Cannabidiol for Reduction of Brain Neuroinflammation

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.

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).