Effects of serotonin 2A/1A receptor stimulation on social exclusion processing
Katrin H. Preller, Thomas Pokorny, Andreas Hock, Rainer Kraehenmann, Philipp Stämpfli, Erich Seifritz, Milan Scheidegger, Franz X. Vollenweider
Proceedings of the National Academy of Sciences April 18, 2016 DOI: 10.1073/pnas.1524187113 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, randomized, counterbalanced, cross-over study Peer reviewed |
|---|---|
| Sample size | 21 |
| Population | Healthy volunteers |
| Intervention | Psilocybin |
| Dose | 0.215 mg/kg |
| Topics | Serotonin |
| Keywords | Stimulation 5-HT Receptor |
| Citations | 175 |
| Key points | Psilocybin reduces the neural response to social exclusion in the dorsal anterior cingulate cortex and middle frontal gyrus, associated with decreased feelings of social exclusion and changes in self-processing and aspartate content. |
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 self-processing 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.
Comparable studies
Other randomized controlled trials on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose?effect study Healthy human subjects | 2004 | Randomized controlled trial | n = 8 |
| Dose-Response Study of N,N-Dimethyltryptamine in Humans Experienced hallucinogen users | 1994 | Double-blind, saline placebo-controlled, randomized study | n = 12 |
| Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects Healthy subjects (8 women, 8 men) | 2014 | Double-blind, randomized, placebo-controlled, crossover study | n = 16 |
| Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Healthy human participants | 2018 | Double-blind, randomized, counterbalanced, cross-over study | n = 24 |
| Activation of Serotonin 2A Receptors Underlies the Psilocybin-Induced Effects on Oscillations, N170 Visual-Evoked Potentials, and Visual Hallucinations Healthy human subjects | 2013 | Randomized controlled trial |
Citations in the library
Cited by 124
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. Pharmacology & Therapeutics May 1, 2019
- Psychedelics, Meditation, and Self-Consciousness Frontiers in Psychology September 4, 2018
- The Challenging Experience Questionnaire: Characterization of challenging experiences with psilocybin mushrooms Journal of Psychopharmacology November 18, 2016
- Effective connectivity changes in LSD-induced altered states of consciousness in humans. Proceedings of the National Academy of Sciences January 28, 2019
and 119 more in the library
Cites 16
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
- Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies Journal of Psychopharmacology September 20, 2010
- Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers Biological Psychiatry April 26, 2014
- Psilocybin Biases Facial Recognition, Goal-Directed Behavior, and Mood State Toward Positive Relative to Negative Emotions Through Different Serotonergic Subreceptors Biological Psychiatry May 9, 2012
and 11 more in the library