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

NCT ID: NCT06081179

Last Updated: 2025-11-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 122 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-24
• Study Completion Date: 2025-09-22

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.

Detailed Description

Psychedelic substances have been shown to be powerful modulators of social perception and behavior during the acute experience. This is of particular interest given that social relationships play a key role in the development and resolution of psychiatric symptoms. However, the neuropharmacological mechanism underlying pro-social effects and time-dependent changes currently remain unclear. This study therefore aims at answering two key questions: 1) Does stimulation of the serotonin system induce lasting effects on pro-social behavior? and 2) Are these effects specific to serotonergic stimulation? The following proposed study will assess these questions by investigating objective, ecologically valid measures of pro-social cognition four weeks after different pharmacological challenges (MDMA, an entactogen and releaser of serotonin, norepinephrine, and dopamine; psilocybin: a classical psychedelic and serotonin 2A receptor agonist, methylphenidate: an amphetamine and norepinephrine-dopamine re-uptake inhibitor) in healthy volunteers.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Psilocybin

40 participants will receive psilocybin

Group Type: ACTIVE_COMPARATOR

Psilocybin

Intervention Type: DRUG

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

MDMA

40 participants will receive MDMA

Group Type: ACTIVE_COMPARATOR

3,4 Methylenedioxymethamphetamine

Intervention Type: DRUG

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

Methylphenidate

40 participants will receive methylphenidate

Group Type: ACTIVE_COMPARATOR

Methylphenidate

Intervention Type: DRUG

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

Interventions

Psilocybin

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

Intervention Type: DRUG

3,4 Methylenedioxymethamphetamine

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

Intervention Type: DRUG

Methylphenidate

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

Intervention Type: DRUG

Other Intervention Names

magic mushrooms; MDMA; Ecstasy; Ritalin

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• 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
• Personal and family history of seizure disorder and strokes (1st and 2nd degree relatives)
• Participation in another study where pharmaceutical compounds are given within the 30 days preceding and during the present study
• Current psychopharmacological treatment or medication that affects brain function
• Use of medications that are contraindicated or otherwise interfere with the effects of the study medications (monoamine oxidase inhibitors, antidepressants, sedatives etc.)
• Women who are pregnant or breast feeding, or have the intention to become pregnant during the study (for safety reasons, a urine pregnancy test will be done at the screening visit and before the substance administration)
• Enrollment of the investigator, his/her family members, employees, and other dependent persons

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Zurich

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Psychiatrische Universitätsklinik Zürich

Zurich, Canton of Zurich, Switzerland

Countries

Switzerland

References

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.

Reference Type: BACKGROUND

PMID: 31849730 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24727974 (View on PubMed)

Other Identifiers

2A-SC-1

Identifier Type: -

Identifier Source: org_study_id