Healthy ControlsPhase 1NCT07710027
Identification of a Safe and Non-Psychedelic Dose of Psilocybin
A Phase 1 study of Healthy Controls, run by Diamond Therapeutics Inc. at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Controls
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 1 siteCanada
- Study dates
- 19 Oct 2021to 12 Mar 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects must meet each of the following inclusion criteria to be eligible for participation in the study:
- 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.
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- 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
- Males who are able to father children must agree to use medically acceptable methods of contraception during the study and for 30 days after the last study drug administration. If a subject's partner should become pregnant during his participation in the study and for 30 days after he has completed his last study drug administration, the subject must inform BioPharma Services Inc. staff immediately. Medically acceptable methods of contraception include:
- using a condom with a female partner of child-bearing potential who is using oral contraceptives; hormonal patch, implant or injection; hormonal or non-hormonal intrauterine device; or diaphragm or cervical cap with spermicide
- complete abstinence, should it be in line with the subject's preferred and usual lifestyle.
- Male subjects must refrain from sperm donation from clinic admission to at least 30 days after the last dose of study drug.
- Must be able to speak, read, and understand English sufficiently to allow completion of all study assessments.
- Must be willing to comply with the requirements and restrictions of the study.
Who cannot join
- Subjects will not be eligible to participate in this study if any of the following exclusion criteria is met:
- 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.
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- 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.
- Is currently using an investigational drug or device or has used such in the 30 days prior to receiving study drug.
- Female subject is pregnant, breastfeeding, or has had a recent positive pregnancy test.
- Subject, in the investigator's opinion, is unsuitable for clinical study participation.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-Blind, Single Ascending Dose Study to Identify a Safe and Non-Psychedelic Dose of Psilocybin
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.
Read more
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.
Read the detailed description
This study in healthy volunteers will evaluate the safety, pharmacodynamic effects, and pharmacokinetics of psilocybin and its primary active metabolite, psilocin, as a potential therapy for anxiety and depressive disorders after single ascending oral doses. The study is intended to support dose selection by identifying a threshold dose (TD) of psilocybin that does not produce psychoactive effects that would preclude outpatient or potential repeated dosing.
The study will use a randomized, double-blind, placebo-controlled, single ascending dose design in healthy adult male and female subjects. Each subject will complete an outpatient Screening Visit (Visit 1), a 3-day/2-night inpatient Treatment Phase (Visit 2), and an outpatient Follow-Up Visit (Visit 3). The Treatment Phase begins the day before dosing (Day -1) and ends on Day 2.
Screening Visit (Visit 1) Subjects will provide written informed consent before protocol-specified procedures. To reduce expectancy effects common in psychedelic studies, subjects will be told verbally and in the informed consent form that they may receive placebo or one of five drug classes/substances-niacin, alprazolam, ibuprofen, psilocybin, or methylphenidate-although they will actually receive only placebo or psilocybin. The informed consent form will describe safety risks associated with the listed substances, with no added risk from substances not administered. Screening will be completed within 28 days before admission for the Treatment Phase.
Treatment Phase (Visit 2) Up to 80 subjects will be enrolled in a maximum of 10 cohorts. Each cohort will include 8 subjects randomized so that 6 receive a single oral dose of psilocybin and 2 receive matching placebo. The first cohort will receive 0.5 mg psilocybin or placebo. Subsequent dose levels will be determined by the Drug Safety Review Committee (DSRC) after review of each completed dosing level. Proposed psilocybin doses are 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, and up to 5 mg. Depending on emerging safety, tolerability, pharmacodynamic, or other relevant data, lower-than-planned doses may be tested, dose levels repeated, or smaller increments used (e.g., 0.25 mg).
Proposed dose levels include 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, up to a maximum dose of 5 mg. Within the planned dose range, a dose lower than the planned dose may be tested, a dose level may be repeated, or smaller dosing increments may be applied (e.g., 0.25 mg), depending on emerging safety, tolerability, and/or other relevant data, such as pharmacodynamic data.
Within each cohort, safety and pharmacodynamic data will be collected through 24 hours post dose. Safety monitoring will include adverse events (AEs), vital signs, electrocardiograms, clinical laboratory tests, physical examinations, concomitant medications, and Columbia-Suicide Severity Rating Scale results. Blood samples for pharmacokinetic assessments will be collected before and after dosing, and whole blood for possible retrospective pharmacogenetic analysis will be collected on Day -1.
Pharmacodynamic assessments will include Alertness/Drowsiness, Agitation/Relaxation, Hallucinations, Any Effects, Bowdle internal/external perceptions, Bond-Lader, 5D-ASC, and State-Trait Anxiety Inventory measures. Cognitive and psychomotor assessments will include the 5-choice reaction time task, rapid visual information processing task, and spatial working memory task. Pupil diameter will serve as an objective physiological pharmacodynamic measure. Subjects will also be encouraged to report effects not captured by scales; such effects may be recorded as AEs at the investigator's discretion.
To assess expectancy, subjects will be asked on Day 1 what treatment they believe they received and again before discharge on Day 2. Subjects will be discharged on Day 2 after completion of study procedures if no medical reason requires a longer stay. They will receive a 24-hour/7-day emergency clinic contact number.
After each cohort, available blinded safety and pharmacodynamic data through 24 hours post dose will be reviewed by the DSRC before the next cohort begins. Escalation and any decision to stop the study will follow prespecified stopping rules. Because the goal is to identify a safe nonpsychoactive dose, the TD will be the dose immediately before the dose at which escalation stops because of neuropsychiatric AEs and/or the collective pharmacodynamic response pattern. Once a TD is identified, or the maximum dose of 5 mg is reached, the study will conclude.
Follow-Up Visit (Visit 3) A Follow-Up Visit will occur 7±2 days after final study drug administration and will include end-of-study procedures.
Dose Selection Rationale The planned starting dose is 0.5 mg, consistent with the objective of identifying a TD without perceptible psychoactive effects that would preclude outpatient or repeated dosing. Perceptible effects have been reported at plasma psilocin concentrations of 4 to 6 ng/mL. In a PET study of healthy subjects receiving single oral psilocybin doses of 3 to 30 mg (n=8), subject-rated effect intensity correlated with plasma psilocin concentration, with an EC50 of 4.5 ng/mL (95% CI: 2.1, 9.8). Dose-related neocortical 5-HT2A receptor occupancy ranged from 1.8% at 3 mg to 72% at 18 mg, with an EC50 of 1.95 ng/mL (95% CI: 1.17, 3.15). Follow-up results indicated that 5-HT2A receptor occupancy up to approximately 15% produced no perceptual subjective effects. Therefore, 0.5 mg and doses up to 2 mg are expected to produce exposures below 2 ng/mL and no perceptible subjective effects, although intersubject variability in exposure and response is recognized.
The planned maximum dose of 5 mg is based on a prior study in 18 healthy subjects showing perceptible effects at this dose, and earlier studies suggesting that 3 to 5 mg psilocybin may produce perceptible sympathomimetic, but not hallucinogenic, effects depending on intersubject differences. Low-dose psilocybin (≤5 mg) is associated with very few or no treatment-emergent AEs, and doses up to about 8 times the proposed maximum (6 to 42 mg/70 kg) have been considered safe and well tolerated; most reported events were mild or moderate, with no serious AEs reported.
The planned maximum oral psilocybin dose of 5 mg is based on a prior study of 18 healthy subjects indicating that this dose level was associated with perceptible effects, as well as earlier studies suggesting that psilocybin 3 to 5 mg (range due to inter-subject differences) may have perceptible sympathomimetic, but not hallucinogenic, effects. In addition, low-dose psilocybin (≤5 mg) is associated with very few or no TEAEs, while doses up to approximately 8 times the proposed maximum dose of 5 mg (6 to 42 mg/70 kg) are considered to be safe and have been well tolerated; the majority of events for which severity has been reported are mild or moderate in severity, and no serious AEs have been reported.
Dose Escalation Stopping Criteria Dose escalation between cohorts will be interrupted and may be discontinued if any drug-related serious adverse event occurs in 1 or more subjects; if drug-related neuropsychiatric AEs of moderate intensity occur in 2 or more subjects; or if the DSRC concludes, based on the pattern, number, and severity of AEs and/or the collective pharmacodynamic response pattern excluding pupillometry, that a dose exceeding a nonpsychoactive dose has been reached.
Removal of Subjects from Therapy or Assessment
Subjects may withdraw consent and discontinue participation at any time for any reason. Subjects may also be discontinued by the investigator and/or sponsor for protocol entry violation, safety reasons including AEs, unacceptable concomitant medication use, noncompliance or major protocol violation, pregnancy, positive urine drug screen or breath alcohol test, administrative reasons such as termination of enrollment or study, or because continuation is not in the subject's best interest.
The investigator will maintain a record of all subjects who discontinue before completion and document the reason(s). If a subject withdraws, the investigator should make a reasonable attempt to obtain and record the reason, although the subject is not required to provide one.
If discontinuation occurs while the subject is at the clinical site, early termination procedures should be completed before discharge. For any early discontinuation, whether or not the subject is on site, the investigator should ask the subject to return for Follow-Up Visit procedures unless consent for those procedures has been withdrawn. Refusal to complete early termination or Follow-Up Visit procedures will be recorded.
In the event that a subject is discontinued while at the clinical site, the early termination procedures should be performed prior to discharge from the study site. For any case of early discontinuation (whether or not the subject is at the clinical site), the investigator should ask the subject to return for the Follow-Up Visit procedures, provided that the subject has not withdrawn consent for those procedures. If a subject refuses to complete early termination procedures and/or the Follow-Up Visit, this information will be recorded.
Study Restrictions In addition to inclusion/exclusion criteria, subjects must abstain from alcohol for 48 hours before Screening and before Treatment Phase admission (Day -1), confirmed by breath alcohol test. They will be asked to avoid strenuous physical activity for 48 hours before Screening and admission and may not perform strenuous exercise during the inpatient stay.
Subjects must abstain from recreational drug use from Screening until after the Treatment Phase, confirmed by urine drug screen. From 1 week before dosing until after the final pharmacokinetic draw, they must avoid grapefruit or grapefruit products, pomegranate, pomelo, star fruit juice/products, poppy seeds, Seville oranges, apple juice, orange juice, and mustard-family vegetables such as kale, broccoli, watercress, collard greens, kohlrabi, brussels sprouts, and mustard. Subjects must fast for at least 10 hours before dosing and 4 hours after dosing; water is allowed except for about 1 hour before and after dosing. Caffeine/methylxanthine products are prohibited for 48 hours before dosing and while housed at the site. Smoking is prohibited for the study duration. Electronic devices are prohibited for 1 hour before and at least 6 hours after dosing. Subjects should avoid driving, machinery, or hazardous activities until they and clinic staff confirm the study drug has not impaired judgment or skilled-task performance. Subjects must remain awake and seated upright for at least 4 hours after dosing, rising only briefly under supervision for study activities or washroom use; afterward, they may ambulate within the clinic. If an AE occurs, they may be placed in an appropriate position at any time. For at least 1 hour after dosing, washroom visits will be monitored and recorded, and subjects may not flush so staff can inspect contents. Subjects must abstain from blood donation during the study and for 30 days after Follow-Up.
- Conditions
- Healthy Controls
- Being tested
- Psilocybin (low dose) or Placebo
- Keywords
- psilocybin, perceptual threshold, psilocin, cognition, perception, anxiety
- Medical subject headings
- Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Psilocybin (low dose) or PlaceboDrug
Single ascending dose escalation.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Psilocybin (low dose) or Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Safety Event Frequency
Safety endpoints include the classification and frequency of Adverse Events, Serious Adverse Events, and Adverse Events leading to discontinuation.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Cmax: maximum observed plasma concentration of psilocin from blood samples.
Measured: 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 used to measure pupil diameter as an objective physiological pharmacodynamic measure of arousal. Pupil measures will be made in millimeters.
Measured: 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
T½: terminal elimination half-life of psilocin in plasma from blood
Measured: 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
AUCINF: area under the plasma concentration vs. time curve, extrapolated to infinity
Measured: 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
AUClast: area under the plasma concentration of psilocin in blood vs. time curve, from time 0 hours to the last measurable concentration.
Measured: 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.
Time to Maximum Plasma Concentration
Tmax: time to maximum observed plasma concentration of psilocin in blood.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2026
- Study start19 Oct 2021
- Primary completion12 Mar 2022
- Study completion12 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Healthy ControlsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Diamond Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- BioPharma Services Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07710027
- Sponsor's protocol ID
- DTI 01 001 - 2626
- Other IDs
- 254766
- Status last verified
- Jul 2026
- First submitted
- 6 Jul 2026
- Last updated
- 17 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
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.
PubMed 35166158Fadiman 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.
PubMed 30925850Davis 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.
PubMed 33146667Carhart-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.
PubMed 27210031Baxter 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.
PubMed 22781489Bonomi 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.
PubMed 28757793Levy-Cooperman N, Sellers E, Glue P, Szeto I, Brown D, Jarecki-Smith J, Tyler WJ, McDonnell MB. A Randomized, Double-Blind, Placebo-Controlled Single-Ascending-Dose Study to Identify a Subperceptual Dose of Psilocybin in Healthy Adults. Pharmaceuticals (Basel). 2026 Sep 21;19(9):1496. doi: 10.3390/ph19091496.
PubMed 42797541
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Single Ascending Dose Study to Identify a Safe and Non-Psychedelic Dose of Psilocybin
- ClinicalTrials.gov ID
- NCT07710027
- Acronym / sponsor ID
- DTI 01 001 - 2626
- Conditions
- Healthy Controls
- Keywords
- psilocybin, perceptual threshold, psilocin, cognition, perception, anxiety
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Diamond Therapeutics Inc.Industry (pharma, biotech, devices)
- Collaborators
- BioPharma Services Inc.
- Study start
- 19 Oct 2021 (actual)
- Primary completion
- 12 Mar 2022 (actual)
- Study completion
- 12 Mar 2023 (actual)
- First posted
- 17 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study in healthy volunteers will evaluate the safety, pharmacodynamic effects, and pharmacokinetics of psilocybin and its primary active metabolite, psilocin, as a potential therapy for anxiety and depressive disorders after single ascending oral doses. The study is intended to support dose selection by identifying a threshold dose (TD) of psilocybin that does not produce psychoactive effects that would preclude outpatient or potential repeated dosing.
The study will use a randomized, double-blind, placebo-controlled, single ascending dose design in healthy adult male and female subjects. Each subject will complete an outpatient Screening Visit (Visit 1), a 3-day/2-night inpatient Treatment Phase (Visit 2), and an outpatient Follow-Up Visit (Visit 3). The Treatment Phase begins the day before dosing (Day -1) and ends on Day 2.
Screening Visit (Visit 1) Subjects will provide written informed consent before protocol-specified procedures. To reduce expectancy effects common in psychedelic studies, subjects will be told verbally and in the informed consent form that they may receive placebo or one of five drug classes/substances-niacin, alprazolam, ibuprofen, psilocybin, or methylphenidate-although they will actually receive only placebo or psilocybin. The informed consent form will describe safety risks associated with the listed substances, with no added risk from substances not administered. Screening will be completed within 28 days before admission for the Treatment Phase.
Treatment Phase (Visit 2) Up to 80 subjects will be enrolled in a maximum of 10 cohorts. Each cohort will include 8 subjects randomized so that 6 receive a single oral dose of psilocybin and 2 receive matching placebo. The first cohort will receive 0.5 mg psilocybin or placebo. Subsequent dose levels will be determined by the Drug Safety Review Committee (DSRC) after review of each completed dosing level. Proposed psilocybin doses are 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, and up to 5 mg. Depending on emerging safety, tolerability, pharmacodynamic, or other relevant data, lower-than-planned doses may be tested, dose levels repeated, or smaller increments used (e.g., 0.25 mg).
Proposed dose levels include 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, up to a maximum dose of 5 mg. Within the planned dose range, a dose lower than the planned dose may be tested, a dose level may be repeated, or smaller dosing increments may be applied (e.g., 0.25 mg), depending on emerging safety, tolerability, and/or other relevant data, such as pharmacodynamic data.
Within each cohort, safety and pharmacodynamic data will be collected through 24 hours post dose. Safety monitoring will include adverse events (AEs), vital signs, electrocardiograms, clinical laboratory tests, physical examinations, concomitant medications, and Columbia-Suicide Severity Rating Scale results. Blood samples for pharmacokinetic assessments will be collected before and after dosing, and whole blood for possible retrospective pharmacogenetic analysis will be collected on Day -1.
Pharmacodynamic assessments will include Alertness/Drowsiness, Agitation/Relaxation, Hallucinations, Any Effects, Bowdle internal/external perceptions, Bond-Lader, 5D-ASC, and State-Trait Anxiety Inventory measures. Cognitive and psychomotor assessments will include the 5-choice reaction time task, rapid visual information processing task, and spatial working memory task. Pupil diameter will serve as an objective physiological pharmacodynamic measure. Subjects will also be encouraged to report effects not captured by scales; such effects may be recorded as AEs at the investigator's discretion.
To assess expectancy, subjects will be asked on Day 1 what treatment they believe they received and again before discharge on Day 2. Subjects will be discharged on Day 2 after completion of study procedures if no medical reason requires a longer stay. They will receive a 24-hour/7-day emergency clinic contact number.
After each cohort, available blinded safety and pharmacodynamic data through 24 hours post dose will be reviewed by the DSRC before the next cohort begins. Escalation and any decision to stop the study will follow prespecified stopping rules. Because the goal is to identify a safe nonpsychoactive dose, the TD will be the dose immediately before the dose at which escalation stops because of neuropsychiatric AEs and/or the collective pharmacodynamic response pattern. Once a TD is identified, or the maximum dose of 5 mg is reached, the study will conclude.
Follow-Up Visit (Visit 3) A Follow-Up Visit will occur 7±2 days after final study drug administration and will include end-of-study procedures.
Dose Selection Rationale The planned starting dose is 0.5 mg, consistent with the objective of identifying a TD without perceptible psychoactive effects that would preclude outpatient or repeated dosing. Perceptible effects have been reported at plasma psilocin concentrations of 4 to 6 ng/mL. In a PET study of healthy subjects receiving single oral psilocybin doses of 3 to 30 mg (n=8), subject-rated effect intensity correlated with plasma psilocin concentration, with an EC50 of 4.5 ng/mL (95% CI: 2.1, 9.8). Dose-related neocortical 5-HT2A receptor occupancy ranged from 1.8% at 3 mg to 72% at 18 mg, with an EC50 of 1.95 ng/mL (95% CI: 1.17, 3.15). Follow-up results indicated that 5-HT2A receptor occupancy up to approximately 15% produced no perceptual subjective effects. Therefore, 0.5 mg and doses up to 2 mg are expected to produce exposures below 2 ng/mL and no perceptible subjective effects, although intersubject variability in exposure and response is recognized.
The planned maximum dose of 5 mg is based on a prior study in 18 healthy subjects showing perceptible effects at this dose, and earlier studies suggesting that 3 to 5 mg psilocybin may produce perceptible sympathomimetic, but not hallucinogenic, effects depending on intersubject differences. Low-dose psilocybin (≤5 mg) is associated with very few or no treatment-emergent AEs, and doses up to about 8 times the proposed maximum (6 to 42 mg/70 kg) have been considered safe and well tolerated; most reported events were mild or moderate, with no serious AEs reported.
The planned maximum oral psilocybin dose of 5 mg is based on a prior study of 18 healthy subjects indicating that this dose level was associated with perceptible effects, as well as earlier studies suggesting that psilocybin 3 to 5 mg (range due to inter-subject differences) may have perceptible sympathomimetic, but not hallucinogenic, effects. In addition, low-dose psilocybin (≤5 mg) is associated with very few or no TEAEs, while doses up to approximately 8 times the proposed maximum dose of 5 mg (6 to 42 mg/70 kg) are considered to be safe and have been well tolerated; the majority of events for which severity has been reported are mild or moderate in severity, and no serious AEs have been reported.
Dose Escalation Stopping Criteria Dose escalation between cohorts will be interrupted and may be discontinued if any drug-related serious adverse event occurs in 1 or more subjects; if drug-related neuropsychiatric AEs of moderate intensity occur in 2 or more subjects; or if the DSRC concludes, based on the pattern, number, and severity of AEs and/or the collective pharmacodynamic response pattern excluding pupillometry, that a dose exceeding a nonpsychoactive dose has been reached.
Removal of Subjects from Therapy or Assessment
Subjects may withdraw consent and discontinue participation at any time for any reason. Subjects may also be discontinued by the investigator and/or sponsor for protocol entry violation, safety reasons including AEs, unacceptable concomitant medication use, noncompliance or major protocol violation, pregnancy, positive urine drug screen or breath alcohol test, administrative reasons such as termination of enrollment or study, or because continuation is not in the subject's best interest.
The investigator will maintain a record of all subjects who discontinue before completion and document the reason(s). If a subject withdraws, the investigator should make a reasonable attempt to obtain and record the reason, although the subject is not required to provide one.
If discontinuation occurs while the subject is at the clinical site, early termination procedures should be completed before discharge. For any early discontinuation, whether or not the subject is on site, the investigator should ask the subject to return for Follow-Up Visit procedures unless consent for those procedures has been withdrawn. Refusal to complete early termination or Follow-Up Visit procedures will be recorded.
In the event that a subject is discontinued while at the clinical site, the early termination procedures should be performed prior to discharge from the study site. For any case of early discontinuation (whether or not the subject is at the clinical site), the investigator should ask the subject to return for the Follow-Up Visit procedures, provided that the subject has not withdrawn consent for those procedures. If a subject refuses to complete early termination procedures and/or the Follow-Up Visit, this information will be recorded.
Study Restrictions In addition to inclusion/exclusion criteria, subjects must abstain from alcohol for 48 hours before Screening and before Treatment Phase admission (Day -1), confirmed by breath alcohol test. They will be asked to avoid strenuous physical activity for 48 hours before Screening and admission and may not perform strenuous exercise during the inpatient stay.
Subjects must abstain from recreational drug use from Screening until after the Treatment Phase, confirmed by urine drug screen. From 1 week before dosing until after the final pharmacokinetic draw, they must avoid grapefruit or grapefruit products, pomegranate, pomelo, star fruit juice/products, poppy seeds, Seville oranges, apple juice, orange juice, and mustard-family vegetables such as kale, broccoli, watercress, collard greens, kohlrabi, brussels sprouts, and mustard. Subjects must fast for at least 10 hours before dosing and 4 hours after dosing; water is allowed except for about 1 hour before and after dosing. Caffeine/methylxanthine products are prohibited for 48 hours before dosing and while housed at the site. Smoking is prohibited for the study duration. Electronic devices are prohibited for 1 hour before and at least 6 hours after dosing. Subjects should avoid driving, machinery, or hazardous activities until they and clinic staff confirm the study drug has not impaired judgment or skilled-task performance. Subjects must remain awake and seated upright for at least 4 hours after dosing, rising only briefly under supervision for study activities or washroom use; afterward, they may ambulate within the clinic. If an AE occurs, they may be placed in an appropriate position at any time. For at least 1 hour after dosing, washroom visits will be monitored and recorded, and subjects may not flush so staff can inspect contents. Subjects must abstain from blood donation during the study and for 30 days after Follow-Up.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 10
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Psilocybin 0.5 mg or Placebo | Experimental | Drug: Psilocybin (low dose) or PlaceboPsilocybin 0.5 mg in 5 mL sucralose randomly administered to 6 participants and placebo (5 mL sucralose) randomly administered to 2 participants. |
| Psilocybin 1.0 mg or Placebo | Experimental | Drug: Psilocybin (low dose) or PlaceboPsilocybin 1 mg in 10 mL sucralose randomly administered to 6 participants and placebo (10 mL sucralose) randomly administered to 2 participants. |
| Psilocybin 1.5 mg or Placebo | Experimental | Drug: Psilocybin (low dose) or PlaceboPsilocybin 1.5 mg in 10 mL sucralose randomly administered to 6 participants and placebo (10 mL sucralose) randomly administered to 2 participants. |
| Psilocybin 2.0 mg or Placebo | Experimental | Drug: Psilocybin (low dose) or PlaceboPsilocybin 2.0 mg in 10 mL sucralose randomly administered to 6 participants and placebo (10 mL sucralose) randomly administered to 2 participants. |
| Psilocybin 2.5 mg or Placebo | Experimental | Drug: Psilocybin (low dose) or PlaceboPsilocybin 2.5 mg in 10 mL sucralose randomly administered to 6 participants and placebo (10 mL sucralose) randomly administered to 2 participants. |
| Psilocybin 3.0 mg or Placebo | Experimental | Drug: Psilocybin (low dose) or PlaceboPsilocybin 3.0 mg in 10 mL sucralose randomly administered to 6 participants and placebo (10 mL sucralose) randomly administered to 2 participants. |
| Psilocybin 3.5 mg or Placebo | Experimental | Drug: Psilocybin (low dose) or PlaceboPsilocybin 3.5 mg in 10 mL sucralose randomly administered to 6 participants and placebo (10 mL sucralose) randomly administered to 2 participants. |
| Psilocybin 4.0 mg or Placebo | Experimental | Drug: Psilocybin (low dose) or PlaceboPsilocybin 3.5 mg in 10 mL sucralose randomly administered to 6 participants and placebo (10 mL sucralose) randomly administered to 2 participants. |
| Psilocybin 4.5 mg or Placebo | Experimental | Drug: Psilocybin (low dose) or PlaceboPsilocybin 4.5 mg in 10 mL sucralose randomly administered to 6 participants and placebo (10 mL sucralose) randomly administered to 2 participants. |
| Psilocybin 5.0 mg or Placebo | Experimental | Drug: Psilocybin (low dose) or PlaceboPsilocybin 5.0 mg in 10 mL sucralose randomly administered to 6 participants and placebo (10 mL sucralose) randomly administered to 2 participants. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (22 listed)
- Subjects must meet each of the following inclusion criteria to be eligible for participation in the study:
- 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.
Key exclusion criteria (19 listed)
- Subjects will not be eligible to participate in this study if any of the following exclusion criteria is met:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Psilocybin (low dose) or PlaceboSingle ascending dose escalation. | Drug | 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 |
Primary outcome
Clinical Safety Event Frequency
Time frame: Monitoring from dosing through treatment (3 days) and Follow-Up (~1 week).
Safety endpoints include the classification and frequency of Adverse Events, Serious Adverse Events, and Adverse Events leading to discontinuation.
Clinical Safety Event Severity
Time frame: Monitoring from dosing through treatment (3 days) and Follow-Up (~1 week).
Safety endpoints include the classification and severity of Adverse Events, Serious Adverse Events, and Adverse Events leading to discontinuation.
Clinical Safety Event Relationship to Treatment
Time frame: Monitoring from dosing through treatment (3 days) and Follow-Up (~1 week).
Safety endpoints include the classification and determined treatment relationship of the Adverse Events, Serious Adverse Events, and Adverse Events leading to discontinuation.
Vital Signs Heart Rate for Clinical Safety and Tolerability
Time frame: Vital signs 0.5, 1, 1.5, 2, 3, 6, 8, 10, 12 hours after dose.
Vital signs include heart rate in beats per minute
Electrocardiogram for Clinical Safety and Tolerability
Time frame: ECG baseline and 3 and 6 hours after dosing.
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.
Five-Dimensional Altered States of Consciousness Scale
Time frame: The 5D-ASC will be administered 6 hours following dosing.
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.
State Trait Anxiety Inventory Scale
Time frame: The STAI will be given at baseline and at the two and six hour time points following dose.
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.
Reaction Time Test Performance
Time frame: Reaction time test will be given at baseline and at the two and six hour time points following dosing.
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.
Rapid Visual Information Processing Test
Time frame: 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 .
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.
Spatial Working Memory
Time frame: 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.
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.
Perceptual Pharmacodynamic Alertness Drowsiness Visual Analog Scale
Time frame: 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.
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.
Perceptual Pharmacodynamic Agitation Relaxation Visual Analog Scale
Time frame: 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.
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.
Perceptual Pharmacodynamic Any Drug Effects Visual Analog Scale
Time frame: 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.
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
Perceptual Pharmacodynamic Hallucinations Visual Analog Scale
Time frame: The Hallucainations VAS will be given at baseline, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours after dosing.
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
Perceptual Pharmacodynamic Bowdle (internal and external perceptions) Visual Analog Scale
Time frame: The Bowdle VAS will be given at baseline, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours after dosing.
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
Perceptual Pharmacodynamic Bond-Lader Visual Analog Scale
Time frame: 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.
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
6 secondary outcomes
Maximum Plasma Concentration
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Time to Maximum Plasma Concentration
Time frame: 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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2026.
- Background: PubMed 35166158Gukasyan 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.
- Background: PubMed 30925850Fadiman 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.
- Background: PubMed 33146667Davis 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.
- Background: PubMed 27210031Carhart-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.
- Background: PubMed 22781489Baxter 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.
- Background: PubMed 28757793Bonomi 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.
- Derived from this study: PubMed 42797541Levy-Cooperman N, Sellers E, Glue P, Szeto I, Brown D, Jarecki-Smith J, Tyler WJ, McDonnell MB. A Randomized, Double-Blind, Placebo-Controlled Single-Ascending-Dose Study to Identify a Subperceptual Dose of Psilocybin in Healthy Adults. Pharmaceuticals (Basel). 2026 Sep 21;19(9):1496. doi: 10.3390/ph19091496.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study of Healthy Controls, run by Diamond Therapeutics Inc. at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Safety Event Frequency (time frame: Monitoring from dosing through treatment (3 days) and Follow-Up (~1 week).). The study lists 16 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07710027, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2026.