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NCT Number: NCT03289949

The Neurobiological Effect of 5-HT2AR Modulation

The investigators wish to investigate neurobiological effects of serotonin 2A receptor modulation in healthy volunteers, contrasting effects of an agonist (psilocybin) and an antagonist (ketanserin). Magnetic resonance imaging (MRI) and positron emission tomography (PET) will be used as neuroimaging tools.

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Key information

Conditions

Basic Science

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Neurobiology Research Unit, Rigshospitalet

Copenhagen, 2100, Denmark

Location status: Recruiting

Location contact

Gitte M Knudsen, Professor

CONTACT

Patrick M Fisher, PhD

CONTACT

[email protected]

+4535456714

About this study

This project applies an experimental medicine strategy coupled with human functional and molecular neuroimaging to elucidate the effects of 5-HT2A receptor (5-HT2AR) modulation on brain function and mood in healthy individuals. We compare psilocybin (5-HT2AR agonist) and ketanserin (5-HT2AR antagonist) effects on brain function to identify neural mechanisms mediating the clinical effects of psilocybin and, more broadly, to establish this comparative strategy as a pathway for delineating pharmacological effects on the brain in humans.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Healthy individuals above 18 years of age.

Exclusion criteria

(For Subprojects 1, 2a, 2b, and 3):

  • Presence of or previous primary psychiatric disease (DSM axis 1 or WHO ICD-10 diagnostic classifications) or in first-degree relatives.
  • Previous or present neurological condition/disease, significant somatic condition/disease or intake of drugs suspected to influence test results.
  • Non-fluent Danish language skills.
  • Vision or hearing impairment.
  • Previous or present learning disability.
  • Pregnancy.
  • Breastfeeding.
  • Contraindications in regard to MRI scanning.
  • Alcohol or drug abuse.
  • Allergy to test drugs.
  • Participation in studies in which participant has received more than 10 mSv of radiation or other significant exposure to radiation.
  • Abnormal ECG or intake of QT prolonging medication.
  • Previous significant side-effects in regard to hallucinogenic drugs.
  • Use of hallucinogenic drugs 6 months previous to inclusion.
  • Blood donation 3 months before and after project participation
  • Body weight under 50 kg.
  • Plasma ferritin levels outside normal range

Exclusion criteria

(For Subproject 2c):

  • Presence of or previous primary psychiatric disease (DSM IV axis 1 or WHO ICD-10 diagnostic classifications).
  • Presence of or previous primary psychiatric disease with psychosis symptoms or hypomania (DSM IV axis 1 [drug/alcohol abuse/dependence, schizophrenia and other psychoses] or WHO ICD-10 diagnostic classifications [F10-29, as well as F30-39 with psychotic symptoms, F60]) in first-degree relatives (parents or siblings).
  • Previous or present neurological condition/disease, significant somatic condition/disease or intake of drugs suspected to influence test results.
  • Non-fluent Danish language skills or pronounced vision or hearing impairment.
  • Previous or present learning disability.
  • Pregnancy.
  • Breastfeeding.
  • Contraindications in regard to MRI scanning.
  • Alcohol or drug abuse.
  • Allergy to test drugs.
  • Abnormal ECG or intake of QT prolonging medication.
  • Previous significant side-effects in regard to hallucinogenic drugs.
  • Previous use of hallucinogenic drugs.
  • Body weight under 45 kg.
  • Ethical concerns regarding the administration of a psychedelic drug.

Treatment and study plan

Psilocybine

Drug

Oral dose of psilocybine.

Other names: Psilocybin

Ketanserin

Drug

Oral dose of ketanserin.

Other names: Ketensin

Primary outcomes

  1. Psilocin/ketanserin blood concentrations and 5-HT2A receptor occupancy (i.e., binding potential).

    Time frame: Change in Cimbi-36 binding potential from baseline PET to intervention PET 1 and PET 2 scans (same day for psilocybin, and two consecutive days for ketanserin).

    The investigators aim to model relations psilocin/ketanserin blood drug concentrations and receptor occupancy, using C11-Cimbi-36 PET imaging.

  2. Effects of psilocybin on Cimbi-36 binding potential at baseline and at one and twelve weeks

    Time frame: Change in Cimbi-36 binding potential from baseline to one week post psilocybin (and potentially also at 12 weeks after psilocybin).

    Cimbi-36 PET scan binding potential at baseline and at one-week post psilocybin, and potentially also at 12 weeks post psilocybin.

  3. Effects of psilocybin and ketanserin on brain function assessed with fMRI and PET

    Time frame: Changes in functional connectivity (fMRI) from Baseline MR to intervention MR scans for ketanserin (one or three weeks after baseline MR) and psilocybin (one or three weeks after baseline)

    Correlations between blood levels of ketanserin and psilocin and the estimated associated receptor occupancy with functional MRI neuroimaging data, including resting state networks. Changes in synaptic density will be assessed with 11C-UCB-J PET scans before and 1 week after psilocybin intervention.

  4. Effects of psilocybin on UCB-J binding potential at baseline and at one week

    Time frame: Change in UCB-J binding potential from baseline to one week post psilocybin.

    Project 2, Subproject B. UCB-J PET scan binding potential at baseline and at one-week post psilocybin.

  5. Effects of psilocybin on brain function assessed with fMRI at baseline and one month

    Time frame: Change in fMRI measures from baseline to one month post psilocybin

    Project 2, Subproject C. Resting-state and task-based fMRI measures at baseline and one month post psilocybin.

  6. Anxiety Outcome Measure 1: Acute psychological effects as assessed using Challenging Experiences Questionnaire (CEQ).

    Time frame: Immediately post-intervention.

    Differences in CEQ scores between groups (psilocybin with music compared to psilocybin without music). Effects are measured on a Likert-scale ranging from 0 (Not all all) to 5 (Extremely; More than ever). Higher scores thus reflect a more challenging experience. Project 2, Subproject C. PsiloZonic.

  7. Anxiety Outcome Measure 2: Acute psychological effects as assessed using 5D-Altered States of Consciousness (5D-ASC) scale.

    Time frame: Immediately post-intervention.

    Differences in 5D-ASC anxiety scores between groups (psilocybin with music compared to psilocybin without music). Effects are measured on a Visual analogue scale (VAS) scale ranging from 0 (No, not more than usually) to 100 (Yes, much more than usually). Higher scores on dimension anxiety thus reflect more anxiety. Project 2, Subproject C. PsiloZonic.

  8. Anxiety Outcome Measure 3: Acute psychological effects as assessed using Extended Subjective Drug Intensity (eSDI) scale.

    Time frame: During intervention.

    Differences in eSDI anxiety scores between groups (psilocybin with music compared to psilocybin without music). Effects are measured on a Likert-scale ranging from 0 (Not all all) to 10 (Very much). Higher scores on item anxiety thus reflect more anxiety. Project 2, Subproject C. PsiloZonic.

  9. Transformative Experiences Outcome Measure 1: Acute psychological effects as assessed using Mystical Type Experiences Questionnaire (MEQ) scale.

    Time frame: Immediately post-intervention.

    Differences in MEQ scores between groups (psilocybin with music compared to psilocybin without music). Effects are measured on a Likert-scale ranging from 0 (Not all all) to 5 (Extremely). Higher scores thus reflect a more profound mystical type experience. Project 2, Subproject C. PsiloZonic.

  10. Transformative Experiences Outcome Measure 2: Acute psychological effects as assessed using Psychological Insights Questionnaire (PIQ) scale.

    Time frame: Immediately post-intervention.

    Differences in PIQ scores between groups (psilocybin with music compared to psilocybin without music). Effects are measured on a Likert-scale ranging from 0 (Not all all) to 5 (Extremely). Higher scores thus reflect more psychological insight. Project 2, Subproject C. PsiloZonic.

  11. Transformative Experiences Outcome Measure 3: Acute psychological effects as assessed using Emotional Breakthrough Questionnaire (EBI) scale.

    Time frame: Immediately post-intervention.

    Differences in EBI scores between groups (psilocybin with music compared to psilocybin without music). Effects are measured on a Visual analogue scale (VAS) scale ranging from 0 (No, not more than usually) to 100 (Yes, much more than usually). Higher scores thus reflect more emotional breakthrough. Project 2, Subproject C. PsiloZonic.

  12. Persisting Effects Outcome Measure 1: Persisting psychological effects as assessed using Persisting Effects Questionnaire (PEQ) scale.

    Time frame: One and three months post-intervention.

    Differences in PEQ scores will be assessed between groups (psilocybin with music compared to psilocybin without music). Effects are measured on a Likert-scale ranging from 0 (Not all all) to 5 (Extremely). Higher scores thus reflect more persisting effects. Project 2, Subproject C. PsiloZonic.

Study contacts

Contact information is provided by the study sponsor or research team.

Gitte M Knudsen, Professor

CONTACT

[email protected]

+45 35456720

Patrick M Fisher, PhD

CONTACT

[email protected]

+45 35456714

Sponsors and collaborators

Lead sponsor

Gitte Moos Knudsen

Other

Registry information

Acronym: NeuroPharm2

Important dates

Study start
2017
Primary completion
2030
Study completion
2030
First posted
Sep 21, 2017
Registry last updated
Dec 16, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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