5-HT 1A receptor blockade potentiates the subjective effects of DMT

Introduction: 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-HT 2A receptor agonism, but the 5-HT 1A receptor may also play a role in the subjective effects. This study elucidates the effects of 5-HT 1A receptor blockade using pindolol pre-treatment on the subjective effects induced by N,N -dimethyltryptamine (DMT). Methods: 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. Results: 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. Conclusions: 5-HT 1A receptor blockade results in a global intensification of DMT-induced subjective effects, suggesting a functional role of 5-HT 1A receptor action in the mechanism of psychedelic-induced subjective effects.