Enhancing Medication-based Analgesia in Humans- STUDY 2

NCT ID: NCT04036968

Last Updated: 2023-12-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-01
• Study Completion Date: 2022-11-01

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.

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.

Conditions

Pain; Cannabis; Opioid Use

Keywords

Clinical Trial; Analgesia; Phase II; Abuse potential

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Placebo+Placebo

Within-subject double-blind, double-dummy administration of placebo + placebo. Order of dose randomized session days 2-5.

Group Type: PLACEBO_COMPARATOR

Within-subject test of blinded study medications

Intervention Type: 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+Placebo

Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + placebo. Always administered during session 1.

Group Type: ACTIVE_COMPARATOR

Within-subject test of blinded study medications

Intervention Type: 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 50mg

Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + cannabidiol (oral) 50mg. Order of dose randomized session days 2-5.

Group Type: EXPERIMENTAL

Within-subject test of blinded study medications

Intervention Type: 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

Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + cannabidiol (oral) 100mg. Order of dose randomized session days 2-5.

Group Type: EXPERIMENTAL

Within-subject test of blinded study medications

Intervention Type: 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 200mg

Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + cannabidiol (oral) 200mg. Order of dose randomized session days 2-5.

Group Type: EXPERIMENTAL

Within-subject test of blinded study medications

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kelly E Dunn, PhD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Claudia Campbell, PhD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins University Bayview Medical Campus

Baltimore, Maryland, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 40839659 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R01DA040644

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00214289

Identifier Type: -

Identifier Source: org_study_id