The Impact of Psilocybin on Pain in Fibromyalgia Patients

Trial details

Who runs it

Maastricht University

Trial code

NCT06368492EU 2024-516890-63-00

Record updated

15 September 2025

Original 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.Read full original descriptionShow less

The Impact of Psilocybin on Pain in Fibromyalgia Patients: a Multicentre Trial.

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.

Inclusion: 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: Previous experience of serious side effects to psychedelic drugs (anxiety or panic attacks); 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; Psychotic disorder in first-degree relatives; Hypertension (diastolic > 90 mmHg; systolic > 140 mmHg); History of cardiac dysfunctions (arrhythmia, ischemic heart disease…); Tobacco smoking (>20 per day); Excessive drinking (>20 alcoholic consumptions per week); Pregnancy or lactation; For women: no use of a reliable contraceptive.

ClinicalTrials.gov NCT06368492 · EU CTIS 2024-516890-63-00