# Pharmacokinetics and Pharmacodynamics of Oral and Vaporized THC in Older Adults

> **NIH NIH R21** · YALE UNIVERSITY · 2022 · $163,625

## Abstract

PROJECT SUMMARY/ABSTRACT
 In this proposal, we seek to investigate the pharmacokinetic (PK) and pharmacodynamic (PD) effects of
the main analgesic and psychoactive constituent of cannabis, delta-9-tetrahydrocannabinol (THC), among
older adults – the fastest growing population of cannabis consumers, and the most likely age cohort to use
cannabinoids to relieve pain. Although THC has been widely studied for its antinociceptive potential, most
studies were conducted among younger individuals; as a result, how THC affects pain in older adults remains
to be investigated. First, due to a combination of age-related physiological changes, older adults may
experience more frequent THC-induced adverse events. Still, there is a dearth of data on the PK effects of
THC among older adults. Second, the PD effects of THC for outcomes that are especially important for older
adults – such as analgesia and abuse liability – remain unknown. Data generated among younger individuals
cannot be generalized to older adults, as accumulating studies indicate that aging produces functional
neuroadaptations in pain and reward systems – likely influencing the analgesic efficacy and abuse liability of
THC. Further, older adults may be more sensitive to the cardiovascular and cognitive/psychomotor effects of
THC. These adverse events may be detrimental to their health, increasing the risk of falls and accidents.
 To close this critical knowledge gap, we have designed a human laboratory study to characterize the
acute PK and PD effects of THC, administered through the oral and inhaled route, among older adults. We
propose a double-blind, placebo-controlled, crossover study, randomizing 20 men and women aged 65 years
or older, to two doses of oral THC (5 mg and 10 mg) and vaporized THC (2 mg and 4 mg). Consistent with
NOT-DA-21-049, these doses translate to one or two standard units (SU) of oral THC, and 0.4 and 0.8 SU of
vaporized THC. Across 6 test sessions, participants will receive a random sequence of 6 conditions: 5 mg oral
THC; 10 mg oral THC; oral placebo; 2 mg vaporized THC; 4 mg vaporized THC; and vaporized placebo. Blood
sampling will be collected from an intravenous line, at regular intervals, up to 8 hours post-dose, to assess the
PK of THC and its phase I and II metabolites (Aim 1). The PD effects of THC on pain responses will be
measured with Quantitative Sensory Testing (QST), a reliable computerized technique used to measure
analgesic efficacy (Aim 2a). The abuse liability of THC will be measured using an established drug
reinforcement paradigm (Aim 2b). General adverse, cardiovascular, and cognitive/psychomotor effects of THC
will be assessed with behavioral, physiological, and neuropsychological methods. We will also assess sex
differences in PK/PD outcomes (Exploratory Aims). Finally, a one-week washout will separate test sessions.
 This timely study will serve as a benchmark to assess cannabinoids as therapeutics to relieve pain in
older adults. Results will ...

## Key facts

- **NIH application ID:** 10569710
- **Project number:** 1R21DA057240-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Joao Paulo De Aquino
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $163,625
- **Award type:** 1
- **Project period:** 2022-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10569710

## Citation

> US National Institutes of Health, RePORTER application 10569710, Pharmacokinetics and Pharmacodynamics of Oral and Vaporized THC in Older Adults (1R21DA057240-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10569710. Licensed CC0.

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