Side Effect Free Medicines from Cannabis
Ruth - Cannabis has lots of potentially useful medicinal properties, but it also has potential side effects. We're trying to crack the issue with making new compounds, new drugs that act in novel innovative ways, such that we can produce effective medicines that lack side effects.
Chris - So get the good bits, lose the bad bits?
Ruth - Exactly, so most people know that cannabis is potentially effective in things like multiple sclerosis and pain, but it also has a potential side effect of inducing psychosis when people misuse cannabis and take certain types of cannabis that are available on the street. So there are a number of issues that we're looking into. First, we're looking at making synthetic small molecule drugs which can actually target the effects of cannabis and the receptors and mechanisms which make it useful, but don't affect the receptors and mechanisms in the brain that will have side effects. The other thing we're looking at is understanding the pharmacology of cannabis itself and understanding more about the physiology of certain people who react badly to cannabis, particularly teenagers.
Chris - What actually is cannabis? When we say cannabis, what are the chemicals that are having those effects?
Ruth - Okay, so cannabis contains about 60 different chemicals called 'cannabinoids'. Until relatively recently we thought that one particular cannabinoid called THC was the active component. THC produces pain relief, it produces the "munchies" [increased appetite], and it produces potential psychosis and mental illness in certain groups of people. But the exciting new thing that we're looking into now is the fact that cannabis contains a number of what were previous thought to be inert compounds which, in fact, do have a whole pharmacology of their own. And that pharmacology seems to include a number of the beneficial effects, but lack the psycho-acive side effects. So for example, cannabidiol (CBD) seems to have interesting anti-psychotic effects, anti-cancer effects, and doesn't cause the high, and doesn't cause some of the detrimental side effects. So interestingly, potentially, CBD could be a medicine alone, or it could be used as an effective combination with THC.
Chris - ...To offset some of the bad effects. Is it just present in much lower amounts, so you see a dominant effect of the THC, the bad effects? So if you put more of that in the mixture, you would negate some of those negative effects whilst still having the positive effects of the THC?
Ruth - Partly that. There's certainly a lot of good scientific evidence that THC produces fewer detrimental effects in the presence of CBD, and in fact interestingly, the cannabis that's available on the street now contains little or no CBD, so skunk cannabis is virtually free of CBD, and has high THC, and seems to be causing a lot more side effects. However, there's another angle to this which is that CBD has beneficial effects and pharmacological effects on its own. So in addition to alleviating some of the side effects, it produces a whole raft of novel pharmacology in its own right.
Chris - If this substance can have anti-psychotic effects, does that mean you could try using it in people who have psychosis, on its own, as a new form of anti-psychotic treatment?
Ruth - Potentially, yes. We're at the very early stages of understanding the pharmacology, so for example, one of the areas I'm working on is a new receptor. Drug pharmacology is based around the fact that drugs interact with receptors and these, often in the case of the brain, control neurotransmitter release and signalling. We're working on a completely new receptor for CBD and we're at the very early stages of understanding what that does in the brain. We will then start to understand potentially how we could manipulate that for therapeutic use.
Chris - In the last few years, scientists have had a go at targeting the marijuana munchies, haven't they? There was the drug Rimonabant which helped to shed 10% of body weight. It seemed quite good initially but then had a number of side effects...
Ruth - Yes. I'm glad you brought that up. There's the cannabinoid CB1 receptor which is located in the hypothalamus, which contains appetite centres, and that was the way in which it [Rimonabant] was reducing appetite. But of course, it also hits CB1 receptors all over the brain and affected mood and so on. However, interestingly, what we've discovered is that there were also cannabinoid receptors in - for example, the liver and fat cells, adipocytes and so on, which have what we would call 'peripheral effects' on metabolism. So, what we are looking at as a new innovative treatment is making molecules similar to Rimonabant, blocking the CB1 receptor, but they don't cross the blood-brain barrier, so don't get into the brain. So what we're hoping for these new therapies is they will reduce a lot of the type 2 diabetes symptoms that are associated with obesity, but they won't have the problems of blocking the CB1 receptor and the cannabinoid system in the brain which is associated with side effects affecting mood and suicidal thoughts, and so on in certain groups of people.
Chris - Are you far away?
Ruth - We've got some nice compounds that look promising, so that's the starting point for a pharmacologist. You work with chemists, you make nice small molecules. They seem to have nice properties in that they look like they could be useful as oral neural-therapeutics, but then that's where the fun starts, with all the clinical trials, raising money to do those studies, and so on. It depends on how you define 'close,' if we're close or not!