Changing minds

A government think-tank’s attempt to peer 20 years into the future and gauge the role drugs will play in society attracted plenty of attention from the national press last week.

Drug use, treatment and control are arguably some of the biggest issues facing the nation, and the Office of Science & Technology’s Foresight report was an ambitious bid to predict some of the dilemmas we may face in a range of possible ‘drug futures’.

Inevitably, most of the headlines focused on the more exotic scenarios envisaged by the 50 scientists, engineers, psychologists and other experts who contributed to the Drug Futures 2025 study.

These ranged from the emergence of a new breed of performance enhancing drugs that could become as commonplace as coffee, to a vaccine against addiction.

The bulk of the Foresight report reads like a beginner’s guide to the world of drugs — legal, illegal, recreational, addictive, benign and dangerous. But within this pharmacological extravaganza lies evidence of the growing role physical technologies are expected to play in the understanding and treatment of drug use and addiction.

For example, the study notes how advances in neuro-imaging technology have the potential to unlock the secrets of the effects of particular drugs on specific areas of the brain.

Two neuro-imaging technologies are highlighted: magnetic resonance imaging (MRI) and position emission tomography (PET). The latter was of particular interest to the Foresight team because of its ability to label the neural receptors deep within the brain on which addictive drugs act to produce craving.

‘PET has the potential by 2025 to allow almost all the currently known neurotransmitters involved in addiction and their receptors to be measured,’ said the report.

But while advanced imaging systems could increase scientific understanding of the process of addiction, another technology is flagged as having the potential to take the battle against addiction to the centre of the brain itself.

This is transcranial magnetic stimulation (TMS), a technology based on the application of pulsed magnetic fields to influence electrical activity in the brain via a magnetic coil placed close to the skull that can be moved to target specific neural functions.

Originally developed as an aid to imaging the brain, the technology is increasingly seen as a promising method of modifying the activity of the organ. If this can help in the treatment of depression — as already appears to be the case — some are asking whether it could also alleviate the cravings and impulses associated with various forms of addiction.

TMS is the application to brain function of the wider discipline of magnetic stimulation technology, which has emerged as a useful tool in the armoury of neuro-scientists since its conception at the University of Sheffield in the early 1980s.

The UK remains home to the major development activity in the field, with Sheffield and University College, London among the academic centres with considerable expertise in TMS.

Alongside the academic work, the UK is also home to one of the few technology companies in the world carrying out TMS-related R&D and manufacturing magnetic stimulation equipment. This is south Wales-based Magstim, which has agreements with a number of universities and hospitals and works with neurologists around the world on research into magnetic stimulation.

‘In basic terms, what we are doing is inducing eddy currents in human tissue,’ said Andrew Thomas, marketing manager for Magstim. ‘The area where there has been a lot of work is in the treatment of depression. If that can be proved as a clinical application, the possibilities for the technology are massive.’

According to Thomas, the use of magnetic stimulation as a possible way of modifying brain activity shot up the agenda in 1996 when an early trial produced extremely promising results in a group of patients. Subsequent trials proved less successful, however.

‘Everybody jumped onto the bandwagon but nobody could replicate the results seen in those first patients. Things went into a bit of a lull after that.’

It seems that 1996 was too early for what is, even now, very much an experimental technology that is still to realise its full potential.

Thomas said TMS has some way to go before it is ready to produce the significant, long-lasting modifications to brain activity needed to affect the complex, deep-rooted functions associated with conditions such as depression and addiction.

‘We can produce an intense magnetic field in the order of 2.2 tesla, but that drops off quite quickly,’ said Thomas. ‘There are many structures deep within the brain that we can’t currently hit.’

Thomas added that until recently the duration of the effect of TMS was extremely short — as little as a minute before the modified brain activity resumed its normal pattern. Progress is being made, however, and Thomas pointed to work carried out at UCL that suggests the application of TMS can produce a longer-lasting impact.

Earlier this year Prof John Rothwell from UCL’s Institute of Neurology outlined the results of trials that produced effects on the brain lasting for more than an hour after 40 seconds of stimulation. The key to the advance was the use of phased bursts of magnetic pulses that closely replicate activity within the brain. Patterns of repetitive pulses were delivered to the scalps of test subjects over a period of between 20 and 190 seconds, aimed at the motor cortex area that controls muscle response.

According to the UCL team, it was able to produce ‘rapid, consistent and controllable’ changes in the motor cortex, suggesting that TMS can not only produce longer-lasting effects but also be precisely targeted to achieve desired outcomes.

The focus of research into TMS continues to be the treatment of conditions such as Parkinson’s disease, aiding the recovery of stroke patients, and the alleviation of depression.

If the Foresight report is to be believed, treatment of addiction will also move onto the agenda. But for all the possibilities offered by the technology, one question will inevitably arise if TMS moves into more mainstream use — is it safe?

Those working in the field insist that all the evidence so far suggests it is. The recent UCL work, for example, demonstrated no side-effects from the stimulations.

There have been a small number of cases around the world where TMS research has resulted in seizures in patients. According to Magstim’s Thomas, however, ‘You could count the number of seizures on one hand. The technique has been around for long enough now that I think if something very bad was going to happen, it would have happened already.’

One problem for TMS technology, if it enters widespread clinical use, could be the perception that it is merely another form of electroconvulsive therapy (ECT), commonly known as ‘electric shock treatment’ and the subject of deep public suspicion as exemplified by the film One Flew Over the Cuckoo’s Nest.

A cursory glance at the technology, however, suggests that TMS is to ECT what the scalpel is to the hammer. While ECT involves the application of intense electrical energy that floods the brain’s neural pathways, TMS offers the prospect of controlled, highly specific stimulation of the region needed to achieve a desired outcome.

Unlike ECT, which is a traumatic process to say the least, TMS could even be delivered in an out-patients’ clinic while the person is fully conscious, according to those working in the field.

Thomas predicted that TMS will eventually take its place alongside ECT and drug therapy as ‘a tool in the box’ for those treating illness and psychiatric disorders.

‘We know it has huge potential,’ he said. ‘We believe that the research will begin to unlock this quite soon.’