A Double-Blind, Randomised Placebo-Controlled Feasibility Trial Assessing Oral Cannabis for The Relief of Fibromyalgia Symptoms

Exclusion Criteria22

• Clinically significant unstable neurologic, psychiatric, ophthalmologic, hepatobiliary, respiratory, hematologic illness or cardiovascular disease (e.g., severe hypotension, uncontrolled cardiac arrhythmia, or myocardial infarction) or any other concurrent disease within 12 months before screening that in the opinion of the investigator would interfere with study participation or assessment of safety and tolerability.
• Anticipation of initiation or significant change to normal daily exercise routines or need for ongoing use of concomitant medications or non-pharmacological pain management techniques that may confound assessments of efficacy and/or safety.
• Unable to undergo pre-study washout (30 days or less as assessed by urinary THC test) of prohibited concomitant medications/substances (including cannabis/medicinal cannabis products).
• Subjects who are at risk of suicide as defined by their responses to the Columbia-Suicide Severity Rating Scale (C-SSRS) or the investigator's opinion. Note: Patients answering “yes” to any of the questions about active suicidal ideation/intent/behaviours occurring within the past 12 months will be excluded (C-SSRS Suicide Ideation section – Questions 3, 4, or 5; C-SSRS Suicidal Behaviour section, any of the suicide behaviours questions). Such patients will be directed to a mental health support service.
• Current moderate severe to severe depression or anxiety disorders as assessed by the Depression Patient Health Questionnaire-9 (PHQ-9, total score of >10) and Generalized Anxiety Disorder-7 questionnaire (GAD-7, total score of >10). Still, mild to moderate depression (PHD-9 total score of 0-10) or anxiety disorders (GAD-7 total score of 0-10) are permitted provided that the investigator assesses the patient as clinically stable and appropriate for entry into the study.
• Any diagnosis of lifetime psychotic or bipolar disorder.
• Subjects with pain due to other conditions (e.g., diabetic peripheral neuropathic pain or post-herpetic neuralgia) that, in the investigator's opinion, would confound assessment or self-evaluation of the pain associated with FMS.
• Subjects with pain due to any widespread inflammatory musculoskeletal disorder (e.g., rheumatoid arthritis, lupus) or widespread rheumatic disease other than FMS.
• Current or history of abuse or dependence on prescription medications, illicit drugs, or heavy alcohol drinking within the past year.
• Any history of a malignant neoplasm other than benign skin cancers within the past five years.
• Pregnant or breastfeeding, or intent to become pregnant during the study period or refusing to do pregnancy tests through the study.
• Subject is currently enrolled in or has not yet completed at least 30 days since ending another investigational device or drug study or is receiving other investigational agents.
• Known hypersensitivity medical cannabis products. Note: Prior exposure is allowed, as long as hypersensitivity to cannabis was not observed.
• Known tree nut allergy, particularly walnut allergy.
• Subjects who are unlikely to comply with the protocol (e.g., uncooperative attitude, inability to return for subsequent visits) and/or otherwise considered by the investigator to be unlikely to complete the study.
• Abnormal investigative tests and laboratory values judged by the investigator to be clinically significant at screening, with particular focus on:
• a. Abnormal renal function defined as calculated creatinine clearance (CrCl) < 60 mL/min determined by the central laboratory using the modified Cockcroft-Gault equation; blood urea nitrogen> 1.5 × upper limit of normal (ULN); creatine kinase > 3.0 × ULN; serum creatinine > 1.6 mg/dL (> 141.4 µmol/L).
• b. Abnormal liver function defined as aspartate aminotransferase (AST) > 2.0 × ULN, alanine aminotransferase (ALT) > 2.0 × ULN; alkaline phosphatase > 1.5 × ULN; total bilirubin> 1.2 × ULN. If a subject has total bilirubin > 1.2 ULN, unconjugated and conjugated bilirubin fractions should be analysed, and only subjects documented to have Gilbert’s syndrome may be enrolled.
• Current antipsychotic use (except for low-dose antipsychotics prescribed by a physician to treat sleep disorders).
• Current chemotherapy, radiation, immune suppressant therapy, or immunotherapy.
• Current warfarin administration.
• Vaccination of any kind in the 14 days prior to commencing IMP administration, planned vaccination during the trial period.