# Cannabinoid control of epilepsy

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $350,432

## Abstract

Temporal lobe epilepsy (TLE) is the most common epilepsy syndrome in adults. Current treatment options for
TLE are inadequate, as too many patients suffer from uncontrolled seizures and from negative side effects of
treatment. Endogenous cannabinoid signaling has been recognized as a major, potent regulator of presynaptic
neurotransmitter release in the brain, and there has been a recent surge of interest in using exogenous
cannabinoid compounds obtained from the marijuana plant for the control of intractable epilepsy. However,
mechanisms underlying cannabinoid control of neuronal excitability are not well understood. Recently, we
discovered a fundamentally new, functionally significant, postsynaptic mechanism by which cannabinoids
control excitability in hippocampal pyramidal cells. This pathway involves the potent, cannabinoid type 1
receptor- (CB1) mediated modulation of the h-current (Ih), a key regulator of dendritic excitability generated by
hyperpolarization-activated, cyclic nucleotide-gated channels (HCNs). Here we propose to test the hypothesis
that that medically relevant cannabinoids exert their anti-convulsant actions in chronic TLE partly through the
regulation of Ih in principal cells and interneurons throughout the cortical mantle. The hypothesis will be tested
in experimental mouse models of TLE, and the assessment will be carried out with in vitro and in vivo
electrophysiology, cell-type-specific nanoscale super-resolution molecular imaging in specific subcellular
profiles of identified pyramidal cells and interneurons at a high throughput, and data-driven supercomputational
network modeling. We anticipate that defining the functional consequences of a novel cannabinoid regulator of
neuronal excitability in chronic epilepsy will lead to significant advances in the understanding of disease
mechanisms in chronic epilepsy, and will aid the development of cannabis-based anti-epileptic treatment
strategies.

## Key facts

- **NIH application ID:** 9899338
- **Project number:** 5R01NS099457-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** IVAN SOLTESZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $350,432
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899338

## Citation

> US National Institutes of Health, RePORTER application 9899338, Cannabinoid control of epilepsy (5R01NS099457-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9899338. Licensed CC0.

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