Repeated Cannabis Administration on Experimental Pain and Abuse Liability

Phase 2

Suspended

Conditions: Cannabis
Pain
Hyperalgesia
Tolerance

Interventions: Drug: 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: SUSPENDED

Sex: All

Target Recruitment: 16

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 - Dose B - Dose A	Cannabis	On the first full inpatient day (Day 1), participants will smoke one specified strength (Dose A; active cannabis, 2.98% THC, 4.91% CBD) of cannabis. Days 2-8 will comprise Phase 1, in which a second strength (Dose B; placebo cannabis, \<0.01% THC, CBD) of cannabis will be administered 3x/day. The next 7 days (Day 9-15) will be Phase 2, in which cannabis Dose A (active cannabis, 2.98% THC, 4.91% CBD) will be administered once again, at the same 3 daily time points. All participants will undergo this same allocation.

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 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

Name	Time	Method
Change in Cannabis Rating Form (CRF) ratings	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,
Change in Quantitative Sensory Testing-Thermal Temporal Summation (QST-TTS) ratings	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,