Role of the 5-HT2AReceptor in Self- and Other-Initiated Social Interaction in Lysergic Acid Diethylamide-Induced States: A Pharmacological fMRI Study
Journal of Neuroscience – March 19, 2018
Source: OpenAlex
Summary
Lysergic acid diethylamide (LSD) profoundly alters social interaction, a key area for Psychology and Mental Health Research Topics. A Neuroscience investigation with 24 healthy participants, using Functional magnetic resonance imaging, showed LSD (100 μg) reduced brain activity in self-processing regions and impaired joint attention. Crucially, 40 mg Ketanserin, a 5-HT2 receptor antagonist, blocked these neurochemical effects, indicating Serotonin 5-HT2 receptor stimulation drives LSD's influence on behavior. This highlights the 5-HT2 receptor as a target for social impairments.
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 2A R) antagonist ketanserin, indicating that effects of LSD are attributable to 5-HT 2A R stimulation. The current results demonstrate that activity in areas of the “social brain” can be modulated via the 5-HT 2A R thereby pointing toward this system as a potential target for the treatment of social impairments associated with psychiatric disorders. SIGNIFICANCE STATEMENT Distortions of self-representation and, potentially related to this, dysfunctional social cognition are central hallmarks of various psychiatric disorders and critically impact disease development, progression, treatment, as well as real-world functioning. However, these deficits are insufficiently targeted by current treatment approaches. The administration of lysergic acid diethylamide (LSD) in combination with functional magnetic resonance imaging and real-time eye-tracking offers the unique opportunity to study alterations in self-experience, their relation to social cognition, and the underlying neuropharmacology. Results demonstrate that LSD alters self-experience as well as basic social cognition processing in areas of the “social brain”. Furthermore, these alterations are attributable to 5-HT 2A receptor stimulation, thereby pinpointing toward this receptor system in the development of pharmacotherapies for sociocognitive deficits in psychiatric disorders.