Repeated Administration of Cannabis Varying in THC and CBD

NCT05563948 | Suspended Phase 2 FDA Drug

• 1 other identifier: 8347
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The majority of the \>3 million medical cannabis patients in the U.S. use cannabis products to manage pain but many questions remain. This project is designed to answer three questions that will fill important voids in the field's understanding of sustained cannabis use: 1) is abrupt cessation of cannabis associated with increased pain sensitivity; 2) does tolerance develop to the analgesic and abuse-related effects of repeatedly administered cannabis with varying ratios of THC and CBD, and is this tolerance reversible following a period of abstinence; 3) how does repeated cannabis use affect levels of endocannabinoids, and are these changes associated with changes in pain sensitivity and abuse liability? In this study, the investigators will enroll participants (N=100 healthy, cannabis-using men and non-pregnant women, ages 21-65) inpatient for 15 days. They will be randomized to one of four cannabis conditions (n=25/group). Following a day of standardization on which participants will receive their assigned cannabis condition (Day 1), cannabis will be administered repeatedly for 14 days (Day 2-15). The investigators will measure abuse-related effects ("Good Drug Effect"), endocannabinoid levels and two distinct types of experimental pain: The Cold Pressor Test and Quantitative Sensory Testing Thermal Temporal Summation. Given the widespread use of cannabis for pain, understanding the consequences of daily repeated administration of cannabis with THC:CBD ratios that are representative of most medical cannabis products on pain, abuse liability, and endocannabinoids is imperative.

Conditions

Cannabis

Outcome Measures

Primary Outcomes (2)

• Cold Pressor Test (Change over time from baseline)

  The Cold Pressor Test (CPT) is a validated and reliable pain-induction procedure that reflects A-delta nerve fiber activity within the autonomic nervous system and closely mimics clinical chronic pain. CPT has been shown to have excellent reliability and predictive validity for medication-induced analgesia, including cannabinoids. For this task, two temperature-controlled circulating water baths maintain warm (36.5-37.5ºC) and cold (3.5-4.5ºC) water. Participants immerse their hand into a warm bath for 3 min (to standardize baseline skin temperature), then the cold bath, indicating when they first experience pain and withdrawing when the pain gets uncomfortable. Study staff will record time (in seconds) until participants: 1) report discomfort (pain threshold), and 2) withdraw their hand from the cold water (pain tolerance).

  8x/day on Days 1, 2, 5, 8, 9, 12, 15.

• Quantitative Sensory Testing-Thermal Temporal Summation (QST-TTS; change over time from baseline)

  (QST-TTS) uses repetitive fixed frequency and intensity heat stimulation to induce central sensitization of C-fibers in the spinal cord and is regarded as an experimental correlate of the 'wind-up' phenomenon in the dorsal horn. As dorsal horn CB-1 activity has been linked to suppression of 'wind-up' and central sensitization (the mechanism purportedly underlying cannabis' efficacy for neuropathic pain), cannabis use may decrease QST-TTS response, mirroring analgesia on the CPT during active cannabis administration vs. placebo. For this task, a Medoc TSA-II NeuroSensory Analyzer with a 30 x 30 mm Peltier thermode applies tonic noxious heat stimulation to the thenar eminence of the palm: the baseline temperature is 32.0°C, increases at a rate of 1°C/s up to 46.5°C, and remains constant for 120 sec. Total duration.

  8x/day on Days 1, 2, 5, 8, 9, 12, 15.

Study Arms (4)

High THC : High CBD

EXPERIMENTAL

Cannabis that is high in THC and high in CBD will be administered.

Drug: Cannabis

High THC : Low CBD

EXPERIMENTAL

Cannabis that is high in THC and low in CBD will be administered.

Drug: Cannabis

Low THC : High CBD

EXPERIMENTAL

Cannabis that is low in THC and high in CBD will be administered.

Drug: Cannabis

Low THC : Low CBD

PLACEBO COMPARATOR

Cannabis that is low in THC and low in CBD will be administered.

Drug: Cannabis

Interventions

Cannabis DRUG

Vaporized cannabis will be administered 3x/day for 15 days.

High THC : High CBD; High THC : Low CBD; Low THC : High CBD; Low THC : Low CBD

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females, 21-65 years old
• For females: not pregnant or breast-feeding, and uses an acceptable form of birth control (e.g., condoms, IUD)
• Uses cannabis on a near-daily basis
• Not seeking treatment for cannabis use
• Able to provide informed consent
• Able to perform study procedures

You may not qualify if:

• Meets DSM-V criteria for any Substance Use Disorder other than cannabis, nicotine or caffeine
• Uses other illicit drugs ≥1 day/week in the prior 4 weeks
• Medical history, physical, psychiatric examination, or significant illness at the clinical discretion of the study physician; for example, history of heart disease, diabetes, hypertension (BP \> 140/90) or uncontrolled asthma
• \. Use of any prescription or daily use of over-the-counter medications 6. Recurrent, ongoing pain 7. Insensitivity to the thermal stimuli of the Cold Pressor Test or Quantitative Sensory Testing 8. History of physical violence or paranoia during cannabis withdrawal

Sponsors & Collaborators

• New York State Psychiatric Institute: lead

Study Sites (1)

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Marijuana Abuse

Interventions

nabiximols

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical professor in Psychiatry

Study Record Dates

• First Submitted: September 26, 2022
• First Posted: October 3, 2022
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): September 30, 2032
• Study Completion (Estimated): September 30, 2034
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

US (1)