Cannabidiol for Reduction of Brain Neuroinflammation

NCT05066308 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2021P002617
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate whether cannabidiol (CBD), the primary centrally and peripherally active non-intoxicating compound in the cannabis plant, exerts anti-neuroinflammatory effects in patients with chronic low back pain (cLBP) with or without mild-to-moderate depression.

Conditions

Back Pain; Depressive Symptoms

Keywords

back pain; depression; depressive symptoms; cannabis; cannabidiol

Outcome Measures

Primary Outcomes (1)

• Changes in Neuroinflammation in the Thalamus

  The investigators will test for the presence of a significant treatment effect in the brain \[11C\]PBR28 signal in the thalamus, in order to test whether patients in the CBD arm will demonstrate significantly larger treatment-related reductions in neuroinflammation, compared to patients in the placebo arm.

  Change from Baseline to Week 4

Secondary Outcomes (7)

• Changes in Neuroinflammation in Limbic Regions

  Change from Baseline to Week 4

• Correlation Between Reductions in Thalamic [11C]PBR28 PET Signal and Reductions in Clinical Pain Ratings

  Change from Baseline to Week 4

• Correlation Between Reductions in Limbic [11C]PBR28 PET Signal and Reductions in Depressive Symptoms

  Change from Baseline to Week 4

• Change in Clinical Pain Ratings

  Change from average score during the 7 days prior to treatment (Baseline) to average score during the final week of treatment

• Change in Pain Bothersomeness

  Change from average score during the 7 days prior to treatment (Baseline) to average score during the final week of treatment

Other Outcomes (11)

• Change in Functional Brain Reward Circuitry [Exploratory]

  Change from Baseline to Week 4

• Change in Pain Severity & Interference with Daily Functioning [Exploratory]

  Change from Baseline to Week 4

• Change in Pain Catastrophizing [Exploratory]

  Change from Baseline to Week 4

Study Arms (2)

Cannabidiol (CBD)

EXPERIMENTAL

The recommended starting dosage is 2.5mg/kg taken twice daily. The titration schedule recommended in the EPIDIOLEX label will be followed, with 2.5 mg/kg twice daily in week 1, 5 mg/kg twice daily in week 2, 7.5 mg/kg twice daily in week 3, and 10 mg/kg twice daily in week 4 with the second PET scan conducted after one week at the maximum labeled dose. Any participant not tolerating a given dose can either go back down to the next lowest dose or delay uptitration at any week in the protocol. Participants will be instructed to take Epidiolex with a meal rather than in a fasted state. Participants will be treated for 4 weeks in total.

Drug: CBD

Placebo

PLACEBO COMPARATOR

The placebo will be taken at identical doses to the active drug condition.

Other: Placebo

Interventions

CBD DRUG

Epidiolex, an agent within the anti-epileptic drug class, will be used. Epidiolex, Greenwich Biosciences Inc.'s CBD formulation, is a 100 mg/mL purified oral solution, dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring. The drug is formulated from extracts prepared from Cannabis sativa L. plants that have a defined chemical profile and contain consistent levels of CBD as the principal phytocannabinoid. Extracts from these plants are processed to yield pure (\>95%) CBD that typically contains less than 0.5% (w/w) THC. Cannabidiol is the active ingredient in Epidiolex; inactive ingredients include dehydrated alcohol, sesame seed oil, strawberry flavor, and sucralose. Of note, CBD has no psychoactive properties.

Also known as: Epidiolex

Cannabidiol (CBD)

Placebo OTHER

Placebo CBD will be identical to the active CBD, a 100 mg/mL purified oral solution, dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring, but with no CBD.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 and ≤ 75;
• The ability to give written, informed consent;
• Fluency in English;
• Average worst daily pain of at least 4 on a 0-10 scale of pain intensity, during a typical day. Pain needs to be present for at least 50% of days during a typical week;
• On a stable pain treatment (pharmacological or otherwise) for the previous four weeks;
• Diagnosis of chronic low back pain, ongoing for at least 6 months prior to enrollment.
• High or mixed affinity binding to \[11C\]PBR28 identified by the Ala147Thr TSPO polymorphism in the TSPO gene (rs6971)

You may not qualify if:

• Outpatient surgery within 2 weeks and inpatient surgery within 1 month of the time of scanning (this timeframe may be extended if they are not fully recovered from the surgery);
• Elevated baseline transaminase (ALT and AST) levels above 3 times the Upper Limit of Normal (ULN), accompanied by elevations in bilirubin above 2 times the ULN;
• Any interventional pain procedures within 6 weeks prior to scanning procedure or at any point during study enrollment;
• Surgical intervention or introduction/change in opioid regimen at any point during study enrollment;
• Contraindications to fMRI scanning and PET scanning (including presence of a cardiac pacemaker or pacemaker wires, metallic particles in the body, vascular clips in the head or previous neurosurgery, prosthetic heart valves, claustrophobia);
• Implanted spinal cord stimulator (SCS) for pain treatment;
• Any history of neurological illness or major medical illness, unless clearly resolved without long-term consequences;
• Harmful alcohol drinking as indicated by an AUDIT score ≥ 16;
• Pregnancy or breast feeding;
• History of head trauma requiring hospitalization;
• Major cardiac event within the past 10 years;
• Regular use of recreational drugs in the past 3 months;
• Use of cannabis-containing products, such as products containing THC or over the-counter or dispensary CBD, for 2 weeks prior to starting the study medication and during the 4 weeks of taking the study medication;
• Use of immunosuppressive medications, such as prednisone, TNF medications within 2 weeks of the visit;
• Current bacterial or viral infection likely affecting the central nervous system;

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Related Publications (1)

• Pike CK, Kim M, Schnitzer K, Mercaldo N, Edwards R, Napadow V, Zhang Y, Morrissey EJ, Alshelh Z, Evins AE, Loggia ML, Gilman JM. Study protocol for a phase II, double-blind, randomised controlled trial of cannabidiol (CBD) compared with placebo for reduction of brain neuroinflammation in adults with chronic low back pain. BMJ Open. 2022 Sep 19;12(9):e063613. doi: 10.1136/bmjopen-2022-063613.

  PMID: 36123113 DERIVED

MeSH Terms

Conditions

Back Pain; Depression; Marijuana Abuse

Interventions

Cannabidiol

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Central Study Contacts

Jodi M Gilman, PhD

CONTACT

617-643-7293; jgilman1@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 23, 2021
• First Posted: October 4, 2021
• Study Start: January 4, 2022
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 15, 2026
• Last Updated: February 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Data will become available beginning one year after publication of the results.
• Access Criteria: Data will be provided pending a scientific review and a completed data use agreement/material transfer agreement. Requests should be submitted to Jodi Gilman at jgilman1@mgh.harvard.edu or to Marco Loggia at marco.loggia@mgh.harvard.edu

Locations

US (1)