Blocking a serotonin receptor with pindolol made DMT's effects feel stronger

The question

Does blocking the serotonin 5-HT1A receptor change how strong the subjective effects of DMT feel?

What they did

Twelve experienced hallucinogen users (10 men, 2 women) took part in a double-blind, randomized, placebo-controlled study in which each person served as their own comparison. On separate occasions they received either 30 mg of oral pindolol (a drug that blocks the 5-HT1A serotonin receptor) or placebo before a sub-hallucinogenic dose of intravenous DMT (0.1 mg/kg of DMT fumarate). Subjective effects were rated using the Hallucinogen Rating Scale, and blood pressure and heart rate were recorded.

What they found

Pre-treatment with pindolol increased the subjective effects of DMT, with a moderate effect size (M = 0.514). Blood pressure and mean arterial pressure were also higher after pindolol, measured 2 minutes after DMT was given. Heart rate did not differ between conditions.

The fine print

Only 12 people took part, nearly all men, and all were experienced psychedelic users, so results may not apply to others. A single low, sub-hallucinogenic dose of DMT was used, and no long-term or clinical outcomes were measured. Pindolol also acts on other receptors, so the effect cannot be pinned entirely on 5-HT1A. This summary is based on the abstract only.

What it means

The findings suggest the 5-HT1A receptor helps dampen the subjective effects of DMT, adding detail to how psychedelics work in the brain, but this was a very small mechanism study with no therapeutic outcomes.

Evidence grade: Very low. A randomized, placebo-controlled crossover study, but with only 12 experienced psychedelic users and a single session per condition.

This summary is based on the study’s published abstract.