Impact of Repeatedly-Administered THC-cannabis on Experimental Pain and Abuse Liability in Humans

NCT04596644 | Suspended Phase 2 FDA Drug

• 2 other identifiers: 8058R21DA050752
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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, and they report experiencing minimal psychoactive effects. However, there are few well-controlled human laboratory studies assessing cannabis' efficacy 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. Carefully controlled research is needed. The proposed randomized, within-subjects, placebo-controlled 16-day crossover inpatient human laboratory study (N = 20 healthy cannabis users; 10 men, 10 women) will address three important gaps in our understanding of the potential therapeutic utility of cannabis for pain: 1) Does tolerance develop to repeated, daily smoked cannabis administration on measures of experimental pain and abuse liability; 2) If so, is tolerance reversed during the 7 days of abstinence from active-THC cannabis; 3) Does abrupt abstinence from active cannabis increase experimental pain sensitivity, i.e. hyperalgesia, relative to baseline, and do these effects parallel measures of cannabis withdrawal such as disrupted mood and sleep? Two distinct modalities of experimental pain will be assessed: The Cold Pressor Test (CPT) and Quantitative Sensory Testing Thermal Temporal Summation (QST-TTS). Throughout the study, experimental pain and abuse-related effects will be assessed, as will sleep and subjective mood assessments.

Conditions

Cannabis; Pain; Tolerance; Hyperalgesia

Outcome Measures

Primary Outcomes (1)

• 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 on days 1, 2, 5, 8, 9, 12, and 15.

  Up to 15 days

Secondary Outcomes (2)

• Change in Quantitative Sensory Testing-Thermal Temporal Summation (QST-TTS) ratings

  Up to 15 days

• Change in Cannabis Rating Form (CRF) ratings

  Up to 15 days

Study Arms (3)

Dose A: Standardization Phase

EXPERIMENTAL

On the first full inpatient day (Day 1), participants smoke one specified strength (Dose A; 75% of two 6.58% cannabis cigarettes) of cannabis at three timepoints.

Drug: Active Cannabis

Dose B: Placebo Phase

PLACEBO COMPARATOR

On Days 2-8, participants smoke a second strength (Dose B; 75% of two \< 0.01%THC:CBD cannabis cigarettes) of cannabis will be administered 3x/day.

Drug: Placebo Cannabis

Dose A: Active Phase

EXPERIMENTAL

On Days 9-15, cannabis Dose A will be administered again (75% of two 6.58% cannabis cigarettes) at three timepoints each day.

Drug: Active Cannabis

Interventions

Active Cannabis DRUG

6.58% THC + \<0.01% CBD cannabis (in one cigarette)

Dose A: Active Phase; Dose A: Standardization Phase

Placebo Cannabis DRUG

\<0.01% THC:CBD cannabis.

Dose B: Placebo Phase

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males/non-pregnant females, 21-60 years old
• Current cannabis user
• Able to perform all study procedures

You may not qualify if:

• 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

Sponsors & Collaborators

• New York State Psychiatric Institute: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Marijuana Abuse; Pain; Hyperalgesia

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Somatosensory Disorders; Sensation Disorders; Nervous System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Clinical Neurobiology (in Psychiatry)

Model Details: 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.

Study Record Dates

• First Submitted: October 16, 2020
• First Posted: October 22, 2020
• Study Start: August 1, 2021
• Primary Completion: August 31, 2024
• Study Completion (Estimated): October 31, 2026
• Last Updated: April 8, 2026

Record last verified: 2026-04

Locations

US (1)