# ICAL: Impact of Cannabinoids Across Lifespan: Cellular Project

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $380,609

## Abstract

Project 2 Summary
The incidence of cannabis use in the US population has been on the rise over the last decade and with
legalization is likely to increase even further in coming years. This includes increases in the prevalence of use
in adolescence both as a therapeutic and in social settings. Adolescent use presents special risks as brain
networks are still developing and malleable. In this context, evidence that cannibis disturbs cognitive function
and can impair learning and memory is a particular concern. Controlled studies with defined doses and
outcome measures are clearly needed to understand these cognitive disturbances, and neurobiological
processes underlying then. Studies in rodent have shown that exposure to cannabinoids (either Δ9-
tetrahydrocannabinol (THC), the psychoactive ingredient in cannabis, or a synthetic mimic) alters brain levels
of components of the endocannabinoid (ECB) system and impairs specific forms of learning and memory. Less
effort has been devoted to analysis of specific forms of synaptic plasticity thought to form the neurobiological
substrate for memory or to projection-specific effects. Project 2 will evaluate both of these issues. Aim 1 will
use electrophysiological (brain slice) techniques to determine if daily THC treatment of adolescent (ado) and
young adult mice (both sexes) influences, and specifically impairs, synaptic transmission and activity-induced
long-term potentiation (LTP) for three systems involved in memory encoding: (1) the lateral perforant path
(LPP) afferents to hippocampus which we have found exhibits an ECB-dependent form of LTP, (2) Schaffer-
commissural afferents to hippocampal field CA1 for which LTP is very well characterized and does not depend
on ECB function, and (3) excitatory afferents to medial/prelimbic frontal cortex. Preliminary results indicate that
THC effects are indeed projection specific: in male mice, daily ado-THC treatment eliminates the ECB-
dependent form of LTP in the LPP. The same THC treatments impair, but do not eliminate non-ECB dependent
field CA1-LTP but disturb processing of gamma-frequency afferent input to this region. Aim 1 studies will
further determine if ado-THC effects on synaptic transmission persist into middle age, and are greater than
effects of similar THC treatments applied to young adults. Aim 2 then will focus on hippocampal systems to
test specific hypotheses as to the neurobiological processes underlying disturbances in synaptic plasticity and
memory with ado-THC exposure: three sets of studies will test if changes in plasticity are associated with
compartment-specific changes CB1R expression and CB1R signaling and if manipulation of ECB levels can
offset impairments in synaptic function otherwise induced by ado-THC exposure. These studies have been
designed to complement activities in other components of ICAL to provide an extensive vertical analysis of
disturbances in substrates that underlie effects of THC on behavioral measures to be as...

## Key facts

- **NIH application ID:** 9934177
- **Project number:** 5P50DA044118-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Christine M Gall
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $380,609
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934177

## Citation

> US National Institutes of Health, RePORTER application 9934177, ICAL: Impact of Cannabinoids Across Lifespan: Cellular Project (5P50DA044118-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9934177. Licensed CC0.

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