# Age-and sex-dependent pharmacodynamics and pharmacokinetics of oral and smoked delta-9-THC

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $661,918

## Abstract

Project Summary: With rapid changes in cannabis regulation (i.e., legalization) and expanded availability
across the United States (US), rates of cannabis use and Cannabis Use Disorder (CUD) have increased
among populations vulnerable to the negative effects of delta-9-tetrahydrocannabinol (THC), the primary
psychoactive constituent of cannabis. These populations include emerging adults (18-25 years of age), older
adults (≥ 55 years of age), and females. Prevalence of cannabis use is highest among emerging adults; this is
of particular concern given the known risks of THC exposure during this period of late-adolescent
neurodevelopment and brain maturation. While rates of use among females used to be half that of males, the
gap between sexes is closing with 5.6% of female emerging adults reporting near daily use. Sensitivity to
THC’s effects in females is also hypothesized to lead to negative outcomes including the accelerated
progression to CUD. The most remarkable increase in cannabis use is among older adults. Prevalence of past
month use among adults ages 55-64 years more than doubled between 2013 to 2019, with over 25% of older
adults reporting use 1-4 times per week. Because of physiological and neurobiological changes that occur
during aging, older adults may be particularly vulnerable to the negative effects of THC. Despite the increase in
cannabis use among these groups, no studies to date have prospectively probed the adverse effects of acute
THC exposure across adulthood. Another trend impacting the vulnerability of older adults and females to
adverse effects of cannabis is the high rate of medical cannabis use in these populations with pain cited as the
predominant symptom for use. This trend further establishes the urgent need to assess THC analgesia
alongside adverse effects that increase risk including abuse liability, intoxication, and impairment.
To understand cannabis’s acute effects that indicate increased risk of exposure among these vulnerable
populations, the proposed study will compare the dose-dependent effects of smoked and oral THC, two
popular routes of administration, on endpoints directly related to adverse consequences of use including abuse
liability, intoxication, and impairment as a function of age and sex. Specifically, healthy male and female
emerging adults (18-25 years; N=30, 15M, 15F), middle-aged adults (35-45 years; N=30, 15M, 15F) and late
middle-aged adults (55-65 years; N=30, 15M, 15F) who occasionally use cannabis will be recruited for this
double-blind, double-dummy, placebo-controlled study. Using a within-subjects design, all participants will be
administered placebo (0mg THC), 2, 5mg unit-doses of THC (10mg), and 4, 5mg unit-doses of THC (20mg) via
smoked cannabis and by oral administration. Adverse effects, analgesia, and THC pharmacokinetics will be
assessed several times after smoked and oral THC administration. Findings from this study will be instrumental
in establishing age and sex as biologica...

## Key facts

- **NIH application ID:** 10708932
- **Project number:** 5R01DA057252-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** ZIVA D COOPER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $661,918
- **Award type:** 5
- **Project period:** 2022-09-30 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10708932

## Citation

> US National Institutes of Health, RePORTER application 10708932, Age-and sex-dependent pharmacodynamics and pharmacokinetics of oral and smoked delta-9-THC (5R01DA057252-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10708932. Licensed CC0.

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