The Impact of Psilocybin on Pain in Fibromyalgia Patients (PsiloFM)

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.

Study Overview

• Status: Recruiting
• Conditions: Fibromyalgia
• Intervention / Treatment: Drug: Psilocybin; Behavioral: Hypnosis script

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.

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mauro Cavarra, MSc; Phone Number: ‭+310683029784‬; Email: fpn-pim_p137@maastrichtuniversity.nl

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6226AK
      • Recruiting
      • Maastricht University
      • Contact: Mauro Cavarra, MSc; Phone Number: +313494438261; Email: m.cavarra@maastrichtuniversity.nl
  • South Holland
    • Leiden, South Holland, Netherlands, 2333
      • Recruiting
      • Leiden University Medical Center
      • Contact: Monique van Velzen, PhD; Email: M.van_Velzen@lumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patient group; Each participant will receive 2 different doses of psilocybin (5mg and 10mg) and a matching placebo on three separate occasions.	Drug: Psilocybin; Each participant will receive 2 different doses of psilocybin (5mg and 10mg) and a matching placebo on three separate occasions.; Behavioral: Hypnosis script; All participants will receive a brief hypnotic induction aimed at producing analgesia before the second administration of CPT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective effects: psychedelic phenomenology	5 Dimensions of altered states of consciousness (5D-ASC)	Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5 and 6 hours after administration
Subjective effects: mood	Profile of mood states (POMS)	Baseline, 1, 2, 3, and 5 hours after administration
Subjective effects: intensity of effects	Intensity of effects Visual Analogue Scale (VAS) (0: not under the influence; 10: very much under the influence)	Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5 and 6 hours after administration
Subjective effects: Dissociation	Clinical Administered Dissociative States Scale (CADSS)	Baseline and 6 hours after administration
Cognitive performance	Digit Symbol Substitution Test (DSST) - time to complete in seconds and number of errors	1.5 and 4 hours after administration
Empathy	Multifaceted Empathy Test (MET) - emotion recognition accuracy (right answers/wrong answers)	1 hour after administration
Creativity	Alternate Use Test (AUT) - Fluency and Originality, Flexibility, and Elaboration scores	2.5 hours after administration
Creativity	Story Writing	2 hours after administration
Autobiographical memory	Autobiographical Memory Test (AMT)	2.5 hours after administration
Autobiographical memory	Autobiographical Recollection Test (ART)	Study baseline and 1 week after last experimental session
Treatment expectancy	Credibility/Expectancy Questionnaire (CEQ)	Study baseline
Treatment expectancy	Treatment Expectations in Chronic Pain (TEC)	Study baseline
Fibromyalgia-related pain	o Fibromyalgia Impact Questionnaire (FIQ)	Baseline and 1 week after each experimental session
Personality	Big Five Inventory (BFI)	Baseline and 1 week after last experimental session
Absorption	Modified Tellegen Absorption Scale (MODTAS)	Baseline and 1 week after the experimental session
Interpersonal Reactivity	Interpersonal Reactivity Index (IRI)	Baseline and 1 week after last experimental session
Depression	o Beck Depression Inventory - II (BDI-II)	Baseline
Subjective effects: Ego dissolution	Ego Dissolution Inventory(EDI)	6 hours after administration
Psychiatric symptoms	Brief Symptom Inventory (BSI)	Baseline and 6 hours after administration
Vigilance	Psychomotor Vigilance Task (PVT) - number of attention lapses	1.5 and 4 hours after administration

Collaborators and Investigators

• Sponsor: Maastricht University
• Collaborators: Leiden University Medical Center
• Investigators: Principal Investigator: Johannes G. Ramaekers, PhD, Maastricht University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: October 31, 2023
• First Submitted That Met QC Criteria: April 12, 2024
• First Posted (Actual): April 16, 2024

Study Record Updates

• Last Update Posted (Estimated): September 15, 2025
• Last Update Submitted That Met QC Criteria: September 8, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: chronic pain; fibromyalgia; psilocybin; psychedelics
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Rheumatic Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Fibromyalgia; Chronic Pain; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Indoles; Indole Alkaloids; Indolizidines; Indolizines; Tryptamines; Psilocybin
• Other Study ID Numbers: P137; 2021-002909-10 (EudraCT Number); NL78008.068.21 (Other Identifier: METC azM/Maastricht University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No