Clinical trial NCT06367738: Investigating the Persisting Effects of a Single Dose of Psilocybin on Structural Plasticity in Healthy Older Adults
Official title: Investigating the Persisting Effects of a Single Dose of Psilocybin on Structural Plasticity in Healthy Older Adults
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Aging
Lead sponsor: University of California, Berkeley
Sponsor class: OTHER
First posted: 2024-04-16
Enrollment: 40
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Participants in this study will undergo a series of non-invasive tests and activities designed to understand how a single dose of psilocybin might influence cognition and emotional well-being in healthy older adults. After providing written informed consent, eligible participants, aged between 60 and 85, will be randomly assigned to receive a dose of psilocybin ranging from a microdose to a moderate-to-high dose. Anatomical magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI) will be used to assess changes in brain structure, while functional magnetic resonance imaging (fMRI) will be used to quantify changes in functional brain activity.

Detailed description: The investigators will use cognitive exams, perceptual tasks, brain imaging, peripheral psychophysiology, and surveys to investigate the persisting effects of psilocybin on cognition, predictive coding, and affect in healthy older adults (60-85 years old). The investigators will measure changes in these measures by comparing baseline to one-week and one-month post-treatment. Participants will be randomly assigned to receive a dose of psilocybin in a range from microdose to moderate-to-high dose (1-30 milligrams).

Anatomical magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI) will be used to assess changes in brain structure, while functional magnetic resonance imaging (fMRI) will be used to quantify changes in functional brain activity. The investigators will assess whether changes in these brain measures underlie observed changes in cognition, predictive coding and affect.

Eligibility criteria: Inclusion Criteria:

Are 60-85 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.

Have normal or corrected-to-normal vision as determined by the study staff. 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.

Have access to a quiet space and a computer to perform online assessments.

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.

Have a history of recent, clinically significant suicidal ideation or behavior.

Have a history of a psychotic disorder, bipolar disorder (type I or II), or a dissociative disorder (determined by history).

History of Hallucinogen Persisting Perception Disorder (HPPD). History of a seizure disorder in adulthood, central nervous system (CNS) metastases or current symptomatic CNS infection.

History of intracerebral hemorrhage, embolic stroke, transient ischemic attack (TIA), or history of any aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial and peripheral arterial vessels) or arteriovenous malformation.

History of valvulopathy or pulmonary hypertension. 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.

Poorly controlled diabetes mellitus (e.g., history of an episode of severe hypoglycemia or hospitalization for hyperglycemia on the current diabetes regimen).

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.

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.

Recent and lifetime use of psychedelics (e.g. psilocybin, LSD, mescaline), entactogens (e.g. MDMA), or dissociative anesthetics (e.g. ketamine) above a predetermined threshold.

Has been diagnosed with any disease that impairs motor function (e.g., Parkinson's disease) At high risk of falls as determined by study physician considering medical history, screening of recent symptoms and medications, and functional mobility testing.

Primary outcomes:
measure: MRI measurements of brain structure
timeFrame: Baseline, week 1, and week 4
Secondary outcomes:
measure: Amplitude and pattern of fMRI cortical responses
timeFrame: Baseline, week 1, and week 4
measure: Vagus nerve reactivity
timeFrame: Baseline, week 1, and week 4
measure: Perceptual measurements
timeFrame: Baseline, week 1, and week 4
measure: Penn Conditional Exclusion Test (PCET)
timeFrame: Baseline, week 1, and week 4
measure: California Verbal Learning Test, Second Ed. (CVLT-II)
timeFrame: Baseline, week 1, and week 4
measure: Visual Reproduction (from Wechsler Memory Scale-Third Edition)
timeFrame: Baseline, week 1, and week 4
measure: Logical Memory (from Wechsler Memory Scale-Third Edition)
timeFrame: Baseline, week 1, and week 4
measure: Recognition memory (REC)
timeFrame: Baseline, week 1, and week 4
measure: Lure discrimination index (LDI)
timeFrame: Baseline, week 1, and week 4
measure: Somatic Symptom Scale-8 (SSS-8)
timeFrame: Baseline, week 1, and week 4
measure: RAND 36-Item Short Form Health Survey 1.0 (SF-36, 3-items)
timeFrame: Baseline, week 1, and week 4
measure: Brief version of the Pittsburgh Sleep Quality Index (B-PSQI)
timeFrame: Baseline, week 1, and week 4
measure: Ryff & Keyes Psychological Wellbeing - Purpose in Life subscale (PWB-PIL)
timeFrame: Baseline, week 1, and week 4
measure: Social Connectedness Scale - Revised (SCS-R)
timeFrame: Baseline, week 1, and week 4
measure: Specific Emotion Experience Questionnaire (SEEQ)
timeFrame: Baseline, week 1, and week 4
measure: Big Five Inventory-2-Extra Short Form (BFI-2-XS)
timeFrame: Baseline, week 1, and week 4
measure: Spontaneous Self-Distancing Questionnaire (SSDQ)
timeFrame: Baseline, week 1, and week 4
measure: Temporal Distancing Questionnaire (TDQ)
timeFrame: Baseline, week 1, and week 4
measure: Emotion Regulation Questionnaire (ERQ)
timeFrame: Baseline, week 1, and week 4
measure: Acceptance and Action Questionnaire (AAQ-II)
timeFrame: Baseline, week 1, and week 4
measure: Perseverative Thinking Questionnaire (PTQ)
timeFrame: Baseline, week 1, and week 4
measure: Brief Resilience Scale (BRS)
timeFrame: Baseline, week 1, and week 4
measure: Apathy Evaluation Scale (AES) self-rated
timeFrame: Baseline, week 1, and week 4
measure: Perceived Stress Scale (PSS)
timeFrame: Baseline, week 1, and week 4
measure: Supernatural Belief Scale (SBS-6)
timeFrame: Baseline, week 1, week 4, and week 8
measure: Brief Multidimensional Measure of Religiousness/Spirituality (BMMRS)
timeFrame: Baseline, week 1, week 4, and week 8
measure: Adapted version of the Credibility/Expectancy Questionnaire (CrEQ)
timeFrame: Week 4
measure: Mystical Experience Questionnaire-30 (MEQ30)
timeFrame: Week 4
measure: Challenging Experience Questionnaire (ChEQ)
timeFrame: Week 4
measure: 11-Dimension Altered States Questionnaire (11D-ASC)
timeFrame: Week 4
measure: Persisting Effects Questionnaire - 4-item (PEQ-4)
timeFrame: Week 4
measure: Narrative report of subjective experience
timeFrame: Week 4
measure: Dose Estimation Scale
timeFrame: Week 4
Other outcomes:
Locations:
city: Berkeley
country: United States
facility: University of California, Berkeley
state: California
Study officials:
References: