Het effect van psilocybine op pijn bij fibromyalgiepatiënten: een multicenter trial

Phase 2

Not yet recruiting

Conditions: Fibromyalgia

Interventions: Drug: Psilocybin
Behavioral: Hypnosis script

Registration Number: 2024-516890-63-00

Lead Sponsor: Universiteit Maastricht

Brief Summary: Primary Objective: The primary objective is to assess the effects of low psilocybin doses on pain perception in FM patients and their association with BDNF levels.

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.

Recruitment & Eligibility

Status: Authorised, recruitment pending

Sex: Not specified

Target Recruitment: 35

Inclusion Criteria

Age between 18 and 65 years

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

Normal weight, body mass index (weight/height2) between 18 and 30 kg/m2

Fulfilment of the American College of Rheumatology criteria for FM diagnosis (43)

A minimum NRS 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, muscle relaxants, anticonvulsants, sleep aids, benzodiazepines, MAO-A inhibitors. 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.

Exclusion Criteria

Presence of inflammatory rheumatic diseases such as ankylosing spondylitis.

History of cardiac dysfunctions (arrhythmia, ischemic heart disease…)

For women: no use of a reliable contraceptive

Presence or history of psychotic, bipolar or substance use disorder as determined by the medical questionnaire, drug questionnaire and medical examination

Current mental health diagnosis

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Patient group	Hypnosis script	Each participant will receive 2 different doses of psilocybin (5mg and 10mg) and a matching placebo on three separate occasions.
Patient group	Psilocybin	Each participant will receive 2 different doses of psilocybin (5mg and 10mg) and a matching placebo on three separate occasions.

Primary Outcome Measures

Name	Time	Method
We hypothesize that psilocybin will induce significant analgesic effects at 5 mg and 10 mg compared to placebo as measured by subjective measures and the outcomes of the PPT and CPT. We also hypothesize that these potential effects will be associated with variations in BDNF levels.		We hypothesize that psilocybin will induce significant analgesic effects at 5 mg and 10 mg compared to placebo as measured by subjective measures and the outcomes of the PPT and CPT. We also hypothesize that these potential effects will be associated with variations in BDNF levels.

Secondary Outcome Measures

Name	Time	Method
The secondary objective is to assess the impact of low psilocybin doses on mood, cognition, personality, autobiographical memory functioning and psychedelic experience. We will also test whether hypnotic suggestions can moderate the potential effects of psilocybin on pain perception and tolerance. Finally, we will test whether the plasma levels of inflammatory biomarkers (IL-1α, IL-1β, IL-6, IL-8, and TNF-α, C-reactive protein (CRP)) will decrease in response to psilocybin administration.		The secondary objective is to assess the impact of low psilocybin doses on mood, cognition, personality, autobiographical memory functioning and psychedelic experience. We will also test whether hypnotic suggestions can moderate the potential effects of psilocybin on pain perception and tolerance. Finally, we will test whether the plasma levels of inflammatory biomarkers (IL-1α, IL-1β, IL-6, IL-8, and TNF-α, C-reactive protein (CRP)) will decrease in response to psilocybin administration.

Trial Locations

Locations (2): LUMC
🇳🇱
Leiden, Netherlands
Universiteit Maastricht
🇳🇱
Maastricht, Netherlands
LUMC
🇳🇱Leiden, Netherlands
Kim B. Gombert-Handoko
Site contact
0031715299599
k.b.gombert-handoko@lumc.nl