# ICAL: Impact of Cannabinoids Across Lifespan: Behavioral Project

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $336,493

## Abstract

PROJECT SUMMARY: BEHAVIORAL PROJECT
ICAL’s core hypothesis is that non-physiological activation of the endocannabinoid (ECB) system by cannabis
exposure during adolescence permanently alters ECB signaling, ultimately causing persistent alterations in
cognition and motivated behavior. In this project, we propose a comprehensive behavioral evaluation of
rodents exposed in adolescence to THC. Using a well-validated set of behavioral tasks and standardized
protocols congruent with other Projects, we will characterize male and female, rat and mouse behavior across
carefully selected measures of reward, memory, cognition and emotion to determine the scope of persistent
THC behavioral effects, and how alterations in ECB signaling within hippocampal and mesocorticolimbic
circuits underlie such effects. We have two Aims. Aim 1: To characterize behavioral phenotypes caused by
adolescent THC exposure. We will phenotype the effects of prolonged THC administration in adolescent mice
and rats of both sexes (PND 30-43), a proxy for daily cannabis use in human teenagers. The animals will be
tested in adulthood (PND 70+) on standardized behavioral assays within the domains of reward, memory,
cognition, and emotion. Additional groups will compare THC effects in adult animals to determine whether
adolescent exposure effects are developmental in nature, and will examine behavioral effects that may emerge
as animals age (PND 300+). Following behavioral testing, brains will be processed for behavior-related c-Fos
immunoreactivity to determine changes in behavior-related neural activity. Aim 2: To identify mechanisms of
induction and maintenance of adolescent THC effects on behavior. We hypothesize that THC, via stimulation of
cannabinoid CB1 receptors (CB1R) in adolescence, changes ECB signaling and plasticity mechanisms within hippocampal
and mesocorticolimbic circuits, resulting in the persistent behavioral effects identified in Aim 1. In Aim 2.1 we will
determine the CB1R-dependence of persistent adolescent THC effects. In Aim 2.2 we will investigate the behavioral
functions served by adolescent THC-induced ECB dysregulation, using microinjections of selective pharmacological
agents or silencing/enhancing of gene expression via targeted viral vectors. In Aim 2.3 we will utilize chemogenetic
manipulations to characterize and correct adolescent THC-induced circuit activity changes. These studies will provide
the first comprehensive examination of the behavioral and circuit-level mechanisms of adolescent THC effects
under a standardized, validated protocol in rodents. In addition, they will provide a mechanistic framework in
which to interpret the results of NIH’s prospective ABCD consortium, and will help reveal the true
neurodevelopmental effects of teen cannabis use.

## Key facts

- **NIH application ID:** 9934179
- **Project number:** 5P50DA044118-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Stephen Vincent Mahler
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $336,493
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934179

## Citation

> US National Institutes of Health, RePORTER application 9934179, ICAL: Impact of Cannabinoids Across Lifespan: Behavioral Project (5P50DA044118-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9934179. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*