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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 \u03bcg, p.o.), or (3) ketanserin (40 mg, p.o.) + LSD (100 \u03bcg, 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<jats:sub>2A<\/jats:sub>R) antagonist ketanserin, indicating that effects of LSD are attributable to 5-HT<jats:sub>2A<\/jats:sub>R stimulation. The current results demonstrate that activity in areas of the \u201csocial brain\u201d can be modulated via the 5-HT<jats:sub>2A<\/jats:sub>R thereby pointing toward this system as a potential target for the treatment of social impairments associated with psychiatric disorders.<\/jats:p><jats:p><jats:bold>SIGNIFICANCE STATEMENT<\/jats:bold>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 \u201csocial brain\u201d. Furthermore, these alterations are attributable to 5-HT<jats:sub>2A<\/jats:sub>receptor stimulation, thereby pinpointing toward this receptor system in the development of pharmacotherapies for sociocognitive deficits in psychiatric disorders.<\/jats:p>","DOI":"10.1523\/jneurosci.1939-17.2018","type":"journal-article","created":{"date-parts":[[2018,3,19]],"date-time":"2018-03-19T18:05:23Z","timestamp":1521482723000},"page":"3603-3611","source":"Crossref","is-referenced-by-count":73,"title":["Role of the 5-HT<sub>2A<\/sub>Receptor in Self- and Other-Initiated Social Interaction in Lysergic Acid Diethylamide-Induced States: A Pharmacological fMRI Study"],"prefix":"10.1523","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0413-7672","authenticated-orcid":false,"given":"Katrin H.","family":"Preller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonhard","family":"Schilbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Pokorny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Flemming","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erich","family":"Seifritz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz X.","family":"Vollenweider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2018,3,19]]},"reference":[{"key":"2023041803302609000_38.14.3603.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1884"},{"key":"2023041803302609000_38.14.3603.2","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2013.00169"},{"key":"2023041803302609000_38.14.3603.3","doi-asserted-by":"publisher","DOI":"10.1080\/02699931.2016.1160869"},{"key":"2023041803302609000_38.14.3603.4","doi-asserted-by":"publisher","DOI":"10.1038\/419269a"},{"key":"2023041803302609000_38.14.3603.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.dcn.2017.01.009"},{"key":"2023041803302609000_38.14.3603.6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1518377113"},{"key":"2023041803302609000_38.14.3603.7","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2014.00020"},{"key":"2023041803302609000_38.14.3603.8","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2002.1199"},{"key":"2023041803302609000_38.14.3603.9","doi-asserted-by":"publisher","DOI":"10.1016\/S0885-2014(01)00037-5"},{"key":"2023041803302609000_38.14.3603.10","doi-asserted-by":"publisher","DOI":"10.1093\/scan\/nst113"},{"key":"2023041803302609000_38.14.3603.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2016.02.022"},{"key":"2023041803302609000_38.14.3603.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2003.10.004"},{"key":"2023041803302609000_38.14.3603.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2016.08.022"},{"key":"2023041803302609000_38.14.3603.14","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-979351"},{"key":"2023041803302609000_38.14.3603.15","unstructured":"Dittrich A , Lamparter D , Maurer M (2006) 5D-ABZ: fragebogen zur erfassung aussergew\u00f6hnlicher bewusstseinszust\u00e4nde. 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