Identification of a Safe and Non-Psychedelic Dose of Psilocybin

NCT07710027 | Completed Phase 1 DMC

• 2 other identifiers: DTI 01 001 - 2626254766
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized, double-blind, placebo-controlled, single ascending dose study will evaluate psilocybin in healthy adult subjects. Each subject will complete Screening within 28 days before admission, a 3-day/2-night inpatient Treatment Phase from Day -1 to Day 2, and Follow-Up 7±2 days after dosing. Up to 80 subjects will be enrolled in up to 10 cohorts of 8 subjects. In each cohort, 6 will receive a single oral dose of psilocybin and 2 matching placebo. The first cohort will receive 0.5 mg psilocybin or placebo. The DSRC will determine subsequent dose levels after each completed cohort. Proposed doses are 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, and up to 5 mg; lower doses, repeated levels, or smaller increments such as 0.25 mg may be used based on emerging data. Within each cohort, safety and pharmacodynamic data will be collected through 24 hours post dose. Safety monitoring will include adverse events, vital signs, ECGs, laboratory tests, physical examinations, concomitant medications, and C-SSRS results. Pharmacokinetic blood samples will be collected before and after dosing, and blood for possible retrospective pharmacogenetic analysis will be collected on Day -1. Pharmacodynamic assessments will include Alertness/Drowsiness, Agitation/Relaxation, Hallucinations, Any Effects, Bowdle, Bond-Lader, 5D-ASC, and STAI measures. Cognitive and psychomotor testing will include RTI, RVP, and SWM tasks. Pupil diameter will be measured as an objective marker. Other subject-reported effects may be recorded as adverse events at the investigator's discretion. Subjects will be discharged on Day 2 if medically appropriate and will receive a 24-hour/7-day emergency clinic contact number. After each cohort, the DSRC will review available blinded safety and pharmacodynamic data through 24 hours post dose before the next cohort begins. Escalation and any decision to stop will follow prespecified rules. The study aims to identify a safe threshold dose (TD) that does not elicit psychoactive effects. The TD will be the dose immediately before the dose at which escalation stops because of neuropsychiatric adverse events and/or a pharmacodynamic response pattern indicating a dose above the nonpsychoactive level. The study will end when a TD is identified or the 5 mg maximum dose is reached.

Conditions

Healthy Controls

Keywords

psilocybin; perceptual threshold; psilocin; cognition; perception; anxiety

Outcome Measures

Primary Outcomes (16)

• Clinical Safety Event Frequency

  Safety endpoints include the classification and frequency of Adverse Events, Serious Adverse Events, and Adverse Events leading to discontinuation.

  Monitoring from dosing through treatment (3 days) and Follow-Up (~1 week).

• Clinical Safety Event Severity

  Safety endpoints include the classification and severity of Adverse Events, Serious Adverse Events, and Adverse Events leading to discontinuation.

  Monitoring from dosing through treatment (3 days) and Follow-Up (~1 week).

• Clinical Safety Event Relationship to Treatment

  Safety endpoints include the classification and determined treatment relationship of the Adverse Events, Serious Adverse Events, and Adverse Events leading to discontinuation.

  Monitoring from dosing through treatment (3 days) and Follow-Up (~1 week).

• Vital Signs Heart Rate for Clinical Safety and Tolerability

  Vital signs include heart rate in beats per minute

  Vital signs 0.5, 1, 1.5, 2, 3, 6, 8, 10, 12 hours after dose.

• Electrocardiogram for Clinical Safety and Tolerability

  12 channel ECG is performed as a safety and tolerability outcome with the QT Interval used as the metric. The QT interval is the start of the Q wave to the end of the T wave in milliseconds. The outcome is the number of participants with an abnormal QT interval from ECG emerging following dosing.

  ECG baseline and 3 and 6 hours after dosing.

• Five-Dimensional Altered States of Consciousness Scale

  The Five-Dimensional Altered States of Consciousness (5D-ASC) Scale is composed of 94 questions. Scores will be clustered into 5 dimensions as follows: oceanic boundlessness (OB), anxious ego dissolution (AED), visionary restructuralization (VR), auditory alterations (AA), and reduction of vigilance (RV). The dimension scores range from 0 no change to 100 maximum intensity of drug effect. The endpoints for the 5D-ASC scale will be total score at the 6-hour time point for each subscale.

  The 5D-ASC will be administered 6 hours following dosing.

• State Trait Anxiety Inventory Scale

  The State Trait Anxiety Inventory (STAI) survey contains 40 questions. Each question has a score of 0-4 for a minimum score of 0 reflecting no anxiety and a score of 80 reflecting high anxiety. Scores will be clustered into state and trait anxiety subscales ranging from 0 minimum to 40 maximum anxiety. Outcomes will be changes in raw state subscale scores from baseline where positive scores indicate an increase in state anxiety from baseline.

  The STAI will be given at baseline and at the two and six hour time points following dose.

• Reaction Time Test Performance

  Acute effects on cognition will be evaluated the CANTAB Reaction time (RTI) test. The test measures reaction times in response to a stimulus in milliseconds. Outcome measures will be the raw reaction times in milliseconds. Slower reaction times (higher milliseconds) indicates more poor performance whereas faster reaction times (lower milliseconds) indicates better performance.

  Reaction time test will be given at baseline and at the two and six hour time points following dosing.

• Rapid Visual Information Processing Test

  Acute effects on cognition will be evaluated the CANTAB Rapid Visual Information Processing (RVP) test. The outcome will be the change from baseline in probability of hits or the percentage of correct targets successfully identified. A higher score reflects better sustained attention.

  Rapid Visual Information Processing test will be given at baseline and at the two and six hour time points following dosing. Performance will be measured as change from baseline across time and to maximum or minimum effect .

• Spatial Working Memory

  Acute effects on cognition will be evaluated the CANTAB Spatial Working Memory (SWM) test. The CANTAB SWM test evaluates visuospatial retention, manipulation, and strategic planning using a computerized token-search task. The outcome measure will be total errors. Lower error scores indicate better performance.

  The Spatial Working Memory (SWM) test will be given at baseline and at the two and six hour time points following dosing. Performance will be measured as change from baseline across time.

• Perceptual Pharmacodynamic Alertness Drowsiness Visual Analog Scale

  The pharmacodynamic endpoints to be evaluated include the scores over time and derived endpoints of the following measures on 0 to 100 visual analog scales including an Alertness/Drowsiness VAS. Changes in scores will be compared across time and maximum and minimum effects.

  The Alertness/Drowsiness VAS will be given at baseline, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours after dosing.

• Perceptual Pharmacodynamic Agitation Relaxation Visual Analog Scale

  The pharmacodynamic endpoints to be evaluated include the scores over time and derived endpoints of the following measures on 0 to 100 visual analog scales including an Agitation/Relaxation VAS. Changes in scores will be compared across time and maximum and minimum effects.

  The Agitation/Relaxation VAS will be given at baseline, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours after dosing.

• Perceptual Pharmacodynamic Any Drug Effects Visual Analog Scale

  The pharmacodynamic endpoints to be evaluated include the scores over time and derived endpoints of the following measures on 0 to 100 visual analog scales including an Any Drug Effects VAS. Changes in scores will be compared across time and maximum and minimum effects

  The Any Drug Effects VAS will be given at baseline, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours after dosing.

• Perceptual Pharmacodynamic Hallucinations Visual Analog Scale

  The pharmacodynamic endpoints to be evaluated include the scores over time and derived endpoints of the following measures on 0 to 100 visual analog scales including an Hallucinations VAS. Changes in scores will be compared across time and maximum and minimum effects

  The Hallucainations VAS will be given at baseline, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours after dosing.

• Perceptual Pharmacodynamic Bowdle (internal and external perceptions) Visual Analog Scale

  The pharmacodynamic endpoints to be evaluated include the scores over time and derived endpoints of the following measures on 0 to 100 visual analog scales including a Bowdle (internal and external perceptions) VAS. Changes in scores will be compared across time and maximum and minimum effects

  The Bowdle VAS will be given at baseline, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours after dosing.

• Perceptual Pharmacodynamic Bond-Lader Visual Analog Scale

  The pharmacodynamic endpoints to be evaluated include the scores over time and derived endpoints of the following measures on 0 to 100 visual analog scales including a Bond-Lader VAS. Changes in scores will be compared across time and maximum and minimum effects

  The Bond-Lader VAS will be given at baseline, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours after dosing.

Secondary Outcomes (6)

• Maximum Plasma Concentration

  Blood samples will be collected at baseline and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24 hours following dosing.

• Psychophysiological arousal

  Pupillometry will be conducted at baseline and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours after dosing.

• Terminal elimination half-life

  Blood samples will be collected at baseline and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24 hours following dosing.

• Plasma Concentration x Time to Infinity Area Under the Curve

  Blood samples will be collected at baseline and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24 hours following dosing.

• Plasma Concentration x Time to Last Measurable Concentration Area Under the Curve

  Blood samples will be collected at baseline and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24 hours following dosing.

Study Arms (10)

Psilocybin 0.5 mg or Placebo

EXPERIMENTAL

Psilocybin 0.5 mg in 5 mL sucralose randomly administered to 6 participants and placebo (5 mL sucralose) randomly administered to 2 participants.

Drug: Psilocybin (low dose) or Placebo

Psilocybin 1.0 mg or Placebo

EXPERIMENTAL

Psilocybin 1 mg in 10 mL sucralose randomly administered to 6 participants and placebo (10 mL sucralose) randomly administered to 2 participants.

Drug: Psilocybin (low dose) or Placebo

Psilocybin 1.5 mg or Placebo

EXPERIMENTAL

Psilocybin 1.5 mg in 10 mL sucralose randomly administered to 6 participants and placebo (10 mL sucralose) randomly administered to 2 participants.

Drug: Psilocybin (low dose) or Placebo

Psilocybin 2.0 mg or Placebo

EXPERIMENTAL

Psilocybin 2.0 mg in 10 mL sucralose randomly administered to 6 participants and placebo (10 mL sucralose) randomly administered to 2 participants.

Drug: Psilocybin (low dose) or Placebo

Psilocybin 2.5 mg or Placebo

EXPERIMENTAL

Psilocybin 2.5 mg in 10 mL sucralose randomly administered to 6 participants and placebo (10 mL sucralose) randomly administered to 2 participants.

Drug: Psilocybin (low dose) or Placebo

Psilocybin 3.0 mg or Placebo

EXPERIMENTAL

Psilocybin 3.0 mg in 10 mL sucralose randomly administered to 6 participants and placebo (10 mL sucralose) randomly administered to 2 participants.

Drug: Psilocybin (low dose) or Placebo

Psilocybin 3.5 mg or Placebo

EXPERIMENTAL

Psilocybin 3.5 mg in 10 mL sucralose randomly administered to 6 participants and placebo (10 mL sucralose) randomly administered to 2 participants.

Drug: Psilocybin (low dose) or Placebo

Psilocybin 4.0 mg or Placebo

EXPERIMENTAL

Psilocybin 3.5 mg in 10 mL sucralose randomly administered to 6 participants and placebo (10 mL sucralose) randomly administered to 2 participants.

Drug: Psilocybin (low dose) or Placebo

Psilocybin 4.5 mg or Placebo

EXPERIMENTAL

Psilocybin 4.5 mg in 10 mL sucralose randomly administered to 6 participants and placebo (10 mL sucralose) randomly administered to 2 participants.

Drug: Psilocybin (low dose) or Placebo

Psilocybin 5.0 mg or Placebo

EXPERIMENTAL

Psilocybin 5.0 mg in 10 mL sucralose randomly administered to 6 participants and placebo (10 mL sucralose) randomly administered to 2 participants.

Drug: Psilocybin (low dose) or Placebo

Interventions

Psilocybin (low dose) or Placebo DRUG

Single ascending dose escalation.

Psilocybin 0.5 mg or Placebo; Psilocybin 1.0 mg or Placebo; Psilocybin 1.5 mg or Placebo; Psilocybin 2.0 mg or Placebo; Psilocybin 2.5 mg or Placebo; Psilocybin 3.0 mg or Placebo; Psilocybin 3.5 mg or Placebo; Psilocybin 4.0 mg or Placebo; Psilocybin 4.5 mg or Placebo; Psilocybin 5.0 mg or Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Must provide written informed consent prior to the initiation of any protocol-specific procedures.
• Male and female adults, between 18 and 55 years of age, inclusive.
• Body mass index (BMI) within 18.0 to 34.0 kg/m2, inclusive (minimum weight of at least 50.0 kg).
• Systolic blood pressure between 95-140 mmHg, inclusive; diastolic blood pressure between 55-90 mmHg, inclusive; and heart rate between 50-100 bpm, inclusive, unless deemed otherwise by the investigator.
• Clinical laboratory values within the clinical site's most recent acceptable laboratory test ranges, and/or values are deemed by the investigator as not clinically significant.
• Non-smoker, for at least 6 months prior to first study drug administration.
• Agrees not to receive the COVID-19 vaccination from 7 days prior to the first study drug dose until at least 7 days after the last study drug administration.
• Female subjects must be non-pregnant and non-lactating and must fulfil at least one of the following:
• Be surgically sterile for a minimum of 6 months (achieved through hysterectomy, oophorectomy, or bilateral salpingectomy; note that tubal ligation is not considered a method of permanent sterilization).
• Post-menopausal for a minimum of 1 year (confirmed by follicle-stimulating hormone test).
• Agree to avoid pregnancy and use a medically acceptable method of contraception with male sexual partners from at least 30 days prior to the study until 30 days after the study has ended (last study procedure).
• Medically acceptable methods of contraception include any of the following:
• double-barrier methods (e.g., male condom, spermicide with diaphragm or spermicide with cervical cap)
• oral contraceptives; hormonal patch, implant or injection; or hormonal or non-hormonal intrauterine device. The male partner should use, at all times, a male condom with spermicide, should the female subject choose to use any of these methods
• complete abstinence, should it be in line with the subject's preferred and usual lifestyle

You may not qualify if:

• History or presence of any clinically significant cardiac, psychiatric, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, renal, or other disease at Screening, which, in the opinion of the investigator, would jeopardize the safety of the subject or the validity of the study results.
• Clinically significant abnormality on ECG, including a QT interval corrected for heart rate (Bazett; QTcB interval) of \>440 milliseconds in males and \>460 milliseconds in females.
• History of allergies to the investigational product or excipients.
• History of seizures, family history of seizures, history of head trauma, history of neurosurgery, or close family history of idiopathic generalized epilepsy or other congenital epilepsies.
• Positive for hepatitis B virus surface antigen, hepatitis C virus antibody, or human immunodeficiency virus (HIV) antibody.
• Positive urine drug screen (UDS) for opioids, amphetamines, cocaine, tetrahydrocannabinol (THC), barbiturates, phencyclidine, or benzodiazepines upon any admission into the clinic.
• Positive breath alcohol test at admission to the clinic.
• Current or history of drug or alcohol dependence (excluding caffeine and nicotine) within the past 2 years, or lifetime history of participation in a drug rehabilitation program (other than treatment for smoking cessation).
• Has used CNS drugs with perception-altering properties (e.g., ketamine, lysergic acid diethylamide \[LSD\], phencyclidine \[PCP\], dextromethorphan, 3,4 methylenedioxymethamphetamine \[MDMA\], mescaline, psilocybin, tryptamine derivatives, or ring-substituted amphetamines with perception-altering effects) for non-therapeutic purposes (i.e., for psychoactive effects) within the past 5 years and/or ≥5 lifetime uses.
• Personal or immediate family history of schizophrenia, bipolar affective disorder, delusion disorder, paranoid disorder, schizoaffective disorder, or personality disorder.
• History of suicidal ideation or active suicidality, based on C-SSRS results.
• Concurrent or recent (within 5 years) history of major depression, obsessive-compulsive disorder, panic disorder, general anxiety disorder, social anxiety disorder, anorexia nervosa, or bulimia nervosa.
• Has donated \>500 mL of blood within 30 days prior to study drug administration.
• Requires concomitant treatment with any prescription or non-prescription medications (with the exception of acetaminophen) or natural health products (herbal remedies) within 14 days prior to receiving study drug.
• Has unsuitable or difficult venous access or is unwilling or unable to undergo direct venipuncture or catheter insertion.

Sponsors & Collaborators

• Diamond Therapeutics Inc.: lead
• BioPharma Services Inc.: collaborator

Study Sites (1)

BioPharma Services Inc.

Toronto, Ontario, M9L 3A2, Canada

Location

Related Publications (6)

• Gukasyan N, Davis AK, Barrett FS, Cosimano MP, Sepeda ND, Johnson MW, Griffiths RR. Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. J Psychopharmacol. 2022 Feb;36(2):151-158. doi: 10.1177/02698811211073759.

  PMID: 35166158 BACKGROUND

• Fadiman J, Korb S. Might Microdosing Psychedelics Be Safe and Beneficial? An Initial Exploration. J Psychoactive Drugs. 2019 Apr-Jun;51(2):118-122. doi: 10.1080/02791072.2019.1593561. Epub 2019 Mar 29.

  PMID: 30925850 BACKGROUND

• Davis AK, Barrett FS, May DG, Cosimano MP, Sepeda ND, Johnson MW, Finan PH, Griffiths RR. Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2021 May 1;78(5):481-489. doi: 10.1001/jamapsychiatry.2020.3285.

  PMID: 33146667 BACKGROUND

• Carhart-Harris RL, Bolstridge M, Rucker J, Day CM, Erritzoe D, Kaelen M, Bloomfield M, Rickard JA, Forbes B, Feilding A, Taylor D, Pilling S, Curran VH, Nutt DJ. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry. 2016 Jul;3(7):619-27. doi: 10.1016/S2215-0366(16)30065-7. Epub 2016 May 17.

  PMID: 27210031 BACKGROUND

• Baxter AJ, Scott KM, Vos T, Whiteford HA. Global prevalence of anxiety disorders: a systematic review and meta-regression. Psychol Med. 2013 May;43(5):897-910. doi: 10.1017/S003329171200147X. Epub 2012 Jul 10.

  PMID: 22781489 BACKGROUND

• Bonomi L, Jiang X. A Mortality Study for ICU Patients using Bursty Medical Events. Proc Int Conf Data Eng. 2017 Apr;2017:1533-1540. doi: 10.1109/ICDE.2017.224. Epub 2017 May 18.

  PMID: 28757793 BACKGROUND

MeSH Terms

Conditions

Anxiety Disorders

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Mental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Neither the subject nor the site personnel (with the exception of designated unblinded pharmacy personnel, compliance auditor(s), and statistician(s) who generate the randomization codes) will know which treatment is being administered during the double-blind Treatment Phase. The randomization scheme will be provided to the site's unblinded personnel for preparation of the individual subject doses. The bioanalytical lab will also be blinded, but if necessary, personnel from the bioanalytical laboratory will have access to the randomization scheme. Decisions for dose escalation will be based on the assessment of the blinded safety and data, as well as a review of select pharmacodynamic measures (i.e., listing of all subjective VAS and cognitive measures \[timepoint data only\]).
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a single ascending dose study that will employ a randomized, double-blind, placebo-controlled design with healthy adult male and female subjects. All subjects will participate in an outpatient medical Screening Visit (Visit 1), a 3-day (2-night) inpatient Treatment Phase (Visit 2), and an outpatient Follow-Up Visit (Visit 3). For each subject, the inpatient Treatment Phase will begin on the day prior to the first study drug administration (Day -1) and end on Day 2. The study has up to 10 treatment arms including 10 escalating doses of psilocybin and a placebo control. We will randomly assign 8 subjects to each arm at a 3:1 randomization schedule such that 6 participants receive active psilocybin and 2 participants receive placebo in each treatment condition.

Study Record Dates

• First Submitted: July 6, 2026
• First Posted: July 17, 2026
• Study Start: October 19, 2021
• Primary Completion: March 12, 2022
• Study Completion: March 12, 2023
• Last Updated: July 17, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: De-identified data and study documents will be made available with reasonable request following publication of the results. Details will be made with the publication of results anticipated December 30, 2026.
• Access Criteria: Reasonable requests may be made to the corresponding author of the manuscript describing the results.

Locations

CA (1)