# Molecular mechanism of astrocytic vulnerability to adolescent cannabis use

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $489,787

## Abstract

Cannabis use during adolescence leads to cognitive abnormalities. However, only some
cannabis users display cognitive impairment, suggesting a genetic predisposition to the
detrimental cognitive effects of cannabis. The mechanisms whereby genetic susceptibility
interacts with cannabis exposure to produce cognitive dysfunction remain unknown.
Cannabinoid receptor type 1 (CB1R) expressed in astrocytes mediates the adverse cognitive
effects of delta-9-tetrahydrocannabinol (Δ9-THC), a major psychoactive ingredient of cannabis.
In order to explore the molecular mechanisms of predisposition to cannabis effects, we will
utilize our mouse model of astrocyte-specific inducible expression of dominant-negative
Disrupted in Schizophrenia 1 (DN-DISC1). Our overarching hypothesis is that astrocytic DN-
DISC1 and adolescent Δ9-THC treatment synergistically up-regulates CB1R-mediated COX-2
signaling, leading to an increase in glutamate release and deficits in adolescent neuronal
maturation and cognitive function.
 Specific Aim 1 will identify the critical period required for the synergistic cognitive effects of
astrocyte-specific DN-DISC1 expression and chronic Δ9-THC exposure.
 Specific Aim 2 will examine the synergistic effects of DN-DISC1 and Δ9-THC on
extracellular and tissue content of glutamate, GABA, and endocannabinoids.
 Specific Aim 3 will examine the synergistic effects of DN-DISC1 and Δ9-THC on adolescent
maturation of pyramidal neurons and GABAergic interneurons.
 Specific Aim 4 will identify the mechanisms by which up-regulation of COX-2 signaling
synergistically induced by DN-DISC1 and Δ9-THC exposure leads to increased glutamate
release and cognitive dysfunction.
 Our proposed research will identify the molecular mechanisms of how adolescent cannabis
use leads to cognitive impairment in susceptible individuals to facilitate an informed search for
preventive treatments of long-term adverse effects of marihuana use.

## Key facts

- **NIH application ID:** 9954036
- **Project number:** 5R01DA041208-05
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Atsushi Kamiya
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $489,787
- **Award type:** 5
- **Project period:** 2016-09-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9954036

## Citation

> US National Institutes of Health, RePORTER application 9954036, Molecular mechanism of astrocytic vulnerability to adolescent cannabis use (5R01DA041208-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9954036. Licensed CC0.

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