Electronic Theses and Dissertations

Date of Award

1-1-2012

Document Type

Dissertation

Degree Name

Ph.D. in Chemistry

Department

Chemistry and Biochemistry

First Advisor

Stephen J Cutler

Second Advisor

Christopher McCurdy

Third Advisor

Mahmoud A. ElSohly

Relational Format

dissertation/thesis

Abstract

Cannabis has been around for thousands of years and has been used recreationally, medicinally, and for fiber. Over 400 compounds have been isolated from Cannabis sativa with approximately 100 being cannabinoids. Of those 100 compounds, Δ9-THC has been determined as the primary constituent, which is also responsible for the psychoactivity associated with Cannabis. Along with Δ9-THC, cannabidiol has been studied in depth for its therapeutic effects. This has currently been the focus of many researchers since cannabidiol does not cause psychotropic effects.

Cannabinoid receptors belong to the large superfamily of G protein-coupled receptors (GPCRs). Approximately 30% of marketed drugs target GPCRs, therefore, furthering the importance of targeting the cannabinoid receptors to treat a variety of conditions such as pain, neurodegeneration, appetite, immune function, anxiety, cancer, and many others. Developing in vitro bioassays to determine binding and functional activity of compounds has the ability to lead researchers to develop a safe and effective drug that may target the cannabinoid receptors. The objective is to display the therapeutic effects associated with Cannabis while eliminating the unwanted effects such as psychoactivity and anxiety.

Using radioligand binding and functional bioassays, a structure-activity relationship (SAR) for major and minor cannabinoids was developed. The importance of SAR is to determine specific characteristics of a compound that allow it to bind to a specific receptor. The objective with cannabinoid receptors is to selectively target CB2 receptors in order to avoid psychoactivity associated with CB1 receptor stimulation. Altering a compound structure based on SARs has the potential to become a lead for a novel therapeutic agent.

These radioligand assays were also used to evaluate the volatile oil of high potency Cannabis sativa. The volatile oil was subjected to bioassay-guided fractionation affording seven different fractions, three of which were active. Of the three, only one fraction did not contain Δ 9-THC. The ability of the volatile oil fraction that lacks Δ 9-THC to activate the cannabinoid receptors may exist due to synergistic relationships between the minor and major components.

The research presented in this dissertation confirms that compounds from Cannabis sativa have the potential for becoming novel therapeutic drugs that specifically target the cannabinoid receptors in order to treat a variety of diseases.

Included in

Chemistry Commons

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.