Effects of serotonin 2A/1A receptor stimulation on social exclusion processing

Abstract

Social ties are crucial for physical and mental health. However, psychiatric patients frequently encounter social rejection. Moreover, an increased reactivity to social exclusion influences the development, progression, and treatment of various psychiatric disorders. Nevertheless, the neuromodulatory substrates of rejection experiences are largely unknown. The preferential serotonin (5-HT) 2A/1A receptor agonist, psilocybin (Psi), reduces the processing of negative stimuli, but whether 5-HT2A/1A receptor stimulation modulates the processing of negative social interactions remains unclear. Therefore, this double-blind, randomized, counterbalanced, cross-over study assessed the neural response to social exclusion after the acute administration of Psi (0.215 mg/kg) or placebo (Pla) in 21 healthy volunteers by using functional magnetic resonance imaging (fMRI) and resting-state magnetic resonance spectroscopy (MRS). Participants reported a reduced feeling of social exclusion after Psi vs. Pla administration, and the neural response to social exclusion was decreased in the dorsal anterior cingulate cortex (dACC) and the middle frontal gyrus, key regions for social pain processing. The reduced neural response in the dACC was significantly correlated with Psi-induced changes in selfprocessing and decreased aspartate (Asp) content. In conclusion, 5-HT2A/1A receptor stimulation with psilocybin seems to reduce social pain processing in association with changes in self-experience. These findings may be relevant to the normalization of negative social interaction processing in psychiatric disorders characterized by increased rejection sensitivity. The current results also emphasize the importance of 5-HT2A/1A receptor subtypes and the Asp system in the control of social functioning, and as prospective targets in the treatment of sociocognitive impairments in psychiatric illnesses.social cognition | serotonin | psilocybin | functional magnetic resonance imaging | magnetic resonance spectroscopy

Decision‐makers are resilient in the face of social exclusion

“…The possibility that our manipulation did not work is further weakened by the fact that, in past research, Cyberball was effective in affecting self-reported perceptions of social exclusion (Van Beest, Williams, & Van Dijk, 2011;Walasek et al, 2015;Williams & Jarvis, 2006;Zadro et al, 2004) and had an impact on relevant brain activity (Eisenberger, Lieberman, & Williams, 2003;Preller et al, 2016) and behaviours (Lustenberger & Jagacinski, 2010;Warburton, Williams, & Cairns, 2006). In our studies, despite the significant and robust effect of a lowered need for belonging, we observed no differences in performance in the judgement and decision-making tasks.…”

The Challenging Experience Questionnaire: Characterization of challenging experiences with psilocybin mushrooms

“…Recent studies have also examined mystical-type (Barrett, Johnson, & Griffiths, 2015; Griffiths, Richards, McCann, & Jesse, 2006; Griffiths et al, 2011) or spiritual (Kometer, Pokorny, Seifritz, & Volleinweider, 2015) experiences, changes in self-referential processing or “ego dissolution” (Carhart-Harris et al, 2014; Tagliazucchi et al, 2016), altered social processing (Preller et al, 2016), visual imagery (Kaelen et al, 2016), changes in emotional experience (Kaelen et al, 2015; Kraehenmann et al, 2015), personality change (Carhart-Harris, Kaelen et al, 2016; Lebedev et al, 2016; MacLean, Johnson, & Griffiths, 2011), positive mental health outcomes (Hendricks, Thorne, Clark, Coombs, & Johnson, 2015; Johansen & Krebs, 2015), and enduring positive changes in attitudes, mood and behavior (Griffiths, Richards, Johnson, McCann, & Jesse, 2008; Griffiths et al, 2011) occasioned by these compounds. However, both recent experimental reports (Griffiths et al, 2006; Griffiths et al, 2011; Johnson et al, 2014; Studerus, Kometer, Hasler, & Vollenweider, 2011) and past clinical reports (Cohen, 1960; Strassman, 1984) indicate that challenging psychological experiences during the acute effects of psychedelics are not uncommon.…”

How does it feel to be on psilocybin? Dose-response relationships of subjective experiences in humans

“…Three publications were duplicates, meaning data from the same experiment was reported (see Table 1). While one duplicate reported identical data [20], two duplicates differed in sample size [21,22]. Based on requests to the authors, we included the bigger samples [23,24].…”