Enhancing Medication-based Analgesia in Humans

Using Dronabinol to Enhance the Analgesic Effect of Hydromorphone in Humans

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).

Study Overview

• Status: Completed
• Conditions: Pain; Cannabis; Opioid Use, Unspecified
• Intervention / Treatment: Drug: Within-subject test of blinded study medications

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.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo + Placebo; 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; 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.
Active Comparator: Hydromorphone (oral) 4mg + Placebo; 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; 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.
Experimental: Hydromorphone (oral) 4mg / Dronabinol (oral) 2.5mg; 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; 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.
Experimental: Hydromorphone (oral) 4mg / Dronabinol (oral) 5mg; 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; 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.
Experimental: Hydromorphone (oral) 4mg / Dronabinol (oral) 10mg; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Kelly Dunn, PhD, Principal Investigator; Principal Investigator: Claudia Campbell, PhD, Principal Investigator

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): March 23, 2020
• Study Completion (Actual): March 23, 2020

Study Registration Dates

• First Submitted: July 28, 2016
• First Submitted That Met QC Criteria: September 9, 2016
• First Posted (Estimated): September 15, 2016

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Analgesia; Clinical Trial, Phase II; Abuse Potential
• Other Study ID Numbers: IRB00097937

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO