Testosterone, Aggression... Confusion

Breaking news from the BBC -

Testosterone link to aggression 'all in the mind'

Work in Nature magazine suggests the mind can win over hormones... Testosterone induces anti-social behaviour in humans, but only because of our own prejudices about its effect rather than its biological activity, suggest the authors.

The researchers, led by Ernst Fehr of the University of Zurich, Switzerland, said the results suggested a case of "mind over matter" with the brain overriding body chemistry.

"Whereas other animals may be predominantly under the influence of biological factors such as hormones, biology seems to exert less control over human behaviour," they said.

Phew, that's a relief - for a minute back there I was worried we didn't have free will. But look a little closer at the study, and it turns out that all is not as it seems. The experiment (Eisenegger et al) involved giving healthy women 0.5 mg testosterone, or placebo, in a randomized double-blind manner, and then getting them to take part in the "Ultimatum Game".

This is a game for two players. One, the Proposer, is given some money, and then has to offer to give a certain proportion of it to the other player, the Receiver. If the Receiver accepts the offer, both players get the agreed-upon amount of money. If they reject it, however, no-one gets anything.

The Proposer is basically faced with the choice of making a "fair" offer, e.g. giving away 50%, or a greedy one, say offering 10% and keeping 90% for themselves. Receivers generally accept fair offers, but most people get annoyed or insulted by unfair ones, and reject them, even though this means they lose money (10% of the money is still more than 0%).

What happened? Testosterone affected behaviour. It had no effect on women playing the role of the Receivers, but the Proposers given testosterone made significantly fairer offers on average, compared to those given placebo. That's not mind over matter, that's matter over mind - give someone a hormone and their behaviour changes.

The direction of the effect is quite interesting - if testosterone increased aggression, as popular belief has it, you might expect it to decrease fair offers. Or, you might not. I suppose it depends on your understanding of "aggression". For their part, Eisenegger et al interpret this finding as suggesting that testosterone doesn't increase aggression per se, but rather increases our motivation to achieve "status", which leads to Proposers making fairer offers, so as to appear nicer. Hmm. Maybe.

But where did the BBC get the whole "all in the mind" thing from? Well, after the testing was over, the authors asked the women whether they thought they had taken testosterone or placebo. The results showed that the women couldn't actually tell which they'd had - they were no more accurate than if they were guessing - but women who believed they'd got testosterone made more unfair offers than women who believed they got placebo. The size of this effect was bigger than the effect of testosterone.

Is that "mind over matter"? Do beliefs about testosterone exert a more powerful effect on behaviour than testosterone itself? Maybe they do, but these data don't tell us anything about that. The women's beliefs weren't manipulated in any way in this trial, so as an experiment it couldn't investigate belief effects. In order to show that belief alters behaviour, you'd need to control beliefs. You could randomly assign some subjects to be told they were taking testosterone, and compare them to others told they were on placebo, say.

This study didn't do anything like that. Beliefs about testosterone were only correlated with behaviour, and unless someone's changed the rules recently, correlation isn't causation. It's like finding that people with brown skin are more likely to be Hindus than people with white skin, and concluding that belief in Brahma alters pigmentation. It could even be that the behaviour drove the belief, because subjects were quizzed about their testosterone status after the Ultimatum Game - maybe women who, for whatever reason, behaved selfishly, decided that this meant they had taken testosterone!

Overall, this study provides quite interesting data about hormonal effects on behaviour, but tells us nothing about the effects of beliefs about hormones. On that issue, the way the media have covered this experiment is rather more informative than the experiment itself.

[BPSDB]

Eisenegger, C., Naef, M., Snozzi, R., Heinrichs, M., & Fehr, E. (2009). Prejudice and truth about the effect of testosterone on human bargaining behaviour Nature DOI: 10.1038/nature08711

Testosterone, Aggression... Confusion

Breaking news from the BBC -

Testosterone link to aggression 'all in the mind'

Work in Nature magazine suggests the mind can win over hormones... Testosterone induces anti-social behaviour in humans, but only because of our own prejudices about its effect rather than its biological activity, suggest the authors.

The researchers, led by Ernst Fehr of the University of Zurich, Switzerland, said the results suggested a case of "mind over matter" with the brain overriding body chemistry.

"Whereas other animals may be predominantly under the influence of biological factors such as hormones, biology seems to exert less control over human behaviour," they said.

Phew, that's a relief - for a minute back there I was worried we didn't have free will. But look a little closer at the study, and it turns out that all is not as it seems. The experiment (Eisenegger et al) involved giving healthy women 0.5 mg testosterone, or placebo, in a randomized double-blind manner, and then getting them to take part in the "Ultimatum Game".

This is a game for two players. One, the Proposer, is given some money, and then has to offer to give a certain proportion of it to the other player, the Receiver. If the Receiver accepts the offer, both players get the agreed-upon amount of money. If they reject it, however, no-one gets anything.

The Proposer is basically faced with the choice of making a "fair" offer, e.g. giving away 50%, or a greedy one, say offering 10% and keeping 90% for themselves. Receivers generally accept fair offers, but most people get annoyed or insulted by unfair ones, and reject them, even though this means they lose money (10% of the money is still more than 0%).

What happened? Testosterone affected behaviour. It had no effect on women playing the role of the Receivers, but the Proposers given testosterone made significantly fairer offers on average, compared to those given placebo. That's not mind over matter, that's matter over mind - give someone a hormone and their behaviour changes.

The direction of the effect is quite interesting - if testosterone increased aggression, as popular belief has it, you might expect it to decrease fair offers. Or, you might not. I suppose it depends on your understanding of "aggression". For their part, Eisenegger et al interpret this finding as suggesting that testosterone doesn't increase aggression per se, but rather increases our motivation to achieve "status", which leads to Proposers making fairer offers, so as to appear nicer. Hmm. Maybe.

But where did the BBC get the whole "all in the mind" thing from? Well, after the testing was over, the authors asked the women whether they thought they had taken testosterone or placebo. The results showed that the women couldn't actually tell which they'd had - they were no more accurate than if they were guessing - but women who believed they'd got testosterone made more unfair offers than women who believed they got placebo. The size of this effect was bigger than the effect of testosterone.

Is that "mind over matter"? Do beliefs about testosterone exert a more powerful effect on behaviour than testosterone itself? Maybe they do, but these data don't tell us anything about that. The women's beliefs weren't manipulated in any way in this trial, so as an experiment it couldn't investigate belief effects. In order to show that belief alters behaviour, you'd need to control beliefs. You could randomly assign some subjects to be told they were taking testosterone, and compare them to others told they were on placebo, say.

This study didn't do anything like that. Beliefs about testosterone were only correlated with behaviour, and unless someone's changed the rules recently, correlation isn't causation. It's like finding that people with brown skin are more likely to be Hindus than people with white skin, and concluding that belief in Brahma alters pigmentation. It could even be that the behaviour drove the belief, because subjects were quizzed about their testosterone status after the Ultimatum Game - maybe women who, for whatever reason, behaved selfishly, decided that this meant they had taken testosterone!

Overall, this study provides quite interesting data about hormonal effects on behaviour, but tells us nothing about the effects of beliefs about hormones. On that issue, the way the media have covered this experiment is rather more informative than the experiment itself.

[BPSDB]

Eisenegger, C., Naef, M., Snozzi, R., Heinrichs, M., & Fehr, E. (2009). Prejudice and truth about the effect of testosterone on human bargaining behaviour Nature DOI: 10.1038/nature08711

B-Movie Medicine

We all know about movies that are so bad, they're good. But could the same thing apply to doctors?

As I described last week, Desiree Jennings is a young woman from Virginia who developed horrible symptoms, including muscle spasms and convulsions, after getting a flu vaccine. It looked a bit like a form of brain damage called dystonia.

Numerous neurologists concluded that her illness was mostly or entirely psychogenic. A certain Dr Rashid Buttar, however, said that she was suffering from neurological damage caused by toxins in the flu vaccine.

Buttar gave her chelation therapy to flush the toxins out. Within 15 minutes, she was cured. Biologically speaking, this is ludicrous. It's flat-out impossible that chelation could reverse brain damage in 15 minutes, even if Jennings did have brain damage in the first place.

But Buttar's treatment worked, amazingly well by all accounts. This is not surprising, because the illness was psychological in nature, and Dr Buttar's treatment was, psychologically, very effective. Jennings was admitted to Dr Buttar's private clinic; she had IV lines put in to her arm; Dr Buttar attached the chelation treatment to the IV drip and, in a textbook example of how to produce a placebo effect:

I told her "Now the magic should start", prepared her for what I expected to happen. (interview with Dr Buttar, 05:30 onwards)

The magic did indeed happen, precisely because Dr Buttar convinced Jennings that it would.

*

What would have happened to Jennings if there were no Dr Buttars in the world? Her doctors would have run scans and tests to check if Jennings had any neurological damage. The results would have been normal. Jennings would probably have interpreted this as "We don't know what's wrong with you", although experts would have suspected that the symptoms were most likely psychogenic.

At some point, someone would have had to raise that possibility with her. But the point about psychogenic illness is that it's not "faking", "acting" or "made up" - the patient believes they are ill. The symptoms don't feel psychogenic. This is why people often interpret the suggestion that symptoms are psychogenic as saying "you're not really ill" and hence "you're either lying, or crazy". Of course, patients suffering from psychogenic illness are neither, and they know it.

So, without complementary and alternative medicine, Jennings might have ended up believing herself to be suffering from an illness so obscure that doctors were unable to diagnose it, and hence, unable to cure it. A hopeless situation. A worse thing for someone with psychogenic symptoms to believe is hard to imagine.

Dr Buttar's treatment was psychologically very powerful - precisely because he believed in it, so he was able to convince Jennings to believe in it. A doctor who realized that Jennings' symptoms were psychogenic would have found it much harder to achieve the same result. In order to do so, they would have to lie to her, by pretending to believe in a treatment which they knew was just a placebo. This is hard - the doctor would need to be an excellent actor as well as a medic - not to mention ethically tricky.

Interestingly, 100 years ago, this problem wouldn't have arisen. Doctors knew much less about diagnosis and there were few laboratory tests or scans in those days, so there was usually no way to prove that some symptoms were organic and others were psychogenic. Everyone got the same treatment. Of course, the treatments back then were less good at treating organic illnesses, but that wouldn't necessarily have made them any worse as placebos. Ironically, as mainstream medicine gets better and better at diagnosing and treating disease, it may be getting worse at dealing with psychogenic symptoms.

[BPSDB]

B-Movie Medicine

We all know about movies that are so bad, they're good. But could the same thing apply to doctors?

As I described last week, Desiree Jennings is a young woman from Virginia who developed horrible symptoms, including muscle spasms and convulsions, after getting a flu vaccine. It looked a bit like a form of brain damage called dystonia.

Numerous neurologists concluded that her illness was mostly or entirely psychogenic. A certain Dr Rashid Buttar, however, said that she was suffering from neurological damage caused by toxins in the flu vaccine.

Buttar gave her chelation therapy to flush the toxins out. Within 15 minutes, she was cured. Biologically speaking, this is ludicrous. It's flat-out impossible that chelation could reverse brain damage in 15 minutes, even if Jennings did have brain damage in the first place.

But Buttar's treatment worked, amazingly well by all accounts. This is not surprising, because the illness was psychological in nature, and Dr Buttar's treatment was, psychologically, very effective. Jennings was admitted to Dr Buttar's private clinic; she had IV lines put in to her arm; Dr Buttar attached the chelation treatment to the IV drip and, in a textbook example of how to produce a placebo effect:

I told her "Now the magic should start", prepared her for what I expected to happen. (interview with Dr Buttar, 05:30 onwards)

The magic did indeed happen, precisely because Dr Buttar convinced Jennings that it would.

*

What would have happened to Jennings if there were no Dr Buttars in the world? Her doctors would have run scans and tests to check if Jennings had any neurological damage. The results would have been normal. Jennings would probably have interpreted this as "We don't know what's wrong with you", although experts would have suspected that the symptoms were most likely psychogenic.

At some point, someone would have had to raise that possibility with her. But the point about psychogenic illness is that it's not "faking", "acting" or "made up" - the patient believes they are ill. The symptoms don't feel psychogenic. This is why people often interpret the suggestion that symptoms are psychogenic as saying "you're not really ill" and hence "you're either lying, or crazy". Of course, patients suffering from psychogenic illness are neither, and they know it.

So, without complementary and alternative medicine, Jennings might have ended up believing herself to be suffering from an illness so obscure that doctors were unable to diagnose it, and hence, unable to cure it. A hopeless situation. A worse thing for someone with psychogenic symptoms to believe is hard to imagine.

Dr Buttar's treatment was psychologically very powerful - precisely because he believed in it, so he was able to convince Jennings to believe in it. A doctor who realized that Jennings' symptoms were psychogenic would have found it much harder to achieve the same result. In order to do so, they would have to lie to her, by pretending to believe in a treatment which they knew was just a placebo. This is hard - the doctor would need to be an excellent actor as well as a medic - not to mention ethically tricky.

Interestingly, 100 years ago, this problem wouldn't have arisen. Doctors knew much less about diagnosis and there were few laboratory tests or scans in those days, so there was usually no way to prove that some symptoms were organic and others were psychogenic. Everyone got the same treatment. Of course, the treatments back then were less good at treating organic illnesses, but that wouldn't necessarily have made them any worse as placebos. Ironically, as mainstream medicine gets better and better at diagnosing and treating disease, it may be getting worse at dealing with psychogenic symptoms.

[BPSDB]

More on Medical Marijuana

Previously I wrote about a small study finding that smoked marijuana helps with HIV-related pain. In the last month, two more clinical trials of medical marijuana - or rather, marijuana-based drugs - for pain have come out.

First, the good news. Johnson et al tested a mouth spray containing the two major psychoactive chemicals in marijuana, THC and CBD. Their patients were all suffering from terminal cancer, which believe it or not, is quite painful. Almost all of the subjects were already taking high doses of strong opiate painkillers: a mean of 270 mg morphine or equivalent each day, which is enough to kill someone without a tolerance. (A couple of them were on an eye-watering 6 grams daily). Yet they were still in pain.

Patients were allowed to use the cannabinoid spray as often as they wanted for 2 weeks. Lo and behold, the THC/CBD spray was more effective than an inactive placebo spray at relieving pain. The effect was modest, but statistically significant, and given what these people were going through I'm sure they were glad of even "modest" effects. A third group got a spray containing only THC, and this was less effective than the combined THC/CBD - on most measures, it was no better than placebo. THC is often thought of as the single "active ingredient" in marijuana, but this suggests that there's more to it than that. This was a relatively large study - 177 patients in total - so the results are pretty convincing, although you should know that it was funded and sponsored by GW Pharma, whose "vision is to the global leader in prescription cannabinoid medicines". Hmm.

The other trial was less promising, although it was in a completely different group - patients with painful diabetic neuropathy. The people in this study were in pain despite taking tricyclic antidepressants, which, curiously, are quite good at relieving neuropathic pain. Again, the treatment was a combined CBD/THC spray, and this trial for lasted 12 weeks. The active spray was no more effective than the placebo spray this time around - both groups improved a lot. This was a small trial (just 29 patients), so it might just have not been big enough to detect any effect. Also, this one wasn't funded by a pharmaceutical company.

Overall, this is further evidence that marijuana-based drugs can treat some kinds of pain, although maybe not all of them. I have to say, though, that I'm not sure that we needed a placebo-controlled trial to tell us that terminal cancer patients can benefit from medical marijuana. If someone's dying from cancer, I say let them use whatever the hell they want, if they find it helps them. Dying patients used to be given something called a Brompton cocktail, a mixture of drugs that would make Keith Richards jealous:  heroin, cocaine, marijuana, chloroform, and gin, in the most popular variant.

And why not? There were no placebo-controlled trials proving that it worked, but it seemed to help, and even if it was just a placebo (which seems unlikely), placebo pain relief is still pain relief. I'm not saying that these kinds of trials aren't valuable, but I don't think we should demand cast-iron proof that medical marijuana works before making it available to people who are suffering. People are suffering now, and trials take time.



Johnson JR, Burnell-Nugent M, Lossignol D, Ganae-Motan ED, Potts R, & Fallon MT (2009). Multicenter, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study of the Efficacy, Safety, and Tolerability of THC:CBD Extract and THC Extract in Patients With Intractable Cancer-Related Pain. Journal of pain and symptom management PMID: 19896326

Selvarajah D, Gandhi R, Emery CJ, & Tesfaye S (2009). A Randomised Placebo Controlled Double Blind Clinical Trial of Cannabis Based Medicinal Product (Sativex) in Painful Diabetic Neuropathy: Depression is a Major Confounding Factor. Diabetes care PMID: 19808912

More on Medical Marijuana

Previously I wrote about a small study finding that smoked marijuana helps with HIV-related pain. In the last month, two more clinical trials of medical marijuana - or rather, marijuana-based drugs - for pain have come out.

First, the good news. Johnson et al tested a mouth spray containing the two major psychoactive chemicals in marijuana, THC and CBD. Their patients were all suffering from terminal cancer, which believe it or not, is quite painful. Almost all of the subjects were already taking high doses of strong opiate painkillers: a mean of 270 mg morphine or equivalent each day, which is enough to kill someone without a tolerance. (A couple of them were on an eye-watering 6 grams daily). Yet they were still in pain.

Patients were allowed to use the cannabinoid spray as often as they wanted for 2 weeks. Lo and behold, the THC/CBD spray was more effective than an inactive placebo spray at relieving pain. The effect was modest, but statistically significant, and given what these people were going through I'm sure they were glad of even "modest" effects. A third group got a spray containing only THC, and this was less effective than the combined THC/CBD - on most measures, it was no better than placebo. THC is often thought of as the single "active ingredient" in marijuana, but this suggests that there's more to it than that. This was a relatively large study - 177 patients in total - so the results are pretty convincing, although you should know that it was funded and sponsored by GW Pharma, whose "vision is to the global leader in prescription cannabinoid medicines". Hmm.

The other trial was less promising, although it was in a completely different group - patients with painful diabetic neuropathy. The people in this study were in pain despite taking tricyclic antidepressants, which, curiously, are quite good at relieving neuropathic pain. Again, the treatment was a combined CBD/THC spray, and this trial for lasted 12 weeks. The active spray was no more effective than the placebo spray this time around - both groups improved a lot. This was a small trial (just 29 patients), so it might just have not been big enough to detect any effect. Also, this one wasn't funded by a pharmaceutical company.

Overall, this is further evidence that marijuana-based drugs can treat some kinds of pain, although maybe not all of them. I have to say, though, that I'm not sure that we needed a placebo-controlled trial to tell us that terminal cancer patients can benefit from medical marijuana. If someone's dying from cancer, I say let them use whatever the hell they want, if they find it helps them. Dying patients used to be given something called a Brompton cocktail, a mixture of drugs that would make Keith Richards jealous:  heroin, cocaine, marijuana, chloroform, and gin, in the most popular variant.

And why not? There were no placebo-controlled trials proving that it worked, but it seemed to help, and even if it was just a placebo (which seems unlikely), placebo pain relief is still pain relief. I'm not saying that these kinds of trials aren't valuable, but I don't think we should demand cast-iron proof that medical marijuana works before making it available to people who are suffering. People are suffering now, and trials take time.



Johnson JR, Burnell-Nugent M, Lossignol D, Ganae-Motan ED, Potts R, & Fallon MT (2009). Multicenter, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study of the Efficacy, Safety, and Tolerability of THC:CBD Extract and THC Extract in Patients With Intractable Cancer-Related Pain. Journal of pain and symptom management PMID: 19896326

Selvarajah D, Gandhi R, Emery CJ, & Tesfaye S (2009). A Randomised Placebo Controlled Double Blind Clinical Trial of Cannabis Based Medicinal Product (Sativex) in Painful Diabetic Neuropathy: Depression is a Major Confounding Factor. Diabetes care PMID: 19808912

The Needle and the Damage (Not) Done

You may already have heard about Desiree Jennings.

If not, here's a summary, although for the full story you should consult Steven Novella or Orac, whose expert analyses of the case are second to none. Desiree Jennings is a 25 year old woman from Ashburn, Virginia who developed horrible symptoms following a seasonal flu vaccination in August. As she puts it:

In a matter of a few short weeks I lost the ability to walk, talk normally, and focus on more than one stimuli at a time. Whenever I eat I know, without fail, that my body will soon go into uncontrollable convulsions coupled with periods of blacking out.

For some weeks the problems were so bad that she was almost completely disabled, and feared the damage was permanent. Vaccines had destroyed her life. You can see a video here - American TV has covered the story in a lot of detail (the fact that she is quite... photogenic can't have put them off). Desiree and the media described her illness as dystonia, a neurological condition characterised by uncontrollable muscle contractions. Dystonia is caused by damage to certain motor pathways in the brain.

However, Desiree Jennings does not have dystonia. The symptoms look a bit like dystonia to the untrained eye, but they're not it. This is the unanimous opinion of dystonia experts who've seen the footage of Jennings. A blogger discovered that it was also seemingly the view of the neurologist who originally examined her.

So what's wrong with her? The answer, according to experts, is that her symptoms are psychogenic - "neurological" or "medical" symptoms caused by psychological factors rather than organic brain damage. It's important to be clear on what exactly this implies. It doesn't mean that Jennings is "making up" or "faking" the symptoms or that they're a "hoax". The symptoms are as "real" as any others, the only thing psychological about them is the cause. Nor are psychogenic symptoms delusions - Jennings isn't mentally ill or "crazy".

Almost certainly, she is in her right mind, and she sincerely believes that she is a victim of brain damage caused by the flu shot. The belief is false, but it's not crazy - in 1976 one flu vaccine may have caused neurological disorders and today many, many otherwise sane people believe that vaccines cause all kinds of damage. (It could well be that this belief is actually driving Jennings' symptoms, but we can't know that - there could be other psychological factors at work.)

*

One of the hallmarks of psychogenic symptoms is that they improve in response to psychological factors. Neurologist blogger Steven Novella predicted that:

I predict that they will be able to “cure” her, because psychogenic disorders can and do spontaneously resolve. They will then claim victory for their quackery in curing a (non-existent) vaccine injury.

They being anti-vaccination group Generation Rescue who were swift to offer Jennings their support and, er, expertise. And this is exactly what seems to be happening: Dr Rashid Buttar, a prominent anti-vaccine doctor who treats "vaccine damage" cases, began giving Jennings (amongst other things) chelation therapy to flush out toxic metals from her body, on the theory that her dystonia was caused by mercury in the vaccine. It worked! Dr. Buttar tells us - 15 minutes after the chelation solution started entering her body through an IV drip, all of the symptoms had disappeared (on the podcast it's about 6:00 onwards).

It's completely implausible that mercury in the vaccine could have caused dystonia, and even if it somehow did, it's impossible that chelation could reverse mercury-induced brain damage so quickly. If you are unfortunate enough to get mercury poisoning the neurological damage is permanent; flushing out the mercury wouldn't cure you. There's now no question that Jennings is a textbook case of psychogenic illness.

*

On this blog I've often written about the mysterious "placebo effect". A few weeks ago, I said -

People seem more willing to accept the mind-over-matter powers of "the placebo" than they are to accept the existence of psychosomatic illness.

We certainly seem to talk about placebos more than we talk about psychosomatic or psychogenic illness. There are 20 million Google hits for "placebo", just 1.6 million for "psychosomatic", and 500,000 for "psychogenic". (Even "placebo -music -trial" gives 8.7 million, which excludes all of the many placebo-controlled clinical trials and also hits about the band.)

Why? One important factor is surely that it's very difficult to prove that any given illness is "psychosomatic". Even if a patient has symptoms with no apparent medical cause, leading to suspicions that they're psychogenic, there could always be an organic cause waiting to be discovered. Just as we can never prove that there were no WMDs in Iraq, we can never prove that a given illness is purely psychological in origin.

But occasionally, there are cases where the psychogenic nature of an illness is so patent that there can be little doubt, and this is one of them. Watch the videos, listen to the account of the cure, and marvel at the mysteries of the mind.

[BPSDB]

The Needle and the Damage (Not) Done

You may already have heard about Desiree Jennings.

If not, here's a summary, although for the full story you should consult Steven Novella or Orac, whose expert analyses of the case are second to none. Desiree Jennings is a 25 year old woman from Ashburn, Virginia who developed horrible symptoms following a seasonal flu vaccination in August. As she puts it:

In a matter of a few short weeks I lost the ability to walk, talk normally, and focus on more than one stimuli at a time. Whenever I eat I know, without fail, that my body will soon go into uncontrollable convulsions coupled with periods of blacking out.

For some weeks the problems were so bad that she was almost completely disabled, and feared the damage was permanent. Vaccines had destroyed her life. You can see a video here - American TV has covered the story in a lot of detail (the fact that she is quite... photogenic can't have put them off). Desiree and the media described her illness as dystonia, a neurological condition characterised by uncontrollable muscle contractions. Dystonia is caused by damage to certain motor pathways in the brain.

However, Desiree Jennings does not have dystonia. The symptoms look a bit like dystonia to the untrained eye, but they're not it. This is the unanimous opinion of dystonia experts who've seen the footage of Jennings. A blogger discovered that it was also seemingly the view of the neurologist who originally examined her.

So what's wrong with her? The answer, according to experts, is that her symptoms are psychogenic - "neurological" or "medical" symptoms caused by psychological factors rather than organic brain damage. It's important to be clear on what exactly this implies. It doesn't mean that Jennings is "making up" or "faking" the symptoms or that they're a "hoax". The symptoms are as "real" as any others, the only thing psychological about them is the cause. Nor are psychogenic symptoms delusions - Jennings isn't mentally ill or "crazy".

Almost certainly, she is in her right mind, and she sincerely believes that she is a victim of brain damage caused by the flu shot. The belief is false, but it's not crazy - in 1976 one flu vaccine may have caused neurological disorders and today many, many otherwise sane people believe that vaccines cause all kinds of damage. (It could well be that this belief is actually driving Jennings' symptoms, but we can't know that - there could be other psychological factors at work.)

*

One of the hallmarks of psychogenic symptoms is that they improve in response to psychological factors. Neurologist blogger Steven Novella predicted that:

I predict that they will be able to “cure” her, because psychogenic disorders can and do spontaneously resolve. They will then claim victory for their quackery in curing a (non-existent) vaccine injury.

They being anti-vaccination group Generation Rescue who were swift to offer Jennings their support and, er, expertise. And this is exactly what seems to be happening: Dr Rashid Buttar, a prominent anti-vaccine doctor who treats "vaccine damage" cases, began giving Jennings (amongst other things) chelation therapy to flush out toxic metals from her body, on the theory that her dystonia was caused by mercury in the vaccine. It worked! Dr. Buttar tells us - 15 minutes after the chelation solution started entering her body through an IV drip, all of the symptoms had disappeared (on the podcast it's about 6:00 onwards).

It's completely implausible that mercury in the vaccine could have caused dystonia, and even if it somehow did, it's impossible that chelation could reverse mercury-induced brain damage so quickly. If you are unfortunate enough to get mercury poisoning the neurological damage is permanent; flushing out the mercury wouldn't cure you. There's now no question that Jennings is a textbook case of psychogenic illness.

*

On this blog I've often written about the mysterious "placebo effect". A few weeks ago, I said -

People seem more willing to accept the mind-over-matter powers of "the placebo" than they are to accept the existence of psychosomatic illness.

We certainly seem to talk about placebos more than we talk about psychosomatic or psychogenic illness. There are 20 million Google hits for "placebo", just 1.6 million for "psychosomatic", and 500,000 for "psychogenic". (Even "placebo -music -trial" gives 8.7 million, which excludes all of the many placebo-controlled clinical trials and also hits about the band.)

Why? One important factor is surely that it's very difficult to prove that any given illness is "psychosomatic". Even if a patient has symptoms with no apparent medical cause, leading to suspicions that they're psychogenic, there could always be an organic cause waiting to be discovered. Just as we can never prove that there were no WMDs in Iraq, we can never prove that a given illness is purely psychological in origin.

But occasionally, there are cases where the psychogenic nature of an illness is so patent that there can be little doubt, and this is one of them. Watch the videos, listen to the account of the cure, and marvel at the mysteries of the mind.

[BPSDB]

Real vs Placebo Coffee

Coffee contains caffeine, and as everyone knows, caffeine is a stimulant. We all know how a good cup of coffee wakes you up, makes you more alert, and helps you concentrate - thanks to caffeine.


Or does it? Are the benefits of coffee really due to the caffeine, or are there placebo effects at work? Numerous experiments have tried to answer this question, but a paper published today goes into more detail than most. (It caught my eye just as I was taking my first sip this morning, so I had to blog about it.)

The authors took 60 coffee-loving volunteers and gave them either placebo decaffeinated coffee, or coffee containing 280 mg caffeine. That's quite a lot, roughly equivalent to three normal cups. 30 minutes later, they attempted a difficult button-pressing task requiring concentration and sustained effort, plus a task involving mashing buttons as fast as possible for a minute.

The catch was that the experimenters lied to the volunteers. Everyone was told that they were getting real coffee. Half of them were told that the coffee would enhance their performance on the tasks, while the other half were told it would impair it. If the placebo effect was at work, these misleading instructions should have affected how the volunteers felt and acted.

Several interesting things happened. First, the caffeine enhanced performance on the cognitive tasks - it wasn't just a placebo effect. Bear in mind, though, that these people were all regular coffee drinkers who hadn't drunk any caffeine that day. The benefit could have been a reversal of caffeine withdrawl symptoms.

Second, there was a small effect of expectancy on task performance in the placebo group - but it worked in reverse. People who were told that the coffee would make them do worse actually did better than those who expected the coffee to help them. Presumably, this is because they put in extra effort to try to overcome the supposedly negative effects. This paradoxical placebo response reminds us that there's more to "the placebo effect" than meets the eye.

Finally, no-one who got the decaf noticed that it didn't actually contain caffeine, and the volunteer's ratings of their alertness and mood didn't differ between the caffeine and placebo groups. So, this suggests that if you were to secretly replace someone's favorite blend with decaf, they wouldn't notice - although their performance would nevertheless decline. Bear that in mind when considering pranks to play on colleagues or flatmates.

It looks like science has just confirmed another piece of The Wisdom of Seinfeld:

Elaine: Jerry likes Morning Thunder.
George: Jerry drinks Morning Thunder? Morning Thunder has caffeine in it. Jerry doesn't drink caffeine.
Elaine: Jerry doesn't know Morning Thunder has caffeine in it.
George: You don't tell him?
Elaine: No. And you should see him. Man, he gets all hyper, he doesn't even know why! He loves it. He walks around going, "God, I feel great!"
- Seinfeld, "The Dog"

[BPSDB]

Harrell PT, & Juliano LM (2009). Caffeine expectancies influence the subjective and behavioral effects of caffeine. Psychopharmacology PMID: 19760283

Real vs Placebo Coffee

Coffee contains caffeine, and as everyone knows, caffeine is a stimulant. We all know how a good cup of coffee wakes you up, makes you more alert, and helps you concentrate - thanks to caffeine.


Or does it? Are the benefits of coffee really due to the caffeine, or are there placebo effects at work? Numerous experiments have tried to answer this question, but a paper published today goes into more detail than most. (It caught my eye just as I was taking my first sip this morning, so I had to blog about it.)

The authors took 60 coffee-loving volunteers and gave them either placebo decaffeinated coffee, or coffee containing 280 mg caffeine. That's quite a lot, roughly equivalent to three normal cups. 30 minutes later, they attempted a difficult button-pressing task requiring concentration and sustained effort, plus a task involving mashing buttons as fast as possible for a minute.

The catch was that the experimenters lied to the volunteers. Everyone was told that they were getting real coffee. Half of them were told that the coffee would enhance their performance on the tasks, while the other half were told it would impair it. If the placebo effect was at work, these misleading instructions should have affected how the volunteers felt and acted.

Several interesting things happened. First, the caffeine enhanced performance on the cognitive tasks - it wasn't just a placebo effect. Bear in mind, though, that these people were all regular coffee drinkers who hadn't drunk any caffeine that day. The benefit could have been a reversal of caffeine withdrawl symptoms.

Second, there was a small effect of expectancy on task performance in the placebo group - but it worked in reverse. People who were told that the coffee would make them do worse actually did better than those who expected the coffee to help them. Presumably, this is because they put in extra effort to try to overcome the supposedly negative effects. This paradoxical placebo response reminds us that there's more to "the placebo effect" than meets the eye.

Finally, no-one who got the decaf noticed that it didn't actually contain caffeine, and the volunteer's ratings of their alertness and mood didn't differ between the caffeine and placebo groups. So, this suggests that if you were to secretly replace someone's favorite blend with decaf, they wouldn't notice - although their performance would nevertheless decline. Bear that in mind when considering pranks to play on colleagues or flatmates.

It looks like science has just confirmed another piece of The Wisdom of Seinfeld:

Elaine: Jerry likes Morning Thunder.
George: Jerry drinks Morning Thunder? Morning Thunder has caffeine in it. Jerry doesn't drink caffeine.
Elaine: Jerry doesn't know Morning Thunder has caffeine in it.
George: You don't tell him?
Elaine: No. And you should see him. Man, he gets all hyper, he doesn't even know why! He loves it. He walks around going, "God, I feel great!"
- Seinfeld, "The Dog"

[BPSDB]

Harrell PT, & Juliano LM (2009). Caffeine expectancies influence the subjective and behavioral effects of caffeine. Psychopharmacology PMID: 19760283

Deconstructing the Placebo

Last month Wired, announced that Placebos Are Getting More Effective. Drugmakers Are Desperate to Know Why.

The article's a good read, and the basic story is true, at least in the case of psychiatric drugs. In clinical trials, people taking placebos do seem to get better more often now than in the past (paper). This is a big problem for Big Pharma, because it means that experimental new drugs often fail to perform better than placebo, i.e. they don't work. Wired have just noticed this, but it's been being discussed in the academic literature for several years.

Why is this? No-one knows. There have been many suggestions - maybe people "believe in" the benefits of drugs more nowadays, so the placebo effect is greater; maybe clinical trials are recruiting people with milder illnesses that respond better to placebo, or just get better on their own. But we really don't have any clear idea.

What if the confusion is because of the very concept of the "placebo"? Earlier this year, the BMJ ran a short opinion piece called It’s time to put the placebo out of our misery. Robin Nunn wants us to "stop thinking in terms of placebo...The placebo construct conceals more than it clarifies."

His central argument is an analogy. If we knew nothing about humour and observed a comedian telling jokes to an audience, we might decide there was a mysterious "audience effect" at work, and busy ourselves studying it...

Imagine that you are a visitor from another world. You observe a human audience for the first time. You notice a man making vocal sounds. He is watched by an audience. Suddenly they burst into smiles and laughter. Then they’re quiet. This cycle of quietness then laughter then quietness happens several times.

What is this strange audience effect? Not all of the man’s sounds generate an audience effect, and not every audience member reacts. You deem some members of the audience to be “audience responders,” those who are particularly influenced by the audience effect. What makes them react? A theory of the audience effect could be spun into an entire literature analogous to the literature on the placebo effect.

But what we should be doing is examining the details of jokes and of laughter -

We could learn more about what makes audiences laugh by returning to fundamentals. What is laughter? Why is “fart” funnier than “flatulence”? Why are some people just not funny no matter how many jokes they try?

And this is what we should be doing with the "placebo effect" as well -

Suppose there is no such unicorn as a placebo. Then what? Just replace the thought of placebo with something more fundamental. For those who use placebo as treatment, ask what is going on. Are you using the trappings of expertise, the white coat and diploma? Are you making your patients believe because they believe in you?

Nunn's piece is a polemic and he seems to be conclude by calling for a "post-placebo era" in which there will be no more placebo-controlled trials (although it's not clear what he means by this). This is going too far. But his analogy with humour is an important one because it forces us to analyse the placebo in detail.

"The placebo effect" has become a vague catch-all term for anything that seems to happen to people when you give them a sugar pill. Of course, lots of things could happen. They could feel better just because of the passage of time. Or they could realize that they're supposed to feel better and say they feel better, even if they don't.

The "true" placebo effect refers to improvement (or worsening) of symptoms driven purely by the psychological expectation of such. But even this is something of a catch-all term. Many things could drive this improvement. Suppose you give someone a placebo pill that you claim will make them more intelligent, and they believe it.

Believing themselves to be smarter, they start doing smart things like crosswords, math puzzles, reading hard books (or even reading Neuroskeptic), etc. But the placebo itself was just a nudge in the right direction. Anything which provided that nudge would also have worked - and the nudge itself can't take all the credit.

The strongest meaning of the "placebo effect" is a direct effect of belief upon symptoms. You give someone a sugar pill or injection, and they immediately feel less pain, or whatever. But even this effect encompasses two kinds of things. It's one thing if the original symptoms have a "real" medical cause, like a broken leg. But it's another thing if the original symptoms are themselves partially or wholly driven by psychological factors, i.e. if they are "psychosomatic".

If a placebo treats a "psychosomatic" disease, then that's not because the placebo has some mysterious, mind-over-matter "placebo effect". All the mystery, rather, lies with the psychosomatic disease. But this is a crucial distinction.

People seem more willing to accept the mind-over-matter powers of "the placebo" than they are to accept the existence of psychosomatic illness. As if only doctors with sugar pills possess the power of suggestion. If a simple pill can convince someone that they are cured, surely the modern world in all its complexity could convince people that they're ill.

[BPSDB]

Nunn, R. (2009). It's time to put the placebo out of our misery BMJ, 338 (apr20 2) DOI: 10.1136/bmj.b1568

Deconstructing the Placebo

Last month Wired, announced that Placebos Are Getting More Effective. Drugmakers Are Desperate to Know Why.

The article's a good read, and the basic story is true, at least in the case of psychiatric drugs. In clinical trials, people taking placebos do seem to get better more often now than in the past (paper). This is a big problem for Big Pharma, because it means that experimental new drugs often fail to perform better than placebo, i.e. they don't work. Wired have just noticed this, but it's been being discussed in the academic literature for several years.

Why is this? No-one knows. There have been many suggestions - maybe people "believe in" the benefits of drugs more nowadays, so the placebo effect is greater; maybe clinical trials are recruiting people with milder illnesses that respond better to placebo, or just get better on their own. But we really don't have any clear idea.

What if the confusion is because of the very concept of the "placebo"? Earlier this year, the BMJ ran a short opinion piece called It’s time to put the placebo out of our misery. Robin Nunn wants us to "stop thinking in terms of placebo...The placebo construct conceals more than it clarifies."

His central argument is an analogy. If we knew nothing about humour and observed a comedian telling jokes to an audience, we might decide there was a mysterious "audience effect" at work, and busy ourselves studying it...

Imagine that you are a visitor from another world. You observe a human audience for the first time. You notice a man making vocal sounds. He is watched by an audience. Suddenly they burst into smiles and laughter. Then they’re quiet. This cycle of quietness then laughter then quietness happens several times.

What is this strange audience effect? Not all of the man’s sounds generate an audience effect, and not every audience member reacts. You deem some members of the audience to be “audience responders,” those who are particularly influenced by the audience effect. What makes them react? A theory of the audience effect could be spun into an entire literature analogous to the literature on the placebo effect.

But what we should be doing is examining the details of jokes and of laughter -

We could learn more about what makes audiences laugh by returning to fundamentals. What is laughter? Why is “fart” funnier than “flatulence”? Why are some people just not funny no matter how many jokes they try?

And this is what we should be doing with the "placebo effect" as well -

Suppose there is no such unicorn as a placebo. Then what? Just replace the thought of placebo with something more fundamental. For those who use placebo as treatment, ask what is going on. Are you using the trappings of expertise, the white coat and diploma? Are you making your patients believe because they believe in you?

Nunn's piece is a polemic and he seems to be conclude by calling for a "post-placebo era" in which there will be no more placebo-controlled trials (although it's not clear what he means by this). This is going too far. But his analogy with humour is an important one because it forces us to analyse the placebo in detail.

"The placebo effect" has become a vague catch-all term for anything that seems to happen to people when you give them a sugar pill. Of course, lots of things could happen. They could feel better just because of the passage of time. Or they could realize that they're supposed to feel better and say they feel better, even if they don't.

The "true" placebo effect refers to improvement (or worsening) of symptoms driven purely by the psychological expectation of such. But even this is something of a catch-all term. Many things could drive this improvement. Suppose you give someone a placebo pill that you claim will make them more intelligent, and they believe it.

Believing themselves to be smarter, they start doing smart things like crosswords, math puzzles, reading hard books (or even reading Neuroskeptic), etc. But the placebo itself was just a nudge in the right direction. Anything which provided that nudge would also have worked - and the nudge itself can't take all the credit.

The strongest meaning of the "placebo effect" is a direct effect of belief upon symptoms. You give someone a sugar pill or injection, and they immediately feel less pain, or whatever. But even this effect encompasses two kinds of things. It's one thing if the original symptoms have a "real" medical cause, like a broken leg. But it's another thing if the original symptoms are themselves partially or wholly driven by psychological factors, i.e. if they are "psychosomatic".

If a placebo treats a "psychosomatic" disease, then that's not because the placebo has some mysterious, mind-over-matter "placebo effect". All the mystery, rather, lies with the psychosomatic disease. But this is a crucial distinction.

People seem more willing to accept the mind-over-matter powers of "the placebo" than they are to accept the existence of psychosomatic illness. As if only doctors with sugar pills possess the power of suggestion. If a simple pill can convince someone that they are cured, surely the modern world in all its complexity could convince people that they're ill.

[BPSDB]

Nunn, R. (2009). It's time to put the placebo out of our misery BMJ, 338 (apr20 2) DOI: 10.1136/bmj.b1568

Placebos Have Side Effects Too

The placebo is the most talked-about treatment in medicine.

Everyone's heard of the "placebo effect", by which pills containing no drugs at all, just chalk and sugar, often seem to make people feel better. But if the mere expectation of improvement can produce improvement, then the expectation of unpleasant consequences, such as side effects, should make people feel worse. This is sometimes called the "nocebo" effect.

Two recently published papers tried to measure it. They looked at people who took part in randomized controlled trials of various drugs, and who were given placebos. Because different drugs have different known side effects, if the nocebo effect is real, the side effects reported by the placebo group should depend on the drug they think they might be taking. As the authors of one of the papers put it:

In a typical clinical trial, the subjects know they can receive either the active medication or the placebo and, accordingly, they are informed about the possible adverse events they may experience during the trial. ... Therefore, informing subjects about the possible adverse events they may experience, may have a significant impact on their expectations and experiences of negative effects.

Accordingly, Rief et al compared the side effects reported in the placebo groups of a large number of antidepressant drug trials. At the same time a separate group of researchers, Amanzio et al, did the same thing for trials of migraine drugs, which is a nice coincidence.

Both papers found that reported side effects do indeed depend on the drug being studied. In the antidepressant paper, people who believed they might be on tricyclic antidepressants (TCAs) reported many more "side effects" than those in trials of SSRIs. These included dry mouth, drowsiness, constipation, and sexual problems. This makes sense, because TCAs do have worse side effects than SSRIs.

Likewise, for the migraine trials, the placebo groups in trials of anticonvulsants reported more symptoms associated with those drugs, such as dizziness and sleepiness. Placebo groups in trials of NSAIDs (like aspirin) were more likely to report upset stomachs and so forth. Finally, in trials of triptans, which have very mild side effects, the placebo group reported few problems.

It's also interesting to compare the two papers. None of the migraine trial placebo patients reported experiencing sexual problems, while many of the antidepressant placebo patients did. Some antidepressants can cause sexual problems, while migraine drugs generally don't.

So, was the "nocebo effect" really making people feel worse? It could well have been, although there are other interpretations. People might just be more willing to report symptoms that they believe are drug side effects. Researchers might be more likely to write them down. And different kinds of people end up in trials of different drugs: some people might be more likely to report certain symptoms. Just as with placebos, we shouldn't rush to ascribe incredible mind-over-matter powers to the "force of suggestion" when there are more prosaic explanations.

Nevertheless, there's an important lesson here. Anecdotal evidence about drug's side effects shouldn't be accepted at face value, any more than anecdotes about their benefits. Drugs do, of course, cause adverse effects. But some drugs have worse reputations than they deserve in this regard. In such cases, nocebo effects might account for some of the reported problems...


Rief W, Nestoriuc Y, von Lilienfeld-Toal A, Dogan I, Schreiber F, Hofmann SG, Barsky AJ, & Avorn J (2009). Differences in Adverse Effect Reporting in Placebo Groups in SSRI and Tricyclic Antidepressant Trials: A Systematic Review and Meta-Analysis. Drug safety : an international journal of medical toxicology and drug experience, 32 (11), 1041-56 PMID: 19810776


Amanzio M, Corazzini LL, Vase L, & Benedetti F (2009). A systematic review of adverse events in placebo groups of anti-migraine clinical trials. Pain PMID: 19781854

Placebos Have Side Effects Too

The placebo is the most talked-about treatment in medicine.

Everyone's heard of the "placebo effect", by which pills containing no drugs at all, just chalk and sugar, often seem to make people feel better. But if the mere expectation of improvement can produce improvement, then the expectation of unpleasant consequences, such as side effects, should make people feel worse. This is sometimes called the "nocebo" effect.

Two recently published papers tried to measure it. They looked at people who took part in randomized controlled trials of various drugs, and who were given placebos. Because different drugs have different known side effects, if the nocebo effect is real, the side effects reported by the placebo group should depend on the drug they think they might be taking. As the authors of one of the papers put it:

In a typical clinical trial, the subjects know they can receive either the active medication or the placebo and, accordingly, they are informed about the possible adverse events they may experience during the trial. ... Therefore, informing subjects about the possible adverse events they may experience, may have a significant impact on their expectations and experiences of negative effects.

Accordingly, Rief et al compared the side effects reported in the placebo groups of a large number of antidepressant drug trials. At the same time a separate group of researchers, Amanzio et al, did the same thing for trials of migraine drugs, which is a nice coincidence.

Both papers found that reported side effects do indeed depend on the drug being studied. In the antidepressant paper, people who believed they might be on tricyclic antidepressants (TCAs) reported many more "side effects" than those in trials of SSRIs. These included dry mouth, drowsiness, constipation, and sexual problems. This makes sense, because TCAs do have worse side effects than SSRIs.

Likewise, for the migraine trials, the placebo groups in trials of anticonvulsants reported more symptoms associated with those drugs, such as dizziness and sleepiness. Placebo groups in trials of NSAIDs (like aspirin) were more likely to report upset stomachs and so forth. Finally, in trials of triptans, which have very mild side effects, the placebo group reported few problems.

It's also interesting to compare the two papers. None of the migraine trial placebo patients reported experiencing sexual problems, while many of the antidepressant placebo patients did. Some antidepressants can cause sexual problems, while migraine drugs generally don't.

So, was the "nocebo effect" really making people feel worse? It could well have been, although there are other interpretations. People might just be more willing to report symptoms that they believe are drug side effects. Researchers might be more likely to write them down. And different kinds of people end up in trials of different drugs: some people might be more likely to report certain symptoms. Just as with placebos, we shouldn't rush to ascribe incredible mind-over-matter powers to the "force of suggestion" when there are more prosaic explanations.

Nevertheless, there's an important lesson here. Anecdotal evidence about drug's side effects shouldn't be accepted at face value, any more than anecdotes about their benefits. Drugs do, of course, cause adverse effects. But some drugs have worse reputations than they deserve in this regard. In such cases, nocebo effects might account for some of the reported problems...


Rief W, Nestoriuc Y, von Lilienfeld-Toal A, Dogan I, Schreiber F, Hofmann SG, Barsky AJ, & Avorn J (2009). Differences in Adverse Effect Reporting in Placebo Groups in SSRI and Tricyclic Antidepressant Trials: A Systematic Review and Meta-Analysis. Drug safety : an international journal of medical toxicology and drug experience, 32 (11), 1041-56 PMID: 19810776


Amanzio M, Corazzini LL, Vase L, & Benedetti F (2009). A systematic review of adverse events in placebo groups of anti-migraine clinical trials. Pain PMID: 19781854