The Neurobiological Effect of 5-HT2AR Modulation

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Psilocybine
  Oral dose of psilocybine.
• Препарат Ketanserin
  Oral dose of ketanserin.

Первичные конечные точки

• Psilocin/ketanserin blood concentrations and 5-HT2A receptor occupancy (i.e., binding potential). [Срок оценки: 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).]
• Effects of psilocybin on Cimbi-36 binding potential at baseline and at one and twelve weeks [Срок оценки: Change in Cimbi-36 binding potential from baseline to one week post psilocybin (and potentially also at 12 weeks after psilocybin).]
• Effects of psilocybin and ketanserin on brain function assessed with fMRI and PET [Срок оценки: 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)]
• Effects of psilocybin on UCB-J binding potential at baseline and at one week [Срок оценки: Change in UCB-J binding potential from baseline to one week post psilocybin.]
• Effects of psilocybin on brain function assessed with fMRI at baseline and one month [Срок оценки: Change in fMRI measures from baseline to one month post psilocybin]
• Anxiety Outcome Measure 1: Acute psychological effects as assessed using Challenging Experiences Questionnaire (CEQ). [Срок оценки: Immediately post-intervention.]
• Anxiety Outcome Measure 2: Acute psychological effects as assessed using 5D-Altered States of Consciousness (5D-ASC) scale. [Срок оценки: Immediately post-intervention.]
• Anxiety Outcome Measure 3: Acute psychological effects as assessed using Extended Subjective Drug Intensity (eSDI) scale. [Срок оценки: During intervention.]
• Transformative Experiences Outcome Measure 1: Acute psychological effects as assessed using Mystical Type Experiences Questionnaire (MEQ) scale. [Срок оценки: Immediately post-intervention.]
• Transformative Experiences Outcome Measure 2: Acute psychological effects as assessed using Psychological Insights Questionnaire (PIQ) scale. [Срок оценки: Immediately post-intervention.]

Критерии участия

Критерии включения

1\) 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Простое слепое

Основная цель

Фундаментальное исследование

Центры проведения

Дания · 1 центр

• Neurobiology Research Unit, Rigshospitalet — Copenhagen

Публикации

• Johansen A, Plaven-Sigray P, Madsen MK, Sondergaard A, Messel C, Geisler M, Nasser A, McCulloch DE, Beliveau V, Vassilieva A, Lund A, Lehel S, Ozenne B, Stenbaek DS, Fisher PM, Svarer C, Knudsen GM. Psilocybin's effect on human brain synaptic plasticity. Transl Psychiatry. 2026 Jul 15. doi: 10.1038/s41398-026-04285-y. Online ahead of print. PMID 42457666
• Brendstrup-Brix K, Ozenne B, Fisher PM, Stenbaek DS, Petersen AS, Armand S, McCulloch DE, Marstrand-Joergensen MR, Ulv Larsen SM, Johansen A, Jensen RH, Knudsen GM, Madsen MK. Effects of psilocybin on sleep quality and brain microstructure in chronic cluster headache. J Psychopharmacol. 2026 May 29:2698811261449380. doi: 10.1177/02698811261449380. Online ahead of print. PMID 42212900

Идентификаторы

NCT: NCT03289949 · H-16026898

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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