Psilocybin-assisted Therapy for Phantom Limb Pain

Sponsor

University of California, San Diego (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05224336

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Phantom Limb Pain	Drug: Psilocybin Drug: Placebo Niacin	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

Participants and outcome assessor will not be made aware if participants are receiving psilocybin or placebo niacin.

Primary Purpose:

Treatment

Official Title:

Behavioral and Neural Mechanisms Supporting Psilocybin-assisted Therapy for Phantom Limb Pain

Anticipated Study Start Date :

Mar 1, 2022

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Psilocybin 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 25mg oral psilocybin
Placebo Comparator: Niacin 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 100mg oral niacin

Arm

Intervention/Treatment

Experimental: Psilocybin

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

25mg oral psilocybin

Placebo Comparator: Niacin

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

100mg oral niacin

Outcome Measures

Primary Outcome Measures

Changes in Phantom Limb Pain Intensity [Baseline to Post-Intervention Session (within 2 weeks after session)]
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.

Secondary Outcome Measures

Change in Visual Analog Scale Pain ratings [Baseline to Post-Intervention Session (within 2 weeks after session)]
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.
Cerebral Blood Flow (CBF) [Baseline to Post-Intervention Session (within 2 weeks after session)]
Changes in CBF during rest, after intervention session, and during noxious heat stimulation.
Brief Pain Inventory [Baseline to Post-Intervention Session (within 2 weeks after session)]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 <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
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