Ecstasy & Agony
BBC2 9.00pm Thursday 15th February 2001

NARRATOR (DILLY BARLOW): Five years ago at the age of 34 stuntman Tim Lawrence was told he had Parkinson's Disease, a condition that is slowly freezing his body, but has left his mind intact. Three years ago Tim found an unusual way of relieving his symptoms. The trouble is it involves a street drug, which is illegal and dangerous. This is the story of how one man's discovery could overturn 30 years of scientific thought and might eventually lead to an entirely new treatment for Parkinson's.

TIM LAWRENCE: The first time I ever noticed that something was amiss was I was getting onto a bus and I found that I couldn't manipulate my left thumb very well and just paid with my right and thought no more of it, but from that point my left arm started to lose some of its mobility. Then my left leg started to get the same degree of laziness and slowness to it. I can remember saying to friends and people around me that if I could get a name for what this is then I'd know what to fight. I went to see a consultant and I can remember having to make a, a, a half hour journey back to my Mum's flat and just blinking back tears and just reeling in shock because I'd got a, I'd got a name, but in my mind I was going but no, no, I didn't want that name. My whole image of Parkinson's Disease at that point was just the received image that most of us get which is just of elderly people having great difficulty dealing with cups of tea and funnily enough elderly people always offered cups of tea on saucers, but anyway so my whole world just dropped out.

NARRATOR: Tim Lawrence was diagnosed with Parkinson's Disease in 1994. It's a condition which slowly freezes the body. One in 500 of us is destined to get Parkinson's, probably in our sixties, but occasionally much younger and when it hits the young it can be especially aggressive. Tim is prescribed drugs to unlock his limbs, but these drugs often produce distressing side-effects: twitching movements, for which there is little treatment. Science has tried for years to find better drugs, but it has failed. As yet, there is no cure for Parkinson's.

TIM LAWRENCE: You, you can make it 5% of your life or 95% of your life. You choose, and then of course there's, there's things that you have to adjust to and you know job changes you have to do and jobs you realise that you'll never be able to do, you know, like bomb disposal.

LYNNE MICHELLE (Friend): The guy I first met I was 17 and this was the coolest guy to be around because like we'd be in Bayswater in a shopping mall and Tim would be there like walking down the aisles on his hands and when he'd finished that he'd be like juggling the baked bean cans or doing Monty Python sketches at the till and making everyone laugh and constantly, you know, had this aura about him that was this incredibly physical, funny, inspired and exciting person and that was Tim.

NARRATOR: Tim worked as a stunt performer for ten years, on the film Braveheart and other Hollywood movies and on TV shows such as London's Burning. Acrobatics, martial arts and sky-diving were also part of a very active life. Today there are times when Tim can barely move. The drugs that make him mobile sometimes don't work and when they don't it exposes the raw symptoms of his condition. This is Parkinson's Disease: rigidity, slowness of movement and tremor.

TIM LAWRENCE: Everything in the body will start getting heavier and heavier and heavier. Eyelids, vocal chords, tongue, everything just, just goes really heavy. It's like every cell in the body has just had a dead horse attached to it.

NARRATOR: What is making Tim feel so weighed down is not a problem in his body, but in his brain. Tim is missing a vital brain chemical, a chemical called dopamine. Inside one tiny part of his brain the cells which make dopamine are dying. Without dopamine Tim is becoming paralysed because it is dopamine that triggers the whole chain-reaction in the brain which tells the body how to move. Thirty years ago there was no effective treatment for Parkinson's Disease. Victims were trapped frozen in bodies which could no longer move, but in the late 1960s science found a way to restore the lost dopamine with a synthetic chemical equivalent taken in the form of a drug. It was called Levadopa or L-DOPA for short and it was hailed as a miracle.

PROF. PETER JENNER (King's College, London): The introduction of L-DOPA was just, just an absolute revolution. People who had been bed-bound for years suddenly were able to, to get up and walk. They had control of their lives back, they had mobility, they were able to become integrated back into society and it really is the sort of discovery, the sort of revolution that has affected the lives of tens, if not hundreds of thousands of people world-wide.

NARRATOR: For a while L-DOPA magically unfroze Tim too, replacing the lost dopamine in his brain and helping him move normally again.

TIM LAWRENCE: When I first went on to L-DOPA the first few months of being on it are just brilliant. You just get this, all this movement back again.

NARRATOR: For a time L-DOPA kicked Tim's system back to normal, but just years after starting on the drug there are serious side-effects. This is what happens when Tim takes L-DOPA today. The drug still gives him mobility, but his movements are no longer normal.

PETER JENNER: The real problem is that later in the illness the drugs don't work as well as they, they used to in the early stages and one of the common side-effects is unfortunately the introduction of involuntary movements so they're, they're mobile, but in fact they have movement that they can't control. They will get twisting of their limbs and their bodies and our problem is that we can make them mobile but they then have a degree of mobility which is of little use to them.

TIM LAWRENCE: This is, this is known as dyskinesias which is, it's, it's to do with the fact that the, that the chemical dopamine that I'm, that I'm given is not as subtle as the, as the dopamine that the, the body itself produces. Whereas normally one could talk and pour liquid out, for example, for, for me to do that and focus on if I'm experiencing this involuntary movement I would have to go silent because even the process of talking is using muscles, vocal chords, these are all demands on the, on the, on the system really.

NARRATOR: Tim can spend half his waking hours twitching uncontrollably and no one knows quite why the drug has this effect. It is thought that after a while the brain cannot cope with the way in which L-DOPA floods it with dopamine. In a healthy person natural dopamine is released in tune with the body's needs. It is a devastating side-effect which often appears most severely in young Parkinson's and young people can face decades on L-DOPA. That's why scientists are so anxious to find something new.

TIM LAWRENCE: I've had a friend's five year old daughter asking her Mum, 'Why is Timmy dancing?' to which my response was, 'I've got my own internal rhythm, free form jazz'. I've had another friend's son every time I'd see him he'd come back with more ingenious ways of keeping me still: nailing me down, sellotaping me to the chair, how about if I hold you really tightly, and it was, he used to get quite inventive and I used to be known as wiggling Tim. It is something though when you have 65 year old women helping you with your shopping. You do start to see how flexible this thing pride is.

NARRATOR: Few people realise just how many young people there are with Parkinson's, many of whom will have to cope with the side-effects of L-DOPA for years. There's long been a need to find something better for them.

PETER JENNER: I mean we might ask how old were you when you got the illness?

MALE SUFFERER: I was 36 when I was diagnosed.

MALE SUFFERER: I was the age of 34.

FEMALE SUFFERER: Yes, I was 32 just.

MALE SUFFERER: Yeah, I was 27.

PETER JENNER: You see I mean this is, this is absolutely sort of classical and it's…

NARRATOR: In the UK alone there are seven to eight thousand young sufferers.

PETER JENNER: We have a general concept of what causes the illness, but beyond that we're still really grasping at straws…

NARRATOR: There is still no consensus about what causes Parkinson's. Head trauma, viruses, faulty genes and toxins in the environment have all been suggested, but not proved, but what is known is that those who get it when they're young can get it very badly.

PETER JENNER: Often their disease appears to be very much more aggressive than the form of illness which is shown by older individuals. The progression of the illness is more rapid, their response to drug treatment is lost more quickly and they also unfortunately will develop many of the long-term side-effects of therapy, such as the involuntary movements, very much more rapidly than you would see in an elderly population.

MALE SUFFERER: I had Requip which was supposed to replace it.

NARRATOR: Without L-DOPA they cannot move; with L-DOPA many will become disabled through too much movement and there is yet another problem. The drug sometimes stops working altogether leaving them completely paralysed. It is a particular issue for young people as they have to live with Parkinson's for many years. For 30 years science has struggled to find a replacement for L-DOPA, or something that makes it work better and most of this work has been focussed on the belief that dopamine is the sole key to treating Parkinson's. Dozens of new compounds which affect dopamine levels in the brain have been tried. Some work in some patients, but to date science has failed to come up with anything that is better than L-DOPA, or which calms its terrible side-effects, which makes Tim Lawrence's story extraordinary. For Tim seems to have stumbled by accident on a drug which tames the involuntary movements caused by L-DOPA. It's a drug which has never been tried in Parkinson's before, indeed in the treatment of any physical illness, but it is a drug which has been part of Tim's life as a young person. Coming out in the open about his discovery could lead to a completely new approach to the treatment of Parkinson's.

TIM LAWRENCE: Three or four years ago I was in this club with some friends and I was just suddenly aware that all these dyskinetic movements, I was just suddenly aware that everything was completely smooth as, as though I, as though I'd never had the disease in the first place.

NARRATOR: The drug Tim took was Ecstasy, or MDMA.

LYNNE MICHELLE: I remember one particular time at Glastonbury. It was about two foot deep in mud and he was having a really hard time and this Ecstasy kicked in with him and I noticed the mobility. I just, I'd often seen it, but this time it really hit me. I, he, he started ploughing through this mud and charging ahead and dancing and, and co-ordinating himself really well.

TIM LAWRENCE: We take risks every day of our life. It, it is illegal, but there's not really a, a punishment out there that could match what I actually go through myself on a day-to-day basis.

NARRATOR: Within an hour and a half of taking Ecstasy in combination with L-DOPA, Tim is transformed, not quite into the stuntman he once was, but into someone confident enough to tackle moves he hasn't tried for six years. What you're about to see, according to conventional science, is impossible.

TIM LAWRENCE: Today Matthew I'm going to be Olga Korbut. Great, brilliant. Just to feel that fluidity of movement again. Everything you tell your body to do it more or less does. It's complete symmetry and fluidity of movement. It's just an amazing, liberating feeling. I couldn't have done this without being on Ecstasy because my co-ordination would have been impaired. I may have had the strength to do it, but the, the signals would have been erratic.

NARRATOR: Tim's discovery is all the more extraordinary because no one has ever thought Ecstasy could help someone with Parkinson's, but despite the liberating qualities of Ecstasy for Tim, he knows the drug is not a practical solution for him in its current form. He takes it mainly when he goes out clubbing, at most twice a month.

TIM LAWRENCE: I wouldn't want to feel like that all day every day. It's, it's an unreal state and because of its unreality it's to be enjoyed as a novelty. I, I wouldn't like to function every day on it.

NARRATOR: The dangers of Ecstasy are now well documented. It is rarely fatal, but those who take the illegal drug do risk serious long-term harm. It can cause memory blackouts and depression and research suggests the drug may be specially damaging to people with Parkinson's. The big question is: might there be a way to adapt Ecstasy into something that Tim and others with Parkinson's could safely take every day? Shown the footage of Tim at the gym, scientists at Hammersmith Hospital were keen to find out more.

PROF. DAVID BROOKS (Hammersmith Hospital): Well like a lot of young onset cases Tim has got an aggressive form of the disease. In seven or eight years he's now reached the stage where he's having severe involuntary movements, dyskinesias, on levels of medication that are required to keep him mobile. One of the major problems that we're facing in the clinic is that there are no good drugs to combat this situation. Tim inadvertently has discovered that Ecstasy seems to work very well for him which is fascinating and we need to find out why that is.

NARRATOR: The reason Professor Brooks is intrigued is because Ecstasy is thought to cause virtually no increase in the levels of dopamine, the brain chemical Tim is missing and certainly not enough to have any effect on movement. In fact, the main effect of Ecstasy is to cause a massive release in the brain of a completely different brain chemical, serotonin.

TIM LAWRENCE: I'm 39.

NARRATOR: Both dopamine and serotonin are brain chemicals known as neuro-transmitters. Neuro-transmitters are chemicals which relay messages between the brain's ten billion nerve cells telling us how to feel, move and react. There are at least 300 different neuro-transmitters and each of these chemicals carry different types of messages between the brain and the body. Dopamine, as we've seen, is the critical chemical that kick-starts movement. That's why its loss in Parkinson's has become such a focus for science. High levels of serotonin, which occur when you take Ecstasy, make you feel happy, euphoric. Serotonin is not thought by scientists to have anything to do with movement. Professor Brooks decided to run a series of special tests. Tim's discovery might just be the breakthrough everyone in Parkinson's has been hoping for, so finding out how Ecstasy is working in Tim is vital.

DAVID BROOKS: What we thought we might do, Tim, is get you to have two scans with a tracer called raclopride which measures the levels of dopamine in the brain and we'd ask you to have one scan when you're not taking any medication (Right.) and then a second scan after you take some of your Ecstasy just to see whether that is producing a release of dopamine and giving you the benefit you experience.

NARRATOR: Tim will be injected with a radioactive marker and then scanned to reveal if Ecstasy is somehow causing a release of dopamine in his brain, as the doctors suspect must be the case.

RADIOGRAPHER: …together to me. Designed by Americans so it doesn't work that well. How you doing?

NARRATOR: So as not to confuse the tests Tim has cleared his body of L-DOPA.

RADIOGRAPHER: The lights are going down Timothy.

NARRATOR: For the first 90 minute scan Tim takes no drugs at all and his body reverts to the rigid and immobile state of untreated Parkinson's. The following day, for the second scan, Tim again takes no L-DOPA, but this time took an Ecstasy tablet before he arrived at the hospital. Tim has never taken Ecstasy without L-DOPA before and the first big surprise is revealed as Tim emerges from the scanner.

RADIOGRAPHER: Just swing your legs over the side and sit on the side. That's it, just have a rest there.

NARRATOR: After the second scan, on the right, Tim is more mobile. Ecstasy alone has unfrozen his limbs.

RADIOGRAPHER: Now then, can you try wriggling your toe. Bear with me, you come towards me. (INAUDIBLE REMARK)

NARRATOR: The drug does not give him nearly as much mobility as when it is taken in conjunction with L-DOPA, but that it gives him any movement is surprising.

WOMAN: Now, just the finger tapped you know. Quicker than that.

NARRATOR: Until now no one thought Ecstasy alone could ease the paralysing effects of Parkinson's.

WOMAN: Going to do it together.

NARRATOR: And then comes the biggest surprise of all. Dopamine, the neuro-transmitter that the entire medical profession believed was the key to treating Parkinson's, seems to be playing no part in the unfreezing process.

DAVID BROOKS: It's not at all clear why MDMA, or Ecstasy as it's known, should help his involuntary movements so effectively. There were two possibilities. One is that it might be stimulating his natural dopamine in some way that helped the situation. The other is that it might be working by a completely different route by acting on other chemical receptors. If one looks at his scans on the screen here one can see the dopamine binding sites in the centre of his brain before and after he took his Ecstasy and really there has been very little change, a few percent difference, so he is releasing very little dopamine because he doesn't have much, having Parkinson's. After he takes his Ecstasy, so the mechanism of action of the Ecstasy must be via a different neuro-transmitter system and so we're very keen now to try and find out what that system is. It may be that we can find a drug that would act on that and helps him but be potentially far less harmful to him in the long-term than taking Ecstasy.

NARRATOR: Tim it seems really has stumbled on something new. The question now is: can science take it any further? David Brooks suggested that two scientists at Manchester University, Professor Alan Crossman and Dr. Jon Brotchie, might have the answer. Professor Brooks knew they'd be interested in Tim's case because for the past 15 years these scientists have been trying to prove to the world that it is possible to treat Parkinson's with something other than dopamine. Their mission started when Alan Crossman noticed that dyskinesias, the involuntary movements caused by L-DOPA in patients like Tim, bore an uncanny resemblance to an extremely rare condition called hemiballism. This is hemiballism and it is not caused by anything to do with dopamine.

PROF. ALAN CROSSMAN (University of Manchester): Hemiballism is a fascinating condition characterised by wild, flailing movements, throwing movements. It was known to be caused by a small lesion, a destruction, of a tiny region of the brain called the sub-thalamic nucleus. This little group of nerve cells about the size of half a peanut.

NARRATOR: The sub-thalamic nucleus sits here deep in the brain. It is close to the key area where dopamine is produced, but there is no direct connection between these two structures and until Alan Crossman came along no one thought the sub-thalamic nucleus was involved in Parkinson's. No one knew this tiny area of the brain might offer a whole new way of treating the illness.

ALAN CROSSMAN: The sub-thalamic nucleus was regarded as nothing more than a, a neurological curiosity. The only significance that it appeared to have in brain function was that once in a blue moon somebody had a stroke in this region and the consequence was that they had these exuberant abnormal movements: hemiballism. That was its only function. The only function was to prevent you having hemiballism. There was no, there was no other purpose for its existence.

NARRATOR: Intrigued by the similarity between hemiballism and the dyskinesias suffered by patients like Tim, Crossman studied the sub-thalamic nucleus to see if it might also be involved in Parkinson's. It was something no one had ever considered before and what Crossman discovered amazed him. The sub-thalamic nucleus in the Parkinson's brain was hyperactive, quite different than in a normal brain. It meant this tiny nucleus clearly was involved in Parkinson's. It was a revelation. Until this point everyone in Parkinson's research had been focussed on dopamine and the area in the brain which produced it, but Crossman had found the first direct evidence that a completely different structure, the sub-thalamic nucleus, which had no direct connection with dopamine, played a crucial role in Parkinson's too. It was a discovery that has led directly to a new technique to treat those in whom the side-effects from L-DOPA have become intolerable. Not a new drug, but surgery. This operation is graphic proof of Crossman's discovery that the sub-thalamic nucleus plays a vital role in Parkinson's and it shows that it is possible to control the illness by manipulating this area of the brain.

(ACTUALITY OPERATION CHAT)

Neuro-surgeon Steve Gill is going to place an electrode in the sub-thalamic nucleus of 36 year old Simon Burrell who has had Parkinson's for 13 years. If all goes to plan the surgery should alleviate his Parkinson's symptoms, but it is risky and it doesn't always work. Sometimes it leaves patients with depression, speech problems or blurred vision. It can even paralyse or kill.

(ACTUALITY OPERATION CHAT)

To provide vital feedback the patient must be awake and has been off all medication for 24 hours to expose his raw Parkinson's. At the moment he is frozen. If the surgeon hits the right place in the sub-thalamic nucleus Simon will be able to move again. The surgeon advances the probe millimetre by millimetre and then…

WOMAN: Hold your right hand up. Just make big movements, big (TALKING TOGETHER) Really wide.

MAN: It's switched him on.

WOMAN: How does it feel?

MAN: Plain sailing from there on.

WOMANL: That's fantastic Simon, well done, that has gone really well, doing very, very well Simon. Right, big movements.

NARRATOR: This surgery can improve symptoms by up to 70%, for a while at least. It is not a cure and it remains a last resort. Because of the high risk, Tim is not prepared to undergo this surgery.

TIM LAWRENCE: This is something I never thought I'd, I'd be using. It's a sort of adult toddler tippy, something they'd use so they wouldn't spill when they're going up the north face of the Matterhorn.

NARRATOR It is acknowledged that a new treatment less risky than surgery is needed desperately and that's why Tim's discovery about Ecstasy could be so important.

ALAN CROSSMAN: You know haven't you ever noticed the sub-thalamic nucleus…

NARRATOR: Alan Crossman's early work showing the sub-thalamic nucleus was key in Parkinson's was to change everything. It prompted the Manchester team to hunt for a drug which could help patients like Tim, a drug which could do the same as surgery, but be far less dangerous. Jon Brotchie, a pharmacologist, knew that if he could find out which neuro-transmitter was operating in the sub-thalamic nucleus there might be a way to manipulate it with a drug which, like Ecstasy, would bypass the dopamine route, but there are more than 300 different neuro-transmitters in the brain and there was no existing technique sensitive enough to show which one was operating in such a small part of it.

DR JONATHAN BROTCHIE (University of Manchester): I mean the big problem is that the sub-thalamic nucleus is very, very small and so exactly, and so you can't, you, you can't use some of the techniques that you might use if you were looking at connections between two big pieces of brain.

NARRATOR: It took Brotchie two painstaking years to devise a method he hoped would reveal which crucial neuro-transmitter was controlling the sub-thalamic nucleus. Finally he discovered a way to do it. Brotchie took tiny samples of brain tissue and broke them down into individual cells. The cells were then bathed in radioactive markers which would stick only to specific neuro-transmitters. Once the cells were separated back out the radioactive markers for each neuro-transmitter could be counted and this revealed that the neuro-transmitter which controlled the sub-thalamic nucleus was one called glutamate. It soon became clear that a compound which controlled glutamate did have a small effect on Parkinson's and this was a major breakthrough because it established the principle that it was possible to treat the illness with a new type of drug which had nothing to do with dopamine.

JONATHAN BROTCHIE: It was quite a surprise to most of the other people in the field at the time because there really had been this dogma that, that the only way of treating Parkinson's Disease was by putting dopamine back.

NARRATOR: But they needed something better than glutamate, so the Manchester team began looking for receptors for all the neuro-transmitters operating in the area of the brain which controls movement. There turned out to be dozens and eventually they discovered that one of them was serotonin, the neuro-transmitter that floods Tim's brain when he takes Ecstasy. It was a real hint that serotonin could be involved in movement after all and more proof soon followed.

JONATHAN BROTCHIE: We did an experiment where we looked at the levels of this receptor in the brains of Parkinsonian patients who had, had died with very severe L-DOPA-induced dyskinesias. What we found was that this receptor was dramatically increased in, in its numbers so suggesting that serotonin was actually one of the key components of the process that actually leads to the generation of disconesia.

NARRATOR: It confirmed that serotonin probably was involved in Parkinson's. The Manchester team was intrigued, but they were still years away from proving that a drug which affected serotonin could actually work in someone with Parkinson's. It was still just a theory and then they heard about Tim Lawrence and his experience with Ecstasy.

PETER JENNER: While we like to think that we all do logically designed experiments based on real scientific logical reasons for going forward, very often it's the unexpected that opens new doors and allows new impetus to come into science and propels us forward.

NARRATOR: Tim appears to be living proof of the Manchester findings, but while fascinating to science his is only one man's experience. Before any scientist could commit time and resources to developing a drug based on the properties of Ecstasy they would need to be more confident that the effect on Tim is real and not something called the placebo effect.

TIM LAWRENCE: It's just…

NARRATOR: It may seem extraordinary, but the belief that a pill will do you good can sometimes result in a genuine physical improvement which has nothing to do with the drug itself. It's caused by the brain deceiving the body. One placebo study in the US revealed that patients who took sugar pills believing they were anti-depressants showed almost as much improvement in their condition as those who took the real thing.

JONATHAN BROTCHIE: The placebo effect is very, very powerful and it's one of the major factors that needs to be taken into account when determining whether a drug works or not. For instance, in Parkinson's Disease up to 30% of the anti-Parkinsonian action of the drugs that are currently available actually just comes from the fact that the patients are taking a tablet every day. As a scientists that's the, that's the question I would like answered before we know whether this is, this is real and worth pursuing further.

NARRATOR: Tim volunteers to take part in an independent two-day trial. On both days he will be given L-DOPA, but only on one day will he take Ecstasy. On the other he will take a simple sugar pill. Before the tests start Tim again has to clear his body of all medication. Once more it reveals how, without drugs, Parkinson's freezes his limbs. Tim is monitored throughout by neurologist Dr. Susan Fox, a specialist in movement disorders. The whole test is recorded on video which Crossman and Brotchie agreed to assess.

DR SUSAN FOX: Can you try and do that for me?

NARRATOR: For the Manchester team, it could provide the evidence that there is something genuinely worth pursuing. For Tim, it is a moment of truth. Is the effect of Ecstasy all the work of his imagination, or has he really discovered something new?

SUSAN FOX: Morning Tim. You clearly haven't had any of your medication this morning. How are you feeling?

TIM LAWRENCE: Reserved.

SUSAN: Right. Do you, do you feel quite stiff?

TIM: Yeah.

SUSAN: Yeah.

NARRATOR: On both days Tim takes a tablet. On one day it is the simple sugar pill. The other day it is Ecstasy but they look identical. No one, including the film crew, Dr. Fox or Tim, knows which is which.

SUSAN FOX: Try and open and close your hand.

NARRATOR: Before the drug has a chance to work Dr. Fox assesses Tim's raw Parkinson's. On both days he is slow and rigid, particularly on his left side, which is the most affected.

ALAN CROSSMAN: Yeah he's got major trouble on his left side.

SUSAN FOX: There you go Tim. That's levadopa if you'd like to take that.

NARRATOR: Then at the same time each day Dr. Fox gives Tim some L-DOPA. The clock is set to zero marking the official start of the test. Twenty minutes later there is the first sign of a difference between the two days. On Day Two, on the right, he can already lift his left arm and pick up the mug smoothly.

ALAN CROSSMAN: That's much, much more fluent on his mostly Parkinsonian side, yeah. Greatly different. Much, much more smooth movement.

JONATHAN BROTCHIE: Uh-huh.

NARRATOR: 90 minutes into the test the L-DOPA that Tim took on both days had kicked in, but nonetheless it is affecting Tim quite differently. On Day One he is mobile but has dyskinesias. On Day Two he is also mobile but appears to have almost no dyskinesias.

JONATHAN BROTCHIE: If that was replicated in him the next time he tried it would be... clinically significant because you've actually changed that guy's ability to perform some pretty important tasks, yeah.

NARRATOR: After 2¼ hours on Day One, the effect of the L-DOPA has worn off and Tim has returned to his untreated Parkinsonian state, but after the same amount of time on Day Two he is still mobile and moving smoothly. The difference is particularly marked when Tim is asked to put on a jacket.

SUSAN FOX: Have a go.

TIM LAWRENCE: No I can't.

SUSAN: You can't, OK. Tim, put your coat on and zip it up.

JONATHAN BROTCHIE: Was the best thing I've ever seen in, in a patient, in a, the best difference yeah. Honestly I think that, that is, that is, you're not going to show me anything that's better than that. I don't think so. That was brilliant.

NARRATOR: On Day Two a further twenty minutes later Tim is still mobile and fluid. By the end of the test Tim has stayed mobile for 30% longer than on Day One with almost no dyskinesias. By now Tim himself has realised he has taken Ecstasy because of the effect on his mood. It was later confirmed that it was, indeed, on Day Two that he took Ecstasy.

JONATHAN BROTCHIE: The reason that we're, we're interested and excited by this is that we've spent the last well shall we say how many years I don't know between us, probably between us best part of 50 years trying to understand dyskinesias and movement disorders generally and the effect that we see here is probably one of the biggest effects I've ever seen. We've been involved with several clinical trials for potential drugs that you could add to levadopa and I've not seen a patient who has shown such a big difference on two films. It is, as I said, one of the most interesting pieces of footage I've, I've seen with a potential to develop completely new drugs for Parkinson's Disease.

NARRATOR: News of the outcome of the placebo test reaches the Parkinson's Disease Society, the national charity which supports the 120,000 people in the UK who have the illness.

MARY BAKER (Parkinson's Disease Society): The Society of course has to say quite properly, quite understandably, that it absolutely cannot get in, condone in any way the taking of an illegal substance, no matter what it can do, but actually there's a lot more in here for the Society, because the Society I believe has a moral obligation to ensure that some research follows Tim's experience, because there just may be in his experience a clue, a vital clue that is going to help us find a way forward in the better management of Parkinson's Disease.

JONATHAN BROTCHIE: The, the Tim story's really increased my faith that we can develop a serotonin based therapy for Parkinson's Disease, although of course we can't condone what he did and he shouldn't have been taking the drug. He's given us a clue I think, that's fair to say, and that's a clue that we really can't overlook if we're going to push forward and make the lives of patients with Parkinson's Disease better.

NARRATOR: Tim's experience has helped convince the Manchester team that it is worth dedicating time and money to teasing out exactly how Ecstasy works in Tim, but it won't be by working with the drug itself.

JONATHAN BROTCHIE: We're not going to be using Ecstasy for, for the research, we're going to be looking at experimental compounds which mimic individual actions of Ecstasy. We don't want to use Ecstasy. It's going to have too many side-effects to be a realistic treatment. If we can dissect out the, the pharmacology then we can, we can take, if you like, the good out of Ecstasy without the bad and, and actually develop a treatment based around that.

MARY BAKER: You really cannot ignore what has happened to Tim. You cannot dismiss it just because it's illegal. Life isn't like that. Life is complicated. It's not about black and white issues. It's about many varying shades of grey and I think this, there is evidence here which needs to be followed up, for the sake of the people living with this extremely challenging illness.

NARRATOR: Tim's experience is intriguing, but without proper research there must be caution. That Ecstasy works for him doesn't necessarily mean it could be developed into a useful treatment for others and there is worry about the long-term damage Tim could be doing to himself by taking Ecstasy. There is now evidence that the drug may be destroying what little natural dopamine he has left in his brain. Many believe that Ecstasy could cause great long-term harm to anyone with Parkinson's.

PETER JENNER: I can understand fully why, why Tim resorts to Ecstasy because basically classical medicine has failed him, but is he damaging himself further for the future? We know Ecstasy in recreational doses can be toxic to remaining dopaminergic neurons. There's excellent science being done in this area and what I would hate to happen to Tim is that in fact by having short-term relief of his involuntary movements he is producing a worse outcome as far as his Parkinson's Disease is concerned and that his rate of progression might be enhanced.

STATION ANNOUNCER: The 10.58 to Manchester Piccadilly now boarding at Platform 13, calling at Milton Keynes…

NARRATOR: Tim has now offered to go to Manchester to help with further research.

TIM LAWRENCE: This, this whole experience has been incredible and quite a journey. I certainly would never have thought that I'd be having the medical academia looking over me and interested in something that I just used to look upon as a recreational thing of a night out. If something could be developed from this that could be used on a daily basis the change that that would have on my life, if something like that was available on the market, would be, I think it would be pretty much total.


PRESENTATION VOICE: If you have been affected by tonight's programme and would like information or details of organisations that can offer you support and advice then call the BBC Actionline on 0800 077 077.