Marijuana: Risk or Remedy?

24 February 2015
Presented by Chris Smith, Kat Arney.

Cannabis is as controversial as it is complicated. Does smoking it cause schizophrenia, and can chemicals from the plant cure cancer? Plus in the news, the new breed of chemicals that are putting our ozone layer at risk and why teenage sperms are more likely to be mutants.

In this episode

01:03 - A nanotech treatment for heart disease

One in three people is affect by heart disease. A new development in nanotech could help prevent the build up of blockages in the blood.

A nanotech treatment for heart disease
with Dr Prabhas Moghe, Rutgers University at New Brunswick

Two hands forming a heart shapeOne person in every three is affected by heart disease and strokes, which are caused by our arteries becoming clogged with deposits of cholesterol. This builds up inside cells called macrophages that accumulate in the walls of damaged blood vessels. Now a team of scientists in America have developed nanoparticles that can be injected into the bloodstream, where they home in on areas where blockages are destined to occur and stop the buildup of cholesterol. Prabhas Moghe explained the study to Chris Smith...

Prabhas - Our technology is focused on developing a nanoparticle which can then reach the sites of these lesions and then block the uptake of the lipoproteins, the bad cholesterol, as they say, within the lesions. And here is where it gets very interesting because the primary character in this entire cascade is a macrophage which is an inflammatory blood cell whose job it is to clear out these lipoproteins. It's only when this process gets out of control that the macrophages tend to become inflammatory and then recruit more blood cells and essentially lead to this festering of the lesion.

Chris - I see. So, when one has damage to a blood vessel, some fats can move into the damaged site and also, some cells, macrophages go in there, initially "intending" to clear up the mess. But actually, what then is happening is that they're making an inflammatory damaged area which in and of itself then attracts more fat to go in. S o, you almost have a self-fulfilling prophecy, if you've got damage, you get more damage and this grows and slowly blocks a blood vessel up. You've made nanoparticles that can home-in on these sites and arrest the process of this growth of this plaque.

Prabhas - Yeah, you're spot on.

Chris - So, how do they do that? What are the nanoparticles doing?

Prabhas - The way that we've designed these nanoparticles was to have a high affinity to certain molecules that the inflamed macrophages express to counteract how the fats might have a way to get into the cells.

Chris - So in essence, you have got a particle which pretends to be one of the bad fats that would normally go into and damage the wall of the blood vessel and it gets in the way, stopping the bad fats from being taken up by these macrophages at these sites. So, it should stop the plaque from getting any bigger.

Prabhas - That's right.

Chris - How do you know this works and how have you proved it?

Prabhas - In this paper, we have moved from taking the lab work in vivo using animals that have a high propensity to develop heart disease. You can take these animals, give them a suitable dose of the nanoparticles, and what was exciting, these articles, not only homed-in on the sites of these lesions but also, the animals that were treated showed a significant reduction in the amount of fat that was deposited in these blood vessels. And there was a significant reduction in the obstruction.

Chris - Are these particles likely to have some side effects?

Prabhas - I'm optimistic that the safety profiles look strong. Of course, this is something that we all have to verify using longer term studies. So, that will be the part of developing this technology. We have tried this out in the conventional smaller animals. Some of which tend to be very sensitive to these nanoparticles and yet, the animals have shown no sign of adverse events, as you will. I'm hopeful that these molecules are well-tolerated, particularly because they degrade into molecules that are basically secreted outside the body.

Kat - Prabhas Moghe. He's from Rutgers University in the US.

05:10 - The hidden threat to the ozone layer

Despite international efforts, our ozone layer may still be at risk from chemicals that are currently unregulated...

The hidden threat to the ozone layer
with Professor Martyn Chipperfield, University of Leeds

If you were around in the 1980s you probably remember the concern about theHole in the Ozone layer hole in the ozone layer that protects the Earth from harmful UV rays. This was caused by man-made chemicals known as chloro-fluoro-carbons, or CFCs, escaping from the Earth's surface and heading up into the stratosphere where they reacted with the ozone layer and depleted it. An international effort led to a worldwide ban on CFCs, and the ozone layer began to recover. But now researchers led by Martyn Chipperfield at the University of Leeds, have shown that other, similar chemicals with shorter lifespans are still getting up into the atmosphere and could be having an impact on ozone. He spoke to Kat Arney about this chemical threat, and where it comes from...

Martyn - These so-called shorter-lived gases come from both natural and anthropogenic sources.

 Kat - So, that's human sources.

 Martyn - Yes, that's right. The natural sources for the compounds that contain bromine are related to ocean processes. They're released by seaweed and by phytoplankton in the ocean. And then more recently, it's become apparent that human activity is making a contribution through mainly chlorine compounds. What is known is compounds such a dichloromethane. They're used as feedstocks in the production of other chemicals such as hydrofluorocarbons. Ironically, these are the compounds which were supposedly ozone-friendly replacements for the chlorofluorocarbons. In our paper, we showed some results that show quite large recent increases in some of these chlorinated compounds, but in fact although we can see them in the atmosphere and we see regions where they're very elevated such as South East Asia, around China, India, the exact sources of these compounds is not known. That's a topic for future research, now we've detected that they're present.

 Kat - So, now that we know that they're present, what are they doing? Is there evidence that they are causing a significant impact on the ozone layer?

 Martyn - Yes, there is. I mean, certainly for the natural brominated compounds we've known for a few years that these compounds reach the stratosphere and they make about 25% contribution to the bromine amount in the stratosphere, and therefore a similar proportion to the ozone depletion caused by those overall bromine compounds. For the anthropogenic chlorine compounds, we can see that they do reach the stratosphere. Their contribution is smaller than the chlorine that comes from CFCs, but as CFCs are now controlled and their abundance is decreasing and, as far as we can see, the contribution of these short-lived compounds is increasing, we expect that contribution to become more important in the future.

 Kat - Why haven't they been banned if they're causing these problems?

 Martyn - The treaty that protects the ozone layer, called the Montreal Protocol, has been very successful. It's one of these sort of - maybe the prime example of a - global, international treaty to address an environmental problem. So, why it's been very effective at controlling gases such as chlorofluorocarbons, it hasn't paid attention to these so-called short-lived compounds. That's partly because scientists thought that the shorter lived species wouldn't be around in the atmosphere long enough to actually reach the stratosphere and their abundance had not been detected to appreciable extents in the atmosphere.

 Kat - A lot of scientists around the world are making various models of how our climate is changing, how our activity and natural activities are affecting our climate. Is this something now that needs to be added into the mix of these climate models?

 Martyn - Well already, these kind of models do include chemistry. in our group, we are doing lots of work which includes adding detailed chemical processes into these models because climate change is not just about CO2 which is relatively inert. It's about other gases as well such as methane and CFCs, ozone. So, we're building those models. In fact, the coming state of the art is to work towards what's called "Earth system models" that include a whole range of processes from land surface processes, oceanographic processes that can really get feedbacks of how changes to chemistry in the atmosphere is impacting climate change.

 Kat - Martyn Chipperfield there from the University of Leeds.

09:35 - FameLab: Astrobiology

This month, Cambridge scientists are battling it out in an effort to become the city's FameLab champion! We hear from the semi-finalist.

FameLab: Astrobiology
with Patrick Short, University of Cambridge

FameLab International Semi-Final 2014Cambridge is currently in the run up the local FameLab final! FameLab is a competition where scientists battle it out to be the best at giving engaging short talks on their favourite areas of research. Six finalists have been chosen by a panel of judges and they're set to go head to head on 9th March. Before the final, we're hearing from a selection of them.  Patrick Short gave Kat Arney a whirlwind introduction to his research and chosen talk area: astrobiology...

Patrick - Right. So, I'm a first year PhD student here at Cambridge. My programme is mathematical genomics and medicine. But my topic actually is quite different from mathematical genetics but that's what I'm studying here so far.

Kat - So, what is your chosen topic?

Patrick - So, I'm talking about the existence or non-existence of extraterrestrial, intelligent life outside of Earth.

Kat - If you're working in genetics, what drew you to that? is there nothing interesting enough in your own field?

Patrick - Well, there's plenty interesting. The thing about this topic is...

Kat - Maybe next year then.

Patrick - Right. It doesn't affect your life even remotely, right? Your everyday life, but it fascinates us for some reason. Is there something else out there? People have been wondering it for a long time and really, we don't have many answers. so, I thought I'd kind of explore why that might be.

Kat - So, as with all our FameLab finalists, we're going to hear from you. So, you have - I believe your 3-minute talk prepared. Do you want a little counting to it?

Patrick - Yes, that would be great. 

Kat - 3, 2, 1, go!

Patrick - Alright, so many of the listeners out there have probably looked out into the night sky and tried to contemplate how vast the universe is. And probably, many of us too have wondered if there's some sort of intelligent life somewhere out there. 

Any physicists that are listening will tell you that the universe is billions of light-years across. If they know anything about Drake's equation, they'll tell you that for every grain of sand on Earth, there are a hundred habitable planets out there somewhere in the universe. So surely, with a hundred habitable planets for every grain of sand, the universe must be absolutely teaming with life. 

But if that's the case then where is everybody? 

This was noticed by Enrico Fermi and it's called Fermi's paradox. He wondered the same thing. There are really a few possibilities why this might be and scientists have debated and questioned them for centuries. They range from the practical, to the terrifying, to what is in my opinion, somewhat depressing. 

So possibly, there's plenty of intelligent life out there but much like us, they have trouble getting out of their own neighbourhood. We only got to the moon pretty recently, we're trying to find our way to Mars with people. Maybe everybody else has trouble just getting off their own planet as well. But then again, our civilisation is fairly young in the history of the universe. So, if another one had started just a million years before us, you can imagine how advanced they'd be by now. 

So sort of taking that to the other extreme, maybe there's plenty of intelligent life out there and they're actually watching us. We're in some sort of zoo or a national park. Maybe they're studying us, running experiments, trying to figure out what will happen first: Will they all kill each other or destroy the environment? 

And then if you take that to its more extreme end, then maybe they're so intelligent that compared to us, that we, compared to them are the same as a colony of ants are compared to us. So, you've probably not recently tried to explain to your local colony of ants what the importance of space shuttle design is, or why you need to keep an updated LinkedIn profile, chances are, you just don't really bother. They communicate in pheromones and have about 4 words and we have far more than that. 

So really, the truth I guess is we really have no idea. 

We've been searching the night sky for radio waves and haven't heard a peep for 40 years. So maybe we are all alone here, just a statistical improbability in a vast universe. But then again, maybe there is something else out there and if that's the case, then we can either stay here on Earth, continue building our anthills and digging our tunnels, or we can look towards the sky and try to see what's out there.

Chris - Patrick, that was actually 2.5 minutes.

Patrick - Great!

Chris - Brilliant timing. Well done.

Patrick - Blasted through it.

Chris - Had me spellbound. I mean, it's a very important topic whether or not there is life out there because of course, it tells us a lot about where we came from as well and the likelihood of us happening again.

Patrick - Right, no doubt.

14:16 - Teenagers produce more mutant sperm

A new study claims that teenage dads might be more likely to have babies with birth defects.

Teenagers produce more mutant sperm
with Dr Peter Forster, University of Cambridge

Graffiti sperm A new study claims that teenage dads might be more likely to have babies with birth defects, due to higher rates of mutation in their sperm. Chris Smith asked Peter Forster from Cambridge University about the paper...

Peter - Teenage fathers have a much higher mutation rate than we have thought up to now. You would've thought young fathers have good DNA and therefore, the children should be healthy at least healthier than on average. But what you see is the opposite. It is the teenage fathers who are associated with pregnancies which turn out to have birth defects at an increased percentage.

Chris - What sort of rates are we seeing?

Peter - So, in the USA overall, we see that 1.5% of the births have birth defects. In the teenage father's cases, the birth defects increased by about 30%, so to about 2%.

Chris - Well, what do you think is going on?

Peter - Well, that is a question we didn't directly ask in our current research, but it turns out that we may have found a solution because what we see in our own research is that the teenage fathers have an unexpectedly high number of mutations. It is 6 times higher than the teenage girls and secondly, the fathers are even more highly mutated in their sperm and in the children they produce than the fathers who are 20, 25, 30 years old.

Chris - So, there's a sort of bleep. When they first become potentially reproductively active post puberty, their sperm contain more genetic errors, mutations then than they do later.

Peter - I'd say so. It's the case that, to begin with, you have these hump of mutations and we don't know the reason for this yet. But there are two potential explanations. One is that, to produce a sperm cell, you need precursor cells which have to divide and each time it divides, there's the opportunity for an error to creep into the DNA. There might be cell divisions going on long before puberty during boyhood which we don't know anything about and this is causing this accumulation of errors. The alternative explanation is that you have the cells which have been quiet for 10, 15 years have not divided, have not done anything during boyhood. And now, these precursor cells suddenly have to start producing sperm as puberty sets in and they're not quite ready yet. And they have a higher error rate than would normally be the case.

Chris - How did you track this down? How did you find this relationship?

Peter - What we have are our clients who come into our institute who want a paternity test. And so, we generally have the mother, the father, and the child in question. And also, we have asylum seekers who wish reunite their families and therefore, they want their children and their wife tested to prove to the authorities that they are indeed one biological family and have a right to be granted asylum as a whole. It is these clients who, over the past 20 years have generated us with a nice database of 24,000 parents with their children from which we can see how often these mutations happen and how these mutations relate to the ages of the parents.

Chris - How old does a father have to be then in order not to have this increased risk of passing on more genetic changes?

Peter - Well roughly, the best time to be a father, so the minimal risk of having a child with defects is between 20 and 35 years of age. But to put it into perspective, even a 40-year-old father or 15-year-old father will, with more than 97% probability have a healthy child.

18:14 - Measuring the world's happiness

Do you use more happy phrases in a day? A new study shows that languages are biased towards more positive words.

Measuring the world's happiness
with Professor Peter Dodds, Vermont University

Happy wordsScientists have come up with a way to measure the mood of a whole nation by looking at the words being used. And the analysis - of over 100,000 words from ten languages spoken across the world - has also found that there are twice as many words with happy meanings as sad ones, as Khalil Thirlaway heard from Vermont University's Peter Dodds...

Peter D - The motivation from the start was to build an instrument that would measure the emotional signal coming out of populations. The way we could do this is through text. We needed to cover as much of the world as we could. So, we have Spanish, Portuguese, Korean, Chinese, Russian, we have Arabic, we have English - so, very, very distributed. So obviously, there are many languages in the world. We do feel like this has spanned the globe, spanned cultures, spanned kinds of languages.

Khalil - How did you choose which words to analyse within those languages?

Peter D - If you want to say anything about a language, you have to of course, really survey a language properly. And so, we needed to created word lists based on the words that people really use. So, there's no way to say, "Oh, here are the 10,000 most common words in English." You can't do that. you have to say, "I'm going to go to this body of text and there could be 20 years of the New York Times, it might be 3 years of Twitter, and we went to Google books as well. We went to movie and TV subtitles. We chose the most commonly used words. The fundamental aspect that we needed was that we needed to know what the happiness scores are for words. And so, we asked people his word in isolation. You know, and it could be laughter or truck or banana, and how do you feel about that word. So neutral is one star and you go up to 5 stars of happiness and then 5 stars the other way for sadness, making kind of a 9-point scale.

Khalil - What did you find you analysed these words?

Peter D - We just noticed that there were more happy words than sad words. So, that was kind of a curious thing. There are definitely negative words. People talk about negative things, but if you look across a large enough range of words, big enough texts, we see confirmation if you like that natural language is positively biased that people talk about things and they describe them in certain ways that have - on average - a more positive skew to them. It's pretty strong. So, if you take out the words that were rated as basically neutral, one Spanish copy has 90% to 10% in terms of positive to negative. For Chinese books, it was something like 70 to 30%. So, that's kind of a range. So, it's more than double. What we've got now is a really large scale study of the words that people really use.

Khalil - What do you think might be causing this positive bias in languages?

Peter D - Language is our great social technology. We are social beings, so I think it's encoding the fact that languages is this glue that connect us together. Of course, we use it to talk about negative things. We must do that, but for the most part, we're discussing things that help us keep moving along.

Khalil - What does this mean for the future?

Peter D - Our sort of main hope has been to contribute another dial on the dashboard of society, next to the very traditional ones - GDP kind of things and economic measures. It's very hard to know what a billion people are thinking or 10 million or 100 million. Everyone's wealth might be going up, but if well-being is not going up then that's a problem. It may be that we need some level of grumpiness for societies to kind of prosper, stiff upper lip sort of thing. But we need to quantify this much murkier aspect.

Khalil - So, you're saying that being able to take the temperature of society's feelings will make it easier for well-being to be paid attention to in policy making rather than just easily numerical things like productivity or tax revenue or stuff like that.

Peter D - Absolutely. This happens over and over again. If you can put a number on something, then it has much more chance of being taken notice of. It is a mistake, right? So, we know that well-being matters. There are certain things you can measure well and they get much more attention paid to them. And you eventually can make the mistake that they're the meaningful ones as well or the important ones. So, instead of complaining about that, we're trying to get a number out there that people can focus on.

23:03 - What is cannabis?

You've probably heard a lot about weed, and maybe even tried it, but how much do you know about the controversial plant?

What is cannabis?
with Professor Monique Simmonds, Kew Gardens

Cannabis plantIt goes by many names: pot, grass, dope, draw, hash, weed, Mary Jane,  blow, buds and even broccoli. These nicknames refer to the drug cannabis, which comes from the marijuana plant. But as well as being used as a recreational drug by humans for hundreds if not thousands of years, it's also been put to medical use. It's the cannabinoid chemicals made by the plant, concentrated chiefly in the flowers and seeds, that are responsible for its infamous high, as well as its medicinal properties.

Graihagh Jackson took a trip down to Kew Gardens to meet Deputy director of Science, Monique Simmonds, and learn more about the drug and the plant it is from.

Graihagh - I'm sat, fanning myself underneath a banana tree. I'm shrouded in a fine humid mist and around me is an assortment of beautiful tropical trees and brightly coloured shrubbery. All I need is a piña colada and I might as well be in paradise. Except I'm in London and it's a bleak winter's day outside. Kew Garden has the most incredible array of plants from across the world. Currently, I'm in the iconic Victorian Palm House where all the tropical triffids live. But this is only one of many greenhouses which contain many, many more plants. Ironically though, I'm here to talk about a plant that Kew doesn't have. It's actually illegal for them to grow it and that plant is cannabis.

Monique - I'm Monique Simmonds and I'm the Deputy Director of Science at the Royal Botanic Gardens of Kew. Cannabis is a plant that is found in parts of Asia. There are different species. There's about 3 different species of cannabis but they're actually whats termed chemotypes and they're the ones that vary in the chemical composition. They vary because of environmental conditions but also, people have selected lines that are high in the group of compounds that are often associated with hallucinogen, their activity, and that's the cannabinoid compounds, often called THCs.

Graihagh - While there are only 3 species of the cannabis plant, there are many variations which produce different amounts of different chemicals and these are called chemotypes. This variation can occur naturally but more recently, humans have been selectively breeding them to contain more of a certain chemical called THC.

Monique - It's the chemotypes that are the key here, where they're grown and what they're grown for because of course, traditionally in the west, cannabis was grown as a form of hemp.

Graihagh - So, what's the difference between the cannabis you smoke then and hemp?

Monique - Well, hemp is low in the THC compounds. So, you could grow a field of them and you'd extract very low levels of the active ingredients whereas if you're in parts of Asia, those are traditionally used, it would often be the seeds etc, which were traditionally used in medicines. They all have the higher levels of the active compounds of THCs.

Graihagh - So, what is it in cannabis that gives us this mind altering highs if you like?

Monique - THC which is one of the compounds is often referred to as being associated with its highs. But there's a range of different compounds. There are about 19 compounds that are thought to contribute to the beneficial effects. I will emphasise that the plant has got a long use for benefits for treating different forms of pain also, for affecting depression. Well, we have big challenges at the moment because it's very, very difficult to study the plant because you need to have a license. Because it's being used as a recreational drug for people to get a high, and it can cause really bad effects on a lot of people who do take it, there are negative impacts. It's banned and therefore, there are restrictions on how it can be researched. So here at Kew, what we'd really like to have is more research being done on the chemistry, a better understanding of the use of these plants, the effect that they can have on the body. But it's clear from the work that has been done that they affect different parts of the brain, they had effects on mood, plus also relaxant and on pain relief.

Graihagh - Is it only cannabis that has these compounds that could be beneficial?

Monique - The range of THCs, yes, they are very often restricted and nature often does that. It comes up with a group of plants where they are restricted. And that's often associated with the genes in those groups of plants affecting the biosynthetic pathways that will result in the expression of these compounds. Most likely, the next question is, what role do they play in the plants?

Graihagh - Precisely. I was going to say, it's like a defence tactic?

Monique - We actually don't know exactly the role that they do have. They're known to have a negative effect on insects and one of the activities is antifeedants for a group of insects. But they most likely have other roles in the plant. It's just very difficult to study that. Nature would have evolved them I'm sure for some purposes. It's expensive for a plant to produce these compounds. They must have a role in the plant.

Kat - That's Monique Simmonds, Deputy Director of Science at Kew Gardens speaking with Graihagh Jackson.

29:22 - Medical uses of marijuana

Why do the chemicals from marijuana affect our brains and are there any medical applications for these compounds?

Medical uses of marijuana
with Dr Willie Notcutt, James Paget Hospital

Sativex Cannabis produces hundreds of chemicals, called cannabinoids, which can affect people in different ways. As well as the well known high, there are other potential medical benefits from these cannabinoids. Dr Willie Notcutt, a pain specialist from James Paget Hospital in Norfolk, took Chris Smith through these chemicals, explaining why chemicals from a plant have such a marked effect on both body and mind...

Willie - Well, there is a range of chemicals there. Perhaps to understand them how they work, we need just to backtrack and think of morphine. Everyone knows about endorphins and talks about endorphins, which are the brain's own morphine-like chemicals. These chemicals lock on to what we call opiate receptors or nerve cells and relieve pain for example. But endorphins are very different chemically from the morphine, which comes from the opium plant. 

Similarly, we have a group of chemicals in the brain and receptors called the endocannabinoids, like endorphins, endocannabinoids. This is a system of chemicals and receptors in the brain, which have a range of effects. But again, endocannabinoids that work in the brain are totally different from the THC and CBD, which are the two of the main chemicals that people know about that come from the marijuana plant.

Chris - And your point being that it just so happens that because the plant makes those chemicals and they bear a resemblance - chemically speaking - to what the brain is using when they're put into the body, they can produce brain altering effects.

Willie - Yes, they mimic just like morphine does. Morphine mimics the endorphins in the brain.

Chris - When they're in the brain, what in fact do those, either the natural compounds, the endocannabinoids or the THC and the CBD you've mentioned coming out of the cannabis plant, what effect do those chemicals have on nerve cells in the brain?

Willie - The two broad effects I think, which we've been studying, the first is, they're rather like a damping mechanism. They damp down pain for example. They're rather like, I would think the sprinkler system in a building. When there's a fire, it breaks out, the sprinkler system comes on. It doesn't necessarily put the fire out but damps it down. I think endocannabinoids and the cannabinoids from the plant do much the same sort of job. But they also have a role in damping down inflammation, both within the nervous system and outside of it as well.

Chris - I was going to ask you, are they active only in the brain or do other parts of the body also have the ability to respond to these chemicals?

Willie - No, the second, outside the body, I mean, there are studies going on into ulcerative colitis and inflammatory condition of the bowel. They've been used in treating the pain of rheumatoid arthritis and found to reflect not only the pain but also, the inflammation that's going on in the various joints that are affected by the condition.

Chris - Have they actually been proper clinical trials or is most of the knowledge about the medical properties and potential medical properties, is that based on largely hearsay and people saying, "Well, I've tried this myself at home in my living room and then I seem to get some relief by using this stuff." What's the situation with that?

Willie - This really led to trials getting underway, was what particularly the patients with multiple sclerosis were telling us. But there's been an extensive programme of proper clinical trials, which have been passed by the MHRA, the home office in London, as being standardised in good quality clinical trials. These have been going on now for 15 years and broadening out now into other areas - and again, based on basic science, there's been basic science onto these compounds going on now for 40 to 50 years. And they, and almost the clinical research can't keep up with what is coming out of the basic science labs and similar sorts of research.

Chris - How are doctors seeking to administer the agent because obviously, one doesn't want to be encouraging people to smoke this stuff? So, there must be safer ways to administer the agent.

Willie -  Yes. This was a major challenge in the late '90s, was to develop extracts of cannabis that were of medicinal quality. The first was to standardise the amount of THC and CBD that we were going to be using. And so, it needed to be extracted from the plant so that there were no impurities. And then we had to have a delivery system. The one that we've been currently using principally spraying it under the tongue so it's absorbed through the lining of the mouth. We had to prove in the clinical trials that this was safe to do it and didn't produce the sorts of psychosis that you're going to be talking about later. Most of all of course, that it was going to be effective for patients. That patients were going to get benefit from it and actually, prove by clinical trial, what people have described for many, many years as anecdotes about their own experiences, now to prove it. so, we can say: "here is a proven medicine that can be used and can be applied in different ways."

Chris - Apart from the conditions you've mentioned, ulcerative colitis in the intestine. Multiple sclerosis and some pain states, what other conditions might be amenable and treatable using these sorts of chemicals - THC and CBD?

Willie - Well, there's a huge range of - if I just stick on pain - there's a huge range of pain states that don't have treatments for them or have insufficient treatment out there. But there's been some work in diabetes, psychosis. There are some new, very exciting work going on with the agent, cannabidiol or CBD, which really has no effect, no psychoactive effect on the brain in terms of like the high of THC. But there's work going on with that in the treatment of childhood epilepsy and some very exciting results being seen of people who, of children who have continuous fits and then been given the agent, are given CBD and finding that the fits are totally controlled. So, there's a range of things going on. There's also work on, consideration of work on autism, even there's some work going on possibly or into Alzheimer's disease because we know that the cannabinoids are protective and protect against inflammation, particularly within the brain. So, there's a huge range of exciting possibilities out there to be researched into.

36:22 - Could cannabis cure cancer?

Chemicals in cannabis have shown promising results in halting the growth of cancerous cells in the lab. But will this translate into a cure?

Could cannabis cure cancer?
with Dr Wai Liu, St George's, University of London

Cannabis plantCannabis contains many chemicals, some of which can be used to help people with MS in the drug Sativex. Another disease that might stand to benefit from certain compounds from the plant is cancer. But will the exiting lab results translate to an actual medical treatment, and is self medicating a good idea? Wai Liu, from St George's University of London, took Kat Arney through the research...

Kat - So, I mean when it comes to talking about cannabinoids and cancer, there's the aspect of relieving pain and palliative care. But there's a whole other aspect that's very exciting and that's potential of cannabinoids to treat cancer. Tell me about the kind of research that's been done into these cannabis chemicals and whether they have any effect on cancer cells.

Wai - Yeah, so these cannabis type drugs, the ones we really focus on are the THC every people have been talking about and also the CBD compound which seems to lighten the psychoactive properties. And most of these work have been really performed in lab based studies and also, some animal studies. And they've been shown to be quite active. They have the ability to really reverse that effects that cancer cells have on bodies and in doing so, somehow reverse the whole process that we don't want to see cancer breeding and growing.

Kat - So, tell me a little bit more about how cannabinoids are actually acting on cancer cells? What do they seem to be doing?

Wai - So, what we've seen is that cannabinoids, how they get in, we're not too sure. Sometimes they bind to these receptors that people have been mentioning and sometimes they can actually enter the cancer cells using different pathways which we're not too sure right now. What they seem to do, they tend to target these so-called signalling pathways. What these are, these are some pathways that are mutated in cancer cells which turns a normal cell into a cancer cell.

Kat - They're like the signals that tell cells to kind of keep growing, grow out, control.

Wai - Absolutely. So, these cells are growing out to control and lots of drugs out there, currently at the moment are trying to target these particular signalling pathways. And what we've shown that this THC and CBD compounds can actually turn these signals off and in doing so, reverse the process of cancer.

Kat - Now, there's a lot of very exciting lab research, things in animal studies but also from all kinds of cancer drugs that people are researching, they seem to work really well in the lab. you get great results in animal tumours and then you take them into the clinic and they don't seem to work in patients. Where are we with turning the lab research and the huge number of papers that have been published into finding out whether this actually works in patients?

Wai - I think we actually are really in exciting time right now. It is this transition from lab based research and transiting it into medicine into the clinic.

Kat - But have there been any clinical trial so far?

Wai - There's clinical trials ongoing at the moment and I do know 1 or 2 are actively recruiting in the UK and in the US. But the only one that's been reported in the past, the results haven't been great. The reason being, it's difficult to actually get the right mixture of the drugs that everyone's been talking about in this programme. So, the difficulty is to optimise the doses that we need to use of either THC or CBD and once we establish those - and these are precisely what these clinical trials are attempting to do. I'm almost certain we should get some good results.

Kat - And in terms of cannabis for cancer, sometimes people might say, should you just go down to the corner shop, buy some cannabis and start taking it. Is that going to treat people's cancer? Is that going to be effective?

Wai - That's one question I get asked quite a bit. This whole idea that, "Can we take cannabis rather than cannabinoids?" I suppose, the honest answer is, we don't know. There's lots of anecdotes. We often see on the net many, many times where cannabis oil can be used effectively to treat cancers. I'm not saying this is not the case, but we live in an age where clinical trials have to be performed to ensure that safety is of paramount importance and people who do take these so-called cannabinoids do more harm than good. I suppose this all halts back to this idea of aspirin and we talk about aspirin quite a bit. This whole idea aspirin is quite good to deviate pain, but the aspirin came from the white willow and no one suggested that we should be chewing on white willow.

Kat - I mean, the thing I understand about the original white willow compounds because then it was changed and made to be less irritating to the stomach and to be better. the cannabinoid chemicals from plants, are they actually the best drugs, the best cannabinoid drugs?

Wai - Yes. So, the difficulty is that cannabis plant itself contains quite a few - that people say, between 100 to 200 different chemicals and each one has their own activity. There's lots of data that suggest that some cannabinoids, the minor cannabinoids can actually reverse antagonise the activity of things like THC and CBD. So, what you could do by smoking cannabis or taking cannabis, the whole plant itself is to remove or reverse the actual effects that...

Kat - Counteract it. so, you're doing one good on one hand and actually, counter balancing it.

Wai - Exactly. And so, we have a situation where the patient doesn't benefit at all by taking a whole cannabis. I suppose one thing Kat, that's important to stress is that some of these cannabinoids can actually antagonise medicines that people are already taking. So, if you've got a cancer patient who's taking Cisplatin or some kind of drug, cannabis can actually antagonise that if not taken carefully.

Kat - So, if you look on social media, things like Facebook, for my day job, when I'm not doing this, I work for cancer research UK and often, we get people saying, "Weeds that cure man". If I put it to you bluntly, is cannabis the cure for cancer? What's your take on this?

Wai - Well, first of all, there's no all-out cure for cancer unfortunately, but what I can say is that these cannabinoids, these cannabis based substances can have a role to play. If used correctly and if possible, in combination with other drugs, you can actually reverse certain aspects of cancer. You probably won't cure it, but you'll go a long way in making cancer more of a chronic condition. I think you can live with and you end up dying with cancer rather than dying of cancer. I suppose that's the ultimate aim. Of course, everyone wants to cure cancer, but unfortunately, there's no one single drug that can do that.

Kat - In terms of where the research is going now, we heard from Monique that it's hard to do this kind of research. give us a picture of maybe over the next 5 years because I certainly watched with interest in America where the legislative frameworks eased up a bit. Where do you think things are going to be going? Where are the needs to research these drugs?

Wai - Sure. If we take a medicine that can treat cancer as one that can target these cell signalling pathways which I eluded to earlier, cannabinoids can do that and we have lots of data to suggest that. and if we're serious about trying to find a new medicine and to fight some forms of cancer, we really need to investigate these cannabinoids. I'm not saying we should investigate cannabis. We might investigate cannabis as a whole plant, but right now, we have certain chemicals from the plant that can work against cancer and that's something we should be doing hopefully in the next few years. We can start exploring these, what's the mechanisms, how do these drugs work, what drugs can we use this with, and essentially just to maximise the opportunities that these plants, these drugs can provide us with.

Kat -   And I guess ultimately, getting benefit to as many patients as possible through this kind of information.

Wai - Absolutely. That's the most important. Let's not forget, we're not talking, not like cannabis that's a drug that causes you these highs. We're talking about the potential of these cannabis based drugs that can help patients with cancer.

Kat - Thank you very much. That's Wai Liu from St. George's University of London.

   

43:33 - Skunk and schizophrenia

Many headlines report on the risk of cannabis users developing schizophrenia, but the real story is much more complicated...

Skunk and schizophrenia
with Suzi Gage, University of Bristol

Smoking a spliffOn the streets, cannabis is one of the most commonly used illegal drugs. Recent news headlines announced that 1 in 4 cases of mental psychosis might be due to the super-strong "skunk" form of cannabis and that the risk of psychosis is five times higher for those who use it every day compared with non-users. But does cannabis cause mental illness, or are people who are destined to become mentally ill just more likely to use it in the first place? Suzi Gage from Bristol University works on the link between cannabis and psychotic episodes, and explained to Chris Smith why the association between cannabis and schizophrenia is more complicated than many headlines imply... 

Suzi - Psychosis is one aspect of Schizophrenia but you can also just have psychosis on its own and it refers to things that are present that shouldn't be there. So, you might have hallucinations. So, you could hear voices or see things, but hallucinations can affect any of the senses as well. You might experience delusions. So, you might feel like someone is out to get you, feelings of persecution or you might feel like your're a very important person, like you're sort of a king or something but no one realises those kind of thoughts that don't really have any real world truth to them. There's also sort of thought insertion or broadcaster withdrawal where you think that someone else is interfering with your thoughts or other people can hear your thoughts, that sort of thing.

Chris - So, why might cannabis - let's not say that it does or it doesn't at this stage - but why might exposure to the chemicals in cannabis provoke those sorts of symptoms in a patient?

Suzi - Well, the reason that it was first investigated was because intoxication effects of cannabis can induce  transient psychotic-like experiences. This has been shown in randomised trials as well that if you give people THC - the compound that we've been talking about a lot through the show that this will induce transient psychotic experiences. But of course, that's not the same as saying that long term use will cause something like Schizophrenia. That's much harder to research because you can't randomly assign a group of teenagers, half of them to take cannabis for however, many years, and half of them not to and see what happens. So, you can only look observationally and the people who choose to smoke cannabis are going to be different from the people who choose not to smoke cannabis for all sorts of reasons other than the cannabis use.

Chris - Including potentially because they're already feeling in some way mentally unwell or unstable. And they find perhaps in their case that cannabis helps to put them on a more, even kill or helps them to cope better the symptoms they're experiencing.

Suzi - Well absolutely. That's obviously not necessarily the case. But it's something that when people are conducting these observational studies, they have to be really careful to try and exclude anyone who already had any kind of psychotic experiences before they started using cannabis in order to try and get a bit of a better handle and whether it's actually the cannabis causing the psychosis.

Chris - So, what work have you done to try to disentangle those two and try to work out which it is whether the cannabis comes first and causes the Schizophrenia or whether the predisposition to mental illness comes along and causes people to use more cannabis?

Suzi - So, I've been using a data set based in Bristol where I work which is called Children of the '90s. This is a longitudinal birth cohort. So, lots of pregnant women in Bristol and the surrounding areas were recruited in the 1990s. And them and their kids have been followed up ever since. So, the kids are now not kids anymore. They're in their 20s. So, I'm not actually looking at Schizophrenia as an outcome. I'm looking at psychotic experiences. So,  non-clinical unusual experiences that people might have that are sort of akin to psychosis.

What I found was that although we see an association between cannabis and later, psychotic experiences, like lots and lots of other studies have shown as well, what I found was after I took into account a lot of the other things that might have also been impacting on this, the size of the association actually got quite a lot smaller until we couldn't be really sure that it was actually any different from no effect.

Chris - So, where do these headlines from researchers elsewhere in the UK that surfaced in the last month saying that maybe 1 in 4 cases - that's a lot isn't it - 1 in 4 of mental cases and presentations might be due to exposure to super strong forms of cannabis? And that in fact, people are 5 times more likely to develop these mental illnesses if they smoke this stuff.

Suzi - So, a lot of these headlines came from one particular paper and the paper itself is absolutely brilliant. But the headlines slightly overegged it as  can often be the case when it's such on an emotive issue. So, this particular study was looking at sort of hospitalisation or initial hospitalisation for first episode of psychosis. So, this is a more severe outcome than the one I've been looking at. And what they found was that people who'd smoked skunk every day had a much higher likelihood to have been a psychosis case compared to a control group that they also sampled.

But they're very clear  in their journal article that they can't be sure that the association seen in their study is causal. They also split their sample into people who reported using skunk and people who reported using hash. So, they kind of used these terms as shorthand for skunk being very high in THC and very low in cannabidiol which we've been talking about earlier. Whereas hash being slightly less high in THC but having a sort of equivalent amount of cannabidiol. But this was only people self-reporting what type of cannabis they were using. They didn't collect samples or anything, so they can't actually be really sure. But there does seem to be evidence that cannabidiol might be anti-psychotic. That's something that's being actively researched at the moment. Which if was the case, would certainly - their results would be well on the way to helping, to try and tease these apart whether it might be that cannabis, that's now grown under hydroponic lights which seems to be much higher in THC but much lower in cannabidiol could be what's driving this link that we see between cannabis and psychosis.

49:26 - Q&A: Researching cannabis

The panel discuss the various frustrations and complications of working with such a controversial plant.

Q&A: Researching cannabis
with Dr Willie Notcutt, Dr Wai Liu, Dr Suzi Gage

CannabisThe guests from the show return for a Q&A on the marijuana plant and the research into it's medical uses, discussing also the frustrations of working with such a controversial plant. Chris Smith began by asking Willie Notcutt for his take on whether we could minimise some of the negative impacts of cannabis in medical applications...

Willie - Well, I think in a way, we have done - this has been done already. I mean, the work that's been done over the last 15 years on the cannabis extract called Sativex has shown virtually no psychoactive effect at all. And certainly, no more than one would expect with an equivalent group of drugs which we use for example for pain management or managing spasticity. So, from that point of view, I think that - and sorry, the compound that we've been using is a mixture, is a blend of THC and CBD  which have been known since the early '80s. CBD has been known to block some psychoactive effects of THC. It's been a well-received drug. We found that when used properly as a medicine, we need very low doses of it in controlling spasticity or in controlling pain. Patients, yes, they may get some side effects of dizziness, drowsiness, but nothing equivalent to the sort of effects that your last correspondent was talking about.

Chris - Thank you and Wai Liu, what about the point that some people are asking us, what about the fact that some forms of cannabis when you smoke them for example can be very carcinogenic?

Wai - Yeah. Some people always argue that the carcinogenic properties could be due to mixture with tobacco. whether or not cannabinoids or cannabis themselves are cancerous really the jury's still out. But it's really I suppose this whole idea that the tobacco, you mixed it, which is mixed with it can actually be the one that's causing the cancer.

Kat - And I was going to ask, in terms of things like the one clinical trial that's been done and what people are working towards for using cannabinoids for treating cancer, how would they be administered? Presumably, you wouldn't go to a doctor and they hand you over a massive bifta?

Wai - Hopefully, not. When it comes to clinical trials, I think the ones that are being tested predominantly were ones that were used as a spray. And then the Sativex people have talked about in the past and that's, I think the major one or the ones that people being investigating.

Kat - And we hear also of people for example on the internet using cannabis oil again and I believe so, ingesting it, eating it. is that a good way of delivering cannabinoids into the cancers, into the places where they're needed?

Wai - The problem with ingesting cannabis or in any form is the whole idea that these cannabinoids have different types of chemicals that can actually antagonise one another. And depending on how you get it into your system, you can actually cause more harm than good. That's the reason why people try to purify in a first instance to see if the concepts is correct, that is they are anti-cancerous.

Kat - And I did see something about the risk of increased pesticides and things like that in these oils because they're concentrating them right down. Is that also a risk?

Wai - Depending on the source of these marijuana plants, you can actually get other things interfering with your whole procedure of extraction, and that can cause more problems than you need.

Chris - Suzi, there's an interesting Tweet here which is coming from Jimmy Cullen who says, "Are cannabinoids getting more research attention because they're a very promising option now or just because cannabis is a hot topic?"

Suzi - I think that's a good question, but in terms of Schizophrenia, Schizophrenia is such a debilitating disorder and of all the risk factors that are known about it, most are really, really hard to modify. So, if cannabis is a modifiable risk factor for psychosis or Schizophrenia then it presents a quite unique opportunity. So, that's why I think there's lots of research in it rather than it being a sort of hot topic. But there've been longitudinal studies being ran looking at cannabis since the early 1990s. So perhaps it's getting more media attention now because it's a hot topic. But I think the research has been going on for a long time.

Chris - One Tweet we did have to @nakedscientists, someone saying, "Is it just frustrating that these chemicals that are so useful and so powerful are also bound up in a - to all intents and purposes - recreational drug and this is a major frustration in terms of stopping research effort.

Wai - Yeah, that's a very, very good point. The whole idea that it's cannabis that are so-called evil which the psychoactive substance that can possibly be helpful in cancer. And things like - I normally say to people is, if we were to call something else, let's call it the BBC drug for the sake of argument, would there more interest in it and if so, where's the problem?

Kat - So, you're really arguing that we should be talking about the cannabinoids, the chemicals themselves as in, we would talk about aspirin rather than white willow.

Wai - Absolutely and it's because it's all a murky, it's all mixed together cannabis; cannabinoids. I suppose to stress that these are cannabinoids. These are agents that have been derived from the cannabis plant which have these anti-cancer properties and that's something that we should really be exploring.

Kat - And people are trying to make synthetic cannabinoids and these kind of chemicals that look like THC or CBD and trying to make those in the lab.

Wai - Yeah, absolutely. And these synthetic ones have been trialled in some cases and in lab based studies, they've also been shown to be effective in certain situations and people argued they're not as effective as the other drugs, the natural stuff. It's probably because they contain other impurities which are supporting the activities of these THC CBDs but again, people do not know what's going on. To suffice to say, at least cannabinoids, these chemicals do have an effect.

55:26 - Why do I urinate more often in cold weather?

Ever noticed that you urinate more often in cold weather? What causes this?

Why do I urinate more often in cold weather?

Why do people urinate more in the cold? We went to Dr Matthew Mason from the Department of Physiology, Development and Neuroscience at the University of Cambridge to find out the answer to this pressing question. Matthew - This phenomenon is known as cold diuresis, diuresis being the production of more dilute urine. The idea is that when it's cold, your body tries to conserve heat by constricting the blood vessels in the skin. That means that less heat is lost to the environment. However, if you constrict the blood vessels to the skin, it means that relatively more blood accumulates in the interior of the body and that tends to raise blood pressure.

Khalil - A good way to imagine this is as if constricting blood flow in one part of the body squeezes the blood into other parts, just like if you squeeze a balloon at one end, the other end bulges out.

Matthew - In response to raised blood pressure, the body wants to try to get rid of a little bit of the water in the blood to bring the blood volume, and thus the blood pressure, back down to where it should be.

Khalil - This response prevents your body from being damaged by excessively high blood pressure, just like a safety valve on a boiler.

Matthew - What happens is that in response to the raised pressure, the levels of a hormone called anti-diuretic hormone will fall. With reduced anti-diuretic hormone, the kidney produces more dilute urine and that translates to an increase in urine production.

Khalil - What a relief! Next time, Claire asks if our furry friends are giving us more than just love and affection.

Claire - I'd like to know what parasites you can catch from your pets.

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