Can you sum up this award-winning research?
This study aimed to address whether the success of cannabidiol (CBD) in treating Dravet syndrome in clinical trials relies on the drug-drug interaction that occurs with the first-line treatment clobazam. We found that the combined treatment of CBD and clobazam resulted in greater anticonvulsant efficacy than either treatment alone, but only when intrinsically anticonvulsant doses of each drug were used. A sub-anticonvulsant dose of CBD did not potentiate the anticonvulsant effect of clobazam despite it increasing plasma concentrations of clobazam. Our study suggests that anticonvulsant efficacy of CBD is not simply explained by a drug-drug interaction with clobazam.
What led you into this line of research?
I somewhat fell into this line of research as I had not originally planned to study epilepsy when I started graduate school in the United States. I wanted to pursue research that had a direct translational application and was interested in pharmacology of human diseases associated with brain function. By joining the laboratory of Dr Alfred George Jr., a leader in the field of voltage-gated ion channels and genetics of channel mutations associated with epilepsy, I became engrossed in the field of epilepsy and began investigating pharmacological treatments for idiopathic epilepsies.
When the neighbour laboratory of Dr Jennifer Kearney developed a mouse model of Dravet syndrome (Scn1a +/- ), I transitioned into Dravet syndrome research to develop and validate a phenotyping platform for preclinical drug screening of potential therapies. Meanwhile in Australia, Katelyn Lambert, a Dravet syndrome patient benefitting greatly from medicinal cannabis, inspired her grandparents Barry and Joy Lambert to make a historic donation to the University of Sydney to help establish the Lambert Initiative for Cannabinoid Therapeutics, a world-first research centre aiming to unlock the medicinal potential of cannabis and the cannabinoids.
Within the Lambert Initiative, Associate Professor Jonathon Arnold advertised a position to explore the potential of novel cannabis-based treatments for drug-resistant childhood epilepsies. I took a leap of faith to travel halfway across the world to join the Lambert Initiative team in Sydney. Upon arrival I realised that my view of CBD in the treatment of epilepsy was
somewhat at odds with that of my new colleagues. Like many in the epilepsy field, I was skeptical of CBD and attributed its anticonvulsant effects to a pharmacokinetic interaction with clobazam. This doubt in the anticonvulsant efficacy of CBD gave rise to the research question addressed in this Epilepsia paper. The results of this study changed my opinion; I am now convinced of the intrinsic anticonvulsant effects of CBD and its legitimate place in the treatment of Dravet syndrome.
What’s a little known fact about cannabidiol?
Both CBD and THC have the same molecular formula and the structures differ by just one chemical bond. THC has a closed cyclic ring that is open in CBD. Interestingly, this open ring structure affords the completely different molecular targets and pharmacological properties of CBD compared to THC. While THC is psychoactive by activating cannabinoid receptors, CBD does not activate these receptors so has no intoxicating effect.
What aspect of this research excites you the most?
Conducting research in the medicinal cannabis field has been a unique experience for me. Since there is a plethora of anecdotal stories and media surrounding medicinal cannabis, this field is unlike traditional drug development. Public opinion is often leading the charge and primary research, both clinical and preclinical, has largely been running in parallel to its use in the
community. Being part of this highly relevant, somewhat contentious field has been nothing short of exciting. The Lambert Initiative has a vibrant, translational research team working across many disciplines such as medicinal chemistry, cellular pharmacology, animal models of disease and clinical trials. Additionally, through community outreach our expertise is used to educate many different spheres of society, including not only patients, caregivers, and medical doctors but also lawyers, public servants and politicians. During my four years working in this space, I have found it really exciting to contribute to the scientific dialogue surrounding the introduction of legal medicinal cannabis.
How long before this work might impact on patient care?
The impact that this research has on patient care is actually occurring presently as the epilepsy field is beginning to better recognise the anticonvulsant effects of CBD. This research has the capacity to impact the perception that the epilepsy and medical fields have about CBD. Hopefully, neurologists are gaining confidence in adding CBD to their treatment armamentariums to assist patients suffering from intractable childhood epilepsies such as Dravet syndrome and
Lennox-Gastaut syndrome.
What has been your biggest research hurdle?
The biggest challenge that I have encountered in research has been to balance time at the bench with writing. Both aspects are vital to a successful research career. I tend to prefer being at the bench so I have been making an effort to take time to step away from the bench to publish results and reflect on the direction of my research.
What’s your Holy Grail – the one thing you’d like to achieve in your research career?
If I could achieve just one thing in my research career, it would be that my work makes an impact. I hope that my research makes meaningful contributions to the field of epilepsy to improve health outcomes for epilepsy patients.
Who has inspired you most – in work or life?
The coaches, teachers and professors I have had over the years have been my biggest inspiration. They have shown me the power of hard work, challenged me to step out of my comfort zone and encouraged me to strive for the best.
How do you maintain work-life balance?
When I first landed in Australia, my supervisor Associate Professor Jonathon Arnold picked me up from the airport and took me directly to Bondi. We were having a coffee and he said, “I reckon you should live here.” I followed his advice and moved to Bondi, a decision that has contributed tremendously to maintaining a healthy work-life balance. Having grown up in Wisconsin, a land-locked state in the US, the culture in Bondi that is focused around the beach and the ocean was certainly a change of pace. I have become immersed in this beach culture, spending as much time in the ocean as possible and becoming part of the Bondi Surf Bathers Lifesaving Club. My work-life balance has been maintained by embracing the Aussie beach lifestyle.
There’s an app for that. What’s new on your phone?
Audible. The coronavirus health crisis and stay at home order had me searching for an alternate leisure activity that did not involve looking at a screen. Audible, an app that plays audiobooks, was a favourite way to fill my time. Sitting with a cup of tea, listening to a story reminded me families huddling around an old-time radio and became a great way to unwind.