Using cannabidiol to reduce brain inflammation in patients with back pain and depression

Evaluation of Cannabidiol for Reduction of Brain Neuroinflammation

This study is testing whether cannabidiol (CBD) can help reduce brain inflammation and improve symptoms in people with chronic low back pain and depression.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Massachusetts General Hospital (Academic / other)
• Drugs / interventions: crizotinib, imatinib, prednisone
• Locations: 1 site (Boston, Massachusetts)
• Trial ID: NCT05066308 on ClinicalTrials.gov

What this trial studies

This study investigates the effects of cannabidiol (CBD) on neuroinflammation in patients suffering from chronic low back pain (cLBP) with or without mild-to-moderate depression. It is a randomized, double-blind, two-arm trial comparing CBD to a placebo. Participants will undergo integrated positron emission tomography/magnetic resonance imaging (PET/MRI) scans to assess neuroinflammation and striatal function. The study aims to provide insights into the potential therapeutic effects of CBD on both pain and depressive symptoms.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with chronic low back pain and mild-to-moderate depression.

Not a fit: Patients with recent surgeries, elevated liver enzymes, or those not meeting the pain criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could offer a novel treatment option for patients with chronic low back pain and depression.

How similar studies have performed: Other studies have shown promise in using CBD for pain and inflammation, but this specific approach is novel.

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;
8. Current or past history of major psychiatric illness (PTSD, depression, and anxiety are exclusion criteria only if the conditions were so severe as to require hospitalization in the past year);
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).

Where this trial is running

Boston, Massachusetts

• Massachusetts General Hospital — Boston, Massachusetts, United States (Recruiting)

Study contacts

• Study coordinator: Jodi M Gilman, PhD

Conditions Back Pain; Depressive Symptoms; back pain; depression; depressive symptoms; cannabis; cannabidiol