Cannabidiol for Reduction of Brain Neuroinflammation (CBD)

This is an interventional basic science trial for Back Pain focused on measuring back pain, depression, depressive symptoms, cannabis, cannabidiol Read More

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, as identified by rs6971 polymorphism

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 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. 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. Any marijuana use, medical or recreational, in the past 2 weeks;
15. An abnormal physical exam (e.g., peripheral edema);
16. Use of immunosuppressive medications, such as prednisone, TNF medications within 2 weeks of the visit;
17. Current bacterial or viral infection likely affecting the central nervous system;
18. Epilepsy or any prescription of an anti-epileptic drug;
19. Use of the medications valproate and clobazam, which may increase risk of hepatic AEs;

20. 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;
21. The following CNS depressants including all antipsychotics, benzodiazepines (except for alprazolam, clonazepam, and lorazepam, which have low binding affinity to TSPO), and non-benzodiazepine sleep aids that have a known reaction with CBD;
22. Use of opioids ≥ 30 mg morphine equivalents on average per month;
23. 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;
24. Allergy to sesame oil, and any other ingredients of EPIDIOLEX;
25. Any other contraindications to CBD administration noted by the study physician;
26. Any significant change in drug use and pain treatment from screening visit;
27. 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).