Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers

Kraehenmann, Rainer; Preller, Katrin H.; Scheidegger, Milan; Pokorny, Thomas; Bosch, Oliver G.; Seifritz, Erich; Vollenweider, Franz X.

doi:10.1016/j.biopsych.2014.04.010

Cited by 244 publications

(255 citation statements)

References 76 publications

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“…in this review on 5-HT 2A receptor expression in the amygdala) and may be implicated in the pathogenesis of depression. Kraehenmann et al (2015) used BOLD fMRI to evaluate the effects of psilocybin (0.16 mg/kg, p.o.) on brain activity during emotion processing in 25 healthy, right-handed subjects, focusing on the amygdala as a region of interest (ROI).…”

Section: B Possible Use In Depressionmentioning

confidence: 99%

Psychedelics

2016

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Section: B Possible Use In Depressionmentioning

confidence: 99%

Psychedelics

2016

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“…efforts into the effects of Psi on emotional processing and cognition have solely focused on the individual's response to external stimulus manipulations (10,20), as opposed to truly interactive, real-time social encounters. Indeed, studies investigating the neuropharmacological and neurochemical substrates of social interaction processing are rare.…”

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confidence: 99%

“…Notably, an increased reactivity to social exclusion is clinically relevant in depression, borderline personality disorder, social anxiety disorder, and other psychiatric disorders (24)(25)(26). Given previous reports of the capacity of Psi to attenuate negative stimulus processing (10,20), we predicted a reduced response to social exclusion after Psi administration.…”

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confidence: 99%

“…In addition, recent evidence suggests that Psi at moderate doses can enhance mood and attenuate the processing of negative emotional stimuli (e.g., negative facial expressions or threat-related scenes) (10,(19)(20)(21) via 5-HT2A receptor activation (20). Thus, Psi may have antidepressant properties (10,(19)(20)(21)(22). Nevertheless, it is unclear whether this shift in emotional processing translates into the social domain, particularly regarding negative social interaction processing, and is therefore of relevance to real-life functioning in patients suffering from psychiatric disorders.…”

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confidence: 99%

“…Recent evidence suggests that the serotonin [5-hydroxytryptamine (5-HT)] system encompassing 14 subtypes of 5-HT receptors not only plays a key role in the regulation of mood, affect, learning, and memory (2,9,10), but is also implicated in social cognition (11,12). Psilocybin [4-phosphoryloxy-N,N-dimethyltryptamine (Psi)] is a serotonergic hallucinogen that induces an altered state of consciousness characterized by changes in sensory perception, emotion, thought, and the sense of self in a dose-dependent manner (13).…”

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

Preller¹,

Pokorny²,

Höck

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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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

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