Role of the Serotonin 2A Receptor in Psilocybin-induced Altered States of Consciousness

NCT06796361 | Recruiting Phase 1 DMC

• 1 other identifier: BASEC 2024-01503
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Psilocybin (active compound of "magic mushrooms") is a prototypical psychedelic substance that acts via agonism on serotonin (5-HT) 2A receptors. Psilocybin is rapidly metabolized into its active metabolite psilocin. Psilocybin is currently under investigation as potential treatment for various neuropsychiatric disorders. Psilocybin is also widely used for recreational purposes and as research tool in neuroscience. Besides its current clinical development, a clear characterization of the dose-response relationship of psilocybin is lacking. With the present study the investigators aim to close this knowledge gap by administering low (5mg) to high (40mg) single doses of psilocybin to healthy participants. Besides its agonism on 5-HT2A receptors, psilocin also binds to other receptors and inhibits serotonin transporters (SERT). To this data only few studies have investigated these effects and never at a high dose.

Conditions

Healthy

Keywords

Hallucinogens; Physiological Effects of Drugs; Psychotropic Drugs; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Receptor Agonists; Psilocybin

Outcome Measures

Primary Outcomes (1)

• 5 dimensions of altered state of consciousness (5D-ASC) total OAV score

  Visual analog scale consisting of 94 items. Constructed of five scales and allows assessing mood, anxiety, derealization, depersonalization, changes in perception, auditory alterations, and reduced vigilance. Scales will be presented as 100 mm long horizontal lines marked with vertical lines by the participant.

  10 hours after substance administration

Secondary Outcomes (24)

• Visual Analog Scales (VAS) good effect rating

  One hour before, right after and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10 and 24 hours after substance administration

• Adjective Mood Rating Scale AMRS

  One hour before as well as 3, 6, 10 and 24 hours after substance administration

• States of consciousness questionnaire (SCQ)

  10 hours after substance administration

• Phenomenological-Autobiographical-Existential Psychedelic Scale extended (PAE-PS-ext)

  This questionnaire is administrated once before the first substance day (during screening), and then again 10h after substance administration on everx study visit..

• Acute autonomic effects I (blood pressure)

  One hour before, right after and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10 and 24 hours after substance administration

Study Arms (6)

40mg Psilocybin plus 40mg Ketanserin

EXPERIMENTAL

40mg Ketanserin oral followed by 40mg Psilocybin oral one hour later

Drug: Ketanserin 40mg plus Psilocybin 40mg

40mg Psilocybin

EXPERIMENTAL

40mg Psilocybin oral

Drug: 40mg Psilocybin

20mg Psilocybin

EXPERIMENTAL

20mg Psilocybin oral

Drug: 20mg Psilocybin

10mg Psilocybin

EXPERIMENTAL

10mg Psilocybin oral

Drug: 10mg Psilocybin

5mg Psilocybin

EXPERIMENTAL

5mg Psilocybin oral

Drug: 5mg Psilocybin

Placebo

PLACEBO COMPARATOR

Placebo followed by Placebo

Other: Placebo

Interventions

Ketanserin 40mg plus Psilocybin 40mg DRUG

40mg Ketanserin oral will be administered followed by 40mg Psilocybin.

40mg Psilocybin plus 40mg Ketanserin

40mg Psilocybin DRUG

Placebo oral followed by 40mg Psilocybin one hour later.

40mg Psilocybin

20mg Psilocybin DRUG

Placebo oral followed by 20mg Psilocybin one hour later.

20mg Psilocybin

10mg Psilocybin DRUG

Placebo oral followed by 10mg Psilocybin oral one hour later.

10mg Psilocybin

5mg Psilocybin DRUG

Placebo oral followed by 5mg Psilocybin one hour later

5mg Psilocybin

Placebo OTHER

Oral Placebo followed by oral Placebo one hour later

Placebo

Eligibility Criteria

• Age: 25 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 25 and 75 years.
• Sufficient understanding of the German language.
• Understanding the procedures and the risks that are associated with the study.
• Participants must be willing to adhere to the protocol and sign the consent form.
• Participants must be willing to refrain from taking illicit psychoactive substances during the study (not including cannabis).
• Participants must be willing not to drive a traffic vehicle or to operate machines within 48 h after substance administration.
• Women of childbearing potential must be willing to use effective birth-control throughout study participation

You may not qualify if:

• Chronic or acute medical condition, including a history of seizures.
• Body mass index 18-29.9 kg/m2
• Current or previous major psychiatric disorder (e.g. psychotic disorders, mania / hypomania, anxiety disorders).
• Psychotic or bipolar disorder in first-degree relatives, not including psychotic disorders secondary to an apparent medical reason, e.g., brain injury, dementia, or lesions of the brain.
• Hypertension (SBP\>140/90 mmHg) or hypotension (SBP\<85 mmHg)
• Psychedelic substance use (with the exception of cannabis) more than 20 times or any time within the previous two months
• Pregnant or nursing women.
• Participation in another clinical trial (currently or within the last 30 days).
• Use of medications that may interfere with the effects of the study medications (any psychiatric medications and any medication with known to interact with the study substances).
• Tobacco smoking (\>10 cigarettes/day).
• Consumption of alcoholic drinks (\>15 drinks / week).
• Body weight \< 45 kg.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

Clinical Trial Unit

Basel, Canton of Basel-City, 4056, Switzerland

RECRUITING

MeSH Terms

Interventions

Ketanserin; Psilocybin

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinazolinones; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indole Alkaloids; Alkaloids; Indoles; Tryptamines; Indolizidines; Indolizines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 6-period random order, placebo-controlled, double-blind cross-over study

Study Record Dates

• First Submitted: January 13, 2025
• First Posted: January 28, 2025
• Study Start: April 21, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: May 28, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)