Psilocybin-assisted Therapy for Phantom Limb Pain

NCT05224336 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 200626
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Phantom Limb Pain

Keywords

Phantom Limb Pain; Psilocybin; Psychedelic Therapy; fMRI; Pain; Chronic Pain; Psychedelics; Hallucinogens; Physiological Effects of Drugs; Psychotropic Drugs

Outcome Measures

Primary Outcomes (1)

• Changes in Phantom Limb Pain Intensity

  A validated visual analogue scale will be used to quantify the intensity and unpleasantness ratings of phantom limb pain. The minimum rating will be represented as "no pain sensation" or "not at all unpleasant," whereas the maximum was designated with "most intense imaginable" or "most unpleasant imaginable." Higher numbers correspond to higher pain.

  Baseline to Post-Intervention Session (within 2 weeks after session)

Secondary Outcomes (3)

• Change in Visual Analog Scale Pain ratings

  Baseline to Post-Intervention Session (within 2 weeks after session)

• Cerebral Blood Flow (CBF)

  Baseline to Post-Intervention Session (within 2 weeks after session)

• Brief Pain Inventory

  Baseline to Post-Intervention Session (within 2 weeks after session)

Study Arms (2)

Psilocybin

EXPERIMENTAL

Participants will receive 25mg oral psilocybin one day to two weeks after baseline psychophysical and fMRI testing. Psychophysical and fMRI testing will then be employed one day to two weeks after drug administration.

Drug: Psilocybin

Niacin

PLACEBO COMPARATOR

Participants will receive 100mg oral niacin one day to two weeks after baseline psychophysical and fMRI testing. Psychophysical and fMRI testing will then be employed one day to two weeks after drug administration.

Drug: Placebo Niacin

Interventions

Psilocybin DRUG

25mg oral psilocybin

Psilocybin

Placebo Niacin DRUG

100mg oral niacin

Niacin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 \<3 out of 10 on the VAS
• Presence of another type of chronic pain that cannot be differentiated from phantom limb pain by the participant
• Amputation of more than one extremity
• MRI related contraindications including pacemakers, metal implants, spinal cord stimulators etc.
• Meet DSM-V criteria for bipolar disorder, schizophrenia, or other psychotic disorder
• Have a first-degree relative (parent or full-sibling) with a history of bipolar disorder, schizophrenia, or other psychotic disorder
• Judged to present a suicide risk
• Not able to complete an MRI scan
• Active substance use disorder (excluding tobacco and caffeine)
• Subjects prescribed methadone or buprenorphine for any indication
• Require concomitant treatment with efavirenz
• Participants who are prescribed antidepressants or antipsychotics for an axis I diagnosis

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

University of California, San Diego

San Diego, California, 92093, United States

Location

MeSH Terms

Conditions

Phantom Limb; Pain; Chronic Pain

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Pain, Postoperative; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants and outcome assessor will not be made aware if participants are receiving psilocybin or placebo niacin.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Two sequential studies will be conducted (Study 1 and Study 2). Study 1: The goal of the first study is to assess the feasibility and the corresponding neural mechanisms of administering psilocybin to amputees who are experiencing phantom limb pain. We will perform validated quantitative sensory testing before and after drug administration. Study 1 will have an abbreviated design where participants will receive a single dose of psilocybin (25 mg orally) or placebo (niacin, 100 mg) on one occasion. We will assess psychological, psychophysical pain responses (thermal stimulation) and neural effects before and after administration of psilocybin or placebo. Once the first 10 participants complete Study 1, a report documenting their outcomes will be submitted to the UCSD IRB. Once the report is submitted, Study 2 will begin. Study 2: The second study will involve two treatment groups; one group will receive psilocybin (25 mg orally) on two occasions, and the second group will receive placeb

Study Record Dates

• First Submitted: January 24, 2022
• First Posted: February 4, 2022
• Study Start: October 3, 2022
• Primary Completion: March 7, 2024
• Study Completion: March 7, 2024
• Last Updated: January 9, 2026

Record last verified: 2026-01

Locations

US (1)