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

This interventional, randomised, double-blind, triple-masked crossover study (n=16) will assess dose-response and the role of 5-HT2A receptors on psilocybin effects using single oral doses (5, 10, 20, 40 mg), a 40 mg ketanserin pretreatment condition, and placebo.

Target Enrollment
16 participants
Study Type
Phase I interventional
Design
Randomized, triple Blind

Detailed Description

Randomised, placebo-controlled, double-blind, triple-masked six-period crossover in healthy adults to characterise subjective dose–response to single oral doses of psilocybin (5–40 mg).

A mechanistic arm uses 40 mg ketanserin pretreatment to probe the contribution of 5‑HT2A receptor antagonism to psilocybin-induced alterations of consciousness.

Primary assessments include modern psychometric instruments of altered states and safety; pharmacokinetic sampling will relate plasma concentrations to subjective effects. Sessions are separated by at least 10 days.

Study Protocol

Preparation

sessions

Dosing

6 sessions

Integration

sessions

Study Arms & Interventions

40mg Psilocybin + Ketanserin

experimental

40 mg ketanserin oral followed 1 h later by 40 mg psilocybin oral (single session).

Interventions

  • Psilocybin40 mg
    via Oral• single dose

    Psilocybin 40 mg given 1 h after pretreatment.

  • Placebo
    via Oral• single dose

    Ketanserin 40 mg oral given 1 h before psilocybin (encoded as non-psilocybin comparator).

40mg Psilocybin

experimental

Placebo pretreatment followed by 40 mg psilocybin oral (single session).

Interventions

  • Psilocybin40 mg
    via Oral• single dose

    Placebo pretreatment 1 h before psilocybin.

  • Placebo
    via Oral• single dose

    Placebo pretreatment.

20mg Psilocybin

experimental

Placebo pretreatment followed by 20 mg psilocybin oral.

Interventions

  • Psilocybin20 mg
    via Oral• single dose
  • Placebo
    via Oral• single dose

    Placebo pretreatment.

10mg Psilocybin

experimental

Placebo pretreatment followed by 10 mg psilocybin oral.

Interventions

  • Psilocybin10 mg
    via Oral• single dose
  • Placebo
    via Oral• single dose

    Placebo pretreatment.

5mg Psilocybin

experimental

Placebo pretreatment followed by 5 mg psilocybin oral.

Interventions

  • Psilocybin5 mg
    via Oral• single dose
  • Placebo
    via Oral• single dose

    Placebo pretreatment.

Placebo

inactive

Placebo pretreatment followed by placebo oral (control).

Interventions

  • Placebo
    via Oral• single dose

    Placebo followed by placebo 1 h later.

Participants

Ages
25 – 75
Sexes
Male & Female

Inclusion Criteria

  • 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 substances during the study (not including cannabis).
  • 6. Participants must be willing not to drive a traffic vehicle or to operate machines within 48 h after substance administration.
  • 7. Women of childbearing potential must be willing to use effective birth-control throughout study participation

Exclusion Criteria

  • 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 psychotic disorders secondary to an apparent medical reason, e.g., brain injury, dementia, or lesions 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 any time 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 (any psychiatric medications and any medication with known to interact with the study substances).
  • 10. Tobacco smoking (>10 cigarettes/day).
  • 11. Consumption of alcoholic drinks (>15 drinks / week).
  • 12. Body weight < 45 kg.

Study Details

Locations

Clinical Trial Unit — Basel, Canton of Basel-City, Switzerland

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