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

Last updated: May 26, 2025
Sponsor: University Hospital, Basel, Switzerland
Overall Status: Active - Recruiting

Phase

1

Condition

N/A

Treatment

10mg Psilocybin

5mg Psilocybin

40mg Psilocybin

Clinical Study ID

NCT06796361
BASEC 2024-01503
BASEC 2024-01503
  • Ages 25-75
  • All Genders
  • Accepts Healthy Volunteers

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Age between 25 and 75 years.

  2. Sufficient understanding of the German language.

  3. Understanding the procedures and the risks that are associated with the study.

  4. Participants must be willing to adhere to the protocol and sign the consent form.

  5. Participants must be willing to refrain from taking illicit psychoactive substancesduring the study (not including cannabis).

  6. Participants must be willing not to drive a traffic vehicle or to operate machineswithin 48 h after substance administration.

  7. Women of childbearing potential must be willing to use effective birth-controlthroughout study participation

Exclusion

Exclusion Criteria:

  1. Chronic or acute medical condition, including a history of seizures.

  2. Body mass index 18-29.9 kg/m2

  3. Current or previous major psychiatric disorder (e.g. psychotic disorders, mania /hypomania, anxiety disorders).

  4. Psychotic or bipolar disorder in first-degree relatives, not including psychoticdisorders secondary to an apparent medical reason, e.g., brain injury, dementia, orlesions of the brain.

  5. Hypertension (SBP>140/90 mmHg) or hypotension (SBP<85 mmHg)

  6. Psychedelic substance use (with the exception of cannabis) more than 20 times or anytime within the previous two months

  7. Pregnant or nursing women.

  8. Participation in another clinical trial (currently or within the last 30 days).

  9. Use of medications that may interfere with the effects of the study medications (anypsychiatric medications and any medication with known to interact with the studysubstances).

  10. Tobacco smoking (>10 cigarettes/day).

  11. Consumption of alcoholic drinks (>15 drinks / week).

  12. Body weight < 45 kg.

Study Design

Total Participants: 16
Treatment Group(s): 6
Primary Treatment: 10mg Psilocybin
Phase: 1
Study Start date:
April 21, 2025
Estimated Completion Date:
August 31, 2026

Study Description

Psilocybin is widely used for recreational and spiritual purposes. Additionally Psilocybin is currently reused in experimental studies with healthy subjects and in studies investigating its effects on patients suffering from anxiety, depression, addiction personality disorders and other pathological conditions.

The present PDR-study will characterize the subjective effects of different doses of psilocybin using modern psychometric instruments, explore the relationship between the plasma-concentration of psilocybin and its subjective effects, and examine the contribution of the 5-HT2A receptor in the psilocybin-induced alterations of consciousness in a mechanistic study in healthy subjects.

Participants will recieve doses of 5, 10, 20, and 40 mg psilocybin, 40 mg of psilocybin with pretreatment of 40 mg ketanserin, and placebo (control for psilocybin). Placebo pretreatment (control for ketanserin) will be used for all psilocybin administrations without ketanserin. Administrations will be separated by at least 10 days and are in random and counter-balanced order.

Connect with a study center

  • Clinical Trial Unit

    Basel, Basel-Stadt 4056
    Switzerland

    Active - Recruiting

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