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Phantom Limb PainPhase 1NCT05224336

Psilocybin-assisted Therapy for Phantom Limb Pain

A Phase 1 study testing Psilocybin in people with Phantom Limb Pain, run by University of California, San Diego at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Phantom Limb Pain
What is being tested?
Psilocybin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
10 participants
Where
1 siteUnited States
Study dates
3 Oct 2022to 30 Apr 2031
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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
  • Participants who are taking a serotonergic dietary supplement (e.g., 5-hydroxytryptophan, St. John's wort, SAM-e)
  • Participants with any neurological conditions resulting in altered perception or cognition (e.g., dementia, traumatic brain injury, mild cognitive impairment) [with the exception of phantom limb syndrome and its sequelae (depression or anxiety)]
  • Participants with a positive urine drug screen for amphetamines, barbiturates, buprenorphine, cocaine, methamphetamine, MDMA, methadone, opiates (morphine, oxycodone), or phencyclidine (PCP)
  • Have used psilocybin, psilocybin-containing mushrooms, or another serotonergic hallucinogen (e.g., LSD, mescaline, ayahuasca) for recreational purposes within the last 12 months
  • Require concomitant treatment with anti-psychotic medications (aripiprazole, asenapine, brexpiprazole, cariprazine, chlorpromazine, clozapine, fluphenazine, haloperidol, iloperidone, loxapine, mesoridazine, molindone, olanzapine, paliperidone, perphenazine, pimavanserin, pimozide, prochlorpromazine, quetiapine, risperidone, thioridazine, thiothixene, trifluperazine, or ziprasidone)
  • Require concomitant treatment with an antidepressant medication or other medications that act as MAO inhibitors or serotonin reuptake inhibitors (amitriptyline, amoxapine, bupropion, citalopram, clomipramine, desipramine, doxepin, duloxetine, escitalopram, fluoxetine, fluvoxamine, imipramine, isocarboxazid, levomilnacipram, maprotiline, milnacipram, mirtazapine, nefazodone, nortriptyline, paroxetine, phenelzine, protriptyline, selegiline, sertraline, tramadol, tranylcypromine, trazodone, trimipramine, venlafaxine, vilazodone, vortioxetine) [trazodone ≤50mg/24hr for insomnia is allowed, but not within 48hr of the psilocybin session]
  • Require concomitant treatment with medications known to inhibit UGT1A9 and UGT1A10 (e.g., diclofenac, probenecid, valproic acid)
  • Severe hearing or visual impairment
  • History of seizure disorder or epilepsy
  • History of migraine or other severe recurring headaches necessitating treatment by a neurologist or headache specialist
  • History of adverse reactions or intolerance to niacin or the rescue medications used in the study (benzodiazepines, antipsychotics, labetalol, nitroglycerin)
  • Presence of uncontrolled cardiovascular disease or uncontrolled hypertension (SBP > 140 mmHg or DBP > 90 mmHg)
  • Require concomitant treatment with an antihypertensive medication
  • QTc prolongation (QTc > 0.045 for man, QTc > 0.047 for women)
  • Subjects with history of stroke, angina, clinically significant ECG abnormality (e.g. atrial fibrillation), or artificial heart valve
  • Participants with severe renal impairment (GFR < 30 mL/min/1.73 m2)
  • Participants with any clinically significant lab abnormalities as determined by a physician on the study team
  • Myocardial infarction within the last 12 months
  • Participants who meet criteria for Child-Pugh class B or higher
  • Participants who are prescribed opioid medications
  • Participants taking other medications that may be associated with serotonin syndrome: carbamazepine, dextromethorphan, lithium, linezolid, buspirone
  • Evidence of severely compromised hepatic function

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California, San Diego

    San Diego, California, 92093

Other trials in United States

About this study

Official title: Behavioral and Neural Mechanisms Supporting 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.

Being tested
Psilocybin, Placebo Niacin
Keywords
Phantom Limb Pain, Psilocybin, Psychedelic Therapy, fMRI, Pain, Chronic Pain, Psychedelics, Hallucinogens, Physiological Effects of Drugs, Psychotropic Drugs
Medical subject headings
Phantom Limb, Pain, Chronic Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PsilocybinDrug

    25mg oral psilocybin

  • Placebo NiacinDrug

    100mg oral niacin

Study groups in NCT05224336
Study groupRoleWhat they receive
PsilocybinExperimentalParticipants 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.
Receives: Drug: Psilocybin
NiacinPlacebo comparatorParticipants 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.
Receives: Drug: Placebo Niacin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (3)

  1. Change in Visual Analog Scale Pain ratings

    Pain ratings will be assessed in response to the noxious heat stimulation. Pain intensity and unpleasantness ratings will be assessed with a validated visual analog scale. The minimum rating ("0") is labeled as "no pain sensation" or "not at all unpleasant," whereas the maximum ("10") is labeled as "most intense imaginable" or "most unpleasant imaginable." Higher numbers correspond to higher pain.

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

  2. Cerebral Blood Flow (CBF)

    Changes in CBF during rest, after intervention session, and during noxious heat stimulation.

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

  3. Brief Pain Inventory

    This is a 7-item self-report measure of pain interference with general activity, mood, walking ability, work, relationships with others, sleep, and enjoyment of life.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Feb 2022
  2. Study start3 Oct 2022
  3. Primary completion7 Mar 2024
  4. Study completion30 Apr 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05224336
Sponsor's protocol ID
200626
Status last verified
Oct 2026
First submitted
24 Jan 2022
Last updated
9 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Psilocybin in people with Phantom Limb Pain, run by University of California, San Diego at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 9 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in Phantom Limb Pain Intensity (time frame: Baseline to Post-Intervention Session (within 2 weeks after session)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05224336.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2026; AzTrials last refreshed its copy on 26 Oct 2026.

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