Role of the 5-HT2A Receptor in Self- and Other-Initiated Social Interaction in Lysergic Acid Diethylamide-Induced States: A Pharmacological fMRI Study

This double-blind, placebo-controlled, fMRI study (n=24) found that LSD (100 μg) reduced activity in brain areas responsible for self-processing and social cognition. This also translated to subjective effects and reduced joint attention.

Abstract

“Distortions of self-experience are critical symptoms of psychiatric disorders and have detrimental effects on social interactions. In light of the immense need for improved and targeted interventions for social impairments, it is important to better understand the neurochemical substrates of social interaction abilities. We therefore investigated the pharmacological and neural correlates of self- and other-initiated social interaction. In a double-blind, randomized, counterbalanced, crossover study 24 healthy human participants (18 males and 6 females) received either (1) placebo + placebo, (2) placebo + lysergic acid diethylamide (LSD; 100 μg, p.o.), or (3) ketanserin (40 mg, p.o.) + LSD (100 μg, p.o.) on three different occasions. Participants took part in an interactive task using eye-tracking and functional magnetic resonance imaging completing trials of self- and other-initiated joint and non-joint attention. Results demonstrate first, that LSD reduced activity in brain areas important for self-processing, but also social cognition; second, that change in brain activity was linked to subjective experience; and third, that LSD decreased the efficiency of establishing joint attention. Furthermore, LSD-induced effects were blocked by the serotonin 2A receptor (5-HT_2AR) antagonist ketanserin, indicating that effects of LSD are attributable to 5-HT_2AR stimulation. The current results demonstrate that activity in areas of the “social brain” can be modulated via the 5-HT_2AR thereby pointing toward this system as a potential target for the treatment of social impairments associated with psychiatric disorders.”

Authors: Katrin H. Preller, Leonhard Schilbach, Thomas Pokorny, Jan Flemming, Erich Seifritz & Franz X. Vollenweider

Notes

This paper is included in our ‘Top 12 Articles on Psychedelics and Serotonin (5HT) Receptors‘