Clinical trial NCT06081179: Does Serotonin System Stimulation Increase Pro-social Behavior? - A Comparative Pharmacological Neuroscientific Study in Healthy Humans
Official title: Does Serotonin System Stimulation Increase Pro-social Behavior? - A Comparative Pharmacological Neuroscientific Study in Healthy Humans
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy
Keywords: MDMA
Psilocybin
Methylphenidate
pro-social behavior
healthy controls
psychedelics
serotonin
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2023-10-13
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: single-center, double-blind, parallel-group, randomized study design
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Multifaceted Empathy Test
timeFrame: t0 - 10 days (+/- 7 days) and t0 + 4 weeks (+/- 3 days); t0 being the day of substance administration
measure: Moral Inference Task
timeFrame: t0 - 10 days (+/- 7 days) and t0 + 4 weeks (+/- 3 days); t0 being the day of substance administration
measure: Zurich Prosocial Game
timeFrame: t0 - 10 days (+/- 7 days) and t0 + 4 weeks (+/- 3 days); t0 being the day of substance administration
measure: Social Gaze Task
timeFrame: t0 - 10 days (+/- 7 days) and t0 + 4 weeks (+/- 3 days); t0 being the day of substance administration
measure: Moral Expansion Task
timeFrame: t0 - 10 days (+/- 7 days) and t0 + 4 weeks (+/- 3 days); t0 being the day of substance administration
measure: Social Network Questionnaire
timeFrame: t0 - 10 days (+/- 7 days) and t0 + 4 weeks (+/- 3 days); t0 being the day of substance administration
measure: Pro-social Voting Behavior
timeFrame: t0 - 10 days (+/- 7 days) and t0 + 4 weeks (+/- 3 days); t0 being the day of substance administration
measure: Oxford Utilitarianism Scale
timeFrame: t0 - 10 days (+/- 7 days) and t0 + 4 weeks (+/- 3 days); t0 being the day of substance administration
measure: Compassion Scale
timeFrame: t0 - 10 days (+/- 7 days) and t0 + 4 weeks (+/- 3 days); t0 being the day of substance administration
measure: Inclusion of others in the self
timeFrame: t0 - 10 days (+/- 7 days), t0, and t0 + 4 weeks (+/- 3 days); t0 being the day of substance administration
Secondary outcomes:
measure: 5-Dimensional Altered States of Consciousness Rating Scale
timeFrame: t0 (the day of substance administration)
measure: 5-Dimensional Altered States of Consciousness Rating Scale short
timeFrame: t0 (the day of substance administration)
measure: Mystical Experience Questionnaire
timeFrame: t0 (the day of substance administration)
measure: Persisting Effects Questionnaire
timeFrame: t0 + 4 weeks (+/- 3 days) and t0 + 16 weeks (+/- 7 days); t0 being the day of substance administration
measure: Epistemic and personal transformation (pre and post versions)
timeFrame: t0 (the day of substance administration)
measure: Symptom Checklist 90-R
timeFrame: t0 - 10 days (+/- 7 days) and t0 + 16 weeks (+/- 7 days); t0 being the day of substance administration
measure: The Positive and Negative Affect Schedule
timeFrame: t0 - 10 days (+/- 7 days), t0, t0 + 4 weeks (+/- 3 days), and t0 + 16 weeks (+/- 7 days); t0 being the day of substance administration
measure: FEELINGS
timeFrame: t0 - 10 days (+/- 7 days) and t0 + 16 weeks (+/- 7 days); t0 being the day of substance administration
measure: Ego Consciousness Change of Perspective Questionnaire (1 & 2)
timeFrame: t0 and t0 + 4 weeks (+/- 3 days); t0 being the day of substance administration
Other outcomes:
Locations:
city: Zürich
country: Switzerland
facility: Psychiatrische Universitätsklinik Zürich
Study officials:
References:
citation: 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.
citation: 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.