Comparing the Effects of Psilocin and Psilocybin in Healthy Adults

Comparison of the Effects of PEX20 (Oral Psilocin), PEX30 (Sublingual Psilocin), and PEX10 (Oral Psilocybin) in Healthy Adults

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 psilocybin taken by pill in healthy adults.

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy
• Intervention / Treatment: Drug: Psilocin; Drug: Psilocybin; Drug: Sublingual Psilocin

Detailed Description

The primary goal of this study is to compare the physiological and psychological effects of psilocin taken orally by pill or sublingually dissolved under the tongue to those of psilocybin taken by pill. Twenty participants, ages 25 to 50, with one previous experience with psychedelics, and who meet all other inclusion and exclusion criteria at screening will be enrolled. After baseline assessments, participants will engage in preparatory visits with trained facilitators, followed by drug administration, supervised by the facilitators and a clinician who will conduct safety monitoring throughout. Participants will then complete assessment and integration sessions with the facilitators in order to help process the experience. The same preparation, procedures, integration, and supervision will be repeated up to three more times with each participant.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 46 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age 25 to 50
• Comfortable speaking and writing in English
• Commit to attending all study visits and remote data collection tasks
• No planned surgeries during the study
• Had at least one prior experience with a psychedelic substance
• Generally mentally and physically healthy
• Agree to abstain from THC, CBD, or nicotine products during study

Exclusion Criteria:

• Participated in another clinical trial within 30 days of entry to this trial
• Regular use of medications that may have problematic interactions with psilocybin, including but not limited to dopamine agonists, MAO inhibitors, N-methyl-D-aspartate (NMDAR) antagonists, antipsychotics, and stimulants
• A health condition that makes study unsafe or unfeasible, determined by study physicians

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oral & Sublingual Psilocin, & Oral Psilocybin; Every participant will be administered Oral Psilocin, Sublingual Psilocin, and oral psilocybin in a randomized order.	Drug: Psilocin; 17.5mg oral psilocin with psychological support and physiological monitoring; Drug: Psilocybin; 25mg oral psilocybin with psychological support and physiological monitoring; Drug: Sublingual Psilocin; 2.18mg - 4.36mg sublingual psilocin with psychological support and physiological monitoring
Active Comparator: Sublingual Psilocin; Depending on a number of factors, participants may complete a fourth session where they receive sublingual psilocin for the second time.	Drug: Sublingual Psilocin; 2.18mg - 4.36mg sublingual psilocin with psychological support and physiological monitoring

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physiological Effects	blood pressure	Baseline to 8 hours following drug delivery
Physiological Effects	heart rate	Baseline to 8 hours following drug delivery
Psychological Effects	- Peak psychedelic intensity ratings will be measured using Likert scale (0-10 rating scale, 0=not intense at all, 10=highest intensity imaginable)	Baseline to 4 weeks after drug delivery
Psychological Effects	- Peak psychological effects will be measured by the Altered States of Consciousness (5D-ASC) questionnaire at the end of each dosing session	Baseline to 4 weeks after drug delivery
Psychological Effects	- Peak psychological effects will be measured by the Challenging Experiences Questionnaire at the end of each dosing session	Baseline to 4 weeks after drug delivery
Psychological Effects	- Persistent changes in attitude, mood, and behavior will be assessed using Persisting Effects Questionnaire, administered 4 weeks after each dosing session	Baseline to 4 weeks after drug delivery
Psychological Effects	- Personality profiles will be measured using the Big Five Inventory at baseline and 4 weeks after each dosing session	Baseline to 4 weeks after drug delivery
Adverse Effects	Acute hypertension, hypotension, tachycardia, or bradycardia will be detected through blood pressure and heart rate monitoring at 10 minutes prior to drug administration and measured frequently up to 360 minutes following administration; Other dosing-related side effects including descriptive reports of nausea, headaches, dizziness, weakness, drowsiness, paresthesia, or blurred vision will be assessed during check-ins, after dosing effects have waned, and 24 hours following dosing	Baseline to 24 hours after dosing session

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Filament Health Corp.
• Investigators: Principal Investigator: Joshua Woolley, MD/PhD, University of California, San Francisco

Publications and helpful links

General Publications

• Anderson BT, Danforth A, Daroff PR, Stauffer C, Ekman E, Agin-Liebes G, Trope A, Boden MT, Dilley PJ, Mitchell J, Woolley J. Psilocybin-assisted group therapy for demoralized older long-term AIDS survivor men: An open-label safety and feasibility pilot study. EClinicalMedicine. 2020 Sep 24;27:100538. doi: 10.1016/j.eclinm.2020.100538. eCollection 2020 Oct.
• Barrett FS, Bradstreet MP, Leoutsakos JS, Johnson MW, Griffiths RR. The Challenging Experience Questionnaire: Characterization of challenging experiences with psilocybin mushrooms. J Psychopharmacol. 2016 Dec;30(12):1279-1295. doi: 10.1177/0269881116678781. Epub 2016 Nov 17.
• Benet-Martinez V, John OP. Los Cinco Grandes across cultures and ethnic groups: multitrait multimethod analyses of the Big Five in Spanish and English. J Pers Soc Psychol. 1998 Sep;75(3):729-50. doi: 10.1037//0022-3514.75.3.729.
• Bogenschutz MP, Johnson MW. Classic hallucinogens in the treatment of addictions. Prog Neuropsychopharmacol Biol Psychiatry. 2016 Jan 4;64:250-8. doi: 10.1016/j.pnpbp.2015.03.002. Epub 2015 Mar 14.
• Brown RT, Nicholas CR, Cozzi NV, Gassman MC, Cooper KM, Muller D, Thomas CD, Hetzel SJ, Henriquez KM, Ribaudo AS, Hutson PR. Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. Clin Pharmacokinet. 2017 Dec;56(12):1543-1554. doi: 10.1007/s40262-017-0540-6.

Helpful Links

• Individuals interested in participating in the clinical trial, please notify the study team of interest by completing the pre-screening survey on the website located under the specific study heading.

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2022
• Primary Completion (Actual): January 16, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: March 7, 2022
• First Submitted That Met QC Criteria: March 30, 2022
• First Posted (Actual): April 8, 2022

Study Record Updates

• Last Update Posted (Actual): June 10, 2025
• Last Update Submitted That Met QC Criteria: June 5, 2025
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Healthy; Psilocybin; Psychedelics; Psilocybin Therapy; Psilocin; San Francisco
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Psychotropic Drugs; Hallucinogens; Psilocybin; Psilocin
• Other Study ID Numbers: IRB#21-33765; PR#202143H (Other Identifier: Research Advisory Panel - California); 156917 (Other Identifier: FDA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No