The Impact of Psilocybin on Pain in Fibromyalgia Patients

NCT ID: NCT06368492

Last Updated: 2025-09-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-03
• Study Completion Date: 2025-12-31

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.

Conditions

Fibromyalgia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Patient group

Each participant will receive 2 different doses of psilocybin (5mg and 10mg) and a matching placebo on three separate occasions.

Group Type: EXPERIMENTAL

Psilocybin

Intervention Type: DRUG

Each participant will receive 2 different doses of psilocybin (5mg and 10mg) and a matching placebo on three separate occasions.

Hypnosis script

Intervention Type: BEHAVIORAL

All participants will receive a brief hypnotic induction aimed at producing analgesia before the second administration of CPT

Interventions

Psilocybin

Each participant will receive 2 different doses of psilocybin (5mg and 10mg) and a matching placebo on three separate occasions.

Intervention Type: DRUG

Hypnosis script

All participants will receive a brief hypnotic induction aimed at producing analgesia before the second administration of CPT

Intervention Type: BEHAVIORAL

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Leiden University Medical Center

OTHER

Sponsor Role: collaborator

Maastricht University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Johannes G. Ramaekers, PhD

Role: PRINCIPAL_INVESTIGATOR

Maastricht University

Locations

Maastricht University

Maastricht, Limburg, Netherlands

Site Status: RECRUITING

Leiden University Medical Center

Leiden, South Holland, Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Mauro Cavarra, MSc

Role: CONTACT

fpn-pim_p137@maastrichtuniversity.nl

‭+310683029784‬

Facility Contacts

Mauro Cavarra, MSc

Role: primary

m.cavarra@maastrichtuniversity.nl

+313494438261

Monique van Velzen, PhD

Role: primary

M.van_Velzen@lumc.nl

References

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.

Reference Type: BACKGROUND

PMID: 32371500 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

2021-002909-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NL78008.068.21

Identifier Type: OTHER

Identifier Source: secondary_id

P137

Identifier Type: -

Identifier Source: org_study_id