One Pill Makes Your Libido Larger

It's every man's dream - a pill to make women want more sex. According to Boehringer Pharmaceuticals, that dream could be a reality in a few years, in the form of the strangely-named flibanserin. But is it the latest wonder-drug or just a glorified sleeping pill? Read on.

Flibanserin was originally developed as an antidepressant, but in clinical trials against depression it reportedly failed to perform better than placebo. The standard for getting approved as an antidepressant is low, so this is quite an achievement.

The BBC today described flibanserin as the "Female Viagra", which is rather confusing, because it's meant to increase sexual desire, which is one thing Viagra (sidenafil) doesn't do. The reason for the Female Viagra headline is that, as Professor John Thorp says:

"It's essentially a Viagra-like drug for women in that diminished desire or libido is the most common feminine sexual problem, like erectile dysfunction is in men"
Yes, one in ten women suffer apparently from "Hypoactive Sexual Desire Disorder" (HSDD) as Boehringer Pharmaceuticals helpfully informs us. And “As many as two out of every 10 women describe some degree of decreased sexual desire" according to the unfortunately named Dr Charles de Wet, Boehringer medical director for the UK.

HSDD is a diagnosis in the DSM-IV, the American Psychiatric Association's listing of psychiatric illnesses, and it's been recognised as a disorder since 1980. It is not, however, a very popular diagnosis yet. There are only 60,000 Google hits for it, as opposed to 1,600,000 for "major depression" and, er, 90,000 for "neuroskeptic". Odd for a disorder apparently plaguing at least 10% of women.

Indeed, some people say that it's no more than a label invented by psychiatrists who didn't understand women and then promoted by drug companies in order to sell drugs. This is almost certainly true, but it's also a bit simplistic, because there are people who perceive themselves as suffering from low libido, and if flibanserin really helps them, that's surely a good thing.

How is flibanserin supposed to work? According to a paper on the Pharmacology of Flibanserin, it's a serotonin receptor 5HT1A agonist and a 5HT2A antagonist. This makes it a kind of cross between the antidepressants nefazadone and buspirone. Neither of these are widely used as antidepressants because they're not considered highly effective. Flibanserin is also a weak dopamine D4 receptor partial agonist. This might underlie its aphrodisiac properties, because drugs which increase dopamine levels are known to enhance motivation and libido (or indeed cause problematic hypersexuality.) In rats and mice, flibanserin has sedative effects and enhances the effects of other sedatives. It also has antidepressant-like effects in some tests but not all. Drug geeks can click the image on the left for more details.

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Now for the big question - does it actually work? Well, there have been no published clinical trials yet. At all. The trials in depression, where it failed to work, have never been published. Hmm. However, four trials in "Hypoactive Sexual Desire Disorder" were recently completed and the results were presented yesterday at a sexual medicine conference in Europe (ESSM) in the form of three posters (1,2,3). The trials were known as - groan - VIOLET, ORCHID, DAISY and DAHLIA. I probably don't have to tell you that they were all funded by Boehringer Pharmaceuticals.

The main poster is Efficacy of flibanserin 100 mg qhs as a potential treatment for Hypoactive Sexual Desire Disorder in premenopausal women which pools the data from three trials with a total of about 1,400 women. They found that taking flibanserin 100 mg every night had small beneficial effects. Relative to placebo, it increased the number of "satisfying sexual encounters" by 0.7 per month. It also improved scores on questionnaire measures of sexual function, a bit.

In any trial like this you have to ask whether there is result cherry-picking going on. Maybe they asked dozens of questions about the women's sex lives, and they're only telling us about the minority where the drug seemed to work? People often do that but in this case, the Clinical Trials Register suggests there was no funny business of that kind. It also shows that there have been no trials using 100mg which weren't included in the poster, so the trials themselves weren't cherry picked either. That's reassuring. But it looks like the effects were only significant when all three trials were pooled - one poster shows the results of the ORCHID trial alone, and most were non-significant.




What about the side effects? There's a whole poster about them. 100 mg flibanserin nightly caused 14% of patients to drop out due to side effects, vs 7% in the placebo group - so an extra 7% decided it wasn't worth it. It caused dizziness, nausea, fatigue, somnolence - and bizarrely, also insomnia. Notably, 50mg daily was much worse than 100 mg nightly, which suggests that taking this at night, rather than in the morning, is a good idea. But given what it is meant to treat, you'd want to do that anyway, right?

But this leads onto my biggest problem with these findings. It's obvious from the side effects data that this drug is a sedative - it makes you tired and sleepy. The animal data confirm this. It's much more likely to put you to sleep than it is to make you enjoy sex in any given month. Off the top of my head, I suspect its sedative properties are a result of its 5HT2A antagonism.

Any sedative can increase sexual desire, as anyone who has ever been to a bar will know. So whether this drug actually has an aphrodisiac effect, as opposed to just being a sleeping pill, is anyone's guess. To find out, you'd need to compare it to a sleeping pill, say, Valium. Or a couple of glasses of wine. Until someone does that, we don't know if this drug is destined to be the next big thing or a big disappointment.

Edit: Just noticed that Dr Petra Boynton has a fantastic post about the background to flibanserin and the manufacturer's apparent attempt to recruit her to write about HSDD.

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ResearchBlogging.org

Borsini F, Evans K, Jason K, Rohde F, Alexander B, Pollentier S (2002). Pharmacology of flibanserin. CNS drug reviews, 8 (2), 117-42 PMID: 12177684

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.

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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.

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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.

ResearchBlogging.org

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

Book: Deep Brain Stimulation

Jamie Talan's Deep Brain Stimulation: A New Treatment Shows Promise In The Most Difficult Cases is the first book to offer a popular look at DBS, one of the more exciting emerging treatments in neurology and psychiatry.

Deep Brain Stimulation is not a textbook and the depth of scientific detail is kept pretty low, but the breadth of the material is good. Talan reviews the many kinds of disorders for which DBS has been trialled, from the early 1990s when it was used in Parkinson's disease up to the past five years where it's been tried for everything from epilepsy, depression and Tourette's Syndrome up to lifting patients out of persistent vegetative states (maybe).

Unfortunately, Talan doesn't discuss the controversial history of the first era of human brain stimulation, including the morally murky work of Robert G. Heath at Tulane University in the 1960s. She mentions Tulane once in passing but more detail would have been welcome, if only because it's a rather spicy tale.

The book's most engaging passages are the stories of individual patients. There's the man with Parkinson's who experienced amazing benefits from DBS, and who was so keen to keep them that he didn't tell doctors about the infection which developed a few weeks after surgery, in case they took the electrode out. After literally keeping the infected site under his hat for a few days, it progressed to a brain abscess, and he nearly died. Happily, he not only survived but was able to get the electrodes reimplanted.

Then there's the most moving case, that of the woman suffering from severe OCD and depression, who was given experimental DBS for the former condition. She died by suicide several months later, but said in her suicide note that the DBS had worked - her OCD symptoms were gone. Her depression was as bad as ever, though, and this is what led her to suicide. She wanted people to know that deep brain stimulation helped her, and didn't want her death to go down in the records as a mark against it.

The precursor to DBS was ablative neurosurgery - destroying particular parts of the brain in order to relieve symptoms. Talan describes its use in movement disorders such as Parkinson's, but she glosses over the history of "psychosurgery", the use of surgery to treat mental illness. People using DBS in psychiatry often prefer not to talk about psychosurgery - it's not exactly good PR. But clearly it is relevant. For all its faults, psychosurgery did seem to help some patients, which is why it's still used today in rare cases, although DBS may soon replace it.

DBS for depression and OCD usually target the same prefrontal white matter pathways that psychosurgery severed, so scientifically, psychosurgery has lessons for DBS. The ethical issues overlap too. Although DBS is reversible, unlike brain lesioning, it carries the same risks of serious complications like infection or brain bleeding. And there's the same question of whether seriously mentally ill people can give informed consent.

The book's strongest chaper is the last, which covers the ethical and practical difficulties of DBS. The danger is that enthusiastic doctors with no experience of the procedure, encouraged by the tales from other hospitals, might start doing it inappropriately. There's also a risk that patients or their families might volunteer for DBS prematurely or have impossibly high expectations. The initial results have been very promising, but there have been no large placebo-controlled trials so far (except in some movement disorders). And even with the best surgeons, in most disorders the response rate seems to hover around the 50-60% mark. Talan warns that DBS risks being a victim of its own hype. That's an important message.

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.)

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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.

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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.

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The Politics of Psychopharmacology

It's always nice when a local boy makes good in the big wide world. Many British neuroscientists and psychiatrists have been feeling rather proud this week following the enormous amount of attention given to Professor David Nutt, formerly the British government's chief adviser on illegal drugs.

Formerly being the key word. Nutt was sacked (...write your own "nutsack" pun if you must) last Friday, prompting a remarkable amount of condemnation. Critics included the rest of his former organisation, the Advisory Council on the Misuse of Drugs (ACMD), and the Government's Science Minister. The UK's Chief Scientist also spoke in favour of Nutt's views. Journalists joined in the fun with headlines like "politicians are intoxicated by cowardice".

Even Nature today ran a bluntly-worded editorial -

"The sacking of a government adviser on drugs shows Britain's politicians can't cope with intelligent debate... the position of the Labour government and of the leading opposition party, the Conservatives, which vigorously supported Nutt's sacking, has no merit at all. It deals a significant blow both to the chances of an informed and reasoned debate over illegal drugs, and to the parties' own scientific credibility."
They also have an interview with the man himself.

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What happened? The short answer is a lecture Nutt gave on the 10th October, Estimating Drug Harms: A Risky Business? I'd recommend reading it (it's free). The Government's dismissal e-mail gave two reasons why he had to go - firstly, "Your recent comments have gone beyond [matters of evidence] and have been lobbying for a change of government policy" and secondly, "It is important that the government's messages on drugs are clear and as an advisor you do nothing to undermine public understanding of them."

Many people believe that Nutt was fired because he argued for the liberalization of drug laws, or because he claimed that the harms of some illegal drugs, such as cannabis, are less severe than those of legal substances like tobacco and alcohol. On this view, the government's actions were "shooting the messenger", or dismissing an expert because they didn't like to hear to the facts. It seems to me, however, that the truth is a little more nuanced, and even more stupid.


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Nutt's lecture, if you read the whole thing as opposed to the quotes in the media, is remarkably mild. For instance, at no point does he suggest that any drug which is currently illegal should be made legal. The changes he "lobbies for" are ones that the ACMD have already recommended, and this lobbying consists of nothing more than tentative criticism of the stated reasons for the rejection of the ACMD's advice. The ACMD is government's official expert body on illicit drugs, remember.

The issue Nutt focusses on is the question of whether cannabis should be a "Class C" or a "Class B" illegal drug, B being "worse", and carrying stricter penalties. It was Class B until 2004, when it was made Class C. In 2007, the Government asked the ACMD to advise on whether it should be re-reclassified back up to Class B. This was in response to concerns about the impact of cannabis on mental health, specifically the possibility that it raises the risk of psychotic illnesses.

The resulting ACMD report is available on the Government's website. They concluded that while cannabis use is certainly not harmless, "the harms caused by cannabis are not considered to be as serious as drugs in class B and therefore it should remain a class C drug."

Despite this, the Government took the decision to reclassify cannabis as Class B. In his lecture Nutt criticizes this decision - slightly. Nutt quotes the Home Secretary as saying, in response to the ACMD's report -
"Where there is a clear and serious problem [i.e. cannabis health problems], but doubt about the potential harm that will be caused, we must err on the side of caution and protect the public. I make no apology for that. I am not prepared to wait and see."
Nutt describes this reasoning as -

"the precautionary principle - if you’re not sure about a drug harm, rank it high... at first sight it might seem the obvious decision – why wouldn’t you take the precautionary principle? We know that drugs are harmful and that you can never evaluate a drug over the lifetime of a whole population, so we can never know whether, at some point in the future, a drug might lead to or cause more harm than it did early in its use."
But he says, there's more to it than this. Firstly, we don't know anything about how classification affects drug use. The whole idea of upgrading cannabis to Class B to protect the public relies on the assumption that it will reduce drug use by deterring people from using it. But there is no empirical evidence as to whether this actually happens. As Nutt points out, stricter classification might equally well increase use by making it seem forbidden, and hence, cooler. (If you think that's implausible, you have forgotten what it is like to be 16.) We just don't know.

Second, he says, the precautionary principle devalues the evidence and is thereby self-defeating because it means that people will not take any warnings about drug harms seriously - "[it] leads to a position where people really don’t know what the evidence is. They see the classification, they hear about evidence and they get mixed messages. There’s quite a lot of anecdotal evidence that public confidence in the scientific probity of government has been undermined in this kind of way." Can anyone really dispute this?

Finally, he raises the MMR vaccine scare as an example of the precautionary principle ironically leading to concrete harms. Concerns were raised about the safety of a vaccine, on the basis of dubious science. As a result, vaccine coverage fell, and the incidence of measles, mumps and rubella in Britain rose for the first time in decades. The vaccine harmed no-one; these diseases do. We just don't know whether cannabis reclassification will have similar unintended consequences.

That's what the Home Secretary described as "lobbying for a change of government policy". I wish all lobbyists were this reasonable.

The Home Secretary's second charge against Nutt - "It is important that the government's messages on drugs are clear..." - is even more specious. Nutt's messages were the ACMD's messages, and as he points out, the only lack of clarity comes from the fact that the government and their own Advisory Council disagree with each other. This is hardly the ACMD's fault, and it's certainly not Nutt's fault for pointing it out.

All of this is doubly ridiculous because of one easily-forgotten fact - cannabis was downgraded from Class B to Class C in 2004 by the present Labour Party government. Nutt's "lobbying" therefore consists of a recommendation that the government do something they themselves previously did. And if the government are worried about the clarity of their message, the fact that they themselves were saying that cannabis was benign enough to be a Class C drug just 5 years ago might be somewhat relevant.

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Nutt has said that he was surprised to learn that he had been sacked. I'm sure this surprise was genuine because Nutt is an academic, and in academia, Nutt's "criticisms" would hardly even be considered as such. Here by contrast is an extract from a peer review comment I got a couple of days ago regarding a scientific paper I wrote:
The manuscript falls short of its goals in several respects: The basic phenomenon ... is barely presented... The style and language of the review leave a lot to be desired... The citations and reference list are appalling.
The same reviewer also criticized the basic argument of my article, implicitly branding the whole paper - all 10,000 words of it, which took dozens of hours to write - a complete waste of time.

Ouch. But as an academic, giving, and receiving, this kind of treatment is all part of the job, and that's just as it should be. I'm confident that my argument is sound, so I'm going to take the criticisms on board, rewrite the paper appropriately, and submit it to another journal. What I'm not going to do is bear a grudge against the reviewer. (Well maybe a little: the references weren't that bad.) To be fair, unlike Nutt's, this review was not made in the public domain, but then, I'm not a Government elected by the public.

Nutt's mistake was to think that it's possible to have a serious debate about a serious political issue. In fact, it was probably not such a bad mistake, since the job of the ACMD, as the Government sees it, is a fairly pointless one: their job is to give expert advice and then let it be ignored. As various ACMD members have noted, they work for free, in the public interest. If I were on the Committee, I would resign now, not just out of sympathy for Nutt, but because it's a crap job.

In his dismissal letter, the Home Secretary told Nutt, "It is not the job of the Chair of the Government's advisory Council to initiate a public debate on the policy framework for drugs". I would have thought he was exactly the person who should do this if such a debate was necessary, as it obviously is. Well, now we know better. It wasn't his job. Although, thanks to the government who sacked him, a drug debate is now going on in the British media for the first time in years. In the long run, Nutt's most important action as Chair of the ACMD may well have been getting sacked from it.

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ResearchBlogging.orgNature (2009). A drug-induced low Nature, 462 (7269), 11-12 DOI: 10.1038/462011b

Daniel Cressey (2009). Sacked science adviser speaks out Nature

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"

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

 
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