Could New Research Bring Cannabis-Based Medicine to the Clinic?

Dr. Saoirse O'Sullivan, Associate Professor, University of Nottingham, UK 

Dr. Saoirse O'Sullivan is a leading researcher in the field of cannabinoid research. Awarded the title of International Cannabinoid Research Society Young Investigator of the Year in 2016, Dr O’Sullivan has published numerous papers on the role of cannabinoid receptors in health and disease. SelectScience spoke to Dr O’Sullivan to find out more about her work.

SS: Dr O’Sullivan, please confirm your job title and place of work, and tell us a little bit about your professional area of expertise.

SO: I am an Associate Professor at the University of Nottingham, based at the Royal Derby Hospital, UK. I have a background in physiology, with a degree in Natural Sciences, specializing in physiology, and a PhD in Physiology from Trinity College, Dublin, Ireland. I came to work at the University of Nottingham in 2002 as a Research Fellow, then moved over to the Royal Derby Hospital as a Lecturer in 2007. I was promoted to my current appointment as Associate Professor in 2015, where I now work part-time, juggling my research commitments with spending time with my young family.

SS: What is your current job role?

SO: My role is a roughly 50:50 split between my research, and my teaching and academic responsibilities. For my academic role, I give lectures, workshops and tutorials in a variety of specialist subject areas. I act as a personal tutor to a number of students, I also perform academic duties such as sitting on interview panels and managing modules.

In my research role, I lead a team of between 8 and 12 undergraduate and postgraduate researchers. My research interests are primarily in investigating the role of the endocannabinoid system in health and disease.

Role of the endocannabinoid system

SS: Can you tell us more about the endocannabinoid system and its role in health and disease?

SO: We used to think that the effects of the cannabis plant were non-specific, and that the plant compounds didn’t interact directly with the cell membrane. However, in 1992, scientists discovered the presence of cannabinoid receptors. These receptors, cannabinoid 1 (CB1) and cannabinoid 2 (CB2), bind to the main active ingredients in cannabis, as well as endocannabinoids produced naturally by the body. These receptors are expressed ubiquitously in cells throughout the human body.

Now we know that these receptors exist, we want to find out what they do, how they work and what their role is in disease processes. Understanding this, opens up the possibility of developing cannabinoid-based medications.

This is a novel area of research that could translate quickly into medical practice. Several new medicines have already been discovered, such as the use of phytocannabinoids to prevent convulsions in epilepsy (Epiodiolex) and the use of Sativex (nabiximols) in multiple sclerosis.

Cannabinoid receptors bind to the main active ingredients in cannabis as well as endocannabinoids in the body
Image: Shutterstock/Atomazul

SS: What is your research project investigating and what results are you achieving?

SO: I have two broad areas of research. I am interested in the role of endocannabinoids in the cardiovascular system. We know that cannabinoids can improve outcomes in animal models of stroke, with protective antioxidant and anti-inflammatory effects. In our research we use a cell model of the blood brain barrier to research endocannabinoids and the feasibility of therapeutic use of cannabadiol (CBD).

My second area of research involves gut inflammation and sepsis. Endocannabinoids protect the gut barrier, preventing bacteria from entering the circulation. We are carrying out research on the potential benefits of cannabinoids on gut health, using cell based assays as well as healthy volunteer human trials.

The value of multiplexing

SS: What Millipore Sigma equipment are you using in your lab?

SO: When we started doing a trial on diabetes several years ago, I sent a quotation to Millipore for some ELISA plates that I needed. I requested something like 10 or 15 plates and someone at the company asked me why I was carrying out single ELISA assays when I could be multiplexing! Since then we’ve used the Luminex MAGPIX^® System, along with numerous MilliporeSigma kits, to analyze biomarkers of interest such as hormones, cytokines, inflammatory markers and proteins in blood samples. We’ve used this system for a number of clinical trials now and I’m a big fan of the technology
.

SS: How does this system help you to achieve your research goals?

SO: Using this multiplex system allows us to get a huge number of results from one very small sample, by carrying out all of our tests in one assay. I’ve used most of the kits available, mostly on human samples but I’ve also used specimens such as hamster plasma and pig urine!

More recently I’ve been looking at cell signaling pathways, with the MILLIPLEX^® MAP Multi-Pathway 9-plex cell signaling multiplex assays. This assay is a screening tool that looks at nine different signaling pathways. The kits have been developed so that you can examine all of the intracellular proteins that you want to detect.

Traditionally, investigations of this nature would be carried out using western blotting techniques, but I don’t personally like this method. Western blotting is very slow, whereas multiplexing is so quick, and you can achieve multiple results from a single sample.

People who haven’t used these multiplex kits before may be put off by the cost, and it may feel like a risk if you haven’t had experience with them. However, I have had a 100% success rate with these kits! I know for a fact that when I use them, I am going to get lots of great data, and I don’t have to carry out the cell culturing that is involved with western blotting. For our pharmaceutical testing, we test many different time points and assess many different influencing factors. This is made possible using the multiplex system; if we were using western blotting we would be buried under a pile of blots!

Financially, from our own rough calculations, when setting up a western blot or multiplexing workflow from scratch, there isn’t likely to be much difference in the costs. I have encouraged many of my colleagues to move over to the MAGPIX^® multiplex system. They are often nervous to make such a big change, but once they have made the switch, they are very happy with the results.

MILLIPLEX^® MAP Multi-Pathway 9-plex Cell Signaling Multiplex Assays

SS: What is next for the field of cannabinoid research?

SO: There is still much more work to be done in this field. For our research, we hope that we’ll be able to move it into clinical practice within the next few years. We are closer to this happening in the area of stroke and cardiovascular benefits, where we are already working with a stroke consultant. There is also existing preclinical evidence for the benefits of using cannabinoids with stroke patients. The value is clear, as the cannabinoid compounds have tolerable side effects and you can’t overdose on them, so there are no toxicological issues.

The other big new area of potential for cannabis-based medicine is in cancer management. There is strong evidence to suggest that cannabinoids help to manage cancer-related pain and I think that this will be next in terms of clinical licensing.

Visit the MilliporeSigma website to learn more about the MILLIPLEX^® MAP Multi-Pathway 9-plex cell signaling multiplex assays.