Enhancing Medication-based Analgesia in Humans- STUDY 2

Evaluating Cannabidiol (CBD) 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 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.

Study Overview

• Status: Completed
• Conditions: Pain; Cannabis; Opioid Use
• 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 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.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins University Bayview Medical Campus

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 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

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+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 + Cannabidiol 50mg; Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + cannabidiol (oral) 50mg. 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 + Cannabidiol 100mg; Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + cannabidiol (oral) 100mg. 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 + Cannabidiol 200mg; Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + cannabidiol (oral) 200mg. 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Cold Pressor Tolerance	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).	8 hour study session
Peak Self-report Rating of "Drug Effect" (0-100), as Measured by the Visual Analog Rating Scale	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.	8 hour study session
Peak Number Accurate on Circular Lights	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.	8 hour study session

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Claudia Campbell, PhD, Johns Hopkins University; Principal Investigator: Kelly E Dunn, PhD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2020
• Primary Completion (Actual): November 1, 2022
• Study Completion (Actual): November 1, 2022

Study Registration Dates

• First Submitted: July 25, 2019
• First Submitted That Met QC Criteria: July 25, 2019
• First Posted (Actual): July 30, 2019

Study Record Updates

• Last Update Posted (Estimated): December 19, 2023
• Last Update Submitted That Met QC Criteria: December 15, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Analgesia; Clinical Trial; Phase II; Abuse potential
• Other Study ID Numbers: IRB00214289; R01DA040644 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No