Psilocybin and MDMA reduce costly punishment in the Ultimatum Game

This two-part study found that MDMA (n=20) and psilocybin (n=19) reduced rejection of unfair offers. MDMA did not reduce rejection in third-party decision-making but produced an increase in the amount offered to others. The authors argue that these compounds altered participants’ conceptualisation of ‘social reward’, placing more emphasis on the direct relationship with interacting partners.

Abstract

“Disruptions in social decision-making are becoming evident in many psychiatric conditions. These are studied using paradigms investigating the psychological mechanisms underlying interpersonal interactions, such as the Ultimatum Game (UG). Rejection behaviour in the UG represents altruistic punishment – the costly punishment of norm violators – but the mechanisms underlying it require clarification. To investigate the psychopharmacology of UG behaviour, we carried out two studies with healthy participants, employing serotonergic agonists: psilocybin (open-label, within-participant design, N = 19) and 3,4-methylenedioxymethamphetamine (MDMA; placebo-controlled, double-blind, crossover design, N = 20). We found that both MDMA and psilocybin reduced rejection of unfair offers (odds ratio: 0.57 and 0.42, respectively). The reduction in rejection rate following MDMA was associated with increased prosociality (R2 = 0.26, p = 0.025). In the MDMA study, we investigated third-party decision-making and proposer behaviour. MDMA did not reduce rejection in the third-party condition, but produced an increase in the amount offered to others (Cohen’s d = 0.82). We argue that these compounds altered participants’ conceptualisation of ‘social reward’, placing more emphasis on the direct relationship with interacting partners. With these compounds showing efficacy in drug-assisted psychotherapy, these studies are an important step in the further characterisation of their psychological effects.”

Authors: Anthony S. Gabay, Robin L. Carhart-Harris, Ndaba Mazibuko, Matthew J. Kempton, Paul D. Morrison, David J. Nutt & Mitul A. Mehta

Summary

Humans have evolved a number of social cognitive mechanisms to aid interaction with others. The psychopharmacology of trust, social norm enforcement and cooperation may provide insight into potential treatment targets.

Psilocybin and MDMA are two compounds that have recently shown promise in treating depression, trauma and anxiety. Further exploration is needed into how these compounds affect different aspects of cognition, including social cognition.

We present two psychopharmacological studies investigating behaviour in the Ultimatum Game14. The study finds that people reject low, unequal offers as a form of altruistic punishment, and is driven by purely ‘prosocial’ considerations or as an act of revenge.

In studies of the UG, participants rejected low offers when 5-HT availability was reduced through acute tryptophan depletion (ATD), and increased availability through single doses of selective serotonin reuptake inhibitors (SSRI).

ATD has been reported to affect willingness to pay a cost to punish in a third-party punishment game, but the task was not directly comparable to the UG. Here, we report two studies to address these questions; one with psilocybin, and the other with MDMA.

Given the evidence from the SSRI studies above, we hypothesised that psilocybin and MDMA would reduce rejection rates of unfair offers in a first-person condition, and not alter rejection rates in a third-party condition.

This manuscript presents the UG data from a drug-free screening session and psilocybin-alone session of a larger study investigating the effects of a src-kinase inhibitor on the effects of psilocybin.

Twenty-three male participants were recruited from the community, and gave written informed consent. All experiments were performed in accordance with relevant guidelines and regulations.

Study one – the effects of psilocybin

Participants attended three sessions, and 2 mg psilocybin was administered via intravenous infusion over 2 minutes during the neuroimaging session. The UG was performed 60 minutes later, when most of the acute effects had diminished.

The Ultimatum Game had two offer origin conditions: first-person and random computer-generated offer. In the first-person condition, participants decided to reject or accept an offer made by another person, while in the random-generated offer condition, participants solely affected their own payoff.

The majority of published studies investigate offers from 10 – 50% of the total stake. We also include “hyper-fair” offers of 80 and 90%.

We tested the reliability of the UG in an independent sample of healthy volunteers and found that rejection rates were highly reliable in both conditions.

The data collected was categorical (accept or reject) decisions on monetary offers. Repeated-measures logistic regression was used to analyse the data, and the results are presented as odds ratios and p-values.

We grouped offers into fair and hyper-fair categories, and excluded 30% and 40% offers because they show wide variation in response.

Results. All fair and hyper-fair offers were accepted, with the exception of one participant who rejected 50% of first-person hyper-fair offers.

Figure 1 displays a boxplot of rejection rates of unfair offers across sessions. There was a main effect of offer origin, such that a reduced probability of rejecting unfair offers was observed in the random-generated condition.

Study two – the effects of MDMA

Methods

Twenty-one male participants were recruited from the community, and all gave written informed consent to take part in the study. All experiments were performed in accordance with relevant guidelines and regulations.

This study followed a double-blind, placebo-controlled, cross-over, counter-balanced design, with 100 mg MDMA administered at 10:15 and UG administered 95 minutes post-dose.

This version of the Ultimatum Game had three offer origin conditions: first-person, third-party, and random computer-generated offer (random). It took a total of 23.5 minutes and was split into two runs, each lasting 11.75 minutes.

We altered the stakes and the proportion of the offers in the task to asses if there was an effect of stake size on UG behaviour. We found that rejection rates were very reliable across sessions in each condition.

MDMA was tested on participant’s sensitivity to reward by completing a modified reaction time (RT) task. The difference in average RT between rewarded and non-rewarded blocks was used as a measure of reward sensitivity.

We asked participants to complete five subjective rating questionnaires at the end of the experimental session, including a nine-item Social Value Orientation questionnaire and a 23-item Social Reward Questionnaire.

Two outcome measures were collected from the UG: categorical (accept or reject) responses to monetary offers and continuous data of monetary offers from the participants to other players.

We tested for differences across runs and for differential effects of high/low utility. A model was defined testing for the main effects of utility, run, treatment, offer origin, and fairness level.

Each participant made an offer, and the average was taken for each session. A paired-sample t-test was performed to examine the difference in offer amount across treatment sessions.

Results

The Ultimatum Game showed no effect of run or utility, and neither showed a statistically significant interaction with treatment.

The rejection rates of unfair offers were not affected by treatment, but were affected by offer origin, fairness, and a three-way interaction. There was no effect of treatment on rejection rates of unfair offers from the game-server.

A paired t-test revealed an increase in average percentage offer from the participants during the MDMA session compared to the placebo session.

A mixed-measures ANOVA showed that participants responded faster for the rewarded trials compared to the unrewarded trials in both experimental sessions. There was no effect of treatment session or order.

MDMA did not alter prosocial or egoistic responses in the SVO. A repeated-measures 6 (subscale) x 2 (treatment) ANOVA was carried out to test for the effect of MDMA on rejection rates for unfair offers.

We conducted a post-hoc regression analysis to determine if the change in SRQ prosociality subscale was related to the change in rejection rates in the UG.

Discussion

Results from two psychopharmacological studies investigating behaviour in the Ultimatum Game (UG) suggest that serotonin partially modulates UG rejection behaviour, notwithstanding other potential pharmacological mechanisms with MDMA (discussed further below).

Psilocybin and MDMA alter the exchange rate of the social reward currency, such that the reward of punishing norm violations no longer outweighs the cost incurred.

One must first consider whether people are less willing to pay the cost of punishment. The reward of punishment was not altered by MDMA or psilocybin, but the prosocial subscale of the SRQ was, which was associated with the magnitude of the decrease in rejection rates.

We argue that the exchange rate of the social reward currency was shifted in favour of social reward with MDMA administration compared to placebo, due to greater concern for the other players’ outcome.

Du and Chang18 argue that different brain regions are involved in first-person versus third-party representations. We found no change in rejection behaviour in the third-party condition, although traditional ‘fairness’ considerations may take precedence due to there being multiple others to consider.

There is some debate around the psychological mechanisms underlying costly punishment in the UG. However, participants rated their own motivations as being due to deterrence significantly more than retribution.

The effect of these compounds on offers suggests that they alter social reward processing in the UG. The anti-depressant effect of psilocybin makes its selection for study relevant, as does the well-documented social effects of MDMA.

MDMA and psilocybin both increase the availability of serotonin through the reversal of 5-HT transporters, as well as possibly acting as a weak direct agonist at the 5-HT2A/C receptor. This supports an interpretation that the behavioural effects seen here are a result of serotonergic modulation.

The studies reported in this manu- script have several limitations, including open-label nature of the psilocybin study and lack of counter-balancing. However, the tasks used in both studies had excellent test-retest reliability, thus allowing confidence in the findings presented.

Different versions of the UG were used in different settings to test reliability. Both produced similar rejection rates and showed good test-retest reliability.

The studies reported here recruited only male participants, and had prior drug experience relevant to the drug they were administered in the study. However, previous studies have found gender differences in the UG55,56 and subjective effects of MDMA58.

Psilocybin and MDMA affect social decision-making by increasing one’s concern for the outcome of interacting partners. This can help to explain how higher-level cognitive processes are disrupted in psychiatric disorders.

Acknowledgements

ASG was supported by an Institute of Psychiatry, Psychology & Neuroscience-Medical Research Council Excellence award to conduct the MDMA study.

Study details

Compounds studied
MDMA Psilocybin

Topics studied
Personality

Study characteristics
Placebo-Controlled Double-Blind Open-Label Within-Subject

Participants
39 Humans

Authors

Authors associated with this publication with profiles on Blossom

Robin Carhart-Harris
Dr. Robin Carhart-Harris is the Founding Director of the Neuroscape Psychedelics Division at UCSF. Previously he led the Psychedelic group at Imperial College London.

David Nutt
David John Nutt is a great advocate for looking at drugs and their harm objectively and scientifically. This got him dismissed as ACMD (Advisory Council on the Misuse of Drugs) chairman.

Institutes

Institutes associated with this publication

King's College London
The Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King's College London is one of Europe's top centres for mental health and related neurosciences research.

Compound Details

The psychedelics given at which dose and how many times

Psilocybin 2 mg | 1x MDMA 100 mg | 1x

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