OPEN Foundation

R. Kraehenmann

The Effect of 5-HT2A/1a Agonist Treatment On Social Cognition, Empathy, and Social Decision-making

Abstract

Social cognition is a crucial factor influencing development, progress, and treatment of psychiatric disorders. However, social cognition skills are insufficiently targeted by current treatment approaches. In particular, patients suffering from depression show an increased negative reaction to social exclusion and deficits in empathy. The 5HT-1A/2A receptor agonist psilocybin has previously been shown to reduce the neural response to negative emotional stimuli. However, it is not known if this extends to negative social interaction and whether 5HT-1A/2A receptor stimulation induces changes in empathy. Given the clear need for improved treatment of socio-cognitive functioning in psychiatric disorders, it is important to better understand the neuronal and neuromodulatory substrates of social cognition.

In a double-blind, randomized, cross-over design we therefore investigated the neural response to ostracism after the acute administration of psilocybin (0.215mg/kg) and placebo in healthy volunteers using fMRI. Furthermore, we assessed cognitive and emotional empathy using the Multifaceted Empathy Test.

The neural response to social exclusion in the ACC – a brain region associated with ‘social pain”- was reduced after psilocybin administration compared to placebo. Furthermore, emotional empathy was enhanced after treatment with psilocybin while no significant differences were found in cognitive empathy.

These results show that the 5HT-1A/2A receptor subtypes play an important role in the modulation of socio-cognitive functioning and therefore may be relevant for the treatment of social cognition deficits in psychiatric disorders. In particular, they may be important for the normalization of empathy deficits and increased negative reaction to social exclusion in depressed patients.

Preller, K. H., Pokorny, T., Krähenmann, R., Dziobek, I., Stämpfli, P., & Vollenweider, F. X. (2015). The Effect of 5-HT2A/1a Agonist Treatment On Social Cognition, Empathy, and Social Decision-making. European Psychiatry, 30, 22. http://dx.doi.org/10.1016/S0924-9338(15)30017-1
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Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers

Abstract

Background
The amygdala is a key structure in serotonergic emotion-processing circuits. In healthy volunteers, acute administration of the serotonin 1A/2A/2C receptor agonist psilocybin reduces neural responses to negative stimuli and induces mood changes toward positive states. However, it is little-known whether psilocybin reduces amygdala reactivity to negative stimuli and whether any change in amygdala reactivity is related to mood change.

Methods
This study assessed the effects of acute administration of the hallucinogen psilocybin (.16 mg/kg) versus placebo on amygdala reactivity to negative stimuli in 25 healthy volunteers using blood oxygen level-dependent functional magnetic resonance imaging. Mood changes were assessed using the Positive and Negative Affect Schedule and the state portion of the State-Trait Anxiety Inventory. A double-blind, randomized, cross-over design was used with volunteers counterbalanced to receive psilocybin and placebo in two separate sessions at least 14 days apart.

Results
Amygdala reactivity to negative and neutral stimuli was lower after psilocybin administration than after placebo administration. The psilocybin-induced attenuation of right amygdala reactivity in response to negative stimuli was related to the psilocybin-induced increase in positive mood state.

Conclusions
These results demonstrate that acute treatment with psilocybin decreased amygdala reactivity during emotion processing and that this was associated with an increase of positive mood in healthy volunteers. These findings may be relevant to the normalization of amygdala hyperactivity and negative mood states in patients with major depression.

Kraehenmann, R., Preller, K. H., Scheidegger, M., Pokorny, T., Bosch, O. G., Seifritz, E., & Vollenwieder, F. X. (2014). Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers. Biological Psychiatry. http://dx.doi.org/10.1016/j.biopsych.2014.04.010
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