Enhancing Medication-based Analgesia in Humans

Study Overview
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Brief Summary
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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
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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.

Official Title
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Using Dronabinol to Enhance the Analgesic Effect of Hydromorphone in Humans

Conditions
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Pain, Cannabis, Opioid Use, Unspecified

Intervention / Treatment
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* Drug: Within-subject test of blinded study medications


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: Each participant completed each of the 5 study conditions (identified here as arms).
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo + Placebo<br>Within-subject double-blind, double-dummy administration of placebo + placebo. Order of dose randomized session days 2-5. | Drug: Within-subject test of blinded study medications<br>* Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.<br>|
| Active Comparator: Hydromorphone (oral) 4mg + Placebo<br>Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + placebo. Always administered during session 1. | Drug: Within-subject test of blinded study medications<br>* Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.<br>|
| Experimental: Hydromorphone (oral) 4mg / Dronabinol (oral) 2.5mg<br>Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + dronabinol (oral) 2.5mg. Order of dose randomized session days 2-5. | Drug: Within-subject test of blinded study medications<br>* Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.<br>|
| Experimental: Hydromorphone (oral) 4mg / Dronabinol (oral) 5mg<br>Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + dronabinol (oral) 5.0mg. Order of dose randomized session days 2-5. | Drug: Within-subject test of blinded study medications<br>* Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.<br>|
| Experimental: Hydromorphone (oral) 4mg / Dronabinol (oral) 10mg<br>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. | Drug: Within-subject test of blinded study medications<br>* Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Seconds to Withdraw Hand From Cold Pressor Laboratory Pain Task | Compare study conditions in seconds to withdraw hand from cold pressor laboratory pain task, where longer time periods reflect higher tolerance to pain. | Baseline and time of hand withdrawal from cold pressor, up to 60 seconds | 
| Mean Peak Rating of Drug Effect (0-100) as Measured by the Visual Analog Rating Scale | Mean peak of Visual Analog Scale ratings of Drug Effect (0-100) compared across each study condition, with higher ratings reflecting stronger drug effects. | 8-hour study session | 
| Mean Change From Baseline in Maximum Percent Correct on Digit Symbol Substitution Test of Cognitive Behavior | 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. | Baseline and 8-hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clinical Trial, Phase II, Analgesia, Abuse Potential