Repeated Cannabis Administration on Experimental Pain and Abuse Liability

• ClinicalTrials.gov Identifier: NCT04576507
• Recruitment Status: Recruiting
• First Posted: October 6, 2020
• Last Update Posted: June 14, 2021
• Sponsor: New York State Psychiatric Institute
• Collaborator: Alkermes, Inc.
• Information provided by (Responsible Party): Caroline A. Arout, Ph.D., New York State Psychiatric Institute

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.

Condition or disease	Intervention/treatment	Phase
Cannabis; Pain; Tolerance; Hyperalgesia	Drug: Cannabis	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention 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)
• Primary Purpose: Basic Science
• Official Title: Effects of Repeated Cannabis Administration on Experimental Pain and Abuse Liability in Humans
• Actual Study Start Date: June 1, 2021
• Estimated Primary Completion Date: December 31, 2023
• Estimated Study Completion Date: December 31, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dose A, followed by Dose B; 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.	Drug: Cannabis; Investigates two strengths of cannabis.

Outcome Measures

Primary Outcome Measures :

1. Change in Cold Pressor Test (CPT) latency [ Time Frame: Up to 15 days ]

   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 :

1. Change in Quantitative Sensory Testing-Thermal Temporal Summation (QST-TTS) ratings [ Time Frame: Up to 15 days ]

   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,

2. Change in Cannabis Rating Form (CRF) ratings [ Time Frame: Up to 15 days ]

   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,

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Contacts

Contact: Caroline A Arout, PhD; 646-774-7777; caroline.arout@nyspi.columbia.edu

Locations

United States, New York

New York State Psychiatric Institute; Recruiting

New York, New York, United States, 10032

Contact: Caroline A Arout, PhD 646-774-7777 caroline.arout@nyspi.columbia.edu

Sponsors and Collaborators

New York State Psychiatric Institute

Alkermes, Inc.

More Information

• Responsible Party: Caroline A. Arout, Ph.D., Assistant Professor of Clinical Neurobiology (in Psychiatry), New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT04576507
• Other Study ID Numbers: 8016
• First Posted: October 6, 2020
• Last Update Posted: June 14, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hyperalgesia; Marijuana Abuse; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Somatosensory Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases