# NCT05351541: A Double-blind, Randomized Trial Examining the Preliminary Efficacy of Psilocybin Therapy for People With Chronic Low Back Pain Registry record: https://clinicaltrials.gov/study/NCT05351541 (retrieved 2026-09-30). Sponsor: Joshua Woolley, MD, PhD. ## What you are forecasting **Primary hypothesis (implied by design (single registered primary outcome is change from baseline; every arm receives psilocybin)):** Pain interference (Brief Pain Inventory interference subscale) falls from baseline to 1 month after the psilocybin session in people with chronic low back pain. **Resolution rule:** Supported if the report shows a statistically significant reduction in BPI interference from baseline to 1 month across participants (all arms pooled, or in the psilocybin + placebo arm if that is the only one reported). Differences between add-on arms (zolpidem, modafinil) are the moderator, not the primary hypothesis. **Alpha:** 0.05, two-sided, unless the report states otherwise **Effect metric for your 90% interval:** Mean change in BPI interference, 0-70 scale, baseline to 1 month (positive = reduction). **Moderator to consider:** Does the add-on drug (zolpidem, modafinil, both, or placebo) change the size of the reduction? ## Design - Allocation: RANDOMIZED; model: PARALLEL; purpose: TREATMENT - Masking: QUADRUPLE ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR'] - Enrollment: 30 (estimated) - Phase: PHASE1, PHASE2 - Status on registry: ACTIVE_NOT_RECRUITING; start 2023-12-01; primary completion 2026-07 (estimated) - Model description: All patients will receive a dose of psilocybin between 1-30 mg, and one of the following: placebo, zolpidem, modafinial, or zolpidem and modafinil. All patients will receive two psilocybin preparation sessions , a single dose of psilocybin within a therapeutic environment (6-8 hours), three integration sessions and two follow up visits. All drugs will be orally administered during the dosing session. The study procedures will follow best practices for administering psilocybin in clinical trials. ## Arms - **Psilocybin in combination with Zolpidem and Modafinil** (experimental): Single dose of Psilocybin (1mg-30mg) in combination with zolpidem and modafinil - **Psilocybin in combination with Zolpidem** (experimental): Single dose of Psilocybin (1mg-30mg) in combination with zolpidem - **Psilocybin in combination with Modafinil** (experimental): Single dose of Psilocybin (1mg-30mg) in combination with modafinil - **Psilocybin in combination with Placebo** (experimental): Single dose of Psilocybin (1mg-30mg) in combination with placebo ## Primary outcome(s) as registered - **Change in pain interference** (Baseline, 1-month after psilocybin session): The Brief Pain Inventory-Interference subscale (BPI) will be used to assess how pain interferes with a variety of daily activities (e.g., walking, lifting, mood, sleep, relationships). Seven items are rated on a scale from 0 (does not interfere) to 10 (completely interferes) for a total possible score ranging from 0 to 70. Higher scores represent greater interference from pain. ## Secondary outcomes (names only) - Change in pain interference (Baseline, 1-week, and 3-months) - Change in average pain intensity (Baseline, 1-week, 1-month, and 3-months after psilocybin session) - Change in clinical depressive symptom severity (Baseline, 1-week, 1-month, and 3-months after psilocybin session) - Change in depressive symptom severity (Baseline, pre-dosing session, 5-days, 11-days, and 77-days after psilocybin session) ## Population Ages 25 Years to 70 Years; sex: ALL; healthy volunteers: False. Inclusion Criteria: * Age 25 to 70 years old * Comfortable speaking and writing in English * Diagnosed with chronic low back pain * Able to attend all in-person visits at UCSF as well as virtual visits * Has tried at least two previous medications/ procedures and physical therapy trials for low back pain Exclusion Criteria: * Chronic low back pain that is attributed to malignancy, subacute or acute fracture or infection * Low back pain with radiation below the knee * Low back pain with neurologic signs present * Regular use of medications that may have problematic interactions with psilocybin, including but not limited to dopamine agonists, MAO inhibitors, antipsychotics, and stimulants * A health condition that makes study unsafe or unfeasible, determined by study physicians ## Registry summary This study evaluates whether psilocybin therapy helps patients cope with chronic low back pain more effectively. Patients may be recruited at Stanford and University of California San Francisco (UCSF), study procedures will occur at UCSF. Each participant will receive a dose of psilocybin with possibly one or more other drugs. Participants will undergo two preparation sessions, a dosing session, three integration sessions to discuss their psilocybin experience, and several follow up sessions. ## Registry detailed description Chronic pain is associated with higher levels of pain-related distress, depression, emotional dysfunction, helplessness, hopelessness, and suicidality. Psilocybin is a psychoactive drug that may be well-suited to easing the psychological and emotional symptoms of distress associated with chronic pain. Previous studies testing psilocybin therapy have shown improvements on multiple behavioral and psychiatric outcomes, but it is unknown whether psilocybin therapy similarly enables patients to cope with chronic pain more effectively. The investigators will determine whether psilocybin therapy improves patients' ability to cope with chronic low back pain. If psilocybin therapy is an effective treatment in this population, its use could be incorporated into interventions for chronic low back pain and other psychological conditions.