inspired harmine+DMT formulation and harmine on embarrassment and shame. In this randomized, double-blind, placebo-controlled crossover trial (N = 28 healthy males), the effects of combined 100mg harmine and 100mg DMT (HAR/DMT), harmine alone (HAR), against placebo (PLA) on self-referential processing was investigated using a karaoke paradigm, where participants listened to recordings of their own singing (Self = S) and control vocal tracks (other bad = OB; other good = OG) and rated emotional responses. Acute emotions were assessed with visual analogue scales (items: pleasant, unpleasant, embarrassing, funny, and objective quality) and the Experiential Shame Scale (ESS). HAR/DMT compared to placebo significantly reduced embarrassment in the Self condition (EMM=-16.83, p=.001), but not in the two other conditions (OB: EMM=-4.38, p=.628; OG: EMM= 2.14, p=.894). HAR/DMT-HAR or HAR-PLA contrasts for embarrassment were not significant for any condition. HAR/DMT compared to placebo reduced ESS global score (F(df)= 4.26(2, 54); p=.019) and ESS emotional subscale (F(df)=5.11(2, 54); p=.009), while harmine alone showed no significant effects. These findings suggest that HAR/DMT acutely modulates negative self-referential emotions and may, thus, offer a promising therapeutic approach, which should be further investigated in clinical populations.
Comparable studies
Other randomized controlled trials on DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Dose-Response Study of N,N-Dimethyltryptamine in Humans Experienced hallucinogen users | 1994 | Double-blind, saline placebo-controlled, randomized study | n = 12 |
| DMT Models the Near-Death Experience Healthy participants | 2018 | Within-subjects placebo-controlled study | n = 13 |
| Human brain effects of DMT assessed via EEG-fMRI. Healthy volunteers | 2023 | Within-subjects, placebo-controlled design | n = 20 |
| Psychological Effects of (S)-Ketamine and N,N-Dimethyltryptamine (DMT): A Double-Blind, Cross-Over Study in Healthy Volunteers Healthy volunteers | 2005 | Double-blind crossover study | n = 9 |
| Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans Experienced hallucinogen users | 1996 | Randomized controlled trial | n = 13 |
Citations in the library
Cites 42
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- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Patients’ Accounts of Increased “Connectedness” and “Acceptance” After Psilocybin for Treatment-Resistant Depression Journal of Humanistic Psychology June 19, 2017
- The Psychedelic State Induced by Ayahuasca Modulates the Activity and Connectivity of the Default Mode Network PLoS One February 18, 2015
- Psychological flexibility mediates the relations between acute psychedelic effects and subjective decreases in depression and anxiety. Journal of Contextual Behavioral Science 2020
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