Enhancing Medication-based Analgesia in Humans

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 dronabinol (Marinol) would enhance analgesia, subjective reports, and cognitive performance when compared to the FDA-approved opioid hydromorphone (Dilaudid).

Detailed Description: This was a human laboratory systematic examination of whether adding the FDA-approved cannabinoid dronabinol (Marinol; 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 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
Taking medications contraindicated with hydromorphone or dronabinol
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 (oral) 4mg + 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 / Dronabinol (oral) 2.5mg	Within-subject test of blinded study medications	Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + dronabinol (oral) 2.5mg. Order of dose randomized session days 2-5.
Hydromorphone (oral) 4mg / Dronabinol (oral) 5mg	Within-subject test of blinded study medications	Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + dronabinol (oral) 5.0mg. Order of dose randomized session days 2-5.
Hydromorphone (oral) 4mg / Dronabinol (oral) 10mg	Within-subject test of blinded study medications	Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + dronabinol (oral) 10mg. Order of dose randomized session days 2-5 but was never the first hydromorphone 4mg + dronabinol combination dose.

Primary Outcome Measures

Name	Time	Method
Mean Change From Baseline in Seconds to Withdraw Hand From Cold Pressor Laboratory Pain Task	Baseline and time of hand withdrawal from cold pressor, up to 60 seconds	Compare study conditions in seconds to withdraw hand from cold pressor laboratory pain task, where longer time periods reflect higher tolerance to pain.
Mean Change From Baseline in Maximum Percent Correct on Digit Symbol Substitution Test of Cognitive Behavior	Baseline and 8-hours	Within-subject comparison of study conditions on the Digit Symbol Substitution Test (DSST), a measure of cognitive performance that is sensitive to drug effects, wherein lower percent scores reflect worse performance and suggest greater drug-related impairment.
Mean Peak Rating of "Drug Effect" (0-100) as Measured by the Visual Analog Rating Scale	8-hour study session	Mean peak of Visual Analog Scale ratings of Drug Effect (0-100) compared across each study condition, with higher ratings reflecting stronger drug effects.