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

University Hospital Basel

Status and phase: Enrolling; Phase 1

Conditions: Healthy

Treatments: Drug: 5mg Psilocybin; Drug: 10mg Psilocybin; Drug: 20mg Psilocybin; Drug: 40mg Psilocybin; Drug: Ketanserin 40mg plus Psilocybin 40mg; Other: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT06796361

BASEC 2024-01503 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 16 estimated patients

Sex: All

Ages: 25 to 75 years old

Volunteers: Accepts Healthy Volunteers

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

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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16 participants in 6 patient groups, including a placebo group

40mg Psilocybin plus 40mg Ketanserin

Experimental group

Description:

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

Treatment:

Drug: Ketanserin 40mg plus Psilocybin 40mg

40mg Psilocybin

Experimental group

Description:

40mg Psilocybin oral

Treatment:

Drug: 40mg Psilocybin

20mg Psilocybin

Experimental group

Description:

20mg Psilocybin oral

Treatment:

Drug: 20mg Psilocybin

10mg Psilocybin

Experimental group

Description:

10mg Psilocybin oral

Treatment:

Drug: 10mg Psilocybin

5mg Psilocybin

Experimental group

Description:

5mg Psilocybin oral

Treatment:

Drug: 5mg Psilocybin

Placebo

Placebo Comparator group

Description:

Placebo followed by Placebo

Treatment:

Other: Placebo