Role of the 5-HT2AReceptor in Self- and Other-Initiated Social Interaction in Lysergic Acid Diethylamide-Induced States: A Pharmacological fMRI Study
Open accessAbstract
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.
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Hallucinogen-induced alterations in self-processing and social cognition are intertwined.
“This is in line with a study showing that hallucinogen-induced alterations in self-processing and social cognition are intertwined (34).”
From Modulation of Social Cognition via Hallucinogens and “Entactogens” (2019) · cites this paper as [34]
LSD-induced effects on joint attention processing, self/other differentiation, and social influence processing were blocked by ketanserin.
“In line with this, LSD-induced effects on joint attention processing, self/other differentiation, and social influence processing were blocked by ketanserin (34, 84).”
From Modulation of Social Cognition via Hallucinogens and “Entactogens” (2019) · cites this paper as [34]
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- Authors
- Preller, K. H., Schilbach, L., Pokorny, T., Flemming, J., Seifritz, E., & Vollenweider, F. X.
- Affiliations
- University Hospital Zurich (CH)
- Max Planck Institute of Psychiatry (DE)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2018-03-19
- Volume
- 38
- Issue
- 14
- Pages
- 3603-3611
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6596041
- OpenAlex
- W2790184875
- Cited by
- 71
- References
- 63
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 10 · 2023: 8 · 2022: 11 · 2021: 7 · 2020: 12 · 2019: 11 · 2018: 1
- FWCI
- 9.11
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Science Foundation
- Heffter Research Institute (1‐190413)
- Usona Institute (2015 - 2056)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (161626, 190413)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- 5-HT2A receptor, lysergic acid diethylamide, ketanserin, self-experience, social cognition, joint attention, social brain, subjective experience, serotonin, pharmacotherapy targets
- MeSH terms
- Adult, Attention, Brain, Cognition, Eye Movements, Female, Hallucinogens, Humans, Interpersonal Relations, Ketanserin, Lysergic Acid Diethylamide, Magnetic Resonance Imaging, Male, Serotonin Antagonists, Serotonin Receptor Agonists
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