Repeated Cannabis Administration on Experimental Pain and Abuse Liability

Phase 2

Completed

Conditions: Cannabis
Pain
Hyperalgesia
Tolerance

Interventions: Drug: Active Cannabis
Drug: Placebo Cannabis

Registration Number: NCT04576507

Lead Sponsor: New York State Psychiatric Institute

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. 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.

This protocol is currently suspended due to the NYSPI human subjects research pause and results cannot currently be analyzed and posted. Upon un-suspension, we will analyze the data and post results immediately.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 10

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dose A: Standardization Phase	Active Cannabis	On the first full inpatient day (Day 1), participants will smoke one specified strength (Dose A; 75% of active cannabis cigarette, 2.98% THC, 4.91% CBD) of cannabis.
Dose B: Placebo Phase	Placebo Cannabis	Days 2-8 comprises the Placebo phase, in which a second strength (Dose B; 75% of one placebo cannabis cigarette, \<0.01% THC, CBD) of cannabis will be administered 3x/day.
Dose A: Active Phase	Active Cannabis	Days 9-15 comprise the Active Phase, cannabis Dose A (75% of one active cannabis cigarette, 2.98% THC, 4.91% CBD) will be administered once again, 3x/day.

Primary Outcome Measures

Name	Time	Method
Change in Cold Pressor Test (CPT) Latency	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 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. Data points reported here represent Percent Change in Pain Tolerance from Day 1 (first timepoint, 15 minutes post-cannabis \[2.98% THC / 4.91% CBD\]) across study days (Day 2, 5, 8, 9, 12, and 15). Other timepoints are not reported.

Secondary Outcome Measures

Name	Time	Method
Change in Cannabis Rating Form (CRF) Ratings	Up to 15 days	Participants rate the "high" experienced as a result of cannabis administration on a 100mm visual analog scale. Data points represent Percent Change from Day 1 (first timepoint, 15 minutes post-cannabis \[2.98% THC / 4.91% CBD\]) across study days (Day 2, 5, 8, 9, 12, and 15) Repeats at days 1, 2, 5, 8, 9, 12, and 15.

Trial Locations

Locations (1): New York State Psychiatric Institute
🇺🇸
New York, New York, United States
New York State Psychiatric Institute
🇺🇸New York, New York, United States