Cannabidiol for Reduction of Brain Neuroinflammation

NCT ID: NCT05066308

Last Updated: 2026-02-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-04
• Study Completion Date: 2026-12-15

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.

Detailed Description

This is a randomized, double-blind, 2-arm mechanistic trial that seeks to assess the effects of CBD and placebo in patients with cLBP with and without mild-to-moderate depression, using integrated positron emission tomography / magnetic resonance imaging (PET/MRI) scans. The use of integrated PET/MRI will make it possible to simultaneously evaluate neuroinflammation (using [11C]PBR28, a second-generation radioligand for TSPO) and striatal function (using the Monetary Incentive Delay task, a validated fMRI task that probes behavioral and neural responses to rewards and losses).

Conditions

Back Pain; Depressive Symptoms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Cannabidiol (CBD)

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.

Group Type: EXPERIMENTAL

CBD

Intervention Type: 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.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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.

Interventions

CBD

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: OTHER

Other Intervention Names

Epidiolex

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 and ≤ 75;

2. The ability to give written, informed consent;

3. Fluency in English;

4. 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;

5. On a stable pain treatment (pharmacological or otherwise) for the previous four weeks;

6. Diagnosis of chronic low back pain, ongoing for at least 6 months prior to enrollment.

7. High or mixed affinity binding to [11C]PBR28 identified by the Ala147Thr TSPO polymorphism in the TSPO gene (rs6971)

Exclusion Criteria

1. 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);

2. 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;

3. Any interventional pain procedures within 6 weeks prior to scanning procedure or at any point during study enrollment;

4. Surgical intervention or introduction/change in opioid regimen at any point during study enrollment;

5. 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);

6. Implanted spinal cord stimulator (SCS) for pain treatment;

7. Any history of neurological illness or major medical illness, unless clearly resolved without long-term consequences;

9. Harmful alcohol drinking as indicated by an AUDIT score ≥ 16;

10. Pregnancy or breast feeding;

11. History of head trauma requiring hospitalization;

12. Major cardiac event within the past 10 years;

13. Regular use of recreational drugs in the past 3 months;

14. 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;

15. Use of immunosuppressive medications, such as prednisone, TNF medications within 2 weeks of the visit;

16. Current bacterial or viral infection likely affecting the central nervous system;

17. Epilepsy;

18. Use of the medications valproate and clobazam, which may increase risk of hepatic AEs;

19. Safety concerns related to use of any of the following medications will be discussed on an individualized basis with a physician:

• Strong and moderate CYP3A4 inhibitors including boceprevir, cobicistat, conivaptan, danoprevir, elvitegravir, ritonavir, indinavir, itraconazole, ketoconazole, lopinavir, paritaprevir and ombitasvir and/or dasabuvir, posaconazole, saquinavir and telaprevir, tipranavir, clarithromycin, diltiazem, idelalisib, nefazodone, nelfinavir, troleandomycin, voriconazole, aprepitant, cimetidine, ciprofloxacin, clotrimazole, crizotinib, cyclosporine, dronedarone, erythromycin, fluconazole, fluvoxamine, imatinib, tofisopam, disulfiram, and verapamil;
• Strong and moderate inhibitors of CYP2C19 including fluoxetine and ticlopidine;
• Sensitive and moderately sensitive substrates of CYP2C19 including clobazam, lansoprazole, omeprazole, S-mephenytoin, and rabeprazole;
• Sensitive and moderately sensitive substrates of CYP1A2 including alosetron, duloxetine, ramelteon, tasimelteon, theophylline, tizanidine, pirfenidone, and ramosetron;
• Sensitive and moderately sensitive substrates of CYP2B6 including bupropion and efavirenz;
• Sensitive and moderately sensitive substrates of CYP2C8 including repaglinide, montelukast, pioglitazone, and rosiglitazone;
• Sensitive and moderately sensitive substrates of CYP2C9 including tolbutamide, celecoxib, glimepiride, and warfarin;
• Sensitive and moderately sensitive substrates of UGT1A9 including diflunisal, propofol, and fenofibrate;
• Sensitive and moderately sensitive substrates of UGT2B7 including, gemfibrozil, lamotrigine, and morphine;

20. CNS depressants including all antipsychotics, benzodiazepines (except for alprazolam, clonazepam, and lorazepam, which have low binding affinity to TSPO44-48), and non-benzodiazepine sleep aids that have a known unsafe reaction with CBD;

21. Use of opioids ≥ 30 mg morphine equivalents on average per month;

22. Actively suicidal, history of suicide attempt or an aborted attempt within the last 5 years, or engagement in non-suicidal self-injurious behavior within the last year;

23. Allergy to sesame oil, and any other ingredients of EPIDIOLEX;

24. Any other contraindications to CBD administration noted by the study physician;

25. Any significant change in drug use and pain treatment from screening visit;

26. In the opinion of the investigators, unable to safely participate in this study and/or provide reliable data (e.g., unable to reliably rate pain; unlikely to remain still during the imaging procedures, etc).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jodi Gilman

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jodi M Gilman, PhD

Role: CONTACT

jgilman1@mgh.harvard.edu

617-643-7293

Facility Contacts

Jodi M Gilman, PhD

Role: primary

jgilman1@mgh.harvard.edu

617-643-7293

References

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.

Reference Type: DERIVED

PMID: 36123113 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2021P002617

Identifier Type: -

Identifier Source: org_study_id