# Neurodevelopmental Effects of Cannabis and its Epigenetic Regulation

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $656,003

## Abstract

The pervasive use of marijuana (cannabis sativa) worldwide, along with its relatively low lethality, has led many
to believe that it is of little harm. As such cannabis use currently exceeds that of tobacco smoking among
adolescents in the USA. However, is now acknowledged that the developing brain is particularly sensitive to
drugs that can impact behavior in adulthood. This is of particular concern given that cannabis is the most
commonly abused illicit drug by teens and pregnant women. Our research continues to focus on the impact of
Δ9-tetrahydrocannabinol (THC), the major psychoactive component of cannabis associated with reward and
psychiatric vulnerability. We demonstrated that THC exposure in the developing brain has protracted effects
long into adulthood on molecular and behavioral outcomes relevant to reward sensitivity, motivated behavior
and negative affect. Our established prenatal animal model mimiced molecular changes in mesocorticolimbic
structures to that seen in our human fetal specimens with maternal cannabis use. Moreover, a number of
molecular changes relevant to epigenetic disturbances and synaptic plasticity are also commonly evident in
adults with adolescent THC exposure emphasizing common underlying mechanisms of developmental THC
effects. We identified a specific epigenetic molecular target (Mll1; multiple leukemia ) directly linked to
abnormal motivated behavior induced by developmental THC and have developed state-of-the-art strategies
such as laser capture microdissection (LCM) to dissect transcriptome and epigenetic alterations in discrete
neuronal pathways. We now employ such strategies to delineate pathway-specific alterations of epigenetic
mechanisms across the genome associated with developmental THC. Our study focuses on the nucleus
accumbens (NAc), which mediates reward, motivated behavior and emotional regulation linked to addiction
vulnerability and related psychopathologies. We propose to (1) characterize changes in the epigenome within
discrete adult NAc pathways associated with developmental THC exposure and its relationship to transcription
using LCM and deep sequencing of chromatin accessibility and overlap with transcriptome data. (2) Establish
causal links between molecular alterations identified in specific NAc output pathways wtih behavioral
phenotypes relevant to addiction psychopathology. (3) Investigate patterns of adult in vivo neural activity within
specific NAc pathways as a consequence of developmental THC exposure using the innovative technique of
fiber photometry calcium imaging in a pathway-specific manner. The databases generated from this in-depth
body of work will be valuable resources and the results will provide novel insights about the role of specific NAc
neural circuits underlying psychopathological vulnerability.

## Key facts

- **NIH application ID:** 9923625
- **Project number:** 5R01DA030359-10
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** YASMIN L. HURD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $656,003
- **Award type:** 5
- **Project period:** 2011-09-30 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9923625

## Citation

> US National Institutes of Health, RePORTER application 9923625, Neurodevelopmental Effects of Cannabis and its Epigenetic Regulation (5R01DA030359-10). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9923625. Licensed CC0.

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