George D. Behrakis Chair in Pharmaceutical Biotechnology Director,
Center for Drug Discovery Northeastern University
Alex Makriyannis is the Director of the Centre for Drug Discovery at Northeastern University. He has been instrumental in advancing the understanding of the endocannabinoid receptors and the Endocannabinoid system as a whole. In August, he and his colleagues assembled for the 4th Annual Chemistry & Pharmacology for Drugs of Abuse (CPDA) Conference. The CPDA was made possible by a grant from the National Institute on Drug Abuse (NIDA), and contributions from Northeastern University and its sponsors
So, tell us about the history of the CPDA summit.
I have been working on Cannabinoids for many years. I started working on Cannabinoids before the receptors were even discovered; I actually had a hand in the discovery of these. I’ve long held an interest in that. The CPDA was more of a panel effort to return some of the benefits I received from the field. We have the summit every year; this year was the fourth repetition and it covers all things to do with the scientific understanding of drug addiction. We try to focus on topics that are current in the field. This year we had a lot of content focused around opioids, cannabinoids and, specifically, a lot on CBD. We brought in high-end speakers to equip attendees with the most current understanding in the field. The NIH, specifically the National Institute on Drug Abuse, have their own part so attendees can find out what the agency is currently doing, and hear from them about research funding opportunities. We had close to 200 people there this year.
What have been your key highlights from the CPDA summit?
During one of our previous meetings, we decided to do an extra day for Cannabinoids. Generally, it is a two-day meeting and last year we had a Nobel Laureate speaking. This year we had very accomplished scientist Bryan Roth as keynote. We really try to grab new scientists who are coming in so they get exposed to what's happening in the field whilst sharing the stage with very well-known and successful scientists. We also have junior scientists who present, so, it's a real mix.
What is the prime motive behind your research?
I've been a scientist for most of my life, and I happened to work on Cannabis early on. I found it to be very interesting. At the time when I got into the field, we didn't really know very much; we knew that cannabinoids are substances that come from cannabis plants. It’s a plant that had been used by many people in the world over the years so it was very mysterious. I’m attracted to finding the function of these things and what they do. So, I started working on that, and it became more and more interesting. And right now I head up something called the Centre of Drug Discovery here at Northeastern University, and about 80% of what we do is based around the cannabinoids system.
Tell us more about the work you do at the Center for Drug Discovery?
The centre is divided into three components, each dedicated to different activities. One of the components is medicinal chemistry, which focuses on developing methods for making these compounds, the endocannabinoids, the Cannabinoids, Cannabis compounds, discovering new medications that could be developed within the centre and taking them daily by modulating the endocannabinoids system. Another component is the biochemistry component where we look at these targets and whether these cannabinoids interact with them. This would be the receptors like the GPCRs versus CB1 and CB2 or the enzymes. We develop these molecules, clone them, modify them and then we study how each of these proteins interact with the ligand. We do a lot of biophysical work there also; we do NMR and mass spectrometry and that enables us to do computational chemistry. So on the whole, the centre is a holistic approach to studying the biology of the cannabinoid system but also trying to develop medications that modulate the cannabinoid system.
Who do you work with at the Centre for Drug Discovery?
We have about 50-60 people working at the CDD and they are made up of graduate students and post-doctoral fellows, as well as several research professors. So it's a mix, but all dedicated to the research they’re doing.
What do you think is the next big discovery that’s going to be integral to moving the cannabinoid field forward?
One way of understanding how these compounds modulate the biology of the system is to know how they interact with the switches (i.e., the receptors) and to do a good job with that you need to know the structure of the receptors. We have been working on the structure of these receptors and we have actually published the structure of the CB1 and the CB2 receptors only recently. We are completing this work as we speak and expect to have it in a scientific paper in the next few months. This will cover all of the different aspects of the structure biology of the receptors, so that’s going to be an important ingredient to being able to develop new medications and rules to understand how these cannabinoids work. I would say this is a good step forward if you are looking at the chemical and biochemical side of it. The other place where I see a lot of opportunities involves cannabis itself: what the ingredients of cannabis are, what they do, and ways of making them more accessible for research etc. So I think it's a two-way approach, one approach is to study the endocannabinoid system and the other is to do more modulating the system via novel compounds, and cannabis itself, for therapeutic effect. I think there's a great future ahead.
What are you going to be sharing at this year’s International Cannabinoid-Derived Pharmaceuticals Summit?
I’m going to discuss some of the work we have been doing to advance some of our preclinical candidates in areas which we hope to advance into humans soon. In addition, I am going to talk about these receptors and their structures; what they mean and what they do. I will also talk about the endocannabinoid system and what to target to make it a more general discussion.
What therapeutic area is the preclinical work you’re doing covering?
One is working on fibrosis, both liver fibrosis and kidney fibrosis; we are quite advanced there. We have the only neutral CB1 antagonist which seems to do very well in animals. We are getting some initial indications using many samples, but not humans yet, so we need to do this. The second direction which we are interested in is removing the inflammation and we have made good progress in the inflammation of the bowels and the disease and colitis and Norvasc [Ph]. Another area I will be talking about is PTSD [Ph]- where PTSD can be helped by cannabis but because of the cannabinoids, the plant cannabinoids may not be the only or the best approach. Cannabis itself has been used for PTSD; we are making something we called the more potent and improved and safer cannabis which is taken as a pill by people who cannot go to sleep because of PTSD.