Effect of psilocybin on empathy and moral decision-making

This placebo-controlled study (n=56) investigated the acute effect of psilocybin (15mg/70kg) on empathy and moral decision-making in healthy human subjects. The results found the first such evidence that psilocybin has distinct effects on social cognition by enhancing emotional empathy but not moral behavior. It also supports previous findings, indicating that psilocybin may promote emotional empathy presumably through activation of serotonin 2A/1A receptors, showing that focusing on serotonin 2A/1A receptors has the potential to treat dysfunctional social cognition.

Abstract

“Background: Impaired empathic abilities lead to severe negative social consequences and influence the development and treatment of several psychiatric disorders. Furthermore, empathy has been shown to play a crucial role in moral and prosocial behavior. Although the serotonin system has been implicated in modulating empathy and moral behavior, the relative contribution of the various serotonin receptor subtypes is still unknown.

Methods: We investigated the acute effect of psilocybin (0.215 mg/kg p.o.) in healthy human subjects on different facets of empathy and hypothetical moral decision-making using the multifaceted empathy test (n=32) and the moral dilemma task (n=24).

Results: Psilocybin significantly increased emotional, but not cognitive empathy compared with placebo, and the increase in implicit emotional empathy was significantly associated with psilocybin-induced changed meaning of percepts. In contrast, moral decision-making remained unaffected by psilocybin.

Conclusions: These findings provide first evidence that psilocybin has distinct effects on social cognition by enhancing emotional empathy but not moral behavior. Furthermore, together with previous findings, psilocybin appears to promote emotional empathy presumably via activation of serotonin 2A/1A receptors, suggesting that targeting serotonin 2A/1A receptors has implications for potential treatment of dysfunctional social cognition.“

Authors: Thomas Pokorny, Katrin H. Preller, Michael Kometer, Isabel Dziobek & Franz X Vollenweider

Summary

Psilocybin (0.215 mg/kg p.o.) improved empathy in healthy human subjects and was shown to influence moral and prosocial behavior.

Introduction

Empathy and moral behavior are fundamental components of human relationships and are thought to play a crucial role in moral and prosocial behavior.

Empathy is a multidimensional construct consisting of at least a cognitive and an emotional component. Empathy deficits are associated with severe negative social effects in several psychiatric disorders, such as major depression disorder, bipolar disorder, borderline personality disorder, and psychopathy.

Morality exerts a regulatory role in social decision-making and actions. Personal moral dilemmas are more emotionally engaging than impersonal moral dilemmas, and are associated with increased utilitarian responses in adults with high-functioning autism, low-anxious psychopaths, alcohol-dependent patients, poly-substance patients, and lesions in prefrontal cortex.

Serotonin (5-hydroxytryptamine, 5-HT) is involved in both social experiences and behavior such as empathy and moral decision-making. The 5-HT system is also involved in moral processes such as the judgment of personal moral dilemmas and the decision to inflict pain on oneself and others for financial gain. Serotonin is involved in social processes and different 5-HT receptor subtypes contribute to different social experiences and behavior.

Psilocybin is a hallucinogen that produces dose-dependently an altered state of consciousness characterized by changes in sensory perception, emotion, thought, and the sense of self. It binds to 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C, 5-HT5, 5-HT6, and 5-HT7 receptors and is partially agonist at 5-HT2A and 5-HT1A receptors.

Psilocybin has been shown to decrease the recognition of negative facial expressions in the reading the mind in the eyes test and to increase emotional empathy. It may also reduce utilitarian choice of action in personal moral dilemmas.

Participants

Thirty-three healthy human subjects were recruited through advertisements placed at local universities. Of these, 32 completed the MET and 24 completed the moral dilemma task.

We screened 39 healthy subjects, including pregnant women, with a self-report drug questionnaire, a mini-international neuropsychiatric interview, a structured psychiatric interview, the Structured Clinical Interview for DSM-IV Axis II Personality Disorders, and the John Hopkins Symptom Checklist-90 revised.

Before participating, all participants received detailed information about the study and the effects and possible risks of psilocybin administration. The study was approved by the Ethics Committee.

Study Design

This study was double-blind, randomized, placebo-controlled, within-subject design with 2 experimental sessions.

Study Procedures

Participants were asked to refrain from drinking alcohol the day before the experimental session and from drinking alcohol and caffeinated beverages during the experimental days. The acute effect of psilocybin on mood was assessed by a trained physician interviewing participants at the end of each session.

Interpersonal Reactivity Index

The Interpersonal Reactivity Index (IRI) measures trait empathy by measuring the tendency to adopt the psychological point of view of others, to identify with fictional characters, and to feel unease and discomfort resulting from the emotions of others.

The MET is a PC-assisted test that assesses cognitive empathy as well as explicit and implicit emotional empathy. It consists of 40 photorealistic stimuli showing people in different emotionally charged situations (20 positive, 20 negative).

For the MDT, 2 sets of matched scenarios were constructed, containing 22 vignettes, illustrating 9 personal dilemmas, 9 impersonal dilemmas, and 4 nonmoral dilemmas. Participants were asked to take the perspective of a protagonist, and to decide whether they would choose a utilitarian or harm avoidance course of action.

5D-ASC

The 5D-ASC is a standardized questionnaire that contains 94 items and is an extension of the OAV. It is used to assess subjective drug effects in both experimental sessions.

PANAS

The PANAS (Watson et al., 1988) was used to assess the self-reported positive and negative affect. Drug-induced mood changes were measured before and 360 minutes after drug intake.

Statistical Analysis

Data were analyzed using STATISTICA 8.0 for Windows (StatSoft). A repeated-measures ANOVA was conducted to analyze data of each empathy component, and a paired t test was conducted to analyze the ratio of utilitarian choices in moral dilemma scenarios. Psilocybin-induced mood changes were controlled for by ANCOVAs, and independent-samples t tests were performed between psilocybin-experienced and psilocybin-naive participants. A repeated-measures ANOVA was performed with drug, time, and scale scores as within-subject factors. Participants’ scores of the 4 IRI subscales are presented in Table 1. Tukey posthoc comparisons followed significant main effects or interactions in the ANOVAs, and multiple regression analyses were conducted to explore the potential effects of altered states of consciousness, mood change, and trait empathy on significant outcome measures.

5D-ASC

Psilocybin increased all scale scores except the anxiety score compared with placebo (all P .0001, except for spiritual experience P .05).

PANAS

There was a significant drug x time x scale interaction, a significant drug x time interaction, a significant main effect of scale, and a significant difference in arousal level between placebo and psilocybin conditions. Psilocybin increased explicit emotional empathy compared with placebo.

Psilocybin increased implicit emotional empathy compared with placebo, but there was no significant interaction between drug and valence or order, nor was there a significant drug x valence x order interaction. Participants had slightly higher scores in their second test session compared with the first test session, independent of drug condition and administration order. They made more mistakes on negative than positive stimuli, independent of drug condition and administration order.

Associations between MET Change Scores and 5D-ACS Change Scores, PANAS Change Score and IRI

Multiple linear regression analysis showed that the 5D-ASC scale scores explained a significant amount of the variance in the increase of implicit emotional empathy scores.

We tested whether the relationship between changed meaning of percepts and implicit emotional empathy was moderated by arousal. The results showed that neither arousal nor the interaction term between changed meaning of percepts and implicit emotional empathy significantly predicted the increase in implicit emotional empathy. To investigate if IRI subscale scores or PANAS change scores predict the increase in emotional empathy, multiple linear regression analyses were performed.

There was no significant drug x category interaction, drug x category x order interaction, or drug x order difference in moral dilemma scores between placebo and psilocybin condition, and no significant differences between psilocybin-experienced and psilocybin-naive participants in the MDT scores.

Discussion

Psilocybin increased emotional empathy independent of stimuli valence and was related to alterations in meaning of percepts but not trait empathy.

Psilocybin modulates the processing and recognition of negative social and nonsocial stimuli, presumably via 5-HT2A and/or 5-HT1A receptor activation. The present results suggest that the 5-HT2A receptor and possibly also the 5-HT1A receptor are involved in the processing of social and nonsocial emotional stimuli, and may also be involved in the experience of sympathy and prosocial attitudes towards others.

The 5D-ASC scale significantly predicted the increase in implicit emotional empathy scores in the psilocybin condition, indicating that the increased sense of significance may not solely refer to surrounding objects but also to the emotional state of other persons.

The acute mood enhancing effects of psilocybin did not significantly predict the increase in emotional empathy. The increase in emotional empathy was also not associated with the trait empathy score of the IRI questionnaire, suggesting that the acute empathy enhancing effect of psilocybin may build up independently from the subject’s baseline or trait empathy level.

A recent fMRI study showed that areas related to emotional empathy include the brainstem, inferior frontal cortex, posterior superior temporal sulcus, temporal lobe, posterior insular cortex, and posterior cingulate cortex. Psilocybin may increase emotional empathy via activation of these areas.

Psilocybin increased explicit and implicit emotional empathy in the MET, similar to the effects of MDMA, but in contrast to LSD, psilocybin impaired cognitive empathy. This suggests that both 5-HT2A and 5-HT1A receptors may be crucially implicated in the generation of empathy.

Psilocybin may also act on other 5-HT receptor subtypes, but further studies with selective 5-HT receptor antagonists are warranted to examine the relative contribution of specific 5-HT receptor subtypes on empathy.

Psilocybin increased emotional empathy but did not affect moral decision-making in any dilemma condition in the MDT. This finding is well in line with the observation that the serotonin-releasing agent MDMA increased emotional empathy but had no effects on moral judgment in moral dilemma tasks. A recent study suggests that moral judgment and choice of action are mediated by distinct psychological processes, and that the 5-HT2A/1A receptor system may not be involved in moral decision-making.

Psilocybin decreased the neuronal response to social exclusion in the ACC and the amygdala, and therefore may have reduced the aversive emotional reactions to harm others. However, participants made more errors in nonmoral dilemmas under psilocybin than under placebo, but the error rate remained very low.

Psilocybin enhanced emotional empathy but not the cognitive component of empathy. This suggests that 5-HT2A/1A receptor agonists may have potential beneficial effects in the treatment of mood disorders or psychopathy.