Psilocybin Biases Facial Recognition, Goal-Directed Behavior, and Mood State Toward Positive Relative to Negative Emotions Through Different Serotonergic Subreceptors

doi:10.1016/j.biopsych.2012.04.005

Biological Psychiatry

Volume 72, Issue 11, 1 December 2012, Pages 898-906

https://doi.org/10.1016/j.biopsych.2012.04.005 Get rights and content

Background

Serotonin (5-HT) 1A and 2A receptors have been associated with dysfunctional emotional processing biases in mood disorders. These receptors further predominantly mediate the subjective and behavioral effects of psilocybin and might be important for its recently suggested antidepressive effects. However, the effect of psilocybin on emotional processing biases and the specific contribution of 5-HT2A receptors across different emotional domains is unknown.

Methods

In a randomized, double-blind study, 17 healthy human subjects received on 4 separate days placebo, psilocybin (215 μg/kg), the preferential 5-HT2A antagonist ketanserin (50 mg), or psilocybin plus ketanserin. Mood states were assessed by self-report ratings, and behavioral and event-related potential measurements were used to quantify facial emotional recognition and goal-directed behavior toward emotional cues.

Results

Psilocybin enhanced positive mood and attenuated recognition of negative facial expression. Furthermore, psilocybin increased goal-directed behavior toward positive compared with negative cues, facilitated positive but inhibited negative sequential emotional effects, and valence-dependently attenuated the P300 component. Ketanserin alone had no effects but blocked the psilocybin-induced mood enhancement and decreased recognition of negative facial expression.

Conclusions

This study shows that psilocybin shifts the emotional bias across various psychological domains and that activation of 5-HT2A receptors is central in mood regulation and emotional face recognition in healthy subjects. These findings may not only have implications for the pathophysiology of dysfunctional emotional biases but may also provide a framework to delineate the mechanisms underlying psylocybin's putative antidepressant effects.

Section snippets

Subjects

Seventeen healthy, right-handed subjects (11 male subjects, 6 female subjects, mean age 26.0 ± 4.36 years, 15 university students/graduates, 1 high school diploma, 1 apprenticeship) were recruited through advertisement from the University of Zürich. All subjects were healthy according to physical examination, including electrocardiography and detailed blood analysis. The Mini-International Neuropsychiatric Interview for DSM-IV (38), the Expert System for Diagnosing Mental Disorders (39), and

PANAS

Repeated-measures analysis of variance (ANOVA) with pretreatment, treatment, and subscale as within-subject factors revealed that psilocybin significantly increased PANAS scores [F(1,16) = 16.608, p < .001, η_p² = .509]. Importantly, the triple interaction between pretreatment × treatment × subscale [F(1,16) = 21.160, p < .001, η_p² = .569] showed that psilocybin significantly increased positive affect subscale after pretreatment with placebo (p < .00001) but not ketanserin (p = 1) (Figure 1). In

Discussion

Our data show that psilocybin biases emotional processing toward positive relative to negative information, an effect that is consistent across different psychological domains. Specifically, psilocybin first enhanced positive mood states; second, decreased recognition of negative facial expression; and third, increased behavior toward positive relative to negative cues. In contrast to these generalized effects of the serotonergic agonist psilocybin, a more specific role for 5-HT2A receptors in

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Priority CommunicationPsilocybin Biases Facial Recognition, Goal-Directed Behavior, and Mood State Toward Positive Relative to Negative Emotions Through Different Serotonergic Subreceptors

Background

Methods

Results

Conclusions

Section snippets

Subjects

PANAS

Discussion

Curr Opin Pharmacol

Biol Psychiatry

Biol Psychiatry

Neuroimage

Pharmacol Biochem Behav

Behav Brain Res

Behav Brain Res

Behav Brain Res

Prog Neuropsychopharmacol Biol Psychiatry

Brain Res Bull

Behav Brain Res

Biol Psychiatry

Pharmacol Ther

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Biol Psychol

Electroencephalogr Clin Neurophysiol

Biol Psychiatry

Trends Cogn Sci

Biol Psychiatry

Brain Res

Arch Clin Neuropsychol

Int J Psychophysiol

J Affect Disord

Neuroimage

Biol Psychol

Clin Neurophysiol

J Affect Disord

Is this happiness I see?Biases in the identification of emotional facial expressions in depression and social phobia

J Abnorm Psychol

Emotional bias and inhibitory control processes in mania and depression

Psychol Med

Mood-congruent bias in affective go/no-go performance of unmedicated patients with major depressive disorder

Am J Psychiatry

Affective cognition and its disruption in mood disorders

Neuropsychopharmacology

Decrease in brain serotonin 2 receptor binding in patients with major depression following desipramine treatment: A positron emission tomography study with fluorine-18-labeled setoperone

Arch Gen Psychiatry

Modifying 5-HT1A receptor gene expression as a new target for antidepressant therapy

Front Neurosci

Dysfunctional attitudes and 5-HT2 receptors during depression and self-harm

Am J Psychiatry

Priority Communication
Psilocybin Biases Facial Recognition, Goal-Directed Behavior, and Mood State Toward Positive Relative to Negative Emotions Through Different Serotonergic Subreceptors