OPEN Foundation

R. Bachmann

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

December 19, 2012 / Anxiety disorders / PTSD, Depression, Mushrooms / Psilocybin, Neuroscience, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / , , , , ,

Abstract

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 g/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.

Kometer, M., Schmidt, A., Bachmann, R., Studerus, E., Seifritz, E., & Vollenweider, F. X. (2012). Psilocybin Biases Facial Recognition, Goal-Directed Behavior, and Mood State Toward Positive Relative to Negative Emotions Through Different Serotonergic Subreceptors. Biological Psychiatry, 72(11), 898-906. http://dx.doi.org/10.1016/j.biopsych.2012.04.005
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The NMDA antagonist ketamine and the 5-HT agonist psilocybin produce dissociable effects on structural encoding of emotional face expressions

July 27, 2012 / Anxiety disorders / PTSD, Depression, Ketamine, Mushrooms / Psilocybin, Neuroscience, Other subjects, Papers, Psychology, Publications / By / , , , ,

Abstract

Rationale
Both glutamate and serotonin (5-HT) play a key role in the pathophysiology of emotional biases. Recent studies indicate that the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine and the 5-HT receptor agonist psilocybin are implicated in emotion processing. However, as yet, no study has systematically compared their contribution to emotional biases.

Objectives
This study used event-related potentials (ERPs) and signal detection theory to compare the effects of the NMDA (via S-ketamine) and 5-HT (via psilocybin) receptor system on non-conscious or conscious emotional face processing biases.

Methods
S-ketamine or psilocybin was administrated to two groups of healthy subjects in a double-blind within-subject placebo-controlled design. We behaviorally assessed objective thresholds for non-conscious discrimination in all drug conditions. Electrophysiological responses to fearful, happy, and neutral faces were subsequently recorded with the face-specific P100 and N170 ERP.

Results
Both S-ketamine and psilocybin impaired the encoding of fearful faces as expressed by a reduced N170 over parieto-occipital brain regions. In contrast, while S-ketamine also impaired the encoding of happy facial expressions, psilocybin had no effect on the N170 in response to happy faces.

Conclusion
This study demonstrates that the NMDA and 5-HT receptor systems differentially contribute to the structural encoding of emotional face expressions as expressed by the N170. These findings suggest that the assessment of early visual evoked responses might allow detecting pharmacologically induced changes in emotional processing biases and thus provides a framework to study the pathophysiology of dysfunctional emotional biases.

Schmidt, A., Kometer, M., Bachmann, R., Seifritz, E., & Vollenweider, F.X. (2012). The NMDA antagonist ketamine and the 5-HT agonist psilocybin produce dissociable effects on structural encoding of emotional face expressions. Psychopharmacology, 225(1), 227-239. http://dx.doi.org/doi:10.1007/s00213-012-2811-0
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30 April - Q&A with Rick Strassman

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