Psilocybin in Chronic Low Back Pain and Depression

Inclusion Criteria: * 21 to 80 years old * Have given written informed consent * Report low back pain as ongoing problem ≥ 3 months and any low back pain on at least half of the days over the past 6 months (consistent with NIH Consensus Recommendations for defining CLBP; other chronic pain problems can be present, but CLBP must be reported as primary) * Report at least moderate depression symptoms Grid-Hamilton Depression Rating Scale (GRID-HAMD) ≥ 17 * Fluent in English * At least high school level of education * Agree to abstain from any psychoactive drugs on the day prior to and the day of the drug administration session * Women who are of childbearing potential and sexually active who are not practicing an effective means of birth control must agree to practice an effective means of birth control throughout the duration of the study * Be judged by study team clinicians to be at low risk for suicidality * Concurrent psychotherapy or pharmacotherapy with selective serotonin reuptake inhibitors (SSRIs), serotonin and norephinephrine reuptake inhibitors (SNRIs), and/or bupropion (\< 300 mg bupropion) is allowed if the type and frequency of the therapy has been stable for at least two months prior to screening and is expected to remain stable during participation in the study. * Concurrent psychotherapy is allowed if the type and frequency of the therapy has been stable for at least two months prior to screening and is expected to remain stable during participation in the study * Be otherwise medically stable as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests; CBC, comprehensive metabolic panel (CMP), urine beta-human chorionic gonadotropin (HCG), urine toxicology screen. * Agree to consume approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) that he/she consumes on a usual morning, before arriving at the research unit on the mornings of drug session days. If the participant does not routinely consume caffeinated beverages, he/she must agree not to do so on session days. * Agree not to take any as needed (PRN) medications on the mornings of drug sessions * Agree not to take sildenafil (Viagra®), tadalafil, or similar medications within 72 hours of each drug administration * Agree that for one week before each drug session, he/she will refrain from taking any nonprescription…