Cannabidiol for Reduction of Brain Neuroinflammation

• Status: Not yet recruiting
• Trial end date: 2026-12-15
• Target enrollment: 0
• Participant gender: All

Summary

We will study 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Massachusetts General Hospital
• Treatments: Cannabidiol

Criteria

Inclusion Criteria:

1. Age ≥ 18 and ≤ 75;

2. The ability to give written, informed consent;

3. Fluency in English;

4. Ongoing pain that averages at least 4, on a 0 -10 scale of pain intensity during a typical week, and is 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.

Exclusion Criteria:

1. Outpatient surgery within 2 months and inpatient surgery within 6 months from the time of scanning;

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 affecting the central nervous system, 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. Any pain condition of greater severity than that of the back pain;

10. Harmful or hazardous alcohol drinking as indicated by an AUDIT score ≥ 8;

11. Pregnancy or breast feeding;

12. History of head trauma requiring hospitalization;

13. Major cardiac event within the past 10 years;

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

15. Any marijuana use, medical or recreational, in the past 2 weeks;

16. An abnormal physical exam (e.g., peripheral edema);

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

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

19. Epilepsy or any prescription of an anti-epileptic drug;

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

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

1. 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;

2. Strong and moderate inhibitors of CYP2C19 including fluoxetine and ticlopidine;

3. Sensitive and moderately sensitive substrates of CYP2C19 including clobazam, lansoprazole, omeprazole, S-mephenytoin, and rabeprazole;

4. Sensitive and moderately sensitive substrates of CYP1A2 including alosetron, duloxetine, melatonin, ramelteon, tasimelteon, theophylline, tizanidine, pirfenidone, and ramosetron;

5. Sensitive and moderately sensitive substrates of CYP2B6 including bupropion and efavirenz;

6. Sensitive and moderately sensitive substrates of CYP2C8 including repaglinide, montelukast, pioglitazone, and rosiglitazone;

7. Sensitive and moderately sensitive substrates of CYP2C9 including tolbutamide, celecoxib, glimepiride, and warfarin;

8. Sensitive and moderately sensitive substrates of UGT1A9 including diflunisal, propofol, and fenofibrate;

9. Sensitive and moderately sensitive substrates of UGT2B7 including, gemfibrozil, lamotrigine, and morphine;

22. The following CNS depressants including all antipsychotics, benzodiazepines (except for alprazolam, clonazepam, and lorazepam, which have low binding affinity to TSPO), and the non-benzodiazepine sleep aids including butabarbital sodium, eszopiclone, phenobarbital, ramelteon secobarbital sodium, suvorexant, zaleplon, and zolpidem;

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

24. 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;

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

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

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

28. 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).