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Investigating the Mechanisms of the Effects of Psilocybin on Visual Perception and Visual Representations in the Brain

Primary Purpose

Perception Disorders

Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Psilocybin
Sponsored by
University of California, Berkeley
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Perception Disorders

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Are ≥21 years of age at time of Informed Consent Form signing
  2. Are able and willing to adhere to study requirements, including attending all study visits, preparatory and follow-up sessions, and completing all study evaluations.
  3. Are able to swallow capsules.
  4. Women of childbearing potential (WOCBP) must agree to practice an effective means of birth control throughout the duration of the study.
  5. Written informed consent obtained from and ability for subject to comply with the requirements of the study.
  6. Have an identified support person and agree to be accompanied home (or to an otherwise safe destination) by the support person, or another responsible party, following dosing.
  7. Agree to inform the investigators within 48 hours of any new or changed medical conditions during the course of their study participation.

Exclusion Criteria:

  1. Breastfeeding, have a positive pregnancy test at screening or at any point during the course of the study, or unwilling to practice birth control during participation in the study.
  2. Have a current psychiatric disorder, general medical condition, or other problem or abnormality that, in the opinion of the study clinician or PI, could compromise safety, render them unsuitable for the study, or would make them unable to comply with study activities.
  3. Have MRI contraindications (e.g., metal implants, pacemakers, claustrophobia etc.) as determined by an MRI contraindications questionnaire.
  4. Uncontrolled hypertension (Systolic BP>139mmHG or Diastolic BP>89mmHG) or tachycardia (average HR>90bpm) averaged over at least two measurements.
  5. Clinically significant cardiovascular disease (e.g., history of myocardial infarction or congestive heart failure); or baseline QT/QTc>500msec; or baseline QT/QTc 451-500msec with repeat QT/QTc >500msec.
  6. Inadequate hepatic function as determined by total bilirubin or alkaline phosphatase >3x institutional upper limit of normal; or AST or ALT >6x institutional upper limit of normal. However, participants with Gilbert syndrome are allowed to enroll.
  7. Inadequate renal function as determined by eGFR < 30 mL/min/1.73 m2 (based on the MDRD equation) or CrCl < 30 mL/min (based on the C-G equation).
  8. The regular use of psychotropic medications, such as antidepressants (i.e., SSRIs, tricyclic antidepressants, and monoamine oxidase inhibitors), antipsychotics, and mood stabilizers.
  9. Concomitant dosing of psilocybin with known UGT1A10 and UGT1A9 inhibitors (e.g., diclofenac and probenecid) will be avoided. [There is no exclusion criterion based on the use of medications or substances that are inhibitors or inducers of CYP450 enzymes.]
  10. The use of Prohibited Medications:

    Serotonin Reuptake Inhibitors (SSRIs and SNRIs) Tricyclic Antidepressants (TCAs) Monoamine Oxidase Inhibitors (MAOIs) Atypical antidepressants (e.g., mirtazapine, trazodone, buspar) Antipsychotics/Neuroleptics (typical and atypical) Anti-epileptics or mood stabilizers (e.g., lithium, valproate) (does not include gabapentin used for non-epilepsy conditions) Efavirenz (Sustiva, in Atripla) Lorcaserin Over-the-counter supplements intended to affect mood or anxiety (e.g., 5HT-P, SAMe or St. John's Wort).

    Other drugs associated with the serotonin syndrome (e.g., ondansetron) used within 48 hours of study drug administration (70).

    Vasoactive drugs (e.g., sildenafil, sumatriptan, calcium channel blockers) used within 48 hours of study drug administration.

  11. Unable to agree to the following required Lifestyle Modifications: Patients will be asked to refrain from consuming alcohol, cannabinoids, prescription analgesics/stimulants/benzodiazepines, and any recreational drugs for 48 hours before, the day of, and for 48 hours after study drug administration. Participants will be advised to consume their usual amount of coffee, tea, or other caffeine-containing beverages on the morning of their Medication Visits.
  12. Have a recent history of suicidal ideation or attempted suicide that, in the opinion of the study clinician or PI, may present a risk of suicidal or self-injurious behavior.
  13. Have received an investigational drug or taken a psychedelic within 30 days of the screening visit.
  14. Have an allergy or intolerance to any of the materials contained in the investigational drug product.

Sites / Locations

  • University of California, Berkeley

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Experimental

Comparator

Arm Description

Psilocybin 0-14 mg, before fMRI measurement

Psilocybin 0-14 mg, before fMRI measurement

Outcomes

Primary Outcome Measures

Amplitude and pattern of fMRI cortical responses
Functional magnetic resonance imaging (fMRI) responses to visual stimuli will be recorded.

Secondary Outcome Measures

Perceptual measurements
Within-subject inferential statistical testing will be used to assess the effects of doses of psilocybin (0-14 mg) on participants' abilities to update prior expectations based on new information. Specifically, paired t-tests will be used to contrast perceptual measures collected at MRI scan sessions.
Voxelwise modeling
Voxelwise modeling results will be quantified by measuring the amount of variance in fMRI responses to presentation of stimuli that is accounted for by the model in each voxel. Cross-validation using held-out data will be used to assess possible overfitting and to facilitate unbiased interpretations. Model weights associated with each parameter will be contrasted between psilocybin and placebo sessions and quantified for individual brain areas using paired t-tests and appropriate corrections for multiple comparisons.
Participant-reported Subjective Effects
Within-subject inferential statistical testing will be used to assess the effects of doses of psilocybin (0 - 14 mg) on subjective effects. Specifically, paired t-tests and between-group effect sizes with 95% confidence intervals will be used to contrast patient-reported outcomes (MEQ-30, ChEQ, 11D-ASC and POMS-SF), corrected for multiple comparisons.

Full Information

First Posted
February 22, 2022
Last Updated
May 17, 2023
Sponsor
University of California, Berkeley
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1. Study Identification

Unique Protocol Identification Number
NCT05265546
Brief Title
Investigating the Mechanisms of the Effects of Psilocybin on Visual Perception and Visual Representations in the Brain
Official Title
Investigating the Mechanisms of the Effects of Psilocybin on Visual Perception and Visual Representations in the Brain
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 15, 2023 (Anticipated)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, Berkeley

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
The long-term objective of this project is to characterize how psilocybin affects visual perception and the brain's representation of the visual environment. We know that psilocybin alters aspects of visual perception, but the underlying brain mechanisms contributing to these effects are poorly understood. The proposed work will address these questions in a large, diverse sample of healthy human subjects by using functional magnetic resonance imaging (fMRI) to measure the brain's responses to visual stimuli. The proposed research will document which brain areas mediate the effects of psilocybin. The technique of fMRI will be employed to measure brain activity in different brain areas while subjects are performing a visual perceptual task.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Perception Disorders

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental
Arm Type
Experimental
Arm Description
Psilocybin 0-14 mg, before fMRI measurement
Arm Title
Comparator
Arm Type
Other
Arm Description
Psilocybin 0-14 mg, before fMRI measurement
Intervention Type
Drug
Intervention Name(s)
Psilocybin
Intervention Description
The effects of different doses of psilocybin (0 - 14 mg) will be compared.
Primary Outcome Measure Information:
Title
Amplitude and pattern of fMRI cortical responses
Description
Functional magnetic resonance imaging (fMRI) responses to visual stimuli will be recorded.
Time Frame
Functional MRI recordings will begin approximately 30 minutes after oral administration of experimental or comparator arm treatment and will continue for up to two hours.
Secondary Outcome Measure Information:
Title
Perceptual measurements
Description
Within-subject inferential statistical testing will be used to assess the effects of doses of psilocybin (0-14 mg) on participants' abilities to update prior expectations based on new information. Specifically, paired t-tests will be used to contrast perceptual measures collected at MRI scan sessions.
Time Frame
Statistical tests will be performed after all data collection is complete.
Title
Voxelwise modeling
Description
Voxelwise modeling results will be quantified by measuring the amount of variance in fMRI responses to presentation of stimuli that is accounted for by the model in each voxel. Cross-validation using held-out data will be used to assess possible overfitting and to facilitate unbiased interpretations. Model weights associated with each parameter will be contrasted between psilocybin and placebo sessions and quantified for individual brain areas using paired t-tests and appropriate corrections for multiple comparisons.
Time Frame
Modeling of fMRI data will be performed after all data collection is complete.
Title
Participant-reported Subjective Effects
Description
Within-subject inferential statistical testing will be used to assess the effects of doses of psilocybin (0 - 14 mg) on subjective effects. Specifically, paired t-tests and between-group effect sizes with 95% confidence intervals will be used to contrast patient-reported outcomes (MEQ-30, ChEQ, 11D-ASC and POMS-SF), corrected for multiple comparisons.
Time Frame
Statistical tests will be performed after all data collection is complete.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Are ≥21 years of age at time of Informed Consent Form signing Are able and willing to adhere to study requirements, including attending all study visits, preparatory and follow-up sessions, and completing all study evaluations. Are able to swallow capsules. Women of childbearing potential (WOCBP) must agree to practice an effective means of birth control throughout the duration of the study. Written informed consent obtained from and ability for subject to comply with the requirements of the study. Have an identified support person and agree to be accompanied home (or to an otherwise safe destination) by the support person, or another responsible party, following dosing. Agree to inform the investigators within 48 hours of any new or changed medical conditions during the course of their study participation. Exclusion Criteria: Breastfeeding, have a positive pregnancy test at screening or at any point during the course of the study, or unwilling to practice birth control during participation in the study. Have a current psychiatric disorder, general medical condition, or other problem or abnormality that, in the opinion of the study clinician or PI, could compromise safety, render them unsuitable for the study, or would make them unable to comply with study activities. Have MRI contraindications (e.g., metal implants, pacemakers, claustrophobia etc.) as determined by an MRI contraindications questionnaire. Uncontrolled hypertension (Systolic BP>139mmHG or Diastolic BP>89mmHG) or tachycardia (average HR>90bpm) averaged over at least two measurements. Clinically significant cardiovascular disease (e.g., history of myocardial infarction or congestive heart failure); or baseline QT/QTc>500msec; or baseline QT/QTc 451-500msec with repeat QT/QTc >500msec. Inadequate hepatic function as determined by total bilirubin or alkaline phosphatase >3x institutional upper limit of normal; or AST or ALT >6x institutional upper limit of normal. However, participants with Gilbert syndrome are allowed to enroll. Inadequate renal function as determined by eGFR < 30 mL/min/1.73 m2 (based on the MDRD equation) or CrCl < 30 mL/min (based on the C-G equation). The regular use of psychotropic medications, such as antidepressants (i.e., SSRIs, tricyclic antidepressants, and monoamine oxidase inhibitors), antipsychotics, and mood stabilizers. Concomitant dosing of psilocybin with known UGT1A10 and UGT1A9 inhibitors (e.g., diclofenac and probenecid) will be avoided. [There is no exclusion criterion based on the use of medications or substances that are inhibitors or inducers of CYP450 enzymes.] The use of Prohibited Medications: Serotonin Reuptake Inhibitors (SSRIs and SNRIs) Tricyclic Antidepressants (TCAs) Monoamine Oxidase Inhibitors (MAOIs) Atypical antidepressants (e.g., mirtazapine, trazodone, buspar) Antipsychotics/Neuroleptics (typical and atypical) Anti-epileptics or mood stabilizers (e.g., lithium, valproate) (does not include gabapentin used for non-epilepsy conditions) Efavirenz (Sustiva, in Atripla) Lorcaserin Over-the-counter supplements intended to affect mood or anxiety (e.g., 5HT-P, SAMe or St. John's Wort). Other drugs associated with the serotonin syndrome (e.g., ondansetron) used within 48 hours of study drug administration (70). Vasoactive drugs (e.g., sildenafil, sumatriptan, calcium channel blockers) used within 48 hours of study drug administration. Unable to agree to the following required Lifestyle Modifications: Patients will be asked to refrain from consuming alcohol, cannabinoids, prescription analgesics/stimulants/benzodiazepines, and any recreational drugs for 48 hours before, the day of, and for 48 hours after study drug administration. Participants will be advised to consume their usual amount of coffee, tea, or other caffeine-containing beverages on the morning of their Medication Visits. Have a recent history of suicidal ideation or attempted suicide that, in the opinion of the study clinician or PI, may present a risk of suicidal or self-injurious behavior. Have received an investigational drug or taken a psychedelic within 30 days of the screening visit. Have an allergy or intolerance to any of the materials contained in the investigational drug product.
Facility Information:
Facility Name
University of California, Berkeley
City
Berkeley
State/Province
California
ZIP/Postal Code
94720
Country
United States

12. IPD Sharing Statement

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Investigating the Mechanisms of the Effects of Psilocybin on Visual Perception and Visual Representations in the Brain

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