Psilocybin-assisted Therapy for Phantom Limb Pain

This double-blind placebo-controlled pilot study seeks to investigate whether psilocybin can be safely administered to people with chronic phantom limb pain (PLP) in a supportive setting with close follow-up, and its effects on pain symptoms and other moods, attitudes, and behaviors. The investigators' primary hypotheses are that psilocybin is safe to administer in people with PLP and that it will reduce scores on measures of pain. The investigators will also assess a number of secondary measures related to the behavioral and neural responses to pain after psilocybin treatment.

Inclusion Criteria: * Between 18 and 75 years of age * Amputation of one extremity * Experience phantom limb pain of at least one month's duration and intensity of at least 3 out of 10 on the VAS * Able to fluently communicate in English * Agree to sign the consent and HIPPA authorization * Willing to refrain from taking serotonergic antidepressant medication during the study period * Willing to refrain from using any non-prescribed psychoactive drugs, including alcohol, within 24 hours before and after study drug administration * Agree not to use any nonprescription medications, herbal medications, or supplements during the week prior to each drug session unless an exception is approved by the study investigators * Willing to refrain from smoking or use of nicotine during the period from 8:00 am on the morning of the drug sessions until they are discharged to go home at the end of the end of the session * Able to remain in an MRI machine without sedation * Women of childbearing potential must agree to practice an effective means of birth control throughout the study, from screening to the final visit * Have a relative or friend who can provide/accompany transportation after the drug session * If pain is currently being treated with analgesic medications, the analgesic regimen must be stable for at least 2 weeks prior to enrollment, and the participant must agree not to change their use of analgesic medication without first consulting with the study investigators \[permissible analgesic medications are as follows: aspirin, acetaminophen, celecoxib, diflunisal, etodolac, fenoprofen, flubiprofen, gabapentin, ibuprofen, indomethacin, ketoprofen, ketorolac, mefenamic acid, meloxicam, nalbumetone, naproxen, pregabalin, proxicam, sulindac, tolmetin, and valdecoxib. PRN use of OTC analgesic medications by participants is also permissible\] * Participants who are taking other medications acting as serotonin antagonists (e.g., cyclobenzaprine, odansetron), dopamine antagonists (e.g., metoclopramide, promethazine, prochlorperazine), dopamine agonists (e.g., levodopa, pramipexole, apomorphine), psychostimulants (e.g., modafinil, armodafinil, solriamfetol, methylphenidate, dexmethylphenidate, atomoxetine, dextroamphetamine, mixed amphetamine salts, lisdexamphetamine), anticholinergics (e.g., benzotropine, trihexyphenidyl, scopolamine, hypscyamine), or N-methyl-D-aspartate receptor antagonists (e.g., amantadine, memantine, ketamine) must be willing to discontinue those medications 1 week prior to each drug session Exclusion Criteria: * Under the age of 18 or over the age of 75 * Pregnant or nursing females * Females of childbearing age who are sexually active but not using birth control * Phantom limb pain intensity \