# Synthesis of cannabidiol dimers as potential agents to treat neurological disorders

> **NIH NIH P20** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 2022 · $223,500

## Abstract

The COVID pandemic has worsened stress, anxiety, and depression in the US population. Current FDA 
approved therapeutics for these ailments are only effective in subpopulations, and it is very common for 
patients to have to attempt multiple regimens to find one that works. Not surprisingly, patients continue 
seeking alternative remedies for self-treatment, e.g., cannabis. However, regardless of the legalization of 
cannabis in many states and its widespread usage for these purposes, cannabis is a diverse mixture of 
hundreds of compounds that widely vary in amount depending on the cannabis source. One active 
component of cannabis, cannabidiol (CBD), has been individually studied for its medicinal activity. 
Epidiolex®, a highly purified form of CBD, is FDA approved to treat rare forms of epilepsy. The issue is that 
CBD – in its natural form – is a non-specific (poly-pharmacological) agent. CBD weakly activates several 
receptors of the following classes: cannabinoid, opioid, serotonin (5-HT1A, 5-HT2A), orphan-GPR55, 
adenosine, and TRP receptors, among others. It remains unclear which receptor(s) and signaling pathway(s) 
are crucial for the positive benefits of CBD. Our long-term goal is to identify and expand novel therapeutics 
with defined, specific mechanisms of action for neurological/mental disorders. In this light, the overall 
objective in this application is to create novel CBD dimers that are proposed to be specific to cannabinoid 
or serotonin receptors. We will assess the hypothesis that CBD homo/heterodimers will enhance the 
selective binding to cannabinoid and serotonin receptors through bivalent or bitopic binding on dimerreceptors 
or a single receptor on two sites, respectively. Upon generation of our CBD homo/heterodimer 
library, we will evaluate their selectivity for the above receptors, and we will also evaluate dimers in a 
psychoactive receptor panel (NIMH-PDSP). This will position us to build key preliminary data for a competitive 
NIH application. Development of these novel dimers as chemical biology probes will elucidate the interactions 
of CBD with serotonin and cannabinoid receptors and the structural details behind these activities. Ultimately, 
these CBD semisynthetic derivatives have the potential to yield favorable therapeutic indices for the treatment 
of stress, anxiety, and depression. Results consistent with our hypothesis will have wide-ranging public health 
implications because of societal interest in CBD despite its poorly understood activities and because of the 
urgent need for safe, effective therapies. Importantly, if successful, the long-term goal is to move promising 
compounds into advanced preclinical testing.

## Key facts

- **NIH application ID:** 10737860
- **Project number:** 5P20GM109091-09
- **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
- **Principal Investigator:** Francisco Leon
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $223,500
- **Award type:** 5
- **Project period:** 2022-11-08 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10737860

## Citation

> US National Institutes of Health, RePORTER application 10737860, Synthesis of cannabidiol dimers as potential agents to treat neurological disorders (5P20GM109091-09). Retrieved via AI Analytics 2026-05-31 from https://api.ai-analytics.org/grant/nih/10737860. Licensed CC0.

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