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 leasthalf of the days over the past 6 months (consistent with NIH ConsensusRecommendations for defining CLBP; other chronic pain problems can be present, butCLBP 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 thedrug administration session

• Women who are of childbearing potential and sexually active who are not practicingan effective means of birth control must agree to practice an effective means ofbirth 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 reuptakeinhibitors (SSRIs), serotonin and norephinephrine reuptake inhibitors (SNRIs),and/or bupropion (< 300 mg bupropion) is allowed if the type and frequency of thetherapy has been stable for at least two months prior to screening and is expectedto remain stable during participation in the study.

• Concurrent psychotherapy is allowed if the type and frequency of the therapy hasbeen stable for at least two months prior to screening and is expected to remainstable during participation in the study

• Be otherwise medically stable as determined by screening for medical problems via apersonal interview, a medical questionnaire, a physical examination, anelectrocardiogram (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 theresearch unit on the mornings of drug session days. If the participant does notroutinely consume caffeinated beverages, he/she must agree not to do so on sessiondays.

• 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 72hours of each drug administration

• Agree that for one week before each drug session, he/she will refrain from takingany nonprescription medication, nutritional supplement, or herbal supplement exceptwhen approved by the study investigators. Exceptions will be evaluated by the studyinvestigators and will include acetaminophen, non-steroidal anti-inflammatory drugs,and common doses of vitamins and minerals.

• Have limited lifetime use of hallucinogens (the following criteria are preferred: nouse in the past 5 years; total hallucinogen use less than 10 times)

Exclusion Criteria:

• Lifetime history of serious psychiatric (other than depression) or neurologicaldisorders, including bipolar disorder, psychosis, or seizure disorder

• Lifetime history of severe substance use disorder or current (past six months)substance use disorder of moderate severity

• Clinically significant suicidal ideation (e.g. with strong intent or means) withinpast 6 months or lifetime history of suicide attempt

• Medical condition incompatible with psilocybin administration (e.g., cardiovascular)

• On unstable/changing dose of opioid, benzodiazepine or other psychoactive or painmedication within 4 weeks prior to enrollment and/or unable to abstain frommedication on drug administration day

• Current use/positive toxicology for illicit drugs or positive breath alcohol test atscreening and prior to each drug administration session.

• Clinically significant transaminitis- aspertate aminotransferase (AST) or alanineaminotransferase (ALT) greater than two times normal value).

• Women who are pregnant (as indicated by a positive urine pregnancy test assessed atintake and before each drug session) or nursing;

• Women who are of childbearing potential and sexually active who are not practicingan effective means of birth control.

• Cardiovascular conditions: coronary artery disease, stroke, angina, uncontrolledhypertension, a clinically significant ECG abnormality (e.g., atrial fibrillation),prolonged corrected QT interval (QTc) interval (i.e., QTc > 450 msec), heart valve,or transient ischemic attack (TIA) in the past year.

• History of seizures and/or epilepsy with history of seizures.

• Type 1 diabetes.

• BMI < 18

• Medical conditions contraindicated for methylphenidate administration:

1. Concomitant use of Monoamine oxidase inhibitors (MAOIs), or use within 14 daysof MAOI discontinuation

2. Family history or diagnosis of Tourette's syndrome

3. Known Fructose intolerance, glucose-galactose malabsorption, orsucrase-isomaltose insufficiency

4. Glaucoma

5. Known hypersensitivity to methylphenidate

6. Marked agitation, anxiety, and tension

7. Motor tics

• Currently taking on a regular (e.g., daily) basis any antidepressant medicationsother than SSRIs, SNRIs, or bupropion, or any other medications that have a primarycentrally-acting serotonergic effect, including MAOIs. Bupropion dosage must be < 300 mg in order to be included. For individuals who have intermittent or PRN use ofsuch medications and/or who taper off such medications after regular use, psilocybinsessions will not be conducted until at least 14 days or 5 half-lives (whichever isgreater) of the agent have elapsed after the last dose.

• Nicotine dependence that would be incompatible with an individual to be nicotinefree for 8-10 hours on a psilocybin session day

• Have a first degree relative with schizophrenia or other psychotic disorders (exceptsubstance/medication-induced or due to another medical condition), or bipolar Idisorder