Repeated Cannabis Administration on Experimental Pain and Abuse Liability
Primary Purpose
Cannabis, Pain, Tolerance
Status
Suspended
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cannabis
Sponsored by
About this trial
This is an interventional basic science trial for Cannabis
Eligibility Criteria
Inclusion Criteria:
- Males/non-pregnant females, 21-60 years old
- Current cannabis user
- Able to perform all study procedures
Exclusion Criteria:
- Use of other illicit drugs
- If medical history, physical and psychiatric examination, or laboratory tests performed during the screening process reveal any significant illness that the study physician deems contraindicated for study participation
- Insensitivity to the cold-water stimulus of the Cold Pressor Test or the heat stimulus of Quantitative Sensory Testing
Sites / Locations
- New York State Psychiatric Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dose A, followed by Dose B
Arm Description
On the first full inpatient day (Day 1), participants will smoke one specified strength (Dose A) of cannabis. Days 2-8 will comprise Phase 1, in which a second strength (Dose B) of cannabis will be administered 3x/day. The next 7 days (Day 9-15) will be Phase 2, in which cannabis Dose A will be administered once again, at the same 3 daily time points.
Outcomes
Primary Outcome Measures
Change in Cold Pressor Test (CPT) latency
The CPT apparatus consists of two refrigerated circulators, filled with warm (36.5-37.5°C). participants will complete the CPT 30 minutes before the 1000h cannabis administration (baseline), and 0, 15, 30, 45, 60, and 90 minutes post-cannabis administration. and cold (3.5 - 4.5°C) water. Participants will insert their non-dominant hand into the warm water and remove it after 3 minutes; skin temperature of the thumb pad will be measured. Participants will then insert their hand in the cold water and will be instructed to report when they first experience pain (pain threshold) and remove their hand when the cold water can no longer be tolerated (pain tolerance). Maximum immersion time will be 3 minutes.
Repeats at days 1, 2, 5, 8, 9, 12, and 15,
Secondary Outcome Measures
Change in Quantitative Sensory Testing-Thermal Temporal Summation (QST-TTS) ratings
The QST-TTS apparatus is a thermal testing analyzer with a 30 x 30 mm Peltier thermode, which will use repetitive nociceptive heat stimulation of a fixed frequency and intensity. At the beginning of the procedure, a research assistant (same gender as the participant) will read a script describing the procedure to the participant. Tonic noxious heat stimulation will be applied to the palm using a ramp-and-hold method, in which the baseline temperature will be set at 32.0°C, and will increase at a rate of 1°C/s up to 46.5°C, remaining constant for 120 sec. During the total duration of stimulation (135 seconds), participants will continuously rate the magnitude of perceived pain using a visual analog scale. participants will complete the CPT 30 minutes before the 1000h cannabis administration (baseline), and 0, 15, 30, 45, 60, and 90 minutes post-cannabis administration.
Repeats at days 1, 2, 5, 8, 9, 12, and 15,
Change in Cannabis Rating Form (CRF) ratings
Participants rate the strength, liking, desire to take again, good drug effect and bad. 7x on each of drug effect of cannabis on a 100mm visual analog scale.
Repeats at days 1, 2, 5, 8, 9, 12, and 15,
Full Information
NCT ID
NCT04576507
First Posted
September 29, 2020
Last Updated
August 9, 2023
Sponsor
New York State Psychiatric Institute
Collaborators
Alkermes, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04576507
Brief Title
Repeated Cannabis Administration on Experimental Pain and Abuse Liability
Official Title
Effects of Repeated Cannabis Administration on Experimental Pain and Abuse Liability in Humans
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Suspended
Why Stopped
In response to quality assurance and compliance concerns, OHRP issued an FWA restriction on NYSPI research that included a pause of human research as of June 23, 2023.
Study Start Date
June 1, 2021 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
New York State Psychiatric Institute
Collaborators
Alkermes, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Chronic pain is a significant public health concern in the U.S., for which prescription opioids have historically been the standard treatment. This has resulted in striking rates of opioid use disorders and fatal overdoses. Identifying non-opioid medications for the management of chronic pain with minimal abuse liability is a public health necessity, and cannabinoids are a promising drug class for this purpose. More than 80% of medicinal cannabis users report pain as their primary medical indication. These patients tend to seek products that are low in delta-9-tetrahydrocannabinol (THC; the primary psychoactive, and thus intoxicating, component of cannabis), and high in cannabidiol (CBD), a cannabinoid that purportedly has therapeutic benefit for pain but does not produce intoxicating effects [1]. However, there are few well-controlled human laboratory studies assessing the efficacy of high-CBD cannabis for pain in the context of abuse, and even less is known regarding the effects of daily repeated use of cannabis on pain and its relationship to abuse liability.
The proposed randomized, within-subjects, placebo-controlled 16-day crossover inpatient human laboratory pilot study (N = 16 healthy cannabis users; 8 men, 8 women) will address important gaps in our understanding of the potential therapeutic utility of cannabis for pain: 1) If repeated cannabis use can result in hyperalgesia; 2) If tolerance to the analgesic and abuse-related effects of cannabis develops and is reversible. Two distinct modalities of experimental pain will be assessed: The Cold Pressor Test (CPT) and Quantitative Sensory Testing Thermal Temporal Summation (QST-TTS), and participants will smoke cannabis 3x/day. Throughout the study, experimental pain and abuse-related effects will be assessed, as will sleep and subjective mood assessments.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cannabis, Pain, Tolerance, Hyperalgesia
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
This study comprises a 16-day inpatient stay. On the first full inpatient day (Day 1), participants will smoke one specified strength (Dose A) of cannabis. Days 2-8 will comprise Phase 1, in which a second strength (Dose B) of cannabis will be administered 3x/day. The next 7 days (Day 9-15) will be Phase 2, in which cannabis Dose A will be administered once again, at the same 3 daily time points.
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dose A, followed by Dose B
Arm Type
Experimental
Arm Description
On the first full inpatient day (Day 1), participants will smoke one specified strength (Dose A) of cannabis. Days 2-8 will comprise Phase 1, in which a second strength (Dose B) of cannabis will be administered 3x/day. The next 7 days (Day 9-15) will be Phase 2, in which cannabis Dose A will be administered once again, at the same 3 daily time points.
Intervention Type
Drug
Intervention Name(s)
Cannabis
Intervention Description
Investigates two strengths of cannabis.
Primary Outcome Measure Information:
Title
Change in Cold Pressor Test (CPT) latency
Description
The CPT apparatus consists of two refrigerated circulators, filled with warm (36.5-37.5°C). participants will complete the CPT 30 minutes before the 1000h cannabis administration (baseline), and 0, 15, 30, 45, 60, and 90 minutes post-cannabis administration. and cold (3.5 - 4.5°C) water. Participants will insert their non-dominant hand into the warm water and remove it after 3 minutes; skin temperature of the thumb pad will be measured. Participants will then insert their hand in the cold water and will be instructed to report when they first experience pain (pain threshold) and remove their hand when the cold water can no longer be tolerated (pain tolerance). Maximum immersion time will be 3 minutes.
Repeats at days 1, 2, 5, 8, 9, 12, and 15,
Time Frame
Up to 15 days
Secondary Outcome Measure Information:
Title
Change in Quantitative Sensory Testing-Thermal Temporal Summation (QST-TTS) ratings
Description
The QST-TTS apparatus is a thermal testing analyzer with a 30 x 30 mm Peltier thermode, which will use repetitive nociceptive heat stimulation of a fixed frequency and intensity. At the beginning of the procedure, a research assistant (same gender as the participant) will read a script describing the procedure to the participant. Tonic noxious heat stimulation will be applied to the palm using a ramp-and-hold method, in which the baseline temperature will be set at 32.0°C, and will increase at a rate of 1°C/s up to 46.5°C, remaining constant for 120 sec. During the total duration of stimulation (135 seconds), participants will continuously rate the magnitude of perceived pain using a visual analog scale. participants will complete the CPT 30 minutes before the 1000h cannabis administration (baseline), and 0, 15, 30, 45, 60, and 90 minutes post-cannabis administration.
Repeats at days 1, 2, 5, 8, 9, 12, and 15,
Time Frame
Up to 15 days
Title
Change in Cannabis Rating Form (CRF) ratings
Description
Participants rate the strength, liking, desire to take again, good drug effect and bad. 7x on each of drug effect of cannabis on a 100mm visual analog scale.
Repeats at days 1, 2, 5, 8, 9, 12, and 15,
Time Frame
Up to 15 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Males/non-pregnant females, 21-60 years old
Current cannabis user
Able to perform all study procedures
Exclusion Criteria:
Use of other illicit drugs
If medical history, physical and psychiatric examination, or laboratory tests performed during the screening process reveal any significant illness that the study physician deems contraindicated for study participation
Insensitivity to the cold-water stimulus of the Cold Pressor Test or the heat stimulus of Quantitative Sensory Testing
Facility Information:
Facility Name
New York State Psychiatric Institute
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Repeated Cannabis Administration on Experimental Pain and Abuse Liability
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