Combined DMT–harmine formulation reduces negative self-referential emotions during social self-evaluation: a randomized placebo-controlled trial in healthy volunteers

A new study examined whether a pharmaceutical formulation inspired by ayahuasca could reduce feelings of shame and embarrassment during socially evaluative situations

A new study examined whether a pharmaceutical formulation inspired by ayahuasca could reduce feelings of shame and embarrassment during socially evaluative situations

This was a Randomised, double-blind, placebo-controlled, crossover trial. 36 healthy men were recruited; 28 completed the full protocol and were included in the primary analyses.

Interventions:

• Harmine (100 mg buccal) + DMT (100 mg intranasal, given as repeated 10 mg doses)

• Harmine alone (100 mg)

• Placebo

• Each participant received all three interventions on separate study days

Key findings

Reduced embarrassment about oneself - Compared with placebo, the harmine + DMT combination significantly reduced embarrassment when participants listened to recordings of their own singing.

Reduced shame - The combined treatment significantly lowered:

• overall shame scores

• the emotional component of shame

Increased positive emotional responses

During self-listening, participants receiving harmine + DMT reported:

• less unpleasantness

• greater pleasantness

than under placebo, suggesting an acute shift towards more positive emotional processing of self-relevant experiences

Harmine alone showed little effect - Harmine without DMT did not significantly reduce embarrassment or shame.

The study provides early experimental evidence that an ayahuasca-inspired harmine + DMT formulation can acutely reduce embarrassment and emotional shame during socially evaluative situations in healthy men. Harmine alone produced no significant benefit. While the findings support further investigation into psychedelic-assisted treatments targeting excessive self-criticism and shame, they should not be interpreted as evidence of efficacy for psychiatric disorders until confirmed in larger clinical trials.

Abstract

Rationale and objectives

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.

Methods

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).

Results

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.

Conclusions

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.

Aicher, H.D., Dornbierer, J., Caflisch, L. et al. Combined DMT–harmine formulation reduces negative self-referential emotions during social self-evaluation: a randomized placebo-controlled trial in healthy volunteers. Psychopharmacology (2026). Read Paper

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