Psilocin vs. Psilocybin Effects in Healthy Adults

Overseen By Cesar Molina

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, San Francisco

Must not be taking: Dopamine agonists, MAO inhibitors

Disqualifiers: Other trial, Health condition, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: 8 hours per session

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how psilocin and psilocybin, both psychedelics, affect the mind and body when administered in different ways. Participants will receive psilocin either as a pill or as a tablet dissolved under the tongue (sublingual psilocin), while psilocybin will be given as a pill. The goal is to compare these methods in terms of physiological and psychological effects. Individuals who have previously tried psychedelics and are generally healthy might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop taking my current medications for the trial?

You may need to stop taking certain medications that could interact with psilocybin, like dopamine agonists, MAO inhibitors, NMDAR antagonists, antipsychotics, and stimulants. It's best to discuss your current medications with the study team to see if any changes are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both psilocin and psilocybin are generally safe when used in a controlled environment. For psilocybin, studies indicate that a single dose usually doesn't cause serious side effects, although some people might experience mild effects like nausea or a faster heartbeat. These effects typically resolve within 48 hours.

Psilocin, similar to psilocybin, is also considered safe under medical supervision. Common side effects can include strong emotions, both positive and negative, and physical effects like dry mouth or higher blood pressure. Both substances can also cause temporary changes in mood or perception.

As this is an early-phase study, the main goal is to understand safety and dosage. Previous studies in other settings provide some reassurance about the safety of both psilocin and psilocybin. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about psilocin and psilocybin treatments because they offer a novel approach to mental health conditions by working directly on serotonin receptors in the brain. Unlike traditional antidepressants, which often take weeks to show effects, these compounds have the potential to produce rapid changes in mood and perception. Psilocin can be administered both orally and sublingually, offering flexibility and potentially faster absorption. Additionally, the unique effects of these compounds could lead to breakthroughs in understanding and treating conditions like depression and anxiety in ways current medications cannot.

What evidence suggests that this trial's treatments could be effective?

This trial will compare the effects of psilocin and psilocybin in healthy adults. Research has shown that psilocin and psilocybin significantly affect the mind and body. The body quickly converts psilocybin into psilocin, which causes the psychedelic effects. Studies suggest that psilocybin treatment might promote healthier aging by extending the lifespan of cells and animals. Since psilocin is the active form, it is expected to have similar effects. Evidence indicates that these substances may improve mental health and possibly slow aging. However, most findings come from early studies conducted in labs or with animals, so the effects on humans remain under investigation. Participants in this trial will receive both oral and sublingual psilocin, as well as oral psilocybin, to further explore these effects. ^{6 7 8 9 10}

Who Is on the Research Team?

Joshua D Woolley, MD, PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 25-50 who are comfortable with English, have had a psychedelic experience before, and can commit to all study visits. They must not use THC, CBD, or nicotine during the study and should not be on certain medications like dopamine agonists or MAO inhibitors.

Inclusion Criteria

You have used psychedelic drugs before.

Commit to attending all study visits and remote data collection tasks

I do not have any surgeries planned during the study period.

Exclusion Criteria

Participated in another clinical trial within 30 days of entry to this trial

A health condition that makes study unsafe or unfeasible, determined by study physicians

I am not on medication that interacts badly with psilocybin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparatory

Participants engage in preparatory visits with trained facilitators

1-2 weeks

Multiple visits (in-person)

Treatment

Participants receive psilocin or psilocybin in a randomized order, supervised by facilitators and a clinician

8 hours per session

Up to 4 sessions (in-person)

Integration

Participants complete assessment and integration sessions to process the experience

1-2 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Psilocin
• Psilocybin
• Sublingual Psilocin

Trial Overview The trial aims to compare the effects of psilocin taken orally or sublingually with those of psilocybin in pill form. It will assess both physiological and psychological responses in participants.

How Is the Trial Designed?

Group I: Oral & Sublingual Psilocin, & Oral Psilocybin Active Control 3 Interventions

Every participant will be administered Oral Psilocin, Sublingual Psilocin, and oral psilocybin in a randomized order.

Group II: Sublingual Psilocin Active Control 1 Intervention

Depending on a number of factors, participants may complete a fourth session where they receive sublingual psilocin for the second time.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Filament Health Corp.

Industry Sponsor

Trials

4

Recruited

220+

Filament Health

Collaborator

Trials

2

Recruited

120+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05317689?limit=100&viewType=Table&intr=Psychedelics&rank=71

Comparing the Effects of Psilocin and Psilocybin in Healthy ... To compare the physiological and psychological effects of psilocin taken orally by pill or sublingually by dissolving a tablet under the tongue to those of ...

2. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT05317689

Comparing the Effects of Psilocin and Psilocybin in Healthy ... The primary goal of this study is to compare the physiological and psychological effects of psilocin taken orally by pill or sublingually ...

3. nature.com nature.com/articles/s41514-025-00244-x

Psilocybin treatment extends cellular lifespan and ... We demonstrate that psilocin/psilocybin treatment extends both cellular and animal lifespan (even when treatment is initiated late in life). An ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12030428/

Pharmacokinetics of Psilocybin: A Systematic Review - PMC Psilocybin is rapidly dephosphorylated to psilocin, which is absorbed with Tmax values ranging from 1.8 to 4 h following oral administration.

5. news.emory.edu news.emory.edu/stories/2025/07/hs_psilocybin_aging_study_10-07-2025/story.html

Psilocybin delays aging, extends lifespan, new Emory study ... “This study provides strong preclinical evidence that psilocybin may contribute to healthier aging — not just a longer lifespan, but a better ...

6. webmd.com webmd.com/vitamins/ai/ingredientmono-1654/psilocybin

Psilocybin - Uses, Side Effects, and More When taken by mouth: Psilocybin is possibly safe when used as a single dose under medical supervision. Single doses of psilocybin have been used in controlled ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S277240852400125X

Safety pharmacology of acute psilocybin administration in ... No serious adverse reactions occurred. These findings suggest that a single administration of psilocybin is safe with regard to acute psychological and physical ...

8. nida.nih.gov nida.nih.gov/research-topics/psilocybin-magic-mushrooms

Psilocybin (Magic Mushrooms) | National Institute on Drug ... People who take psilocybin may also feel intense emotions ranging from bliss to terror and may have physical side effects such as increased ...

9. canada.ca canada.ca/en/health-canada/services/substance-use/controlled-illegal-drugs/magic-mushrooms.html

Psilocybin and psilocin (Magic mushrooms) Physical effects · numbness, particularly in the face · increased heart rate and blood pressure · dry mouth, sometimes leading to nausea and vomiting · muscle ...

10. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2817352

Acute Adverse Effects of Therapeutic Doses of Psilocybin In this meta-analysis, the acute adverse effect profile of therapeutic single-dose psilocybin appeared to be tolerable and resolved within 48 hours.