Enhancing Medication-based Analgesia in Humans- STUDY 2

Phase 2

Completed

Brief Summary: This is a single-group, within-subject, double-blind, double-dummy, placebo and active-controlled study evaluated whether the FDA-approved cannabinoid cannabidiol (CBD; Epidiolex) would enhance analgesia, subjective reports, and cognitive performance when compared to the FDA-approved opioid hydromorphone (Dilaudid). This is study 2 is a series of studies.

Detailed Description: This was a human laboratory systematic examination of whether adding the FDA-approved cannabinoid cannabidiol (CBD; Epidiolex; oral) to the FDA-approved opioid hydromorphone (Dilaudid; oral) would change the experience of hydromorphone as rated by laboratory measures of pain, subjective reports of drug effects, and cognitive performance. Subjects are healthy individuals with no history of drug use disorder. Study subjects and staff were completed blinded to the study drugs and the class of drugs under investigation and were informed that subjects may receive opioids, stimulants, cannabinoids, benzodiazepines, over the counter medications, and/or placebo. All participants completed all sessions. Sessions lasted up to 8-hours and were conducted at least 7 days apart on an outpatient basis. Primary outcomes were collected from participants prior to dosing and at several hour periods post-dosing.

Recruitment & Eligibility

Inclusion Criteria

Aged 18-75
Urine sample tests negative for common illicit substances of abuse, including cannabis
Medically cleared to take study medications
Are not pregnant or breast feeding
Willing to comply with the study protocol.

Exclusion Criteria

Meet DSM-5 criteria for alcohol/substance use disorder
Taking opioids for pain
Previous adverse reaction to a cannabinoid product
Prescribed and taking stimulants or benzodiazepines
Answer "yes" to item 1 of the Brief Pain Inventory indicating chronic pain
Self-report any illicit drug or cannabinoid use in the past 7 days
Presence of any clinically significant medical/psychiatric illness judged by the investigators to put subject at elevated risk for experiencing an adverse event
History of seizure disorder
Have a known allergy to the study medications or sesame seed oil
ALT or AST levels >3x ULN and/or Bilirubin levels >2x ULN during Screening
Current (past 60-day) suicidal thoughts or past year history of suicidal behavior
Taking medications contraindicated with hydromorphone or cannabidiol
Have a history of clinically significant cardiac arrhythmias or vasopastic disease
Have an abnormal and clinically-significant ECG

Arm && Interventions

Group	Intervention	Description
Placebo+Placebo	Within-subject test of blinded study medications	Within-subject double-blind, double-dummy administration of placebo + placebo. Order of dose randomized session days 2-5.
Hydromorphone+Placebo	Within-subject test of blinded study medications	Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + placebo. Always administered during session 1.
Hydromorphone (oral) 4mg + Cannabidiol 100mg	Within-subject test of blinded study medications	Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + cannabidiol (oral) 100mg. Order of dose randomized session days 2-5.
Hydromorphone (oral) 4mg + Cannabidiol 200mg	Within-subject test of blinded study medications	Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + cannabidiol (oral) 200mg. Order of dose randomized session days 2-5.
Hydromorphone (oral) 4mg + Cannabidiol 50mg	Within-subject test of blinded study medications	Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + cannabidiol (oral) 50mg. Order of dose randomized session days 2-5.

Primary Outcome Measures

Name	Time	Method
Peak Self-report Rating of "Drug Effect" (0-100), as Measured by the Visual Analog Rating Scale	8 hour study session	Peak self-report rating of "Drug Effect" on a 0 ("none at all") to 100 ("extremely") visual analog scale as a function of double- blinded study medication, wherein higher values indicate stronger subjectively-experienced drug effects.
Peak Number Accurate on Circular Lights	8 hour study session	Peak number accuracy on the Circular Lights fine motor task as a function of double-blinded study drug administration. Participants were provided 60 seconds to press buttons that are lit in randomized order and displayed automatically on a circular lights wall mounted unit. The primary outcome is the number of lit buttons that were accurately pressed within 60 seconds, which is a metric to assess fine motor impairment. Lower numbers are indicative of greater drug-related impairment. There is no upper limit on the circular lights task.
Peak Cold Pressor Tolerance	8 hour study session	Peak amount of time participant submerged hand in cold pressor (5 degree circulating cold water) laboratory test of pain as a function of double- blinded study medications (range 0 -300).