# Effect of Cannabis Use on Synaptic Density in Older Adults

> **NIH NIH R21** · YALE UNIVERSITY · 2021 · $251,250

## Abstract

PROJECT SUMMARY AND ABSTRACT
Background: This new R21 application is to examine the effects of cannabis use on in vivo hippocampal
synaptic density and cognition among older adults (in response to NOSI (NOT-DA-20-014): “Cannabis,
Prescription Opioid, or Prescription Benzodiazepine Drug Use Among Older Adults”). Cannabis is one of
the most commonly and widely used illicit drugs; cannabis use is increasing among men and women older
than 55 years, and older adults (age>50yrs) represent the fastest growing cannabis-using age group; the
legalization of “medical” and recreational cannabis use continues to spread globally; the potency of cannabis
has been steadily increasing, and the rates of cannabis use and cannabis use disorder (CUD) are
increasing. Therefore, it is important to understand the consequences of chronic cannabis exposure on
brain structure and function in older adults. Contrary to studies in adolescents and young adults, in animal
studies, administration of cannabinoids to older adult rodents has been shown to result in increased
hippocampal synaptic density and improved cognitive function. It is now possible to examine synaptic
density in vivo using [11C]UCB-J, a positron emission tomography (PET) tracer with high specificity for
synaptic vesicle protein SV2A. We recently showed that in young adults with cannabis use disorder (CUD),
in vivo hippocampal synaptic vesicle density, as measured by [11C] UCB-J binding (BPND), was ~10% lower
than healthy controls. Additionally, young adult CUD participants performed worse on a hippocampal verbal
memory task, and verbal memory performance correlated with hippocampal [11C]UCB-J binding. However,
whether cannabis-using older adults have altered in vivo hippocampal synaptic density has not been
examined to-date. The purpose of this study is to compare in vivo hippocampal synaptic vesicle density in
cannabis-using older adults, and to relate changes in in vivo hippocampal synaptic density to hippocampal
function (verbal and spatial memory).
Hypotheses: Cannabis-using older adults (age>50yrs) will demonstrate increased hippocampal [11C]UCB-
J binding (BPND) compared to age-, gender-, BMI-, IQ-matched healthy controls. Furthermore, this increase
in [11C]UCB-J binding will be associated with improved hippocampal function (verbal and spatial memory).
Methods: We will compare in vivo hippocampal synaptic density in cannabis-using older adults (age >50yrs,
first initiation of cannabis use after age 40yrs) using [11C]UCB-J PET and the High Resolution Research
Tomograph and age-, gender-, BMI-, IQ-matched healthy controls (HCs) with due consideration for sex as
a biological variable. 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.
Impact: This is the first study, to our knowledge, to examine the effects of cannabis use on in vivo
hippocampal synaptic density in older adults.

## Key facts

- **NIH application ID:** 10294727
- **Project number:** 1R21DA054491-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Rajiv Radhakrishnan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $251,250
- **Award type:** 1
- **Project period:** 2021-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10294727

## Citation

> US National Institutes of Health, RePORTER application 10294727, Effect of Cannabis Use on Synaptic Density in Older Adults (1R21DA054491-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10294727. Licensed CC0.

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