Evaluation of the Interactions of Cannabidiol (CBD) With Morphine

Phase 1 Drug-drug Interaction of Cannabidiol and Morphine in Recreational Opioid Users

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.

Study Overview

• Status: Recruiting
• Conditions: Opioid Use Disorder
• Intervention / Treatment: Drug: Morphine Sulfate

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Debra Kelsh, MD; Phone Number: 913-696-1601; Email: contact@altasciences.com

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Recruiting
      • Altasciences
      • Principal Investigator: Debra Kelsh, MD
      • Contact: Debra Kelsh, MD; Phone Number: 913-696-1601; Email: contact@altasciences.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CBD (350 mg); CBD 350 mg twice per day for 3 days	Drug: Morphine Sulfate; Morphine sulfate 30 mg tablets as a single dose twice; Other Names: Placebo; Placebo oral capsule
Active Comparator: CBD (700 mg); CBD 700 mg twice per day for 3 days	Drug: Morphine Sulfate; Morphine sulfate 30 mg tablets as a single dose twice; Other Names: Placebo; Placebo oral capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	3 day
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.	3 day
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.	3 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	3 day
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.	3 day
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.	3 day
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	3 day
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	3 day
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	3 day
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	3 day
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	3 day
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	3 day
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	7 + 3/5 days

Collaborators and Investigators

• Sponsor: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2021
• Primary Completion (Actual): September 1, 2023
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: November 9, 2021
• First Submitted That Met QC Criteria: November 22, 2021
• First Posted (Actual): December 3, 2021

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Morphine; CBD; Chemically-Induced Disorders; Mental Disorders; Substance-Related Disorders; Psychotropic Drugs; Cannabidiol; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Marijuana Abuse
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: NIDA-CBD-Phase1a-002

Drug and device information, study documents

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