Cannabis
Vaporized cannabis will be administered 3x/day for 15 days.
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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.
Locally preserved from ClinicalTrials.govOpen ClinicalTrials.govlast source update 2026-09-01
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Interventions
Vaporized cannabis will be administered 3x/day for 15 days.
Eligibility
primary outcomes
Time frame: 8x/day on Days 1, 2, 5, 8, 9, 12, 15.
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).
Time frame: 8x/day on Days 1, 2, 5, 8, 9, 12, 15.
(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.
Publications
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