The Impact of Psilocybin on Pain in Fibromyalgia Patients

Official title

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

Overview

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.

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.

Interventions

• 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

Primary outcome measures

• Ischemic Pain perception [Time frame: 1.5, 2.5 and 4 hours after administration]
• Pressure-evoked Pain perception [Time frame: 1.5 and 4 hours after administration]
• Self-reported pain [Time frame: 1.5, 2.5 and 4 hours after administration]

Secondary outcome measures (12)

• Subjective effects: psychedelic phenomenology [Time frame: Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5 and 6 hours after administration]
• Subjective effects: mood [Time frame: Baseline, 1, 2, 3, and 5 hours after administration]
• Subjective effects: intensity of effects [Time frame: Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5 and 6 hours after administration]
• Subjective effects: Ego dissolution [Time frame: 6 hours after administration]
• Subjective effects: Dissociation [Time frame: Baseline and 6 hours after administration]
• Psychiatric symptoms [Time frame: Baseline and 6 hours after administration]
• Cognitive performance [Time frame: 1.5 and 4 hours after administration]
• Vigilance [Time frame: 1.5 and 4 hours after administration]
• Empathy [Time frame: 1 hour after administration]
• Creativity [Time frame: 2.5 hours after administration]
• Creativity [Time frame: 2 hours after administration]
• Autobiographical memory [Time frame: 2.5 hours after administration]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Netherlands · 2 centers

• Maastricht University — Maastricht
• Leiden University Medical Center — Leiden

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. PMID 32371500

Identifiers

NCT: NCT06368492 · P137 · 2021-002909-10 · NL78008.068.21

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗