# Do hippocampal synaptic density deficits in cannabis use disorder improve following abstinence?

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $524,821

## Abstract

PROJECT SUMMARY AND ABSTRACT
Background: Cannabis is amongst the most commonly used drugs globally. The potency of cannabis has
increased, and the “medical” and recreational use of cannabis is increasingly being legalized across the U.S.
Perceptions of the risks of cannabis use amongst teenagers have declined over the past decade. The initiation
of cannabis use typically occurs during adolescence and young adulthood, when the brain is still developing and
is most vulnerable to insults, particularly drugs. Therefore, it is important to understand the consequences of
chronic cannabinoid exposure on the structure and function of the brain. Repeated administration of
cannabinoids to rodents has been shown to result in lower synaptic density. Consistently, we recently showed
lower synaptic vesicle density in the hippocampus in cannabis use disorder (CUD) participants as measured
using [11C]UCB-J, a positron emission tomography (PET) tracer for imaging of the synaptic vesicle protein SV2A
in vivo. CUD participants performed worse on a hippocampal verbal memory task, and verbal memory
performance correlated with hippocampal [11C]UCB-J binding. However, whether the lower hippocampal
synaptic density and deficits in memory performance normalize with abstinence from cannabis use is not known.
The purpose of this study is to compare synaptic vesicle density in CUDs before and after 4 weeks of abstinence
from cannabis use, and to relate changes in synaptic density to hippocampal function (verbal memory).
Furthermore, the relationship between hippocampal [11C]UCB-J binding, verbal memory, and measures of
cannabis exposure (age of first use and lifetime exposure) will be explored.
Hypotheses: CUDs will show an increase in both hippocampal [11C]UCB-J binding, and verbal memory
performance following 4 weeks of confirmed abstinence. In CUD participants, earlier age of cannabis use and
cumulative exposure to cannabis will be correlated to hippocampal [11C]UCB-J binding.
Methods: We will compare synaptic vesicle density in CUDs before and after 4 weeks of abstinence using
[11C]UCB-J PET and the High Resolution Research Tomograph. Age-, gender matched healthy controls (HCs)
will also be scanned at baseline and at 4 weeks in order to verify longer-term test-retest stability. The relationship
between hippocampal [11C]UCB-J binding, verbal memory, and measures of cannabis exposure (age of initiation
of use and lifetime exposure) will be explored in CUDs.
Pilot data: CUDs (n=12) show lower hippocampal SV2A and verbal memory, which are correlated. CUDs (n=2)
show an increase in [11C]UCB-J binding with confirmed abstinence from cannabis for ~4 weeks.

## Key facts

- **NIH application ID:** 10280518
- **Project number:** 1R01DA054314-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** DEEPAK Cyril D'SOUZA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $524,821
- **Award type:** 1
- **Project period:** 2021-09-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10280518

## Citation

> US National Institutes of Health, RePORTER application 10280518, Do hippocampal synaptic density deficits in cannabis use disorder improve following abstinence? (1R01DA054314-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10280518. Licensed CC0.

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