Clinical trial NCT06796361: Role of the Serotonin 2A Receptor in Psilocybin-induced Altered States of Consciousness
Official title: Role of the Serotonin 2A Receptor in Psilocybin-induced Altered States of Consciousness (PDR-Study)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2025-01-28
Enrollment: 16
Sex: ALL
Minimum age (years): 25
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 6-period random order, placebo-controlled, double-blind cross-over study
Primary purpose: BASIC_SCIENCE

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.

Detailed 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.

Eligibility 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:

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.

Primary outcomes:
measure: 5 dimensions of altered state of consciousness (5D-ASC) total OAV score
timeFrame: 10 hours after substance administration
Secondary outcomes:
measure: Visual Analog Scales (VAS) good effect rating
timeFrame: 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
measure: Adjective Mood Rating Scale AMRS
timeFrame: One hour before as well as 3, 6, 10 and 24 hours after substance administration
measure: States of consciousness questionnaire (SCQ)
timeFrame: 10 hours after substance administration
measure: Phenomenological-Autobiographical-Existential Psychedelic Scale extended (PAE-PS-ext)
timeFrame: This questionnaire is administrated once before the first substance day (during screening), and then again 10h after substance administration on everx study visit..
measure: Acute autonomic effects I (blood pressure)
timeFrame: 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
measure: Acute autonomic effects II (heart rate)
timeFrame: 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
measure: Acute autonomic effects III (body temperature)
timeFrame: 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
measure: Effect moderation by personality traits I (NEO-FFI)
timeFrame: Screening
measure: Effect moderation by personality traits II (FPI-R)
timeFrame: Screening
measure: Effect moderation by personality traits III (SPF)
timeFrame: Screening
measure: Effect moderation by personality traits IV (HEXACO)
timeFrame: Screening
measure: Effect moderation by personality traits V (DSQ-40)
timeFrame: Screening
measure: Psychological Insight Questionnaire (EBI+)
timeFrame: 10 hours after substance administration
measure: Changes in the electrocardiogram (ECG)
timeFrame: One hour before and 2 hours after substance administration.
measure: Adverse effects (acute and subacute)
timeFrame: One hour before, 10 and 24 hours after substance administration
measure: Persisting effects of the psychedelic experiences (PEQ)
timeFrame: End of study (EOS) visit during EOS interview
measure: Cognitive Tasks
timeFrame: 24 hours after substance administration
measure: Peak Plasma concentration of Psilocybin and Metabolites (Cmax)
timeFrame: 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
measure: Time to cmax (Tmax)
timeFrame: 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
measure: Area under the concentration-time curve up to 24 h (AUC0-24)
timeFrame: 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
measure: Elimination half life values (t1/2)
timeFrame: 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
measure: Sleep variables of %REM
timeFrame: 14 hours after substance administration until the end of the study day
measure: REM Latency
timeFrame: 14 hours after substance administration until the end of the study day
measure: REM Efficiency
timeFrame: 14 hours after substance administration until the end of the study day
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: Clinical Trial Unit
state: Basel-Stadt
Study officials:
References: