A Randomized Controlled Trial of Oral CBD for the Treatment of Upper Extremity Musculoskeletal Pain

This randomized controlled trial of CBD will investigate the therapeutic potential of CBD as an oral treatment for the treatment of pain of upper extremity musculoskeletal pain. Rationale: CBD is commonly being used as an over-the-counter treatment for musculoskeletal pain. Clinical trials have demonstrated a pain-relief benefit for hand and wrist osteoarthritis with topical CBD, however patients prefer oral CBD and no clinical trial has been performed to establish efficacy of oral CBD in humans for upper extremity musculoskeletal pain. Hypothesis: CBD is more effective than placebo for relieving pain and improving patient-reported outcomes for upper extremity musculoskeletal pain.

Study Design: The study design will be a double-blind, randomized controlled trial with crossover. Treatment will be blinded to the subjects and investigators. Patients will be randomly assigned 4 weeks of the CBD or control and then crossover to the other condition for 4 additional weeks. Patients will take one oral capsule twice daily, once in the morning and once in the evening. Subjects will be advised to observe for physiologic changes, skin changes, or other adverse effects.

Inclusion criteria

• Provision of signed and dated informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Male or female, aged 18 years or older.
• Daily visual analog pain score >5/10 and <9/10.
• Duration of pain for greater than or equal to 3 months.
• Presence of physician-diagnosed musculoskeletal pain in the upper extremities, including bone or joint-related pain, tendon or ligament-related pain, muscle-related pain, or fibromyalgia or physician-diagnosed postoperative pain in a discrete body region, limited to upper extremities.
• For females, must be willing to use an approved form of birth control during this study. Acceptable forms of birth control:

• Norplant
• Sterilization
• IUD (intrauterine device)
• Birth Control Patch
• Depo-Provera

The following may be used if combined with other birth control methods:

• Condoms
• Diaphragm
• Jellies or foam
• Sponge
• Cervical cap
• For males, must be willing to not father a baby for the duration of the study and for 90 days after the last dose of study drug, or donate to a sperm bank during this time. Must be willing to use an approved form of birth control during this time. Acceptable forms of birth control:

• Condoms
• Sterilization

Exclusion criteria

• Subject does not speak or read English fluently.
• Subject is blind.
• Severe cardiac, pulmonary, liver and /or renal disease, or any other major organ dysfunction.
• Subject with a history of symptoms (e.g., dizziness, light-headedness, blurred vision, palpitations, weakness, syncope) related to a drop in blood pressure due to postural changes.
• Coumadin use at time of screening.
• History of mental illness.
• Subjects who are incarcerated.
• Subjects who satisfy any DSM-V criteria for current psychiatric illness such as bipolar disorder, depression, anxiety, schizophrenia, psychosis, substance use disorder or any other psychiatric diagnosis
• Subjects who have used intra-articular corticosteroids 30 days prior to screening.
• History of drug or substance abuse.
• Pre-existing CBD product usage currently (or within the prior 3 months) using recreational or medicinal cannabis, any cannabinoid-based medications, and is unwilling to abstain for the duration of the study.
• Subject has had a corticosteroid injection ≤ 60 days prior.
• Subjects who are unwilling to agree to no opioid medications or topical analgesic medications during the study period.
• Any woman of child bearing potential or male patient's partner unwilling to ensure that they or their partner use effective contraception, for example, hormonal contraception, double barrier, intra-uterine device, during the study and for females, through 30 days thereafter, and for males, three months thereafter.
• Any male not willing to avoid donating sperm during the duration of the study treatment period and for three months thereafter.
• Any patient with aberrant liver function as defined by either of the following:

• ALT >5x ULN or total bilirubin>2×ULN
• ALT or AST>3 × ULN and total bilirubin>2xULN or INR >1.5
• Participants within 14 days of the study procedure taking prescription or non-prescription medication which are substrates of CYP3A4 :

• Itraconazole,
• Ketoconazole,
• Azamulin,
• Troleandomycin,
• Verapamil,
• John's wart,
• Phenobarbital,
• Participants within 14 days of the study procedure taking prescription or non-prescription medication which are substrates of CYP2C19:

• Nootkatone,
• Ticlopidine,
• Rifampin,
• Omeprazole),
• Subjects taking prescription or non-prescription medication which are substrates of CYP2C8:

• Montelukast,
• Quercetin,
• Phenelzine,
• Rifampin,
• Clopidogrel) ,
• Participants within 14 days of the study procedure taking prescription or non-prescription medication which are substrates ofCYP2C9:

• Sulfaphenazole,
• Tienilic acid,
• Carbamazepine,
• Apalutamide,
• Fluconazole,
• Celecoxib
• Participants within 14 days of the study procedure taking prescription or non-prescription medication which are substrates of CYP1A2:

• alpha-Naphthoflavone,
• Furafylline,
• Phenytoin,
• Rifampin,
• Ritonavir,
• smoking,
• Teriflunomide,
• Ciproflaoxacin,
• oral contraceptives,
• Allopurinol
• Participants within 14 days of the study procedure taking prescription or non-prescription medication which are substrates of CYP2B6:

• Sertraline,
• Phencyclidine,
• Thiotepa,
• Ticlopidine,
• Carbamazepine,
• Efavirenez,
• Rifampin,
• Bupropion.