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• Jeffrey White

  19 December 2007 | 22:46

  I think that the last three questions are the most interesting, so my reply will focus on these issues.

  I have and will continue to boost my own brain power to achieve an analeptic effect. CNS stimulants include a diverse array of comonly used drugs, such as theophylline (tea), caffeine (coffee, soft drinks, NoDOz, etc.) and even nicotine. I do drink both coffee and tea. I do not think however that these encompass an unfair boost in brain power. Moreover, I think that most will agree with that claim since these products can only be used as an analeptic.

  The issue arises when more efficacious compounds that have an effect on cognitive power, rather than wakefulness, are considered. I have not and would not use a compound, such as methylphenidate, to increase my brain power. As mentioned in the article, some persons do need this to function on a normal level. I guess that I am lucky that I do not.

  I interact daily with those people who choose to take drugs, such as methylphenidate and modafinil, to study better. When I was in classes with these people, it was easy to distinguish them: their constant bitter attitude and short temper were just a couple of the signs. I think that their motivation for abusing these drugs is to perform well on examinations. This attitude permeates the academic sectors of U.S. education and is an entirely different discussion. I used the term abuse because, to me, this is an abuse of their intended effects. I would assume that the chronic abuse of these substances would produce tolerance and, eventually, would create a physical dependence. This is only speculation.

  I think that people should be able to take these substances if they so desire since, at least currently, there are no safety restrictions. Personally, I do not take these substances because I am able to perform well on examinations with ample studying and preparation. I think that it is unfortunate, however, that some of my colleagues will depend on these substances to perform well in their future professions. As a MD/PhD student, I do not think that a physician nor a research scientist should have to rely on an exogenous substance for their mental creativity and performance on the job. Therefore, though I think that people should be able to make their own choices, I will be bold enough to predict that, at some point, these substances will be federally regulated to prevent abuse. Unfortunately, I do not think that this will occur until some mishap, either on the operating table or in a loboratory, first occurs.

  I hope that I have not offended anyone with my comments. I realize that some individuals do require these substances to function normally and I am sensitive to those needs.

• Peter Reiner

  20 December 2007 | 00:19

  Sahakian & Morein-Zamir in their Commentary “Professor’s little helper” have done a wonderful job of instigating debate on the topic the ethical issues associated with the emergence of cognitive enhancers. I would view the final question, “How should society react?”, as the most important of all. The full response is far from straightforward, and will occupy us for some time to come, but at least a significant part of the answer to this question can be summarized with one word: honesty.

  With cognitive enhancement already well-established, be it the mild pharmacological boost that comes from a cup of coffee or stronger medicines that are on the doorstep, a range of issues will require serious discussion. Foremost on the regulatory side will be the labeling of new drugs. If the past is any indication, one likely scenario is that the drugs will be developed for a particular disease indication and then off-label use will expand penetration into the general population at large. This ‘wink and nod’ to acceptance of wider distribution is unwise, as it provides little opportunity to assess risks in, or give appropriate counsel to the general population that inevitably will be taking the drugs. A much healthier approach would be to accept the fact that cognitive enhancers will be widely utilized, define populations of individuals in which they can and will be used, carry out appropriate studies to assess not only issues of safety but also of social impact, and use these results to inform the labeling of the drugs. By adopting such an honest approach to this new frontier of neuropharmacology, we will be in a stronger position to grapple with the tangle of thorny issues that are certain to arise.

• Sarah Tomlin

  20 December 2007 | 11:58

  Posted on behalf of Judy Illes: Wednesday, 19 December 2007 23:18 UTC

  The “Professor’s little helper” on cognitive enhancement by Barbara Sahakian and Sharon Morein-Zamir demonstrates the enduring nature of this topic. With their comments in hand, it is now time to explore the range of new issues implicated by their reflections. In particular, the legal and social policies that will guide the setting of parameters and milestones for integrating new enhancing technologies into health care for treatment, and into society for non-therapeutic applications, must be at the heart of the discussion. Policy-making is inherently complex, and is rendered even more complex when the priorities of different health care systems come into play, and the commercial interests of big business pharma – and eventually big business “bio-device” – inevitably influence those priorities. Moreover, it is certain that there will be no one-size-fits-all policies once multiculturalism is taken into consideration. Beyond the call that the authors make for better drugs, our call is for a next generation of research and translation that is focused on regulatory policies – policies that recognize the differential impact of drugs on different segments of society, and policies that protect people from the urge for quick fixes and the risk of new forms of vulnerabilities arising from short-sighted solutions.

  Robin Pierce, J.D., Ph.D. Judy Illes, Ph.D. National Core for Neuroethics The University of British Columbia

• Trevor Liberson

  20 December 2007 | 12:10

  First let me declare an interest in this discussion. As a student of seventy-nine years of age, having recently gained a BSc in biosciences and being at the end of an MRes in biotechnology I view the approach of any sort of neurodegenerative disease with more than a little apprehension. I must congratulate Sahakian & Morein-Zamir on their clear and rational approach to a subject that must be of increasing importance to society as a whole.
  While the abuse of any drug is to be discouraged, the definition of that abuse can vary in different sections of the population; a desperate student may or may not be abusing modafinil in the days before an examination. A desperate soldier with an enemy in hot pursuit is certainly not, and probably wouldn’t care if he was.
  The staggering cost of dementia, which must increase as the demographic gap increases and medical treatment and survival rates improve can only be described as horrifying, and the chance of a 1% improvement would seem to be an offer that we can’t refuse.
  This is not a case of the use of drugs to enhance the financial status of the individual. The cost of maintaining an elderly population represents a crushing and unfair burden on the young, which in its own way is as important as climate change and should be given an equal position of importance.
  Having witnessed degeneration and loss of faculties in friends and family members, the fact that drugs exist which can ameliorate if not cure these effects, indicates to me that these drugs should always be used in the cases where the side effects can be tolerated.
  Incidentally, I’ve never used cognitive enhancing drugs myself.
  Trevor Liberson.

• Sharon Morein

  20 December 2007 | 12:21

  This content has been removed by the forum moderators.

• henry greely

  20 December 2007 | 12:46

  This excellent article covers the territory well, but I am left with a question about our current policy and our current drugs.

  What do we know about long-term, regular use of modafinil? Do we have any useful studies of the differences, if any, in the drug’s effects (good and bad) between occasional users (for jet lag, let’s say)and regular users (four or five days a week)?

  I ask because the benefits of modafinil seem too weak to justify serious social concerns about fairness or coercion, so that only the safety issues seem pertinent. If we do not have long term safety studies, we might want to consider a regime that continues to require a prescription (or other form of professional intermediation but that limits the amount of the drug that can be obtained at any one time.

  If we do and extended use seems reasonably safe (however that is defined) and if we know of no significant drug interactions, it is not clear to me that continuing professional involvement is necessary. If there are significant drug interactions, professional review may still not be required if other methods of cross-checking for interactions are created.

  So I think one interesting side effect of this discussion of cognitive enhancement is that it shines a light on possible changes in prescription requirements – specifically the possible creation of a category of substances somewhere between “over-the-counter” and full prescription. Of course, the justification for such a move depends on the specific facts known about the drug.

  Ultimately, though, if modafinil is, in its safety profile, like tasteless, odorless (and calorie-less, for those who otherwise use milk and sugar) coffee, it seems hard to argue for special controls. More powerful drugs, that are better enhancers or have more dangerous effects, may, as you point, require regulation for reasons other than safety.

  I would raise one other point, minor but perhaps interesting, point to consider – there are some religions that might have objections to modafinil or other stimulating drugs. I am thinking particularly of the Mormons (formally the Church of Jesus Christ of the Latter Day Saints). They ban the use of caffeine and presumably might well consider at least non-medical uses of modafinil as being equivalent. Would any regulatory scheme for modafinil, or other stimulants, need to make special provision (“conscience clauses”?) for those with religious objections?

• Alfredo Pereira Jr

  21 December 2007 | 02:53

  Besides ethical issues, neuropharmacological complexities should be taken into account in this discussion. Supplying the brain with precursors of transmitters causes dependence and reduces endogenous production. Reducing transmiter uptake is more benign but may have corollary effects. Drugs that block or enhance ionotropic receptors activity have dose-dependent effects and do not cause dependence. Drugs that increase transmitter or membrane receptor production, or that increase production of a protein that controls the location of receptors in the post-synapic density, may have unpredicted effects.
  Brain complexity requires an epistemological discussion of neuropharmacology. For instance, reducing inhibitory activity (e.g. inhibiting GABAergic inhibitory transmission) is not the same as increasing excitatory activity (e.g. increasing glutamatergic transmission), but in practice the effects may look the same. Normal brain functionning depends on a balance of excitation and inhibition, but the effects of inhibition are still not well understood. Is inhibition just conterbalancing excitation, or does it also have a constructive role? How does inhibition impact on the EEG and BOLD fMRI? These techniques do not identify the contribution of excitatory and inhibitory activity to the generation of (respectively) electric fields (EEG) or hemodynamic responses (fMRI). Until there is a better understanding of inhibition, and the roles of the balance of excitation and inhibition, it is difficult to predict the long-lasting effect of drugs that interfere with these processes.

• peter freer

  21 December 2007 | 15:09

  Frankly, I think the article is misleading and provides a bit of misinformation regarding cognitive enhnacement. Before even exploring ethical issues, one has to understand the facts about ‘cognitive enhancement’. The facts don’t necessarily reflect what the authors present in the article. I’d review them before debating the ethics of a Ritalin mist as I walk into the classroom.

  The longest study performed on stimulant medication & ADHD was the MTA (Multi-modal Treatment Study of Children with ADHD. A three year observation and assessment of medication compared to behavioral therapy was performed by various ‘experts’ under the National Institutes of Mental Health (USA). At the end of 36 months:

  • There were no significant performance differences between groups that had been medicated and groups that did nothing (no intervention) at all.

  • No global academic improvement

  • No behavioral improvement

  • No social skill improvement

  • Increased weight loss among the medication group

  • Stunted growth among the medication group

  Co-author, Professor William Pelham, of the University at Buffalo, says: “The children had a substantial decrease in their rate of growth so they weren’t growing as much as other kids both in terms of their height and in terms of their weight. And the second was that there were no beneficial effects – none.”

  Here’s the most telling observation of the study: “I think that we exaggerated the beneficial impact of medication in the first study. We had thought that children medicated longer would have better outcomes. That didn’t happen to be the case. There’s no indication that medication’s better than nothing in the long run.”

  The students did demonstrate academic improvement, but only for a short duration.

  Finally, the Drug Effectiveness Review Project, based at Oregon State University released a 731-page report which thoroughly analyzed 2,287 studies – virtually every investigation ever done on ADHD drugs anywhere in the world – to reach its conclusions. To date, it is the most thorough and comprehensive evaluation of all research performed on ADHD drugs.

  In its analysis of published and unpublished research data produced by six prominent ADHD medication producers, the group found that 2,107 studies were unreliable and were subsequently rejected. Now, this is telling in itself. Finding 2,107 funded yet critically poor or fundamentally flawed studies performed by universities and the pharmaceutical industry itself speaks volumes to the nature of that research and those people responsible for it.

  The Project began its review of the remaining 180 studies which demonstrated good controls and methods. Its conclusions regarding ADHD medication were quite astounding.
  Here, bulleted, are some incredible results with comments:
  • “No evidence on long-term safety of drugs used to treat ADHD in young children” or adolescents. Now, if you ask any physician, or the pharmaceutical industry, they will tell you the drugs are completely safe for long-term use based on research. That research doesn’t exist.
  • The research providing any evidence of safety is of “poor quality.” This includes research regarding the possibility that some ADHD drugs could cause heart or liver conditions, tics, or stunt growth.
  • “Good quality evidence … is lacking” that ADHD drugs demonstrate improvement in “global academic performance, consequences of risky behaviors, social achievements,” and other measures. The common perception is that ADHD drugs do improve academic performance and social skills. Many drug makers use ads depicting this. However, evidence for long-term improvement in academics, social skills, or behavior is virtually non-existent.
  • Drug makers have found that they can expand their market by inducing adults into the ADHD experience. However, the Project found that evidence “is not compelling” demonstrating that ADHD drugs actually help adults, nor is there evidence that one drug “is more tolerable than another.”

  Furthermore, the Project found that the U.S. Food and Drug Administration doesn’t require pharmaceutical manufacturers to compare newly developed medications with medications currently on the shelf. Most companies simply use a placebo or sugar pill given instead of their medication as a control. Therefore the Project found that “good quality” studies are lacking that pit one drug against another to provide evidence of effectiveness. It also could not find comparative data which might help determine which ADHD medications are less likely to produce detrimental side effects like heart and liver problems, depression, decreased appetite, tics, or seizures.

  The Project could not find research that clearly provided an understanding of way that ADHD drugs work. It is not well understood for most ADHD drugs. If ADHD stimulants affect neurotransmitters as doctors Barbara Sahakian and Sharon Morein-Zamir suggest, this is pure speculation.

• Brendan Maher

  21 December 2007 | 15:11

  But will they put asterisks next to their Nobels?

  I’m quite pleased to see that neuroscience and ethics blogs all over the place have been picking up this discussion. I posed to a number of them, a question that seems quite simple on the face of it. If a drug could make you smarter, without any negative side effects, would you take it? If you can take away the risk of personal harm (granted, a pretty tall order), it becomes largely an argument of fairness. Is it cheating? When Barry Bonds broke the home run record, many suggested that an asterisk be placed next to the new record indicating that Bonds had taken performance enhancing drugs. Is it the same with brain boosters? The discussions on these blogs have been particularly active. I can’t say that I’m surprised.

  Shelley Batts at Retrospectacle doesn’t think so:
  “…it is difficult to argue that taking a cognitive enhancer is cheating in the academic sense, since a pill will never inform you as to the correct answer on a multiple choice test or give you the answer to any essay question. It will only improve the focus and grasp on information which you already know.”

  Janet Stemwedel at Adventures in Ethics and Science takes more of a purist’s approach saying she wants ownership over her faculties. Then again those who need the drug for medical reasons oughtn’t be penalized in any way.
  “Honestly, I’m conflicted about this attitude of mine towards the products of thinking with my “natural” brain. I don’t think the work of my colleagues who take medications for their depression or ADHD or anxiety is any less their work.”

  Dave Munger at the ever popular Cognitive Daily gave a personal narrative of a situation where using such drugs seems right. And he brings up a slippery slope argument that is worth debating, although it does tend to veer a bit Vonnegut (which isn’t a bad thing for a discussion to do).
  “Ultimately, even if we could create drugs that were truly side-effect free, I think we’d still have to regulate them in order to protect us from ourselves. Just as the regulation of steroids in athletics is done mainly to protect the athletes, so even “perfect” cognitive enhancers will need to be restricted in their use, lest we become of planet of work-immersed zombies.”
  To which one commenter responds:
  “Why do you assume we would use cognitive enhancement to do more work, especially the kind of work we don’t enjoy? If I had a drug that cut my sleeptime by half, I’d use the extra time to enjoy myself. If I had a drug that helped me think better or faster, I’d finish my daily work more quickly and so work less, not more.”

  Probably a coincidence, but Jonathan Eisen on the Tree of Life “confesses” to using cortisone to recover from an injury, and wonders if that’s cheating.
  “Is using steroids to recover from an injury OK (see Andy Pettite). What if I got the steroids to make my typing faster. Would that be cheating?”

  If you see good posts around the internet on this, please share them.

• steven rose

  21 December 2007 | 19:52

  Sahakian and Morein-Zamir reprise many of the arguments over cognitive enhancers that have become familiar in recent years. I however want to raise three issues from the more neuroscientific to the more practical. First, we need to be clearer about what is meant by the term ‘cognitive enhancer.’ Cognition is not a unitary phenomenon, but involves many different processes. The suggestion by Giurgia, who invented the term back in the ‘70s that there might be a drug that could function as a ‘pure’ nootropic agent is almost certainly a fantasy. To take some of Sahakian and Morein-Zamir’s examples, methylphenidate is supposed to enhance attentiveness, thereby enabling pupils to focus better on their school work, Modafanil increases alertness over long periods, which is why it was said to have been used by US pilots during their bombing raids over Iraq. The current generation of cholinergic drugs used to treat early stage Alzheimer’s have a whole range of central and peripheral effects, but were developed to treat memory failure, based on the hypothesis that memory formation (though not retrieval) involves cholinergic neurons – though this may not actually explain their limited efficacy. Drugs designed to treat the specific biochemical lesions in Alzheimer’s may not work in other forms of cognitive decline, or to ‘enhance’ normal memory or cognition where the biochemical systems are more or less optimally set. There are thus many pharmacological ways, via many different neural processes, in which ‘cognition’ can be affected.

  The second issue is whether there is anything different in principle between ‘enhancing’ school or other intellectual performance by taking a drug or by extra coaching or being brought up in a supportive educational household. To argue that there is a fundamental distinction is to be implicitly Cartesian. It is to presume that coaching and an educationally supportive environment don’t change brain processes – or that if they do, this is a more legitimate way of changing those processes than by direct chemical or physical intervention. But if they don’t, how are they supposed to work? The argument, as everyone recognises, is by analogy with the use of drugs in athletics, which is seen as cheating, whereas changing one’s metabolism by training or by the fortune of genetics, is uncontroversial. The fact that it is difficult to draw an in principle distinction between coaching or training and popping a pill doesn’t alter the equally important fact that most people regard the former as acceptable and the latter as cheating – or ‘achieving a competitive advantage,’ as the advocates of using smart drugs describe it.

  The practical question however is whether in any event it is possible to regulate or control the use of performance enhancers. Drug policy in athletics is a mess, with a sort of continuous arms race between the athletes and the authorities, and I suspect that in the case of ‘cognition’ the situation would be even worse. Banned drugs are obtainable readily over the net, and no-one is ever going to ban taking coffee before going into an exam. I have recently been working with a young person’s theatre group, who have been touring a play (‘Mind the Gap’) raising some of these issues for school students. Asked before and after seeing the play whether they would take ‘smart drugs,’ most said no on the grounds that it would be cheating. But if they thought their fellow students were taking drugs, they would too. Of course, as any putative cognitive enhancer, like any other powerful drug, is likely to have adverse or unwanted effects associated with it, what is needed, especially for young users, is decent (but non-directive) education on drug effects rather than attempt coercion.
  One final point should not go unaddressed. Sahakian and Morein-Zamir’s reference to ADHD as heritable and affecting 4-10% of children world-wide is, to put it no more strongly, contentious. The claimed incidence of ADHD varies dramatically over time (less than 0.1% in the UK before 1990, now generally claimed, even by its advocates, to be between 1-5%) and country (highest in the US, followed by Australia and I believe Iceland, low in Italy for instance). The diagnosis is in many cases questionable and evidence on heritability shaky except in highly selected groups. The dramatic increase in the prescription of Ritalin (methylphenidate) – from 2000 a year in 1991 to over 300,000 in the UK today says more about fashions in diagnosis and treatment of naughty or inattentive or badly-parented children than it does about a genuinely heritable ‘disease.’ In the US the FDA has called attention to the ‘epidemic’ of schoolyard Ritalin use. As Sahakian and Morein-Zamir say, there is disturbing evidence of long-term adverse sequelae of the use of such amphetamine-like drugs especially for young and developing brains. But whilst the assumption behind the cognitive enhancer debate is that users are essentially making free choices about whether or not to take the risks, children being prescribed Ritalin are not autonomous agents; they are being drugged as a method of social control.

  That, it seems to me, is a real ethical issue. But if we don’t recognise the real world situation in which drugs are bought, prescribed and used, then the ethical debate is vacuous.
  Steven Rose

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