Anti-epileptic mechanisms of clinically used cannabis components on mitochondrial molecular targets

Cannabis has been used as a medicine for thousands of years. The oldest reports found are from China, where Cannabis was used for the treatment of malaria, rheumatic pains and childbirth since 3000 BC. In the UK, Sativex®, an oral mucosal spray containing a 1:1 ratio of the cannabinoids Δ9tetrahydrocannabinol (THC) and cannabidiol (CBD), is licensed for use in moderate to severe spasticity in multiple sclerosis.

CBD is a non-psychoactive component of the Cannabis plant and is known for its neuroprotective, anti-inflammatory and anticonvulsant properties in humans.For over a decade, CBD, along with cannabidivarin (CBDV), another component of the cannabis plant, have been investigated for their anti-epileptic effects at the Cellular and Molecular Neuroscience Division of the University of Reading. Remarkably, this work has led the drug directly into human clinical trials. Although the drug has been proved to work, its mechanism of action is still unknown.

My UROP placement aims to investigate one of the possible mechanisms of action of CBD and CBDV for the treatment of epilepsy. One of the theories regarding such mechanism is that these cannabinoids act on mitochondria, which are organelles found in cells responsible for respiration and generation of energy. Hence, by measuring their rates of respiration in vitro, we can analyse the action of the drug on these targets.

Throughout my placement, I took part in the experimental design of a method for isolation of mitochondria from rodent brain cells. I am now using the isolated mitochondria for testing with respirometry techniques. This involves the use of a Clark electrode connected to an oxygen meter which measures the consumption of oxygen by the mitochondria in response to the drug. I have also learnt how to use “R”, a software for statistical analysis, which will not only help me analyse the data I have acquired during my placement, but will also be a very valuable tool for my final year research project.

I am a (nearly) fourth-year pharmacy student with a great interest in neuroscience and research. This placement has given me an amazing opportunity to enhance my lab skills and not only take part, but contribute to a much larger research into the anti-epileptic properties of the non-psychoactive components of cannabis. Moreover, it has given me a real insight into what scientific research is like and motivated me even further to pursue a career within this field.

 

Agata Favero, Reading School of Pharmacy