Safety and Effects on Responses to Stress and Pain of Natural Medical Marijuana Products

NCT ID: NCT04226690

Last Updated: 2024-07-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-15
• Study Completion Date: 2023-12-15

Brief Summary

This proposal aims to systematically examine the safety and pharmacokinetic/pharmacodynamic profile and the physiologic, neuroendocrine and behavioral stress and pain responses to acute single doses and repeated dosing of oral tablet formulation of natural Cannabidiol (CBD) alone and in combination with Tetrahydrocannabinol and matched Placebo (PLA).

Detailed Description

This proposal aims to systematically examine the safety and pharmacokinetic/pharmacodynamic (PK/PD) profile and the physiologic, neuroendocrine and behavioral stress and pain responses to acute single doses and repeated dosing of oral tablet formulation of natural Cannabidiol (CBD) at 40 mg and 100 mg alone and in combination with Tetrahydrocannabinol (THC) at 10, 20 and 30 mg, and matched Placebo (PLA) under the following specific aims:

Aim 1: To assess the safety and PK/PD profile of acute single doses of natural oral tablet of CBD (40 mg, 100 mg), and the CBD/THC combination (40/10, 40/20 and 100/30 mg) and matching placebo (PLA) over six separate sessions one week apart in healthy adult men and women who are current recreational cannabis users (STUDY 1).

Aim 2: To examine the effects of separate CBD, THC, CBD/THC combination vs. PLA on subjective, physiological, neuroendocrine, cognitive and behavioral measures of stress, pain and anxiety at baseline and under acute pain provocation using an adapted Cold Pressor Test (CPT) in STUDY 1.

Aim 3: To examine the safety and tolerability of the two specific doses of CBD/THC, selected on the basis of best PK/PD and tolerability profile from Study 1 vs. PLA on baseline and CPT provoked pain in individuals with chronic pain over a 7-day repeated dosing (STUDY 2).

Study 1:

Eight 21-45-year-old men and women , who are recreational marijuana users but do not meet criteria for moderate-severe cannabis use disorder will be recruited to complete six separate inpatient laboratory sessions one week apart during which they will be assigned to receive an acute dose of either 40 mg CBD or 100 mg CBD alone, a CBD/THC combination of 40/10, 40/20 or 100/30 or PLA, in a random, counter-balanced, double-blind, cross-over design over a 6-week period. Sessions will be completed one -week apart to allow for an adequate washout period between sessions.

Study 2:

Adult men and women ages 21-60 (N=24) with chronic pain (not fully controlled by opioid pain medication), will be recruited and randomly assigned to receive the two most tolerable CBD/THC doses (two active doses of n=8 in each) or PLA (n=8) repeated dosing for 7 days. On day 1 and day 6/7 of the 7-day dosing, subjects will complete laboratory sessions. For 14 days after the 7-day dosing, subjects will complete daily ratings of pain and other patient-related outcomes. Subjects cannot meet criteria for moderate to severe levels of cannabis use disorder or other substance use disorders.

This registration will focus on Study 2.

Conditions

Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active Dose 1

Participants will receive the most tolerable CBD/THC dose with repeated dosing for 7 days. On day 1 and 6/7 of the 7-day dosing, subjects will complete laboratory sessions.

Group Type: EXPERIMENTAL

Active CBD/THC Dose 1

Intervention Type: DRUG

Subjects will self-administer the assigned study medication daily at home after pickup and will be tested using medication compliance procedures. Subjects will visit the center 2 times in the 7-day period on days 1 and 7 for blood draws to assess medication compliance.

Matching Placebo

Participants will receive a placebo with repeated dosing for 7 days. On day 1 and 6/7 of the 7-day dosing, subjects will complete laboratory sessions.

Group Type: PLACEBO_COMPARATOR

matched placebo comparator

Intervention Type: DRUG

Subjects will self-administer the assigned study medication daily at home after pickup and will be tested using medication compliance procedures. Subjects will visit the center 2 times in the 7-day period on days 1 and 7 for blood draws to assess medication compliance.

Active Dose 2

Participants will receive the second most tolerable CBD/THC dose with repeated dosing for 7 days. On day 1 and 6/7 of the 7-day dosing, subjects will complete laboratory sessions

Group Type: EXPERIMENTAL

Active CBD/THC Dose 2

Intervention Type: DRUG

Subjects will self-administer the assigned study medication daily at home after pickup and will be tested using medication compliance procedures. Subjects will visit the center 2 times in the 7-day period on days 1 and 7 for blood draws to assess medication compliance.

Interventions

Active CBD/THC Dose 1

Subjects will self-administer the assigned study medication daily at home after pickup and will be tested using medication compliance procedures. Subjects will visit the center 2 times in the 7-day period on days 1 and 7 for blood draws to assess medication compliance.

Intervention Type: DRUG

Active CBD/THC Dose 2

Subjects will self-administer the assigned study medication daily at home after pickup and will be tested using medication compliance procedures. Subjects will visit the center 2 times in the 7-day period on days 1 and 7 for blood draws to assess medication compliance.

Intervention Type: DRUG

matched placebo comparator

Subjects will self-administer the assigned study medication daily at home after pickup and will be tested using medication compliance procedures. Subjects will visit the center 2 times in the 7-day period on days 1 and 7 for blood draws to assess medication compliance.

Intervention Type: DRUG

Other Intervention Names

Medical marijuana medicine; Medical marijuana medicine; Placebo

Eligibility Criteria

Inclusion Criteria

1. Able to read and write English;

2. Recreational cannabis use with a minimum history recent use of at least one joint of smoked marijuana or marijuana edible or other equivalent form;

3. Current chronic pain, as defined by the International Classification of Diseases (ICD)-10, and stabilized for a minimum of 2 weeks on pain medication, (minimum pain ratings of 4 on a 10-point scale) and agree to not change pain medication during course of the study;

4. Body Mass Index (BMI) in the 18-36 range;

Exclusion Criteria

1. Any psychotic disorder or current psychiatric symptoms requiring specific attention, including active symptoms of psychosis or suicidal/homicidal ideation.

2. Any Current moderate/severe Substance Use Disorder, including alcohol and cannabis.

3. Women who are nursing or have premenstrual dysphoric disorder;

4. Women who are pregnant as determined by the urine pregnancy test at each assessment period;

5. Inability to give informed consent;

6. Traumatic brain injury or loss of consciousness;

7. Individuals with current or past history of seizure disorders;

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 68 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Connecticut Pharmaceutical Solutions

UNKNOWN

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

RAJITA SINHA

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The Yale Stress Center: Yale University

New Haven, Connecticut, United States

Countries

United States

Other Identifiers

No NIH funding

Identifier Type: OTHER

Identifier Source: secondary_id

2000020896

Identifier Type: -

Identifier Source: org_study_id