Cannabidiol, Morphine, Pain (CMP)

Human Laboratory Model to Screen Drugs With Opioid Analgesic-sparing Effects: Cannabidiol/Morphine Combinations

The purpose of the proposed study is to investigate the interaction of cannabidiol (CBD) and morphine effects on pain sensitivity. Cannabidiol is a cannabinoid (similar to cannabis, or marijuana) present in marijuana that alters some of the effects of marijuana.

Study Overview

• Status: Recruiting
• Conditions: Chronic Pain; CBD
• Intervention / Treatment: Drug: Immediate-release Oral Morphine Sulfate Tablets; Other: Thermal and Pressure Nociceptive Sensitivity

Detailed Description

Eligible participants will be asked to participate in a total of three experimental sessions with each session day separated by at least one week. Each session day will last approximately 6-7 hours.

In the morning of each of the three study sessions, participants will be asked to complete baseline assessments which include self-report questionnaires (answering questions about how they feel), vital sign measurements (blood pressure, heart rate, oxygen saturation, temperature, and pupillometry) will be taken using a non-invasive (external) vitals monitor, and lastly thermal (heat and cold) and mechanical sensitivity testing will be done.

Participants will be asked to take an oral morphine capsule.

Participants will participate in 2 smoking sessions where they will be asked to smoke cigarettes or a vaporizer balloon containing either cannabidiol or a placebo (a blank).

Participants will be asked to complete the same battery assessments mentioned above, which include self-report questionnaires (answering questions about how they feel); vital sign measurements (blood pressure, heart rate, oxygen saturation, temperature, and pupillometry) will be taken using a non-invasive (external) vitals monitor; and lastly thermal (heat and cold) and mechanical stimulation will be administered to test pain sensitivity.

Participants will be asked to complete subjective questionnaires and have vital signs (blood pressure, heart rate, oxygen saturation, temperature, and pupillometry) measured multiple times throughout the visit; these measurements will be monitored for reasons such as safety.

After completing the second round of smoking and battery assessments, participants will be provided with lunch and can relax, watch television, listen to music, or read.

Once vital signs and questionnaire ratings have returned to baseline levels; participants can leave the laboratory.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Leslie Lundahl, Ph.D; Phone Number: (313)993-3960; Email: llundahl@med.wayne.edu
• Study Contact Backup: Name: Nareen Sadik, B.S; Phone Number: 313-993-3960; Email: fw6362@wayne.edu

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Tolan Park Medical Building
      • Contact: Leslie Lundahl, PhD; Phone Number: 313-993-3960; Email: llundahl@med.wayne.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participants must report having smoked a cigarette (nicotine or marijuana) AND having taken an opioid on 3 or more occasions in their lifetime.
• Participants must be in good health to participate; those with certain contraindications will be excluded.
• All participants will undergo psychiatric evaluation and will be asked to report their substance use history by interview and structured questionnaire methods.
• Participants will undergo medical evaluations using medical history, physical exam, standard lab tests (complete blood chemistry, urinalysis, urine pregnancy test for females), and 12-lead ECG.

Exclusion Criteria:

• Serious psychiatric illness (e.g. psychotic or bipolar disorder, recent suicide attempts; severe depression)
• Substance Use Disorders other than Nicotine Use Disorder and Mild Cannabis Use Disorder
• Neurological diseases; cardiovascular problems (e.g. systolic BP >140 or <95 mmHg, diastolic BP >90 mmHg, abnormal ECG); pulmonary diseases; systemic diseases (e.g. liver, renal, inflammatory)
• Cognitive impairment (<80 IQ)
• Past-month medications that increase study risk
• Women who are pregnant (urine HCG), lactating (self-report), or if heterosexually active and not using (self-report) medically approved birth control (oral or depot contraception, IUD, condom/foam, sterilization, tubal ligation)
• Individuals unable to give informed consent will be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Smoked cannabidiol 0%	Drug: Immediate-release Oral Morphine Sulfate Tablets; 0 mg Immediate release oral morphine; 15 mg Immediate release oral morphine; 30 mg Immediate release oral morphine; Randomized between sessions; Other: Thermal and Pressure Nociceptive Sensitivity; Primary outcome measures of pain threshold and tolerance.
Active Comparator: Smoked cannabidiol 9.7%	Drug: Immediate-release Oral Morphine Sulfate Tablets; 0 mg Immediate release oral morphine; 15 mg Immediate release oral morphine; 30 mg Immediate release oral morphine; Randomized between sessions; Other: Thermal and Pressure Nociceptive Sensitivity; Primary outcome measures of pain threshold and tolerance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CHANGE: PAIN THRESHOLD AND TOLERANCE Pain responses to a range of heat, cold and mechanical pressure stimuli	Change in pain threshold and tolerance is being assessed post each CBD drug use (0%and 9.7%) using Q-Sense Conditioned Pain Modulation™. A randomized series of 7 heat stimuli and 7 cold stimuli will be delivered via a thermode attached to the lower nondominant arm. A series of 7 pressure stimuli will be delivered with a pressure algometer to the opposite arm.	Pain responses measured at the start of the visit, baseline; 25 minutes post CBD 0% drug; 25 minutes post CBD 9.7% drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SAFETY: Systolic blood pressure (physiological effects)	Safety is being assessed.	Systolic blood pressure measured at baseline; 30 and 45 minutes post-morphine; 15 minutes post CBD 0% drug; 15, 65, and 90 minutes post 9.7% CBD drug (final drug).
SAFETY: Diastolic blood pressure (physiological effects)	Safety is being assessed.	Diastolic blood pressure measured at baseline; 30 and 45 minutes post-morphine; 15 minutes post CBD 0% drug; 15, 65, and 90 minutes post 9.7% CBD drug (final drug).
SAFETY: Heart rate	Safety is being assessed.	Heart Rate measured at baseline; 30 and 45 minutes post-morphine; 15 minutes post CBD 0% drug; 15, 65, and 90 minutes post 9.7% CBD drug (final drug).
SAFETY: Temperature	Safety is being assessed.	Temperature measured at baseline; 30 and 45 minutes post-morphine; 15 minutes post CBD 0% drug; 15, 65, and 90 minutes post 9.7% CBD drug (final drug).
SAFETY: Oxygen saturation	Safety is being assessed.	Oxygen Saturation measured at baseline; 30 and 45 minutes post-morphine; 15 minutes post CBD 0% drug; 15, 65, and 90 minutes post 9.7% CBD drug (final drug).
SAFETY: Pupillometry Measurement - Diameter of your eye	Safety is being assessed.	Pupillometry measured at baseline; 30 and 45 minutes post-morphine; 15 minutes post CBD 0% drug; 15, 65, and 90 minutes post 9.7% CBD drug (final drug).
SAFETY & INDICES OF ABUSE LIABILITY: Drug Effect	Indices of abuse liability is being assessed. Visual Analog Scales (0="not at all" and 100= "extremely"): "good drug effect," "bad drug effect," "strength of drug effect," liking," "sedated," "high" and "desire to take again."	Drug Liking measured at baseline; 30 and 45 minutes post-morphine; 15 minutes post CBD 0% drug; 15, 65, and 90 minutes post 9.7% CBD drug (final drug).
SAFETY & INDICES OF ABUSE LIABILITY: Drug Symptoms	Drug Symptoms are being assessed, (0="not at all", 1= "a little", 2="moderately", 3="quite a bit" 4= "extremely").	Drug Symptoms measured at baseline; 30 and 45 minutes post-morphine; 15 minutes post CBD 0% drug; 15, 65, and 90 minutes post 9.7% CBD drug (final drug).
SAFETY & INDICES OF ABUSE LIABILITY: Mood and Feeling	Mood and Feeling is being assessed. Visual Analog Scales (0="not at all" and 100= "extremely"): "Anxious", "Sedated", "Hungry", "Stimulated", "Friendly", "High", "Alert", "Happy", "Tired", "Talkative", "Self-Confident", "Down", "Social", "Upset", "Confused", "Good Drug Effect", "Bad Drug Effect", "Dizzy", "Sleep", "Energetic", "Jittery", "Content", "Unmotivated", "Restless", "Forgetful", "Mellow", "Clumsy", "Numbness or tingling in my extremities", "I'm having difficulty concentrating", "I am sweating", "My heart is pounding or beating faster than usual", "Noises or sounds seem louder than usual", "My limbs feel heavier than usual".	Measured at baseline; 30 and 45 minutes post-morphine; 15 minutes post CBD 0% drug; 15, 65, and 90 minutes post 9.7% CBD drug (final drug).
SAFETY & INDICES OF ABUSE LIABILITY: Feelings about self	One's self-evaluation of feelings is being assessed.	Measured at baseline; 30 and 45 minutes post-morphine; 15 minutes post CBD 0% drug; 15, 65, and 90 minutes post 9.7% CBD drug (final drug).
SAFETY & INDICES OF ABUSE LIABILITY: Brief Pain Inventory	One's self-evaluation of pain is being assessed.	Measured at baseline only.

Collaborators and Investigators

• Sponsor: Wayne State University
• Investigators: Principal Investigator: Leslie Lundahl, PhD, Wayne State University

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Estimated): January 26, 2025
• Study Completion (Estimated): January 26, 2025

Study Registration Dates

• First Submitted: June 17, 2019
• First Submitted That Met QC Criteria: July 17, 2019
• First Posted (Actual): July 24, 2019

Study Record Updates

• Last Update Posted (Actual): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chronic Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: CMP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No