Psilocybin-Assisted Physical Therapy in Chronic Low Back Pain

Change in interoceptive awareness as measured by the Multidimensional Assessment of Interoceptive Awareness-2 from 4 weeks post-dose to 8 weeks post dose

The Multidimensional Assessment of Interoceptive Awareness-2 (MAIA-2) is a validated 37-item, self-report instrument assessing mind-body connections (i.e., interoceptive awareness). MAIA-2 scoring involves rating the 37 items on a 0 (never) to 5 (always) Likert scale, resulting in scores for eight subscales (Noticing, Not-distracting, Not-worrying, Attention regulation, Emotional awareness, Self-regulation, Body Listening, Trusting). Scores for each of the 8 scales are averaged (sum of items divided by number of subscale items). Higher scores indicate better interoceptive awareness. Change = (8-week post-dose score - 4-week post-dose score).

Change in Pain, Enjoyment, and General Activity (PEG) total score at 8 weeks post dose

The Pain, Enjoyment, General Activity (PEG) Scale is a 3-item questionnaire used to measure how chronic pain affects a person's life, focusing on average pain intensity (P), interference with enjoyment (E), and interference with general activity (G) using 0-10 Likert scale for each item. The final PEG score is calculated by adding the three scores and dividing by three. Scores range from 0-10, with higer scores indicating higher pain impact. Change= (8-week post-dose score - 4-week post-dose score).

Change in functional disability measured by the Oswestry Disability Index (ODI) from baseline to 8 weeks post-dose.

The Oswestry Disability Index (ODI) is a widely used, 10-question self-report questionnaire that measures functional disability and quality of life for people with low back pain, assessing activities like walking, sitting, sleeping, and pain intensity, with scores ranging from 0-100% categorized into minimal (0-20%), moderate (21-40%), severe (41-60%), crippled (61-80%), and bed-bound (81-100%) disability. Change = (8-week post-dose score - baseline \[day 0\] score)

Physical activity measured by average daily step count via daily Experience Sampling Monitoring (ESM)

Participants will record their daily step count via study-provided pedometer from 4 weeks post dose to 8 weeks post-dose. The average step count will be assessed.

Change in functional mobility from 4 weeks post-dose to 8 weeks post-dose measured by the 10-Meter Walk Test (10MWT)

The 10-Meter Walk Test (10MWT) is a common physical therapy assessment measuring how fast someone walks over a short distance, typically 10 meters. The 10MWT will be used to evaluate gait velocity. Change= (8-week post dose score - 4-week post-dose score)

Change in functional mobility from 4 weeks post-dose to 8 weeks post-dose measured by the 30-Second Sit to Stand (30STS)

The 30 Second Sit to Stand Test (30STS) is a common physical therapy assessment recording the number of times a person can stand from a chair over 30 seconds. The 30STS will evaluate functional lower extremity strength and endurance. Change= (8-week post dose score - 4-week post-dose score).

Change in back-specific strength from 4 weeks post-dose to 8 weeks post-dose, measured by myotomal dynamometry spanning vertebrae L2 to S2 using an isometric deadlift test.

Myotomal dynamometry spanning vertebral levels L2-S2 will be performed by testing the muscle groups associated with each spinal nerve root using a handheld dynamometer or graded manual resistance. Change scores will be calculated as: 8-week post-dose value minus 4-week post-dose value

Peak Plasma Concentration (Cmax) of Psilocybin

Plasma psilocybin concentrations (Units: ng/mL) will be measured at pre-dose (-30 minutes) and at 60, 120, 240, and 360 minutes post-dose. Cmax (peak observed plasma concentration) of psilocybin will be derived from these timepoints using noncompartmental methods.

Area Under the Plasma Concentration-Time Curve from 0 to 6 Hours (AUC0-6h) of Psilocybin

Plasma psilocybin concentrations will be measured at pre-dose (-30 minutes) and at 60, 120, 240, and 360 minutes post-dose. AUC0-6h for psilocybin will be calculated using noncompartmental analysis (e.g., trapezoidal rule) over the 0-6 hour post-dose period.

Peak Plasma Concentration (Cmax) of Psilocin

Plasma psilocin concentrations (ng/mL) will be measured at pre-dose (-30 minutes) and at 60, 120, 240, and 360 minutes post-dose. Cmax (peak observed plasma concentration) of psilocin will be derived from these timepoints using noncompartmental methods.

Area Under the Plasma Concentration-Time Curve from 0 to 6 Hours (AUC0-6h) of Psilocin

Plasma psilocin concentrations will be measured at pre-dose (-30 minutes) and at 60, 120, 240, and 360 minutes post-dose. AUC0-6h for psilocin will be calculated using noncompartmental analysis (e.g., trapezoidal rule) over the 0-6 hour post-dose period.