Repeated Cannabis Administration on Experimental Pain and Abuse Liability

NCT04576507 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 8016
• Study Type: interventional
• Target: 10
• 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. 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.

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 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.

  Up to 15 days

Secondary Outcomes (1)

• 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 will smoke one specified strength (Dose A; 75% of active cannabis cigarette, 2.98% THC, 4.91% CBD) of cannabis.

Drug: Active Cannabis

Dose B: Placebo Phase

PLACEBO COMPARATOR

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.

Drug: Placebo Cannabis

Dose A: Active Phase

EXPERIMENTAL

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.

Drug: Active Cannabis

Interventions

Active Cannabis DRUG

2.98% THC:4.91% CBD cannabis.

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
• Alkermes, Inc.: 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

Results Point of Contact

• Title: Caroline A. Arout, Ph.D.
• Organization: New York State Psychiatric Institute

caroline.arout@nyspi.columbia.edu

646-774-6167

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Participants are blind to what cannabis dose they are receiving on which day, though it is the same for all: Day 1: active cannabis (2.98% THC and 4.91% CBD) Day 2-8: placebo cannabis (\<0.01% THC, CBD) Day 9-15: active cannabis (2.98% THC and 4.91% CBD)
• 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; active cannabis, 2.98% THC and 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 and 4.91% CBD) will be administered once again, at the same 3 daily time points.

Study Record Dates

• First Submitted: September 29, 2020
• First Posted: October 6, 2020
• Study Start: June 1, 2021
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: August 8, 2025
• Results First Posted: August 8, 2025

Record last verified: 2025-08

Locations

US (1)