ArticlePsychopharmacology2026
Combined DMT-harmine formulation reduces negative self-referential emotions during social self-evaluation: a randomized placebo-controlled trial in healthy volunteers.
Article in Psychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
RATIONALE AND
objectivesNegative 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.
methodsIn 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).
resultsHAR/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.
conclusionsThese 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.
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