Table 1.

Inclusion and exclusion criteria

Inclusion criteria

Age ≥18 and ≤75 The ability to give written, informed consent Fluency in English Diagnosis of chronic low back pain, ongoing for at least 6 months prior to enrollment Average worst daily pain of at least 4, on a 0–10 scale of pain intensity, present for at least 50% of days during a typical week On a stable pain treatment (pharmacologic or behavioural) for the previous 4 weeks High or mixed affinity binding identified by rs6971 polymorphism

Exclusion criteria

Outpatient surgery within 2 weeks and inpatient surgery within 1 month from the time of scanning (this timeframe may be extended if not fully recovered from surgery) 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 Any interventional pain procedures within 6 weeks prior to scanning procedure or at any point during study enrollment Surgical intervention or introduction/change in opioid regimen at any point during study enrollment 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) Implanted spinal cord stimulator (SCS) for pain treatment Any history of neurological illness or major medical illness, unless clearly resolved without long-term consequences 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 hospitalisation in the past year) Harmful alcohol drinking as indicated by an AUDIT score ≥16 Pregnancy or breast feeding History of head trauma requiring hospitalisation Major cardiac event within the past 10 years Regular use of recreational drugs in the past 3 months Any cannabis use, medical or recreational, in the past 2 weeks, including ingestible CBD products A clinically significant abnormality on a physical exam (eg, peripheral edema) Use of immunosuppressive medications, such as prednisone or TNF medications within 2 weeks of the visit Current bacterial or viral infection likely affecting the central nervous system Epilepsy or any prescription of an anti-epileptic drug Use of the medications valproate and clobazam, which may increase risk of hepatic AEs Safety concerns related to use of any of the following medications will be discussed on an individualised basis with a physician: Strong and moderate inhibitors of CYP3A4 and CYP2C19 (eg, diltiazem, erythromycin, fluoxetine) Sensitive and moderately sensitive substrates of CYP2C19, CYP1A2, CYP2B6, CYP2C8, CYP2C9, UGT1A9 and UGT2B7 (eg, omeprazole, bupropion, morphine, lamotrigine) CNS depressants including antipsychotics, benzodiazepines (except for alprazolam, clonazepam, and lorazepam, which have low binding affinity to TSPO100–104, and non-benzodiazepine sleep aids that have a known reaction with CBD Use of opioids ≥ 30 mg morphine equivalents on average per month Active suicidal ideation, suicide attempt or an aborted attempt within the last 5 years, or engagement in non-suicidal self-injurious behaviour within the last year Allergy to sesame oil, and any other ingredients of Epidiolex Any other contraindications to CBD administration noted by the study physician Any significant change in drug use and pain treatment between screening visits In the opinion of the investigators, unable to safely participate in this study and/or provide reliable data (eg, unable to reliably rate pain, unlikely to remain still during the imaging procedures)

AEs, adverse events; AUDIT, Alcohol Use Disorders Identification Test; CBD, cannabidiol; CNS, Central Nervous System; PET, positron emission tomography; PTSD, Post-Traumatic Stress Disorder; TNF, Tumor Necrosis Factor; TSPO, translocator protein.