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Evaluation of the Interactions of Cannabidiol (CBD) With Morphine

Primary Purpose

Opioid Use Disorder

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Morphine Sulfate
Sponsored by
National Institute on Drug Abuse (NIDA)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Opioid Use Disorder focused on measuring Marijuana Abuse, Substance-Related Disorders, Chemically-Induced Disorders, Mental Disorders, Central Nervous System Depressants, Psychotropic Drugs, Neurotransmitter Agents, Cannabidiol, CBD, Morphine, Molecular Mechanisms of Pharmacological Action

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Must understand and provide written informed consent prior to the initiation of any protocol-specific procedures.
  • Males and females 18 to 55 years of age, inclusive.
  • Body mass index (BMI) ranging from 18 to 34 kg/m2, inclusive, and body weight of 56 kg and above.
  • Adequate venous access as assessed by an investigator at screening.
  • No clinically significant concurrent medical conditions determined by medical history, physical examination, clinical laboratory examination, vital signs, and 12-lead ECG.
  • Recreational opioid use (i.e., defined as prescription opioid use for nontherapeutic purposes on at least 3 occasions within the previous year and at least once in the 12 weeks prior to screening), experienced in using opioids of approximately 30 mg morphine equivalents and not seeking treatment for Opioid Use Disorder.
  • If of childbearing potential, a female study subject must agree to use 1 of the accepted contraceptive regimens from at least 30 days prior to the first administration of the study medication, during the study and for at least 30 days after the last dose of the study medication

    1. An acceptable method of contraception includes abstinence from heterosexual intercourse or intrauterine device (with or without hormones)
    2. OR agrees to use a double barrier method (e.g., condom and spermicide) during the study and for at least 30 days after the last dose of the study medication. Oral contraceptives are prohibited.
    3. If a female of non-childbearing potential, she should be surgically sterile (i.e., has undergone compete hysterectomy, bilateral oophorectomy, or tubal ligation) or in a menopausal state (at least 1 year without menses), as confirmed by FSH level.
  • A male study subject must agree to use a double barrier method (e.g., condom and spermicide) and agree to not donate sperm during the study and for at least 90 days after the last dose of the study medication.
  • Agree not to ingest alcohol, drinks containing caffeine >500 mg/day (e.g., Coca Cola®, tea, coffee, etc.), or grapefruit/grapefruit juice or participate in strenuous exercise 72 hours prior to admission through the last blood draw of the study.
  • Able to speak, read, and understand English sufficiently to allow completion of all study assessments.
  • Must be willing and able to abide by all study requirements and restrictions.

Exclusion Criteria:

  • Contact site directly for more information

Sites / Locations

  • AltaSciencesRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

CBD (350 mg)

CBD (700 mg)

Arm Description

CBD 350 mg twice per day for 3 days

CBD 700 mg twice per day for 3 days

Outcomes

Primary Outcome Measures

Establish the Maximum Plasma Concentration (Cmax) of morphine when administered orally with and without CBD
Establish the Maximum Plasma Concentration (Cmax) of morphine when administered orally with and without CBD 350 mg b.i.d. and CBD 700 mg b.i.d.
Establish the Area Under the Curve (AUC 0-t) of morphine and its 2 glucuronide conjugates when morphine is administered with and without CBD
Establish the Area Under the Curve (AUC 0-t) of morphine and its 2 glucuronide conjugates when morphine is administered with and without CBD 350 mg b.i.d. and CBD 700 mg b.i.d.
Establish the Area Under the Curve from zero to infinity (AUC 0-inf) of morphine and its 2 glucuronide conjugates when morphine is administered with and without CBD
Establish the Area Under the Curve from zero to infinity (AUC 0-inf) of morphine and its 2 glucuronide conjugates when morphine is administered with and without CBD 350 mg b.i.d. and CBD 700 mg b.i.d.

Secondary Outcome Measures

Establish the Time of Maximum Plasma Concentration (Tmax) of morphine when administered orally with and without CBD
Establish the Time of Maximum Plasma Concentration (Tmax) of morphine when administered orally with and without CBD 350 mg b.i.d. and CBD 700 mg b.i.d.
Establish the Terminal Phase Elimination Rate Constant of morphine when administered orally with and without CBD
Establish the Terminal Phase Elimination Rate Constant of morphine when administered orally with and without CBD 350 mg b.i.d. and CBD 700 mg b.i.d.
Establish the Apparent Clearance of morphine when administered orally with and without CBD
Establish the Apparent Clearance of morphine when administered orally with and without CBD 350 mg b.i.d. and CBD 700 mg b.i.d.
Establish the Maximum Plasma Concentration (Cmax) of CBD when administered orally with morphine
Establish the Maximum Plasma Concentration (Cmax) of CBD 350 mg b.i.d. and CBD 700 mg b.i.d. when administered orally with morphine
Establish the Time of Maximum Plasma Concentration (Tmax) of CBD when administered orally with morphine
Establish the Time of Maximum Plasma Concentration (Tmax) of CBD 350 mg b.i.d. and CBD 700 mg b.i.d. when administered orally with morphine
Establish the Area Under the Curve of the dosing period of CBD when administered orally with morphine
Establish the Area Under the Curve of the dosing period of CBD 350 mg b.i.d. and CBD 700 mg b.i.d. when administered orally with morphine
Establish the Apparent Clearance of CBD when administered orally with morphine
Establish the Apparent Clearance of CBD 350 mg b.i.d. and CBD 700 mg b.i.d. when administered orally with morphine
Establish the terminal half-life of CBD when administered orally with morphine
Establish the terminal half-life of CBD 350 mg b.i.d. and CBD 700 mg b.i.d. when administered orally with morphine
Establish the terminal-phase elimination rate constant of CBD when administered orally with morphine
Establish the terminal-phase elimination rate constant of CBD 350 mg b.i.d. and CBD 700 mg b.i.d. when administered orally with morphine
Safety and Tolerability of morphine when administered orally with or without CBD by collecting vital signs and recording treatment emergent adverse events
Incidence of treatment Emergent Adverse Events using the most recent version of the Medical Dictionary of Regulatory Activities (MedDRA) preferred terms, its relationship to the treatment, and maximum severity, either reported by the subject or by clinically significant abnormal findings on: i. Physical examination ii. Rate of change in vital signs assessments of heart rate, sitting blood pressure, respiration rate, and temperature iii. Rate of change in ECG assessment iv. Rate of change in venous CO2 concentrations v. Rate of clinical laboratory changes

Full Information

First Posted
November 9, 2021
Last Updated
March 21, 2023
Sponsor
National Institute on Drug Abuse (NIDA)
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1. Study Identification

Unique Protocol Identification Number
NCT05143424
Brief Title
Evaluation of the Interactions of Cannabidiol (CBD) With Morphine
Official Title
Phase 1 Drug-drug Interaction of Cannabidiol and Morphine in Recreational Opioid Users
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 4, 2021 (Actual)
Primary Completion Date
September 1, 2023 (Anticipated)
Study Completion Date
December 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute on Drug Abuse (NIDA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
The purpose of this study is to analyze drug-drug interactions of CBD on co-administered Morphine as first step in understanding CBD-opioid interactions.
Detailed Description
This is an inpatient, single-blind, non-randomized, 1-sequence study involving healthy subjects who have used opioids for recreational use. The primary objective of the study is to establish the pharmacokinetic parameters of morphine 30 mg when administered with and without CBD 350 mg b.i.d. and CBD 700 mg b.i.d.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Opioid Use Disorder
Keywords
Marijuana Abuse, Substance-Related Disorders, Chemically-Induced Disorders, Mental Disorders, Central Nervous System Depressants, Psychotropic Drugs, Neurotransmitter Agents, Cannabidiol, CBD, Morphine, Molecular Mechanisms of Pharmacological Action

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
Participant
Allocation
Non-Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CBD (350 mg)
Arm Type
Active Comparator
Arm Description
CBD 350 mg twice per day for 3 days
Arm Title
CBD (700 mg)
Arm Type
Active Comparator
Arm Description
CBD 700 mg twice per day for 3 days
Intervention Type
Drug
Intervention Name(s)
Morphine Sulfate
Other Intervention Name(s)
Placebo oral capsule, Placebo
Intervention Description
Morphine sulfate 30 mg tablets as a single dose twice
Primary Outcome Measure Information:
Title
Establish the Maximum Plasma Concentration (Cmax) of morphine when administered orally with and without CBD
Description
Establish the Maximum Plasma Concentration (Cmax) of morphine when administered orally with and without CBD 350 mg b.i.d. and CBD 700 mg b.i.d.
Time Frame
3 day
Title
Establish the Area Under the Curve (AUC 0-t) of morphine and its 2 glucuronide conjugates when morphine is administered with and without CBD
Description
Establish the Area Under the Curve (AUC 0-t) of morphine and its 2 glucuronide conjugates when morphine is administered with and without CBD 350 mg b.i.d. and CBD 700 mg b.i.d.
Time Frame
3 day
Title
Establish the Area Under the Curve from zero to infinity (AUC 0-inf) of morphine and its 2 glucuronide conjugates when morphine is administered with and without CBD
Description
Establish the Area Under the Curve from zero to infinity (AUC 0-inf) of morphine and its 2 glucuronide conjugates when morphine is administered with and without CBD 350 mg b.i.d. and CBD 700 mg b.i.d.
Time Frame
3 day
Secondary Outcome Measure Information:
Title
Establish the Time of Maximum Plasma Concentration (Tmax) of morphine when administered orally with and without CBD
Description
Establish the Time of Maximum Plasma Concentration (Tmax) of morphine when administered orally with and without CBD 350 mg b.i.d. and CBD 700 mg b.i.d.
Time Frame
3 day
Title
Establish the Terminal Phase Elimination Rate Constant of morphine when administered orally with and without CBD
Description
Establish the Terminal Phase Elimination Rate Constant of morphine when administered orally with and without CBD 350 mg b.i.d. and CBD 700 mg b.i.d.
Time Frame
3 day
Title
Establish the Apparent Clearance of morphine when administered orally with and without CBD
Description
Establish the Apparent Clearance of morphine when administered orally with and without CBD 350 mg b.i.d. and CBD 700 mg b.i.d.
Time Frame
3 day
Title
Establish the Maximum Plasma Concentration (Cmax) of CBD when administered orally with morphine
Description
Establish the Maximum Plasma Concentration (Cmax) of CBD 350 mg b.i.d. and CBD 700 mg b.i.d. when administered orally with morphine
Time Frame
3 day
Title
Establish the Time of Maximum Plasma Concentration (Tmax) of CBD when administered orally with morphine
Description
Establish the Time of Maximum Plasma Concentration (Tmax) of CBD 350 mg b.i.d. and CBD 700 mg b.i.d. when administered orally with morphine
Time Frame
3 day
Title
Establish the Area Under the Curve of the dosing period of CBD when administered orally with morphine
Description
Establish the Area Under the Curve of the dosing period of CBD 350 mg b.i.d. and CBD 700 mg b.i.d. when administered orally with morphine
Time Frame
3 day
Title
Establish the Apparent Clearance of CBD when administered orally with morphine
Description
Establish the Apparent Clearance of CBD 350 mg b.i.d. and CBD 700 mg b.i.d. when administered orally with morphine
Time Frame
3 day
Title
Establish the terminal half-life of CBD when administered orally with morphine
Description
Establish the terminal half-life of CBD 350 mg b.i.d. and CBD 700 mg b.i.d. when administered orally with morphine
Time Frame
3 day
Title
Establish the terminal-phase elimination rate constant of CBD when administered orally with morphine
Description
Establish the terminal-phase elimination rate constant of CBD 350 mg b.i.d. and CBD 700 mg b.i.d. when administered orally with morphine
Time Frame
3 day
Title
Safety and Tolerability of morphine when administered orally with or without CBD by collecting vital signs and recording treatment emergent adverse events
Description
Incidence of treatment Emergent Adverse Events using the most recent version of the Medical Dictionary of Regulatory Activities (MedDRA) preferred terms, its relationship to the treatment, and maximum severity, either reported by the subject or by clinically significant abnormal findings on: i. Physical examination ii. Rate of change in vital signs assessments of heart rate, sitting blood pressure, respiration rate, and temperature iii. Rate of change in ECG assessment iv. Rate of change in venous CO2 concentrations v. Rate of clinical laboratory changes
Time Frame
7 + 3/5 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Must understand and provide written informed consent prior to the initiation of any protocol-specific procedures. Males and females 18 to 55 years of age, inclusive. Body mass index (BMI) ranging from 18 to 34 kg/m2, inclusive, and body weight of 56 kg and above. Adequate venous access as assessed by an investigator at screening. No clinically significant concurrent medical conditions determined by medical history, physical examination, clinical laboratory examination, vital signs, and 12-lead ECG. Recreational opioid use (i.e., defined as prescription opioid use for nontherapeutic purposes on at least 3 occasions within the previous year and at least once in the 12 weeks prior to screening), experienced in using opioids of approximately 30 mg morphine equivalents and not seeking treatment for Opioid Use Disorder. If of childbearing potential, a female study subject must agree to use 1 of the accepted contraceptive regimens from at least 30 days prior to the first administration of the study medication, during the study and for at least 30 days after the last dose of the study medication An acceptable method of contraception includes abstinence from heterosexual intercourse or intrauterine device (with or without hormones) OR agrees to use a double barrier method (e.g., condom and spermicide) during the study and for at least 30 days after the last dose of the study medication. Oral contraceptives are prohibited. If a female of non-childbearing potential, she should be surgically sterile (i.e., has undergone compete hysterectomy, bilateral oophorectomy, or tubal ligation) or in a menopausal state (at least 1 year without menses), as confirmed by FSH level. A male study subject must agree to use a double barrier method (e.g., condom and spermicide) and agree to not donate sperm during the study and for at least 90 days after the last dose of the study medication. Agree not to ingest alcohol, drinks containing caffeine >500 mg/day (e.g., Coca Cola®, tea, coffee, etc.), or grapefruit/grapefruit juice or participate in strenuous exercise 72 hours prior to admission through the last blood draw of the study. Able to speak, read, and understand English sufficiently to allow completion of all study assessments. Must be willing and able to abide by all study requirements and restrictions. Exclusion Criteria: Contact site directly for more information
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Debra Kelsh, MD
Phone
913-696-1601
Email
contact@altasciences.com
Facility Information:
Facility Name
AltaSciences
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66212
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Debra Kelsh, MD
Phone
913-696-1601
Email
contact@altasciences.com
First Name & Middle Initial & Last Name & Degree
Debra Kelsh, MD

12. IPD Sharing Statement

Learn more about this trial

Evaluation of the Interactions of Cannabidiol (CBD) With Morphine

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