Biosignature of the Response to Treatment With Cannabis Oil in Individuals With Fibromyalgia (CAN-RCT)

Fibromyalgia is a chronic condition that causes widespread pain, fatigue, and other symptoms, significantly affecting quality of life. Unfortunately, there are few effective treatments available. Recently, medical cannabis has gained attention as a potential treatment, leading many countries to approve its use for fibromyalgia. However, its success is limited-only about 25% of patients experience meaningful pain relief, and side effects like dizziness or fatigue are common. Not everyone responds to medical cannabis the same way, and researchers think this variability may partly be explained by differences in the gut microbiome-the community of bacteria and other microorganisms living in our digestive system. These microbes are known to influence various aspects of health, including pain and how the body processes medications. Our research focuses on understanding the link between the gut microbiome and fibromyalgia. We propose a study where 150 fibromyalgia patients will be treated with either cannabis oil or a placebo in a double-blind trial. By analyzing their symptoms and gut microbiome, we hope to identify patterns that could predict who will benefit most from cannabis treatment. If successful, this research could lead to more personalized and effective treatment options for fibromyalgia.

Study Overview

• Status: Recruiting
• Conditions: Fibromyalgia
• Intervention / Treatment: Drug: Cannabis Oil (5% THC/5% CBD); Drug: Sham Cannabis Oil

Detailed Description

This study aims to explore the potential association between the composition of the gut microbiome and the individual response to cannabis oil in individuals with fibromyalgia. We propose a double-blinded randomized controlled trial, where 150 patients with fibromyalgia will be treated with either a careful titration of cannabis oil (5% THC, 5% CBD) or placebo with an allocation ratio of 4:1. Patient reported outcomes, quantitative sensory testing and gut microbiome and metabolome composition will be evaluated at baseline and during treatment. Subjective and objective clinical outcomes will be compared to baseline and end-of-study gut microbiome composition and metabolomic profile.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: May Haddad, PhD; Phone Number: +972 +9724-7772040; Email: ma_haddad@rambam.health.gov.il

Study Locations

• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Rambam Health Care Campus
    • Contact: May Haddad, PhD; Phone Number: +972 +9724-7772040; Email: ma_haddad@rambam.health.gov.il
    • Contact: Amir Minerbi, MD-PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adult men and women aged 30 years and over.
• Diagnosis of fibromyalgia confirmed according to the 2016 diagnostic criteria by a pain specialist, with relevant symptoms lasting 12 months or more.
• An average reported pain ≥ 6 during the preceding week.
• Eligible for cannabis at the discretion of the treating physician.
• Has remained symptomatic despite receiving standard care for fibromyalgia including analgesics, anti-depressants (tricyclic and SNRI) and anti-epileptic agents.

Exclusion Criteria:

• Patients who have used cannabis during the preceding month.
• Any significant comorbid condition at the discretion of the PI (e.g. inflammatory arthritis, inflammatory bowel disease, cancer).
• Personal or family history of psychotic disorders.
• Current or past anxiety disorder.
• Any uncontrolled psychiatric pathology.
• Current or history of substance addiction or abuse.
• Diagnosed dementia or cognitive impairment.
• Personal history of cardiovascular disease.
• Pregnancy, lactation or intention to conceive.
• Known allergy to any of the cannabis oil ingredients.
• Patients with a history of seizure disorder (excluding childhood febrile convulsions) or epilepsy.
• Active liver disease.
• Any contraindication to the use of MC.
• Inflammatory Bowel Disease (IBD).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Comparator: Cannabis Oil (5% THC/5% CBD); Participants in this arm will receive cannabis oil containing a balanced formulation of 5% THC and 5% CBD. The intervention will span three months, including a six-week titration period to optimize dosing, followed by a maintenance phase. Doses will be self-administered sublingually and adjusted based on individual tolerance and efficacy. Comprehensive assessments will monitor clinical outcomes, gut microbiome composition, and circulating metabolomics to explore correlations with treatment response and safety. This arm will comprise 120 patients.	Drug: Cannabis Oil (5% THC/5% CBD); Cannabis oil containing a balanced formulation of 5% tetrahydrocannabinol (THC) and 5% cannabidiol (CBD). Administered sublingually over a three-month period, starting with a six-week titration phase to optimize dosing, followed by maintenance.
Sham Comparator: Sham Comparator: Placebo Oil; Participants in this arm will receive placebo oil, which is visually and chemically matched to the active cannabis oil but contains no active cannabinoids (THC or CBD). Like the active arm, participants will undergo a three-month intervention, including a six-week titration period and maintenance phase. Outcomes, including clinical measures and biological analyses, will be used as a control to evaluate the therapeutic effects of the cannabis oil. This arm will comprise 30 patients.	Drug: Sham Cannabis Oil; Placebo oil visually and chemically matched to the active cannabis oil but devoid of active cannabinoids (THC/CBD). Administered sublingually over three months, mirroring the active arm's titration and maintenance schedule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
correlation of microbiome composition or serum metabolomics with pain reduction	Any correlation of the gut microbiome composition or serum metabolomics with pain reduction following a 3-months treatment period with cannabis oil.	Three Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Intensity	Change in pain intensity as measured by the Numeric Rating Scale	Three Months
Change in sleep quality	Change in Pittsburgh Sleep Quality Index following 3 months of treatment with cannabis oil.	Three Months
Change in quality of life	Change in Short-form health-questionnaire following 3 months of treatment with cannabis oil.	Three Months
Change in anxiety and depression	Change in Hospital anxiety and depression scale following 3 months of treatment with cannabis oil.	Three Months
Patient global impression of changes	Patient global impression of change following 3 months of treatment with cannabis oil.	Three Months
Changes in gut microbiome and blood metabolites following 3 months treatment with cannabis oil	Changes in gut microbiome and blood metabolites following 3 months of treatment with cannabis oil will be measured using 16rRNA sequencing of stool and mass spectrometry of plasma.	Three Months
correlation of microbiome composition and serum metabolomics with clinical measures	Significant correlations (using Kendall rank) of the relative abundance of measured gut bacteria and plasma metabolites with clinical measures including sleep, quality of life, anxiety, depression, and impression of change following a 3-month treatment period with cannabis oil.	Three Months

Collaborators and Investigators

• Sponsor: Rambam Health Care Campus
• Collaborators: American Fibromyalgia Syndrome Association
• Investigators: Principal Investigator: Amir Minerbi, MD-PhD, Rambam Health Care Campus

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: April 1, 2025
• First Submitted That Met QC Criteria: April 19, 2025
• First Posted (Actual): April 27, 2025

Study Record Updates

• Last Update Posted (Actual): April 27, 2025
• Last Update Submitted That Met QC Criteria: April 19, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Microbiome; Chronic Pain; Fibromyalgia; Cannabis
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Rheumatic Diseases; Fibromyalgia; Myofascial Pain Syndromes
• Other Study ID Numbers: 0576-22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study protocol, raw data and analyses will be made available once the data analysis is complete and the study results are ready for peer review.
• IPD Sharing Time Frame: Estimated May 2027 for unlimited time.
• IPD Sharing Access Criteria: All non identified data will be made publicly available.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No