Does Serotonin System Stimulation Increase Pro-social Behavior? - A Comparative Pharmacological Neuroscientific Study in Healthy Humans

NCT06081179 | Completed Phase 1 DMC

• 1 other identifier: 2A-SC-1
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 1

Brief Summary

The study looks into whether administering psychedelic substances that stimulate the serotonin system influences pro-social behavior when compared to administering substances that stimulate the dopamine system in healthy individuals.

Conditions

Healthy

Keywords

MDMA; Psilocybin; Methylphenidate; pro-social behavior; healthy controls; psychedelics; serotonin

Outcome Measures

Primary Outcomes (10)

• Multifaceted Empathy Test

  The Multifaceted Empathy Test is a task assessing the cognitive and emotional aspects of empathy. Participants process 40 photos of people in emotionally charged situations. Each aspect of empathy (implicit and explicit emotional empathy, and cognitive empathy) is tested with 20 positive valence stimuli and 20 negative valence stimuli, yielding a total of 120 trials.

  t0 - 10 days (+/- 7 days) and t0 + 4 weeks (+/- 3 days); t0 being the day of substance administration

• Moral Inference Task

  The Moral Inference task is an approach to evaluate the computational basis of moral inference and its temporal dynamics. Participants observe and predict the decisions of two "agents" who repeatedly choose on administering painful electric shocks to another person in a different room in return for money, and rate them every third trial for their moral character. At the end of the game there is a short trust game. Participants can win actual money in this game (up to 1 CHF).

  t0 - 10 days (+/- 7 days) and t0 + 4 weeks (+/- 3 days); t0 being the day of substance administration

• Zurich Prosocial Game

  The Zurich Prosocial Game is a computer-based pro-social game which allows for assessment of prosocial behavior, considering the influence of helping cost, distress cues in helping behavior, and reciprocity on pro-social behavior through different trial types. Participants can win actual money in this game (up to 6.50 CHF).

  t0 - 10 days (+/- 7 days) and t0 + 4 weeks (+/- 3 days); t0 being the day of substance administration

• Social Gaze Task

  The Social Gaze Task is a paradigm in which participants' gaze is used to control the gaze of a tropomorphic virtual figure. The aim is to capture the reciprocal and interactive nature of joint attention. Participants' gaze behavior is recorded using an eye-tracking device. The outcome measures we will use are pupil size, valence, and arousal ratings.

  t0 - 10 days (+/- 7 days) and t0 + 4 weeks (+/- 3 days); t0 being the day of substance administration

• Moral Expansion Task

  In the Moral Expansion Task, the influence of social distance is elicited by having participants indicate countries with different social distances and decide how much money out of CHF 100 they would like to donate to the Red Cross in each country. One participant's choice is then randomly selected, and the donation is implemented while the chosen participant receives the remaining amount.

  t0 - 10 days (+/- 7 days) and t0 + 4 weeks (+/- 3 days); t0 being the day of substance administration

• Social Network Questionnaire

  The Social Network Questionnaire is used to assess the size of a person's social network and the emotional support and strain experienced from that network. Participants provide the initials of personal contacts from various domains with whom they have had contact with in the past 4 weeks. 28 items are rated on a 6-point scale, asking how much emotional support and emotional burden they have felt from their social contacts. The total score for those items ranges from 28 to 168.

  t0 - 10 days (+/- 7 days) and t0 + 4 weeks (+/- 3 days); t0 being the day of substance administration

• Pro-social Voting Behavior

  The Pro-social Voting Behavior is used to evaluate pro-social voting behavior as a real-world measure of social behavior. The scale consists of 11 items. Each item is rated on a 4-point scale. The total score ranges from 11 to 44. Not all items are accounted equally to capture pro-social voting behavior, as some are reversed.

  t0 - 10 days (+/- 7 days) and t0 + 4 weeks (+/- 3 days); t0 being the day of substance administration

• Oxford Utilitarianism Scale

  The Oxford Utilitarianism Scale measures two dimensions of utilitarian tendencies. The scale consists of 9 items. Each item is rated on a 7-point scale. The total score ranges from 9 to 63.

  t0 - 10 days (+/- 7 days) and t0 + 4 weeks (+/- 3 days); t0 being the day of substance administration

• Compassion Scale

  The Compassion Scale measures an individual's level of compassion towards others. The scale consists of 16 items. Each item is rated on a 5-point scale. The total score ranges from 16 to 80.

  t0 - 10 days (+/- 7 days) and t0 + 4 weeks (+/- 3 days); t0 being the day of substance administration

• Inclusion of others in the self

  The Inclusion of others in the self is designed to assess the perceived relationship between an individual's self and other people/all living things. It consists of two items. Each item is rated as circles corresponding to a numerical score, ranging from 1 to 8. The total score ranges from 2 to 16.

  t0 - 10 days (+/- 7 days), t0, and t0 + 4 weeks (+/- 3 days); t0 being the day of substance administration

Secondary Outcomes (9)

• 5-Dimensional Altered States of Consciousness Rating Scale

  t0 (the day of substance administration)

• 5-Dimensional Altered States of Consciousness Rating Scale short

  t0 (the day of substance administration)

• Mystical Experience Questionnaire

  t0 (the day of substance administration)

• Persisting Effects Questionnaire

  t0 + 4 weeks (+/- 3 days) and t0 + 16 weeks (+/- 7 days); t0 being the day of substance administration

• Epistemic and personal transformation (pre and post versions)

  t0 (the day of substance administration)

Study Arms (3)

Psilocybin

ACTIVE COMPARATOR

40 participants will receive psilocybin

Drug: Psilocybin

MDMA

ACTIVE COMPARATOR

40 participants will receive MDMA

Drug: 3,4 Methylenedioxymethamphetamine

Methylphenidate

ACTIVE COMPARATOR

40 participants will receive methylphenidate

Drug: Methylphenidate

Interventions

Psilocybin DRUG

Single dose of psilocybin (15mg), orally in form of capsules

Also known as: magic mushrooms

Psilocybin

3,4 Methylenedioxymethamphetamine DRUG

Single dose of MDMA (100mg), orally in form of capsules

Also known as: MDMA, Ecstasy

MDMA

Methylphenidate DRUG

Single dose of methylphenidate (60mg), orally in form of capsules

Also known as: Ritalin

Methylphenidate

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or female at the age of 18-40
• Willing and capable to give informed consent for study participation as documented by signature (Informed Consent Form) after the nature of the study has been thoroughly explained
• Willing to refrain from drinking alcohol the day before testing session, from drinking alcohol and caffeinated drinks at the testing days and from consuming psychoactive substances two weeks before the first investigation visit and for the duration of the study
• Willing to abstain from using drugs that may interfere with the effects of the study medications including sleeping aids, cough medications, beta-blocker or other substances with potentially relevant psychoactive and cardiovascular effects.
• Able and willing to comply with all study requirements
• Good physical health with no unstable medical conditions, as determined by medical history, physical examination, routine blood labs, electrocardiogram, urine analysis, and urine toxicology
• Women of childbearing potential (as defined by: 'the age of carrying or giving birth to a child', normally between 14-45 years of age, not in menopause, last menstrual period (LMP) less than 12 months, no removal of ovaries or uterus, no ligature of Fallopian tubes') must be using an effective, established method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices. Note: female participants who are surgically sterilized/hysterectomized or post-menopausal for longer than 2 years are not considered as being of childbearing potential
• Willing not to drive a traffic vehicle or to operate machines within 48h following substance administration
• Have a family member or friend who can pick them up after the substance administration sessions (driving is forbidden at drug treatment days)

You may not qualify if:

• Poor knowledge of the German language
• Previous significant adverse response to a hallucinogenic drug (incl. psilocybin), MDMA, or methylphenidate
• Allergy or hypersensitivity to previous use of MDMA, psilocybin, or methylphenidate
• Lifetime history of hallucinogen (incl. psilocybin), MDMA, or methylphenidate use on more than 10 occasions
• Personal and family history of major psychiatric disease (e.g., schizophrenia, schizoaffective disorder, psychosis, major depression, bipolar disorder, psychotic disorder, substance addiction/abuse other than caffeine and nicotine) as defined in the DSM-V (1st and 2nd degree relatives)
• History of suicidal behavior
• Inability to follow the procedures of the study, e.g., due to language problems, psychological disorders, dementia, etc. of the participant
• Attention-Deficit/Hyperactivity-Disorder (ADHD)
• Any current major medical condition (e.g., neurologic, cardiovascular, metabolic, infectious disease) or any unstable illness as determined by medical history or laboratory tests
• Uncorrected hypo-or hyperthyroidism
• Uncorrected hypo-and hypertension
• Epilepsy
• Abnormal electrocardiogram
• BMI \<17 or \>35
• Personal history of head trauma, brain/cardiac surgery, fainting, or electroconvulsive therapy

Sponsors & Collaborators

• University of Zurich: lead

Study Sites (1)

Psychiatrische Universitätsklinik Zürich

Zurich, Canton of Zurich, 8032, Switzerland

Location

Related Publications (2)

• Preller KH, Vollenweider FX. Modulation of Social Cognition via Hallucinogens and "Entactogens". Front Psychiatry. 2019 Dec 3;10:881. doi: 10.3389/fpsyt.2019.00881. eCollection 2019.

  PMID: 31849730 BACKGROUND

• Cruwys T, Haslam SA, Dingle GA, Haslam C, Jetten J. Depression and Social Identity: An Integrative Review. Pers Soc Psychol Rev. 2014 Aug;18(3):215-238. doi: 10.1177/1088868314523839. Epub 2014 Apr 12.

  PMID: 24727974 BACKGROUND

MeSH Terms

Interventions

Psilocybin; N-Methyl-3,4-methylenedioxyamphetamine; Methylphenidate

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Piperidines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: double-blinded
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: single-center, double-blind, parallel-group, randomized study design

Study Record Dates

• First Submitted: September 25, 2023
• First Posted: October 13, 2023
• Study Start: October 24, 2023
• Primary Completion: September 22, 2025
• Study Completion: September 22, 2025
• Last Updated: November 19, 2025

Record last verified: 2025-11

Locations

CH (1)