Cannabidiol in Opioid Use Disorder and Chronic Pain

Inclusion Criteria:

• Males and females, Veterans and non-Veterans, aged between 18 and 70 years old.

• Diagnosed with OUD and currently enrolled in methadone or buprenorphine maintenancetreatment.

• Having chronic pain, uniformly operationalized as grade II (high-intensity)non-cancer pain for ≥ 6 months.

• Capable of providing informed consent in English.

• Compliant in opioid maintenance treatment and on a stable dose for four weeks orlonger.

• Not meeting DSM-5 criteria for substance use disorders other than OUD or tobacco usedisorder within the last 12 months.

• No current medical problems deemed contraindicated for participation by principalinvestigator.

• For women, not pregnant as determined by pregnancy screening; not breast-feeding;using acceptable birth control methods. Acceptable contraception for femalesincludes oral contraceptives, contraceptive depot injections, contraceptivesubdermal implants, intrauterine devices, or surgical contraception methods.Acceptable contraception for males includes condoms or surgical contraceptionmethods.

Exclusion Criteria:

• Other current major psychiatric disorders deemed clinically unstable by theprincipal investigator, such as severe depression and/or active suicidal ideation.

• Having experienced major psychosocial stressors recently (≤ 6 weeks beforeenrollment), at the discretion of the principal investigator.

• Methadone dose under 30 mg or over 150 mg/day.

• Buprenorphine dose over 24 mg per day.

• Having received inpatient psychiatric treatment recently (≤ 60 days beforeenrollment).

• Candidates receiving products containing either THC or CBD will be excluded. Allparticipants will be asked to abstain from cannabinoids. Prior to receiving thestudy medication on the first test session, participants' cannabinoid use will beassessed using a quantitative point-of-care urine 11-nor-9-carboxy-THC concentrationtest with a cut-off of ≤ 50 mg/mL. If a participant tests greater than ≤50 mg/mL,they will be asked to abstain for an additional 7 to 14 days. If 14 days after theirinitial THC concentration test the participant continues to test positive, they willnot be allowed to participate in the study.

• A physician will carefully evaluate participants for use of over-the-counter orprescription psychoactive drugs known to affect pain threshold or pain tolerance (including NSAIDS, serotonin-norepinephrine reuptake inhibitors (SNRIs) (e.g.venlafaxine, duloxetine), gabapentinoids, tricyclic antidepressants (e.g.,nortriptyline, amitriptyline), anticonvulsant medications (e.g., topiramate,carbamazepine)). Only participants who are on stable doses (i.e., consistent dailyadministration of the medication for at least three months at the same dosefollowing the last dose change, either increase or decrease) of these medications,and whose dosing schedules allow participation in the study visits, thus excludinginstances of single-dose or temporary dosing of the medication, will be eligible asdetermined by principal investigator. If possible, the morning dose will beadministered after the study visit.

• Current, regular use of benzodiazepines, other prescription opioids, or plateletinhibitors (e.g., clopidogrel, apixaban, ticagrelor).

• Current weight of less of 60 kg.

• Allergy to sesame seed oil, which is an ingredient of the CBD formulation used.

• Serious medical or neurological illness or treatment for a medical disorder thatcould interfere with study participation as determined by principal investigator.

• Participants who have elevation of liver enzymes (ALT and/or AST) 2x above thenormal limit or higher.

• Contraindications for exposure to cold temperatures, such as Raynaud's phenomenonand hypertension.