The Impact of Psilocybin on Pain in Fibromyalgia Patients

Last updated: September 8, 2025
Sponsor: Maastricht University
Overall Status: Active - Recruiting

Phase

N/A

Condition

Pain

Chronic Pain

Fibromyalgia

Treatment

Psilocybin

Hypnosis script

Clinical Study ID

NCT06368492
P137
NL78008.068.21
2021-002909-10
  • Ages 18-65
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

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, musclerelaxants, anticonvulsants, sleep aids, benzodiazepines. Non pharmacologicalregimens 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 ofparacetamol (PCM) and non-steroidal anti-inflammatory drugs (NSAIDS) will be allowedand 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, orenergy drinks after midnight of the evening before the study session, as well asduring the study days

  • Willingness not to drive a traffic vehicle or to operate machines within 24 h aftersubstance administration

Exclusion

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 majordepressive disorder, anxiety disorders or substance use disorder as determined bythe medical questionnaire, drug questionnaire and medical examination

  • Previous experience of serious side effects to psychedelic drugs (anxiety or panicattacks)

  • 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

Study Design

Total Participants: 35
Treatment Group(s): 2
Primary Treatment: Psilocybin
Phase:
Study Start date:
May 03, 2024
Estimated Completion Date:
December 31, 2025

Study 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.

Connect with a study center

  • Maastricht University

    Maastricht, Limburg 6226AK
    Netherlands

    Site Not Available

  • Maastricht University

    Maastricht 2751283, Limburg 2751596 6226AK
    Netherlands

    Active - Recruiting

  • Leiden University Medical Center

    Leiden, South Holland 2333
    Netherlands

    Site Not Available

  • Leiden University Medical Center

    Leiden 2751773, South Holland 2743698 2333
    Netherlands

    Active - Recruiting

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