Psilocybin Effects on Healthy Aging Biomarkers and Purpose in Life

Phase 1Not Yet RecruitingNCT07719088

Charles Raison50 enrolled

Overview

The LONG-LIFE study is a randomized Phase I, dose-ranging trial designed to evaluate whether psilocybin impacts aging-related biomarkers, cognitive function, and purpose/meaning in life in medically stable older adults. Up to 50 participants will be enrolled aged 60-80 who will be randomized with equal allocation to one of four intervention groups: (1) receipt of one 25 mg dose of psilocybin; (2) receipt of two 25 mg doses of psilocybin separated by four weeks; (3) receipt of three 25 mg doses, with each dose separated by four weeks; or (4) wait-list comparator condition that does not receive psilocybin. Biomarkers of aging, cognitive performance, and behavioral measures will be assessed at baseline and longitudinally over a 12-month follow-up period. The primary endpoint occurs at the Week 16 visit. Participants randomized to the wait-list condition will be offered a single 25 mg dose of psilocybin following conclusion of the 12-month follow-up period. Findings from this Phase I study will inform dose selection for a Phase II study should results indicate a potential impact of psilocybin on relevant study endpoints.

Aging is accompanied by progressive changes across multiple physiological systems that contribute to functional decline and increased risk for age-related disease. Biomarkers of biological aging, including DNA methylation-based epigenetic clocks, have emerged as tools for assessing age-related biological processes and predicting future health outcomes. Recent preclinical studies have suggested that psilocybin and its active metabolite, psilocin, may influence several pathways implicated in aging, including cellular senescence, oxidative stress, neuroplasticity, and epigenetic regulation. In addition to biological effects, observational studies have demonstrated associations between psychosocial factors, including purpose in life and social connectedness, and reduced morbidity and mortality in older adults. Previous clinical studies have shown that psilocybin may produce changes in psychological well-being, meaning, and related constructs. The LONG-LIFE Study is designed to evaluate multiple domains relevant to healthy aging, including, but not limited to, epigenetic and biological clock measures, cognitive performance, psychosocial well-being, and ecological momentary assessments of daily experience.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Eligibility

Sex: ALLMin age: 60 YearsMax age: 80 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * English speaking and able to provide informed consent and complete study procedures * Medically healthy, as determined by the screening physician, with no significant medical conditions that would interfere with participation or affect the safety of the subject. Exclusion Criteria: * History or presence of any psychiatric or medical condition that, in the opinion of the investigator, could pose a safety risk, interfere with participation, or confound study results. * Abnormal ECG at screening that may increase risk during participation (e.g., prolonged QTc, arrhythmias, or other clinically significant findings as determined by the study physician). * Unwilling or unable to discontinue medications that may interfere with study participation, as determined by the investigator.

Outcomes

Primary Outcomes

Change in Epigenetic/Biological Clock Profiling from Baseline to Week 4 and Week 16

Epigenetic/biological clock profiles; change from Baseline to Week 4 and 16

Time frame: Change from Baseline to Week 4 and Week 16

Change in Purpose in Life (PIL) from Baseline to Week 4 and Week 16

Change from baseline in Purpose in Life score measured using the 7-item Purpose in Life Scale (PIL) from the Health and Retirement Study (score range 1-6; higher scores indicate greater purpose in life).

Time frame: Change from Baseline to Week 4 and Week 16

Secondary Outcomes

Change in Epigenetic/Biological Clock Profiling from Baseline to Week 52

Change in Epigenetic/biological clock profile from Baseline to Week 52

Time frame: Change from Baseline to Week 52

Change in Telomere Length from Baseline to Week 52

Time frame: Change from Baseline to Week 52

Change in Purpose in Life (PIL) from Baseline to Week 52

Time frame: Change from Baseline to Week 52

Change in Satisfaction with Life from Baseline to Week 4 and Week 16

Measured using the Satisfaction With Life Scale (SWLS). Scores range from 5 to 35, where higher scores indicate greater satisfaction with life.

Time frame: Change from Baseline to Week 4 and Week 16

Change in Wellbeing from Baseline to Week 4 and Week 16

Measured using the Warwick Edinburgh Mental Well-Being Scale (WEMWBS). Scores range from 14 to 70, with higher scores indicating higher mental wellbeing.

Time frame: Change from Baseline to Week 4 and Week 16

Change in Optimism from Baseline to Week 4 and Week 16

Measured using the Life Orientation Test - Revised (LOT-R). Scores range from 0 to 24, with higher scores indicating higher dispositional optimism.

Time frame: Change from Baseline to Week 4 and Week 16

Change in Perceived Control/Mastery from Baseline to Week 4 and Week 16

Measured using the Pearlin Mastery Scale (PM). Scores range from 7 to 28; higher totals indicate greater self-mastery.

Time frame: Change from Baseline to Week 4 and Week 16

Change in Loneliness from Baseline to Week 4 and Week 16

Measured using the 3-Item UCLA Loneliness Scale (UCLA-3). Scores range from 3 to 9. Higher scores indicate a greater degree of loneliness.

Time frame: Change from Baseline to Week 4 and Week 16

Psilocybin Effects on Healthy Aging Biomarkers and Purpose in Life

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts