Clinical trial NCT06368492: The Impact of Psilocybin on Pain in Fibromyalgia Patients
Official title: The Impact of Psilocybin on Pain in Fibromyalgia Patients: a Multicentre Trial.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Fibromyalgia
Keywords: fibromyalgia
psychedelics
psilocybin
chronic pain
Lead sponsor: Maastricht University
Sponsor class: OTHER
Collaborators: name: Leiden University Medical Center
First posted: 2024-04-16
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: double-blind, randomized, within-subjects, placebo-controlled design.
Primary purpose: TREATMENT

Brief summary: Rationale: Recent evidence shows that Lysergic Acid Diethylamide (LSD), even when administered in low, non-hallucinogenic doses, can produce analgesic effects and improve pain tolerance in a sample of healthy volunteers. Such results complement what was already observed with other serotonergic psychedelics such as psilocybin: survey studies and case series indicate that its use may lead to improvements in chronic pain conditions such as migraines, cluster headaches and phantom limb pain even at low, non-psychedelic doses. These effects have however not yet been investigated and confirmed in clinical populations under controlled experimental conditions.

Fibromyalgia (FM) is a chronic condition characterised by widespread pain, hyperalgesia, anxiety, disturbed sleep patterns, impaired cognitive functioning and comorbid mood disorders. Most suggested therapies are only associated with small improvements in pain ratings and quality of life. Currently, there is no data concerning the effectiveness of serotonergic psychedelics in improving pain ratings in fibromyalgia patients.

Objective: The present study will explore the effects that the administration of a placebo and 2 low psilocybin doses (5 mg or 10 mg) will have on pain perception in a group of fibromyalgia patients.

Study design: The present study uses a double-blind, randomized, placebo-controlled design. All participants will receive a placebo and 2 doses of psilocybin (5 mg or 10 mg) and will undergo the Cold Pressor Test (CPT) and the Pain Pressure Threshold Task (PPT) o test its analgesic effects.

Detailed description: Rationale: Recent evidence shows that Lysergic Acid Diethylamide (LSD), even when administered in low, non-hallucinogenic doses, can produce analgesic effects and improve pain tolerance in a sample of healthy volunteers. Such results complement what was already observed with other serotonergic psychedelics such as psilocybin: survey studies and case series indicate that its use may lead to improvements in chronic pain conditions such as migraines, cluster headaches and phantom limb pain even at low, non-psychedelic doses. These effects have however not yet been investigated and confirmed in clinical populations under controlled experimental conditions.

Fibromyalgia (FM) is a chronic condition characterised by widespread pain, hyperalgesia, anxiety, disturbed sleep patterns, impaired cognitive functioning and comorbid mood disorders. It has high direct and indirect costs and it is considered challenging to treat. Most suggested therapies, in fact, are only associated with small improvements in pain ratings and quality of life. Currently, there is no data concerning the effectiveness of serotonergic psychedelics in improving pain ratings in fibromyalgia patients.

Objective: The present study will explore the effects that the administration of a placebo and 2 low psilocybin doses (5 mg or 10 mg) will have on pain perception in a group of fibromyalgia patients.

Study design: The present study uses a double-blind, randomized, placebo-controlled design. All participants will receive a placebo and 2 doses of psilocybin (5 mg or 10 mg) and will undergo the Cold Pressor Test (CPT) and the Pain Pressure Threshold Task (PPT) o test its analgesic effects.

Study population: 35 fibromyalgia patients aged 18 to 65 years. Intervention: Placebo, 5 mg or 10 mg of psilocybin in randomized order. Main study parameters/endpoints: Primary outcomes will be subjective and objective measures of pain perception. Secondary measures will assess the effects that placebo and psilocybin will have on mood, cognition and psychedelic experience. Finally, participants will take part to an additional CPT after receiving hypnotic suggestions of analgesia to test whether such intervention may moderate pain ratings of individuals who took small doses of psilocybin.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participants will visit the research lab 5 times during 5 weeks. Before the first study day, subjects will come for a screening visit during which they will also be familiarized with tests and study procedures. This includes a medical screening by a licensed physician (medical history review, laboratory screening, electrocardiogram recording). The study visits will consist of taking the study treatment (5 mg or 10 mg of psilocybin or placebo), taking part to the experimental tasks, taking blood samples, completing computer tasks and filling out questionnaires. Finally, participants will take part to a final online visit to administer post-study questionnaires.

Eligibility criteria: Inclusion Criteria:

* Age between 18 and 65 years
* Normal weight, body mass index (weight/height2) between 18 and 28 kg/m2
* Fulfilment of the American College of Rheumatology criteria for FM diagnosis (43)
* A minimum Numeric Rating Scale (numeric rating scale) pain score of 5 out of 10
* Proficient knowledge of the Dutch or English language
* Written Informed Consent
* Understanding the procedures and the risks associated with the study
* No regular use of psychotropic medication such as opiates, antidepressants, muscle relaxants, anticonvulsants, sleep aids, benzodiazepines. Non pharmacological regimens will be allowed along 1 rescue therapy such as acetaminophen ≤4,000 mg/day, ibuprofen ≤1,200 mg/day, naproxen ≤660 mg/day, or ketoprofen ≤75 mg/day. Use of paracetamol (PCM) and non-steroidal anti-inflammatory drugs (NSAIDS) will be allowed and monitored.
* Willingness to refrain from taking psychoactive substances during the study.
* Willingness to drink only alcohol-free liquids and no coffee, black or green tea, or energy drinks after midnight of the evening before the study session, as well as during the study days
* Willingness not to drive a traffic vehicle or to operate machines within 24 h after substance administration

Exclusion Criteria:

* Presence of any other painful condition such as inflammatory rheumatic diseases, migraines or headaches and of other chronic or acute medical conditions
* Presence or history of any other psychiatric condition such as primary major depressive disorder, anxiety disorders or substance use disorder as determined by the medical questionnaire, drug questionnaire and medical examination
* Previous experience of serious side effects to psychedelic drugs (anxiety or panic attacks)
* Tobacco smoking (\>20 per day)
* Excessive drinking (\>20 alcoholic consumptions per week)
* Psychotic disorder in first-degree relatives
* Pregnancy or lactation
* Hypertension (diastolic \> 90 mmHg; systolic \> 140 mmHg)
* History of cardiac dysfunctions (arrhythmia, ischemic heart disease...)
* For women: no use of a reliable contraceptive

Primary outcomes:
measure: Ischemic Pain perception
timeFrame: 1.5, 2.5 and 4 hours after administration
measure: Pressure-evoked Pain perception
timeFrame: 1.5 and 4 hours after administration
measure: Self-reported pain
timeFrame: 1.5, 2.5 and 4 hours after administration
Secondary outcomes:
measure: Subjective effects: psychedelic phenomenology
timeFrame: Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5 and 6 hours after administration
measure: Subjective effects: mood
timeFrame: Baseline, 1, 2, 3, and 5 hours after administration
measure: Subjective effects: intensity of effects
timeFrame: Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5 and 6 hours after administration
measure: Subjective effects: Ego dissolution
timeFrame: 6 hours after administration
measure: Subjective effects: Dissociation
timeFrame: Baseline and 6 hours after administration
measure: Psychiatric symptoms
timeFrame: Baseline and 6 hours after administration
measure: Cognitive performance
timeFrame: 1.5 and 4 hours after administration
measure: Vigilance
timeFrame: 1.5 and 4 hours after administration
measure: Empathy
timeFrame: 1 hour after administration
measure: Creativity
timeFrame: 2.5 hours after administration
measure: Creativity
timeFrame: 2 hours after administration
measure: Autobiographical memory
timeFrame: 2.5 hours after administration
measure: Autobiographical memory
timeFrame: Study baseline and 1 week after last experimental session
measure: Treatment expectancy
timeFrame: Study baseline
measure: Treatment expectancy
timeFrame: Study baseline
measure: Fibromyalgia-related pain
timeFrame: Baseline and 1 week after each experimental session
measure: Personality
timeFrame: Baseline and 1 week after last experimental session
measure: Absorption
timeFrame: Baseline and 1 week after the experimental session
measure: Interpersonal Reactivity
timeFrame: Baseline and 1 week after last experimental session
measure: Depression
timeFrame: Baseline
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University
state: Limburg
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
state: South Holland
Study officials:
affiliation: Maastricht University
name: Johannes G. Ramaekers, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Castellanos JP, Woolley C, Bruno KA, Zeidan F, Halberstadt A, Furnish T. Chronic pain and psychedelics: a review and proposed mechanism of action. Reg Anesth Pain Med. 2020 Jul;45(7):486-494. doi: 10.1136/rapm-2020-101273. Epub 2020 May 4.