Enhancing Medication-based Analgesia in Humans- STUDY 2

NCT04036968 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB00214289R01DA040644
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Pain; Cannabis; Opioid Use

Keywords

Clinical Trial; Analgesia; Phase II; Abuse potential

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (5)

Placebo+Placebo

PLACEBO COMPARATOR

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

Hydromorphone+Placebo

ACTIVE COMPARATOR

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

Hydromorphone (oral) 4mg + Cannabidiol 50mg

EXPERIMENTAL

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

Hydromorphone (oral) 4mg + Cannabidiol 100mg

EXPERIMENTAL

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

Hydromorphone (oral) 4mg + Cannabidiol 200mg

EXPERIMENTAL

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

Interventions

Within-subject test of blinded study medications DRUG

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.

Hydromorphone (oral) 4mg + Cannabidiol 100mg; Hydromorphone (oral) 4mg + Cannabidiol 200mg; Hydromorphone (oral) 4mg + Cannabidiol 50mg; Hydromorphone+Placebo; Placebo+Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Johns Hopkins University Bayview Medical Campus

Baltimore, Maryland, 21224, United States

Location

Related Publications (1)

• Bergeria CL, Mun CJ, Speed TJ, Huhn AS, Wolinsky D, Vandrey R, Campbell CM, Dunn KE. A within-subject, double-blind, placebo-controlled randomized evaluation of the combined effects of cannabidiol and hydromorphone in a human laboratory pain model. Pain. 2025 Feb 28;166(9):e175-e184. doi: 10.1097/j.pain.0000000000003561.

  PMID: 40839659 DERIVED

MeSH Terms

Conditions

Pain; Marijuana Abuse; Agnosia

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases

Results Point of Contact

• Title: Kelly Dunn, Professor
• Organization: Johns Hopkins University School of Medicine

kdunn9@jhmi.edu

410-550-2254

Study Officials

• Kelly E Dunn, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Claudia Campbell, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study drug administration will be concealed from all study staff and participants to prevent bias in outcomes.
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Within-subject study

Study Record Dates

• First Submitted: July 25, 2019
• First Posted: July 30, 2019
• Study Start: February 1, 2020
• Primary Completion: November 1, 2022
• Study Completion: November 1, 2022
• Last Updated: December 19, 2023
• Results First Posted: December 19, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)