5-HT1A receptor blockade potentiates the subjective effects of DMT.
Zarmeen Zahid, Rick J. Strassman, Clifford Qualls, Sandeep M. Nayak
Journal of Psychopharmacology May 2, 2026 DOI: 10.1177/02698811261443696 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, randomized, placebo-controlled within-subjects design Peer reviewed |
|---|---|
| Sample size | 12 |
| Population | Experienced hallucinogen-using participants |
| Interventions | Pindolol DMT fumarate |
| Dose | 0.1 mg/kg intravenous DMT fumarate, 30 mg oral racemic pindolol |
| Topics | DMT Serotonin |
| Keywords | 5-ht1a 5-ht2a Psychedelics Serotonin receptor Subjective effects |
| Key points | 5-HT1A receptor blockade with pindolol increased DMT-induced subjective effects with a moderate effect size. |
Abstract
Serotonergic psychedelics are being investigated in the treatment of various disorders and in the improvement of well-being. Evidence suggests that their subjective effects may play a role in long-term behavioral outcomes. The subjective effects are mediated by 5-HT2A receptor agonism, but the 5-HT1A receptor may also play a role in the subjective effects. This study elucidates the effects of 5-HT1A receptor blockade using pindolol pre-treatment on the subjective effects induced by N,N-dimethyltryptamine (DMT). In a double-blind, randomized, placebo-controlled within-subjects design, 12 (10 males, 2 females) experienced hallucinogen-using participants received a sub-hallucinogenic dose of intravenous DMT fumarate, 0.1 mg/kg, after pre-treatment with 30 mg oral racemic pindolol. Subjective effects were measured using the Hallucinogen Rating Scale. Pindolol pre-treatment increased DMT-induced subjective effects with a moderate effect size (M = 0.514). Blood pressure and mean arterial pressure also increased with pindolol pre-treatment at 2 minutes following DMT administration, but heart rate was not affected. 5-HT1A receptor blockade results in a global intensification of DMT-induced subjective effects, suggesting a functional role of 5-HT1A receptor action in the mechanism of psychedelic-induced subjective effects.
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
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and 22 more in the library