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.

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.

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

This trial is testing various doses of psilocybin in combination with add-on medications. Participants, study staff and clinical assessors will be blinded to individual treatment conditions until study close-out. The clinician administered instruments will be administered by different clinical study staff than the facilitators who provide the preparation, psilocybin therapy, and integration sessions.