Drugs: Time for a Change?

Khalil Thirlaway gives an account of how marijuana can get you stoned.

Khalil - Weed, pot, skunk. Whatever you call it cannabis is one of the most commonly used drugs in the word. It's made from the leaves and buds of the marijuana plant and is either smoked or baked into foods and consumed. Each bud and leaf of the marijuana plant is composed of hundreds of chemicals, but there are two important ones: tetrahydrocannabinol or THC and cannabidiol or CBD. While CBD contributes to making the smoker relaxed, THC is to blame for its psychoactive effects or 'high.'

Every time someone smokes or eats cannabis, THC seeps through the bloodstream to the brain and attaches to cannabinoid receptors. These cannabinoid receptors are part of the brain's makeup and THC is very similar to a naturally occurring chemical called anandamide which usually binds to these receptors. THC floods your brain in much higher concentrations than the naturally occurring anandamide and causes the neurons that make up your brain to fire continuously upsetting the normal balance of your brain

So, how does a bit of excess firing cause the user to get 'stoned'? Well, cannabinoid receptors are prolific things and found all over the brain. This means that THC can impact on lots of different functions, from memory and hunger to pain and forward planning, giving all those well known effects like the 'munchies' and lack of motivation. Crucially, cannabinoid receptors are also present on the brain's reward system boosting dopamine and causing euphoria and relaxation. The activation of this reward system is thought to be the common factor in all drugs of abuse.

Marijuana is not a totally harmless herb but, with THC, there is no such thing as a fatal overdose. A study on monkeys reported that a person can gobble up to 70 grams of the drug, about 5,000 times more than you needed to get 'high' and still have no toxic effects. Still, if you wanted to eat your weight in weed infused treats, you might experience fragmentary thought, lack of concentration,impaired memory, drowsiness, and anxiety. Not to mention dry mouth, red eyes, and increased appetite and heart rate. Long term use has been linked to schizophrenia and memory loss, although a clear cause and effect link is yet to be found.

While it's true that some cannabis-derived drugs have shown promise in treating anxiety, depression, post-traumatic stress disorder, epilepsy and neuropathic pain, the overall effect of marijuana on brain chemistry isn't crystal clear and much evidence is still awaiting confirmation in clinical trials.

Khalil Thirlaway takes us to the brain, to explore what actually happens when you take heroin.

Khalil - Heroin, like morphine, is an opiate synthesised from the pods of a poppy plant. Although heroin's godfather though he was creating a safer form of morphine for pain relief, he accidentally synthesised an even riskier molecule and named it heroin for the feelings of heroin instilled in the user. But, within a few years, after being marketed and sold as a medicine for conditions like insomnia, heroin was found to be two to three times more potent than morphine and also, way, way more addictive.

Heroin, also known as horse, smack or junk works in different ways. Part of it works as a stimulant which means it speeds up your brain, but a greater portion is a sedative or depressant which slows you down. Whether it's injected smoked or snorted it quickly enters the brain where it's turned back into morphine and binds to proteins called opioid receptors. These are found in areas of the brain associated with pain, reward, and also in the brainstem which regulates automatic processes like breathing. After docking onto the brain cells, heroin triggers the release of  'happy hormone' dopamine, up to the ten times more than normal  which produces feelings of intense euphoria, relaxation, fearlessness and tolerance to pain. Yet heroin and other opioids don't suppress the pain itself, rather they change the subjected experience of pain. This is why people receiving these drugs for pain relief say they still feel the discomfort, but it doesn't bother them anymore.

After more and more exposure to opioids like heroin, users begin to build up a tolerance to these flash floods of dopamine and need more and more of the drug to create the same effect. Heroin can also cause pain systems to go into overdrive once the dose has worn off, meaning the drug is needed just to feel normal. Going without a fix can cause withdrawal symptoms like nausea, cramps, anxiety, fever, and diarrhea.  Long term, heroin wastes the brain, causing damage to areas of the brain associated with memory, decision making and  complex thought.

One of the leading causes of death in users is to simply stop breathing due to the depressive qualities of the drug on the brain stem. In fact, according to a report from the European Monitoring Centre on Drugs and Drug Addiction, opiates, mainly heroin, were involved in four out of every five drug related deaths in Euro

Addiction is a huge problem and it's very difficult to get exact statistics - but estimates from the National Drug Evidence Centre put it in the hundreds of thousands in the UK alone. There's clearly something quite drastic going on in the brain to cause this, and new research from the University of Cambridge might just hold the key, as David Belin explained to Georgia Mills.

David - So addiction is a state. It's a psychiatric disorder characterised by loss of control over habitual drug-seeking behaviour in such a way that people continue searching for drugs, and consuming drugs, despite awareness of negative consequences of doing so.

Georgia - And which drugs do we think of when we think of addiction?

David - Often people tend to think about illegal drugs such as cocaine, heroin but, actually, alcohol and tobacco are highly addictive as well.

Georgia - And how have you been investigating this?

David - We are interested in understanding why only some individuals who are exposed to these drugs will eventually lose control over their consumption. Because clearly, there's an interaction between something in the brain before you start taking drugs and the effects of these drugs that  would eventually make you vulnerable to addiction and you would develop the disorder. And we try to understand it using both clinical and preclinical approaches, and for this we have the help of little   rats that are very clever animals and, interestingly, in humans not all of them if they are given access to drugs would eventually develop addiction.

Connie - So let me get this right Georgia - not everyone forms addiction to these drugs?

Georgia - No - in fact rats, just like humans, have about a 20% chance of become addicted to cocaine.

Connie - So are they giving cocaine to the rats then?

Georgia - Yes they did actually - they allowed them to have small these small amounts they could take freely. But after a while, they would start making them work harder and harder for their next dose. So they'd get them to press a lever once, twice, 10 times, 500 times. And after a certain point most rats decide that actually, the drug is not worth the effort.

But 20%, the 20% that are addicted keep pushing and pushing and pushing the lever, up to 10,000 times to get their next hit.

David - They just can't stop! And they are sweaty, they put everything they've got into pressing this lever to get to the next fix and these rats clearly are addicted.

Georgia - Well that's quite a powerful image there! Did you find out out why some rats were more likely to get addicted than others?

David - We've identified a couple of behavioural traits such as novelty-seeking and impulsivity that predicted this vulnerability to switch from volitional to compulsive cocaine-taking behaviour. So impulsivity, for instance, the example I tend to give my students all the time is, if during one of my lectures - if Chuck Norris is in the room and he stands up and says 'Oh you know I don't really like  your lecture', and I actually engage a fight with him because I'm frustrated, this would be very impulsive, because the consequences would be harmful and then I would regret it. So this is what impulsivity is.

And we've actually identified this trait in cohorts of animals. Three years after we made this discovery, the same vulnerability trait  was identified in humans, so that was a kind of success story.

Georgia - Being more impulsive and novelty-seeking - those are traits identified that makes both rats and humans - you mentioned switched from an adaptive seeking of cocaine to a compulsive one. What is changing in the brain to make this change?

David - Initially volitional drug seeking and taking behaviour depends upon psychological mechanisms which require a pre-existing representation of the outcome. So when you and I work, and we work because we know, for instance, on Friday we may go out to the pub. We have this representation of what we're going to do with the money we've just earnt. When the behaviour become habitual, then the behaviour is subdued, subjected to stimuli in the environment, and stimuli triggers specific behavioural features outside your awareness.

So a good example in your everyday life is, if you go back home tonight and it's dark. What are you going to do? You open your door and then you try to reach the switch and switch on the light. And what if in the morning before you left, the light bulb was broken? When you get back home this is exactly what you would do nevertheless. You would try to switch on the light and then say, oh yes it's broken - this is a habit. And this is exactly what drugs do, they hijack this system and they push the system towards drug seeking becoming habitual. So now every single time you are presented with a cue that you have experienced when you were taking drugs or seeking drugs, all these kinds of cues are going to trigger behavioural repertoire which actually has been designed so that you would get the drug, and you are not aware of what's going on. This is what a habit is. So there is a clear transition psychologically in what's going on.

Connie - So David's arguing that you kind of go into autopilot, trying to get the next hit.

Georgia - Yeah exactly, and they've actually found evidence for this inside the brain. When animals start taking drugs, many parts of the brain are involved, including the pre-frontal cortex which is very closely associated with decision making and control.

But, what happens in addicts is, after a few months the system kind of changes and switches to another area in the brain which we associate with habit, but it completely circumnavigates the prefrontal cortex.

Connie - The area involved in control and decision making?

Georgia - Yes, it forms a kind of backdoor in the brain skipping past your willpower centre implying that it just doesn't come into it.  Which David argues means we should look at addiction in a very different way...

David - Addiction should be considered exactly as schizophrenia or diabetes. It's a chronic disorder and it's not merely a question of willpower. If you suffer from it then there's very little you can do yourself about it and, unfortunately, there are very few effective treatments for drug addiction. There's none for cocaine, for instance, for cocaine addiction.

In terms of social implications, I think it is time to consider drug addicts really as patients and not as criminals. It's not because they want to harm anyone that they may actually go and sell their grandma to get a couple of quid to buy a line. It's because they have to because of their disorder. And, as long as they aren't considered at patients, socially there would be something wrong with the way we handle drug addiction.

Connie - How does this finding correspond to actual therapies ?

Georgia - This work does suggest some new drug candidates and treatment avenues to explore but it's still very much a 'watch this space.'

Around the world there are some very different approaches aiming to reduce drug harm, from legalisation, to the death penalty. So where does the science stand? The UK's Royal Society for Public Health, or RSPH,  recently released a report calling for a change in how the war on drugs is fought. Georgia Mills spoke to Ed Morrow, campaigns officer at the RSPH.

Ed - The 'taking a new line on drugs' report is really the first time that a major public health organisation in this country has come out with a strong line on how drugs policy in this country needs to undergo a major shift. Previously we have been too focused on the criminal justice approach, which is just not working in terms of reducing harms from drugs.

We've seen a situation over the past decade where yes, although use of some of the less harmful drugs, such as cannabis, has continued to go down slightly, actually, use of some of the most harmful substances, things like heroin, has risen slightly and, more importantly, the harm associated with those drugs. Particularly the number of deaths associated with them has risen significantly, so we are not tackling that harm coming from drugs. So what we've set out in this report is a new public health based approach which is focused on reducing the harm from drugs

Georgia - How would you go about doing this?

Ed - So, one of the major pillars which underlies it is the idea of decriminalising possession and use of drugs. That is not the same as full legalisation, but we've been seeing for a long time that criminalising people who have a drug misuse problem does not does not help them get better. It puts a lot more costs onto society in the long run and it also discourages people who have a drug misuse problem from coming forward for the treatment they need because they are scared of being prosecuted. So that's one of the first major steps we need to look at, and we also want to see much better, more universal drug education for young people.

Georgia - Where does the scientific evidence for these arguments lie?

Ed - Well, we've been looking a lot at international examples of different countries that have tried similar approaches to what we are suggesting. One of the biggest examples we've been looking at is Portugal. Now Portugal, in 2001, decriminalised all possession and use of drugs in a similar way to what we would like to see. Now over that period they have seen a great increase in their health outcomes related to drugs. The number of deaths related to drugs misuse has plummeted, I think from round about 80 a year to round about 10 a year. Infection rates for various infections related to drug use, things like HIV and Hep C, those have also fallen through the floor. And, at the same time, drug use has not risen in the way that some people have feared and they still have a level of drug use which is well below the European average and is below what we have in this country.

Georgia - Alcohol and tobacco - two of the most commonly used drugs in this country, and they're the two legal ones. Could this not be a warning that if we do move towards this decriminalisation it might normalise the use of these drugs, maybe not immediately, but eventually lead to greater uptake?

Ed - If we again go backs to the evidence - countries that have tried this approach - the example in Portugal is a 15 year scheme now where they've had this approach and it has not seen a normalisation, it has not seen an uptake in levels of use of other drugs. So we think that what we've seen so far from other countries would disprove that fear.

Georgia - And what about evidence from UK soil, because I know that drug use is very different from county to county, let alone between countries?

Ed - Well, it is interesting to look at the different ways in which police forces in this country are dealing with various types of drug use. So some police forces in certain parts of the country , Durham are one major example, have stopped actively pursuing and prosecuting people for possession and small scale supply of cannabis and we have not seen the effect of usage going up in those areas. But it's also interesting to look at the situation with what happened with cannabis being upgraded to a Class B drug in this country, which did not lead to a fall in use. So  it very much seems, even with this country, that the level of enforcement, the level of penalties, does not have a direct link with the level of use.

The resistance to making this change is not a scientific one, it's a political one because the reality we live in, at the moment, is that drugs policy, both in this country and across the world is driven by politics rather than the science and that is a situation we need to change.

Georgia - Recently legal highs have just been banned in this country. Could you explain to me how this has been done and whether you think this is a good move?

Ed - Legal highs are, or were, substances which are designed to mimic the effects of traditional legal drugs but with a slightly different chemical composition so that they would avoid the existing legislation and classification that would apply. The new Psychoactive Substances Act which has come in to ban what were formerly known as legal highs is an interesting situation. We think it's going to be quite problematic in terms of enforcement because it seeks to ban any new substance which has a psychoactive effect.  And, of course, there are lots of perfectly innocuous substances which do have such an effect and, obviously, they've had to put in exceptions - alcohol and tobacco and many sorts of medicinal products as well.

Georgia - I heard the original drafting accidently banned things like paint, and perfume, and petrol?

Ed - Yes, so it's that kind of thing. They've got themselves in a bit of a mess over this, but they've brought it in now. But the interesting thing as well for us on this is that what it has done is to ban production and sale of these substances and it has not criminalised possession and use. So we think, even though this legislation is a bit of a mess in some ways, there is this inherent recognition from the government that criminalising people for drug use doesn't work. We'd like to see that situation reflected with more traditional, if you like, illegal drugs.

Connie - We asked the government for a response for the Royal Society for Public Health's report and they gave us this statement:

"This government has no intention of decriminalising drugs. The decriminalisation of drugs would not eliminate the crime committed by the illicit trade, nor would it address the harms associated with drug dependence and the misery that this can cause to families and communities. The UK's approach on drugs remains clear; we must prevent drug use in our communities and support people dependent on drugs through treatment and recovery. At the same time we have to stop the supply of illegal drugs and tackle the organised crime behind the drug trade. There has been a reduction of drug use amongst adults and young people compared with a decade ago and more people are recovering from dependency now than in 2009 and 2010."