Cannabidiol, Morphine, Pain (CMP)

• ClinicalTrials.gov Identifier: NCT04030442
• Recruitment Status: Recruiting
• First Posted: July 24, 2019
• Sponsor: Wayne State University
• Information provided by (Responsible Party): Leslie Lundahl, Wayne State University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
CBD; Chronic Pain	Drug: Immediate-release Oral Morphine Sulfate Tablets; Other: Thermal and Pressure Nociceptive Sensitivity	Phase 1

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 answer questions about how they feel and vital signs (blood pressure, heart rate, oxygen saturation, and temperature) will be measured using a non-invasive (external) vitals monitor.

Participants will be asked to take an oral morphine capsule.

Participants will participant in 3 smoking sessions where they will be asked to smoke cigarettes containing either cannabidiol or placebo (a blank).

Participant's response to different intensities of thermal (heat and cold) stimulation will be administered to test pain sensitivity.

Participants will be asked to complete questionnaires and have vital signs (blood pressure, heart rate) monitored.

After completing the third round of smoking and assessment battery, 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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Human Laboratory Model to Screen Drugs With Opioid Analgesic-sparing Effects: Cannabidiol/Morphine Combinations
• Actual Study Start Date: May 1, 2019
• Estimated Primary Completion Date: May 1, 2021
• Estimated Study Completion Date: December 1, 2021

Arms and Interventions

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 3.4%	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 12.7%	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.

Outcome Measures

Primary Outcome Measures :

1. CHANGE. PAIN THRESHOLD AND TOLERANCE Pain responses to a range of heat, cold and mechanical pressure stimuli [ Time Frame: Pain responses measured at 15 minutes post CBD 0% drug using (1015); 15 minutes post CBD 3.4% drug using (11:15); 15 minutes post 12.7% CBD drug using (1155) ]
   Change in pain threshold and tolerance is being assessed post each CBD drug use (0%, 3.4% and 12.7%) using a Medoc 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.

Secondary Outcome Measures :

1. SAFETY Systolic blood pressure (physiological effects) [ Time Frame: Systolic blood pressure measured at baseline (0845); 15 minutes post CBD 0% drug using (1015); 15 minutes post CBD 3.4% drug using (11:15); 15 minutes post 12.7% CBD drug using (1155); 155 minutes post final CBD drug using (1430) ]
   Safety is being assessed.
2. SAFETY Diastolic blood pressure (physiological effects) [ Time Frame: Diastolic blood pressure measured at baseline (0845); 15 minutes post CBD 0% drug using (1015); 15 minutes post CBD 3.4% drug using (11:15); 15 minutes post 12.7% CBD drug using (1155); 155 minutes post final CBD drug using (1430 ]
   Safety is being assessed.
3. SAFETY Heart rate [ Time Frame: Heart Rate measured at baseline (0845); 15 minutes post CBD 0% drug using (1015); 15 minutes post CBD 3.4% drug using (11:15); 15 minutes post 12.7% CBD drug using (1155); 155 minutes post final CBD drug using (1430) ]
   Safety is being assessed.
4. SAFETY Respiratory rate [ Time Frame: Respiratory rate measured at baseline (0845); 15 minutes post CBD 0% drug using (1015); 15 minutes post CBD 3.4% drug using (11:15); 15 minutes post 12.7% CBD drug using (1155); 155 minutes post final CBD drug using (1430) ]
   Safety is being assessed.
5. SAFETY Oxygen saturation [ Time Frame: Oxygen Saturation measured at baseline (0845); 15 minutes post CBD 0% drug using (1015); 15 minutes post CBD 3.4% drug using (11:15); 15 minutes post 12.7% CBD drug using (1155); 155 minutes post final CBD drug using (1430) ]
   Safety is being assessed.
6. INDICES OF ABUSE LIABILITY Drug Liking [ Time Frame: Drug Liking measured at baseline (0845); 15 minutes post CBD 0% drug using (1015); 15 minutes post CBD 3.4% drug using (11:15); 15 minutes post 12.7% CBD drug using (1155); 155 minutes post final CBD drug usin ]
   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."
7. INDICES OF ABUSE LIABILITY Economic demand (drug purchase task (DPT) [ Time Frame: Economic demand will be measured at 40 minutes post CBD 0% drug using (1040); 40 minutes post CBD 3.4% drug using (1130); 40 minutes post CBD 12.7% drug using (1210) ]
   Indices of abuse liability is being assessed. Participants will be asked to make drug purchases based on how they feel at the moment (each DPT assessment is independent from the last CBD cumulative dose received). They will be informed that the amount purchased at each drug unit price (independent observations) must be consumed within 24-hr (i.e., participants cannot save or stockpile drug). Unit prices (UPs) per drug dose will be: $0 (free; no constraint) and $0.01, $0.10, $0.50, $1, $3, $5, $7.50, $10, $12.50, $15, $20, $25, $30, $35, $40, $45, $50, $60, $80 and $100.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Participants must report having smoked a cigarette (nicotine or marijuana) AND having taken an opioid > 3 occasions lifetime.
• Participants must be in good health to participate; those with 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.

Contacts and Locations

Contacts

Contact: Alina Woodford; (313) 993-3960; awoodford@med.wayne.edu

Locations

United States, Michigan

Tolan Park Medical Building; Recruiting

Detroit, Michigan, United States, 48201

Contact: Leslie Lundahl, PhD 313-993-3960 llundahl@med.wayne.edu

Sponsors and Collaborators

Wayne State University

Investigators

• Principal Investigator: Leslie Lundahl, PhD; Wayne State University

More Information

• Responsible Party: Leslie Lundahl, Associate Professor, Wayne State University
• ClinicalTrials.gov Identifier: NCT04030442
• Other Study ID Numbers: CMP
• First Posted: July 24, 2019
• Last Update Posted: January 27, 2020
• Last Verified: January 2020

• 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

Additional relevant MeSH terms:

Chronic Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Morphine; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents