# Effects of Repeated Cannabis Administration on Experimental Pain and Abuse Liability in Humans

> **NIH NIH R21** · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · 2020 · $238,650

## Abstract

Project Summary
Chronic pain is a significant public health concern in the U.S., for which prescription opioids have historically
been the standard treatment. This approach has contributed to the striking rates of opioid use disorders and fatal
overdoses and has had an exorbitant financial impact on our economy. 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
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. This revised randomized, within-subjects, placebo-controlled 16-day crossover
inpatient human laboratory study (N = 20; 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 (6.58% THC) administration on measures of experimental pain and abuse liability; 2) If so, is
tolerance reversed following 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? To comprehensively address these
questions, two distinct modalities of experimental pain will be measured: The Cold Pressor Test and Quantitative
Sensory Testing Thermal Temporal Summation. Following move-in day, the study will start with one day of
“standardization” (Day 1), where participants will smoke 6.58% THC 3x/day, standardizing cannabis exposure
across participants before enforced abstinence in the next phase. A 7-day “inactive phase” will follow (Day 2-8), in
which participants will smoke inactive cannabis (0.00% THC) 3x/day; this phase will determine whether cannabis
withdrawal-induced hyperalgesia develops as a result of abrupt cessation from active cannabis, and will determine
whether analgesic tolerance is reversed with one week of abstinence. Next, participants will undergo a 7-day “active
phase” (Day 9-15) during which they will smoke active cannabis (6.58% THC) 3x/day; this phase will determine
whether tolerance develops to cannabis’ analgesic effects. Throughout the study, experimental pain and abuse-
related effects will be assessed, as will sleep and subjective mood. With rates of chronic pain increasing and limited
availability of safe and effective treatment alternatives to opioids, this study will help define cannabis’ potential
therapeutic utility as an analgesic medication. If medical cannabis patients ...

## Key facts

- **NIH application ID:** 10128045
- **Project number:** 1R21DA050752-01A1
- **Recipient organization:** NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
- **Principal Investigator:** Caroline A Arout
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $238,650
- **Award type:** 1
- **Project period:** 2020-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10128045

## Citation

> US National Institutes of Health, RePORTER application 10128045, Effects of Repeated Cannabis Administration on Experimental Pain and Abuse Liability in Humans (1R21DA050752-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10128045. Licensed CC0.

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