16. Looking Out for Charlie’s Men.


We could just wait and see. Or we could try taking these.

A man goes into Wetherspoon’s and orders a pint of Ruddles. He is handed a yellow Smartie instead. ‘Its a placebo’, says the barman. ‘We’re running a trial and it looks as though you’re in the control group.’

He winks, ‘don’t worry though, its probably just as effective’.

Few people realise that the naked emperor in the ‘Emperors New Clothes’ story was simply taking part in a controlled trial of Nylon.

King Canute famously tried to turn back the tide by issuing a command. Many think he was using irony to demonstrate the point that he had limitations. Even this would surely have been a massive mistake, in as far as the Vikings operated a ‘sticks and stones’ approach to verbal aggression, finding the axe more reliable than sarcasm.

In fact, misunderstood Canute was simply conducting a controlled experiment in Tide Management. Since kings used to think they might have divine powers, this was probably more reasonable than it sounds now.

Its a bit like Prince Charles testing whether he can destroy the South Bank Centre by telekinesis. From the look of the place he is slowly succeeding.

Sadly, modern Royalty don’t value controlled trials so much. Prince Charles, for instance is a big fan of Homeopathy.

Writers such as Ben Goldacre have issued warnings not to say anything rude about Homeopathy, for fear of ‘Charlie’s men’ finding you in a dark alley and rearranging your kneecaps.

Be assured, they can do it with a billionth of the force usually needed.

But now, there is no need for alternative practitioners to feel defensive, as we are entering the Age of the Placebo.

The reason is that it has become too difficult and expensive to invent ‘proper’ drugs and bring them on to the market. And it may not be necessary.

Alternative medicine used to be accused of being an expensive placebo. Now it is acclaimed as being an expensive placebo. The change has been an acknowledgement that placebos can be effective. Further, the more they cost, the better they work.

Even if the patient is told explicitly that the tablet contains no active ingredient.

Even if we write ‘placebo’ on the side of the tablet.

At least as shown in one study on Irritable Bowel Syndrome (IBS):


Think of that. You go to the doctors with a bad knee. Using a pin and a copy of the British National Formulary, he gives you an injection of vitamin B12 and tells you there is no possible way this should help.

But it does.

The word placebo is being rehabilitated slowly, in the light of evolving knowledge that our mind has a life of its own away from consciousness.

In fact the part of the mind that we think of as the Executive Board is more tiny and isolated than we thought and much less in control than we expected.

Much like the government really.

Depression is one of the conditions that responds quite well to placebo, making it difficult to test antidepressant treatments.

Some research has shown that brain function changes occur in depressed people as they respond to placebo treatment. This has been shown by the technique called QEEG, which is a special EEG technique designed to show regional brain activity.

All this comes as no surprise to regular readers of EP, who ‘got over’ the mind/brain problem several weeks ago.

We also know that people with Depression like their doctor or therapist to strike a positive and hopeful tone, but stop short of hype.

Much as we love evidence-based medicine, many of the treatments we offer do not have a strong evidence base. This is particularly true for resistant depression, where various combinations of antidepressants are added together.

Proving a drug therapy is effective is a tough challenge.

Firstly we need to be able to measure the condition itself, using some kind of rating scale that is valid and reliable.

Once we can measure it we can do a randomised controlled double blind trial, either against placebo, or against an established treatment. This is the gold standard test.

However, if the effect of the drug is small, a very large number of patients will be needed in the study to show a statistically significant difference.

Even then, the effect is usually only measured for a short period of time, say 3 or 6 months, before the trial ends.

This process is open to several kinds of bias, some intentional and some accidental. For instance, only trials which show a positive result tend to get published. And if we do enough trials, 5% of them will show a significant difference by chance.

If the trial contains 20 different measurement scales, one of them is likely to be significant by chance.

This has allowed companies to select data and use it out of context in support of their products.

All these problems have conspired to stop people testing products properly and led to the false conclusion that all antidepressants are equally effective, which is not as amazingly effective as we would like.

Randomised controlled trials are a relatively recent invention, so we have only recently discovered how powerful placebos can be in certain situations.

It is probably ethical to prescribe a placebo tablet if we tell the patient what they are getting. Presumably some part of the less-than-conscious mind responds to the treatment paradigm, even though another part has put on its sceptical face.

So, instead of developing new antidepressants and other drugs, we could try and develop better placebos. We might still need to test them though, if we are to suggest they are evidence based.

The reason is that some placebos might be more effective than others.

Instinctively, I know that a tiny purple tablet is better than a big white one. I would expect anything involving electricity, magnetism or machines that go beep to be more effective than anything made of plastic.

I’m sure there is scope for ‘steampunk’ designs, such as the old ECT boxes in mahogany and brass. Obviously, don’t plug them in.

Working specifically on the placebo effect rather than on supposed antidepressant properties based on neurotransmitters seems an easier way forward.

This is a highly convenient position for the alternative therapists, who can now argue that they are the reigning experts in the use of placebos. How long till we have a Professor of Placebo Studies at the University of (e.g) Mexborough?

This is a much better argument than trying to prove their therapies have specific active ingredients, such as water having a memory.

Even memory foam can’t remember anything – I’ve tested it. You don’t want your mattress knowing too much anyway. I subjected it to ruthless interrogation and can assure you it knows nothing.

‘Bigging up’ the treatment with a bit of hard sell seems a good idea.

Referencing a bogus system of how the body works – meridians, humours, animal magnetism, endorphins etc is always popular.

And, as mentioned, charge more to get more benefit. Money doesn’t just talk, it shouts loudly and eloquently.

A few years ago some friends and I devised the ideal placebo treatment, that would use tuning forks. The forks would be tuned precisely to resonate with the person’s brain waves.

This would enhance certain frequencies in the brain. The forks themselves would be very expensive, made of precious ceramics and metals and probably jewel encrusted. The pre-treatment diagnostic test would be an EEG.

Now we know, if we used QEEG instead of ordinary EEG, (note the Q) we could actually predict those likely to respond.

This gives us a business model similar to Harry Enfield’s ‘I saw you coming’ shop, which itself was based on the emperor’s new clothes principle.

How worried should ‘Big Pharma’ be about placebos? After all, if you can knock something useful up in your kitchen out of artichokes, why do we need huge research laboratories in Macclesfield?

Before you sell your Astrazeneca shares, note the Z, be aware that there are very few studies to support the use of explicit placebo.

The most famous is the Harvard study of IBS mentioned above.

With all due respect to IBS sufferers, this is quite a subjective type of health problem, which is very hard to measure. But not unlike Depression or Pain in this regard.

How far would a placebo go in treating a more biologically measurable disease, like hypertension or diabetes?

And attempts to give opiate addicts placebo instead of methadone failed to hit the spot. Opiate addicts are connoisseurs when it comes to pharmacology, much like the man in Wetherspoon’s.

He immediately discerned that the yellow Smartie did not have the same effects as the 22ml of ethanol contained in a pint of Ruddles Best.

The choice of a yellow Smartie is controversial, since yellow foodstuffs have been accused of toxicity. Yellow and blue Smarties were even removed from sale for a while in 2006, as the dyes Quinoline Yellow and Brilliant Blue were replaced with natural dyes.

Please, how can anything called ‘Brilliant Blue’ be bad for you?

My own preference for medication is a bit contrary to all this.

Firstly, if I am looking for placebo power, a bit like Scrabble, I’d go for a tablet with X, Z or Q in the name.

This is probably why ‘Xanax’ was so popular.

Otherwise, my favourite drug therapies are ones that were discovered by accident. The effect was not expected by anyone, it just happened.

That doesn’t really mean the effect was so barn-door obvious that it must be genuine, since people are very open to attribution errors.

Iproniazid was a TB drug that turned out to be an antidepressant, and Chlorpromazine was an antihistamine that turned out to be an antipsychotic. Note the Zs.

The history of drug therapies is fascinating and riddled with such discoveries.

Most of these were spin-offs from the German dye industry, so ironically the Yellow Smartie and mental health tablets share a lot of  heritage.

In the study of explicit placebo for IBS the patients were not told simply that they were taking sugar pills.

They were told they were taking ‘placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self- healing processes’.

That statement serves to stimulate the Suggestiveness Receptors.

So here’s the plan. In our kitchen, we count out Smarties, in non controversial colours like red and place them in proper tablet bottles with child-and-most-adult-proof lids.

With an eye to the potential central Asian market, we label the tablets QOZZAX.

In the small print we say: ‘These tablets contain no conventional western medicine. They work by lexicographic forces, based on the ancient Scrabble system’.

Going one further, for publicity, we get people to go on Radio 4, stating that their life had been ruined by scrabble tablets. They are trying to sue games giant Spear & Co.

I wonder how many placebos are already being used in different walks of life.  I’ve noticed that supermarkets can enhance the quality (and price) of foods simply by adding adjectives. Rhubarb would become Bohemian Wild Rhubarb for instance. As though rhubarb could ever be straight-laced or tame.

I’m certain (OK, I have no evidence) that one Honda garage I visited used to do nothing more for an annual service than apply bright red grease to the door hinges, so you could assume something had happened to the car during the day, apart from being raced along the ring road a few times, to KFC and back.

I spent a lot of time trying to convince our last pharmacist that he should make up a ‘proper mixture’ for each patient in a good strong colour, with a bit of bitter flavouring, in a proper fluted brown bottle with a glass stopper.

Sadly this suggestion was not met with the enthusiasm I felt it deserved.

I was not suggesting a complete sell-out to Charlie. Active antipsychotics and antidepressants are available in colourless liquids that can mix together, so this mixture would not be a placebo. Just an existing treatment with a bit of pzazz. Note the Zs .

It was just that I so wanted to make it Brilliant Blue.

But if the Mexborough department ever gets going, the  first development I would like to see is a dermatological version of Shake N Vac.


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