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

Michael Kometer, André Schmidt, Rosilla Bachmann, Erich Studerus, Erich Seifritz, Franz X. Vollenweider

Biological Psychiatry May 9, 2012 DOI: 10.1016/j.biopsych.2012.04.005 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized, double-blind study Peer reviewed
Sample size 17
Population Healthy human subjects
Interventions Psilocybin Ketanserin
Dose 215 μg/kg psilocybin, 50 mg ketanserin
Topics Psilocybin Serotonin
Keywords Mood Cognitive psychology
Citations 300
Key points Psilocybin shifts emotional processing biases toward positive stimuli across multiple domains, mediated by 5-HT2A receptor activation.

Abstract

BackgroundSerotonin (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.MethodsIn 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.ResultsPsilocybin 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.ConclusionsThis 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.

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

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