The Impact of Psilocybin on Pain in Fibromyalgia Patients

NCT06368492 | Recruiting

• 3 other identifiers: P1372021-002909-10NL78008.068.21
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

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.

Conditions

Fibromyalgia

Keywords

fibromyalgia; psychedelics; psilocybin; chronic pain

Outcome Measures

Primary Outcomes (3)

• Ischemic Pain perception

  Pain tolerance (seconds) in the Cold Pressor Task

  1.5, 2.5 and 4 hours after administration

• Pressure-evoked Pain perception

  Pain threshold (kPa) in the Pressure Pain Threshold

  1.5 and 4 hours after administration

• Self-reported pain

  Painfulness Visual Analogue Scale (0: no pain; 10 worst pain)

  1.5, 2.5 and 4 hours after administration

Secondary Outcomes (20)

• Subjective effects: psychedelic phenomenology

  Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5 and 6 hours after administration

• Subjective effects: mood

  Baseline, 1, 2, 3, and 5 hours after administration

• Subjective effects: intensity of effects

  Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5 and 6 hours after administration

• Subjective effects: Ego dissolution

  6 hours after administration

• Subjective effects: Dissociation

  Baseline and 6 hours after administration

Study Arms (1)

Patient group

EXPERIMENTAL

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

Drug: Psilocybin; Behavioral: Hypnosis script

Interventions

Psilocybin DRUG

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

Patient group

Hypnosis script BEHAVIORAL

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

Patient group

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Maastricht University: lead
• Leiden University Medical Center: collaborator

Study Sites (2)

Maastricht University

Maastricht, Limburg, 6226AK, Netherlands

RECRUITING

Leiden University Medical Center

Leiden, South Holland, 2333, Netherlands

RECRUITING

Related Publications (1)

• 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.

  PMID: 32371500 BACKGROUND

MeSH Terms

Conditions

Fibromyalgia; Chronic Pain

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Johannes G. Ramaekers, PhD

  Maastricht University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mauro Cavarra, MSc

CONTACT

‭+310683029784‬; fpn-pim_p137@maastrichtuniversity.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: Blinding will be handled by one of the study pharmacies and order and allocation of the treatment to each participant will be completely randomized. This setup ensures that neither the participant nor the experimenter running the test day will be aware of the contents of the capsule.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: double-blind, randomized, within-subjects, placebo-controlled design.

Study Record Dates

• First Submitted: October 31, 2023
• First Posted: April 16, 2024
• Study Start: May 3, 2024
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: September 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2)