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

Phase 1

Completed

• Conditions: Pain
• Interventions: Drug: Active CBD/THC Dose 2; Drug: matched placebo comparator; Drug: Active CBD/THC Dose 1

• Registration Number: NCT04226690
• Lead Sponsor: Yale University

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.

Study Timeline

• Study First Submitted: 2020-01-09
• Study First Submitted QC: 2020-01-09
• Study First Posted: 2020-01-13
• Study Start: 2022-11-15
• Primary Completion: 2023-12-15
• Study Completion: 2023-12-15
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-17
• Last Update Posted: 2024-07-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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;

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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;

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active Dose 2	Active CBD/THC 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
Matching Placebo	matched placebo comparator	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.
Active Dose 1	Active CBD/THC 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.

Primary Outcome Measures

Name	Time	Method
Pain Ratings	Day 1 and 7 provocation during 7-day treatment period	Change in provoked pain ratings on day 1 and day 7 on visual analog scale of pain (range 0-10)

Secondary Outcome Measures

Name	Time	Method
Anxiety Ratings	Day 1 and 7 provocation during 7-day treatment period	Change in provoked anxiety ratings on day 1 and day 7 on visual analog scale of anxiety (range 0-10)

Trial Locations

Locations (1)

The Yale Stress Center: Yale University; 🇺🇸 New Haven, Connecticut, United States