One of my colleagues posted a recent commentary from Nature on how the idea of the smart pill has been oversold. The basic theme of the commentary is that there is no good evidence that treatment of ADHD with stimulants improves academic outcomes. The author reviews a few long term studies and contends that differences between the medication and placebo seem to wash out over time and therefore there is no detectable difference. Her overall conclusions seem inconsistent with her view that: "For most people with ADHD, these medications — typically formulations of methylphenidate or amphetamine — quickly calm them down and increase their ability to concentrate. Although these behavioural changes make the drugs useful, a growing body of evidence suggests that the benefits mainly stop there..."
A question for any cognitive psychologists out there - is it possible to improve your concentration and have that not improve learning? I can't imagine how that happens. If you go from not being able to read 2 pages at a time to suddenly reading chapters at a time, how is that not enhanced cognitive performance? If you go from staring out the window all day and daydreaming to being able to focus on what the teacher is saying how will that not lead to an improved outcome? The idea that improved attention - a central factor in human cognition will not affect anything over time suggests to me that the measures being used for follow up are not very robust or that this is a skewed sample of opinion.
For the purpose of cognitive enhancement, the typical users are students trying to gain an edge by increasing their study time. Anyone who has experienced college and professional school realizes that here is a large amount of information to be mastered and it is not presented in an efficient way. I can never recall a professor who advised us of the important guideposts along the way or gave us any shortcuts. The usual message is study all of this material in depth every day or you will fall behind. That approach in general is consistent with gaps in the ability to study either through the normal course of life or the competition for intellectual resources by 3 or 4 other professors who regard their courses as important. That typically results in a pattern of cramming for specific key exams. Although I have not seen any specific studies, stimulant medications are generally used for this purpose and in many cases the use is widespread. There is a literature on the number of college students who may be feigning ADHD symptoms in order to get a prescription and that number could be as high as 50% (4,5).
What about the issue of stimulants acting as a smart pill in people who don't have ADHD? In the most comprehensive review I could find on the subject (6) the authors review laboratory studies and conclude that in those settings stimulants enhance consolidation of declarative learning to varying degrees, had mixed effects on working memory, and mixed effects on cognitive control. On 8 additional tests of executive function, the authors found that stimulant medication enhance performance on two of those tests - non-verbal fluency and non-verbal intelligence. They have the interesting observation that small effects could be important in a competitive environment. Their review also provides an excellent overview of the epidemiology of stimulant use on campuses that suggests that the overall prevalence is high and the pattern of use is consistent with cramming for exams. They cite a reference that I could not find (7) that was a reanalysis of NSDUH data suggesting that as many as 1 in 20 stimulant users may have a problem with excessive use and dependence.
Getting back to the theme of the Nature commentary, it is ironic that the smart pill theme is being called into question when it was the subject of a Nature article years earlier advocating for the use of cognitive enhancement. In that article Greely, et al come to the somewhat astounding conclusion:
"Based on our consideration, we call for a presumption that mentally competent adults should be able to engage in cognitive enhancement using drugs."
They arrive at that conclusion by rejecting three arguments against this practice. Those arguments include that it is cheating, it is not natural and it is drug abuse. Their rejection of the cheating argument is interesting because they accept the idea that performance enhancing drugs (PEDS) in sports is cheating. They reject that in cognitive enhancement claiming that there would need to be a set of rules outlining what forms of enhancement would be outlawed and what would not (e.g. drugs versus tutors). To me that seems like a stretch. I think that sports bodies select performance enhancing drugs as a specific target because it clearly alters body physiology in a way that cannot be altered by any other means. There is also plenty of evidence that the types of PEDS are dangerous to the health of athletes and associated with deaths. Their conclusion about drug abuse: "But drugs are regulated on a scale that subjectively judges the potential for harm from the very dangerous (heroin) to the relatively harmless (caffeine). Given such regulation the mere fact that cognitive enhancers are drugs is no reason to outlaw them." That is a serious misread of the potential addictive properties of stimulants and the previous epidemics that occurred when the drugs were FDA approved for weight loss, the epidemic of street use in the 1970s and the current and ongoing epidemic of meth labs and methamphetamine use throughout much of the USA.
These authors go on to outline four policy mechanisms that they believe would "support fairness, protect individuals from coercion, and minimize enhancement related socioeconomic disparities." At first glance these lofty goals might seem reasonable if society had not already had in depth experience with the drugs in question. The clearest example was the FDA approved indication of amphetamines for weight loss. What could be a more equitable application than providing amphetamines to any American who wanted to use them for weight loss? The resulting epidemic and reversal of the FDA decision is history. A similarly equitable decision to liberalize opioids in the treatment of chronic pain had resulted in another epidemic of higher lethality due to differences in the toxicology of opioids and amphetamines.
The contrast between these two commentaries in Nature also highlight a couple of the issues about the way medical problems and treatment is portrayed in the media. This first is that you can't have it both ways. Quoting a researcher or two out of context does not constitute an accurate assessment of the science involved. Some of the authors in the first commentary are highly respected researchers in cognitive science and they clearly believe that cognitive enhancement occurs and it should be widely applied. Nature or any other journal cannot have it both ways. A more realistic appraisal of the problem is addressed in reference 6. The second issue is that in both cases the authors seem blind to the addictive properties of stimulants and they are ignorant of what happens when there is more access as exemplified by the FDA misstep of approving stimulants for weight loss. Do we really need a new epidemic to demonstrate this phenomenon again? Thirdly, all of this comes paying lip service to non - medication strategies for cognitive enhancement. We can talk about the importance of adequate sleep - a known cause of ADHD like symptoms and if we are running universities and workplaces in a manner that creates sleep deprived states, the next step is reaching for pills to balance an unbalanced lifestyle. The new rules for residency training are a better step in the right direction. Fourth, college is a peak time for alcohol and substance use in the lives of most Americans. These substances in general can lead to a syndrome that looks like ADHD. It is highly problematic to make that diagnosis and provide a medication that can be used in an addictive manner. It is also highly problematic to think that treating an addicted person with a stimulant will cure them of the addiction and yet it happens all of the time.
There is plenty of evidence to suggest that cognitive enhancement is cheating. Much of my career has been spent correcting the American tendency of trying to balance one medication against another and using medications to tolerate a toxic lifestyle or workplace. It does not work and the current group of medications that are being put forward as cognitive enhancers are generally old drugs with bad side effect profiles particularly with respect to the potential for addiction.
If you want safe cognitive enhancers that can be made widely available, they have not been invented yet.
If you want safe cognitive enhancers that can be made widely available, they have not been invented yet.
George Dawson, MD, DFAPA
References:
References:
2: Greely H, Sahakian B, Harris J, Kessler RC, Gazzaniga M, Campbell P, Farah MJ.
Towards responsible use of cognitive-enhancing drugs by the healthy. Nature. 2008 Dec 11;456(7223):702-5. doi: 10.1038/456702a. Erratum in: Nature. 2008 Dec 18;456(7224):872. PubMed PMID: 19060880.
3: Feldman HM, Reiff MI. Clinical practice. Attention deficit-hyperactivity disorder in children and adolescents. N Engl J Med. 2014 Feb 27;370(9):838-46. doi: 10.1056/NEJMcp1307215. PubMed PMID: 24571756.
5: Suhr J, Hammers D, Dobbins-Buckland K, Zimak E, Hughes C. The relationship of malingering test failure to self-reported symptoms and neuropsychological findings in adults referred for ADHD evaluation. Arch Clin Neuropsychol. 2008 Sep; 23(5):521-30.
6: Smith ME, Farah MJ. Are prescription stimulants "smart pills"? The epidemiology and cognitive neuroscience of prescription stimulant use by normal healthy individuals. Psychol Bull. 2011 Sep;137(5):717-41. doi: 10.1037/a0023825. Review. PubMed PMID: 21859174
7: Kroutil LA, Van Brunt DL, Herman-Stahl MA, Heller DC, Bray BM, Penne MA. Nonmedical use of prescription stimulants in the United States. Drug and Alcohol Dependence. 2006; 84:135–143.10.1016/j.drugalcdep.2005.12.011 [PubMed: 16480836]
I agree with almost everything in your post. Amphetamines are definitely performance enhancing drugs, and I think that is perhaps their only "benefit."
ReplyDeleteThe only thing I disagree with is your guess as to why kids treated for "ADHD" do not do better in school in the long run. As you correctly point out, it can't be because stimulants AREN'T performance enhancing drugs. I think it's instead because for the vast majority of kids diagnosed with ADHD, inability to concentrate was never their main problem to begin with. The problem is either that they are not motivated to do well in school and they are acting out, or that they are distracted by a chaotic homelife, or usually both.
Agree completely, in fact Volkow did an interesting study on how stimulants seemed to increase the motivation to do otherwise boring math problems. There may be a tendency of older patients to accelerate the dose just based on motivational factors.
ReplyDeleteI found this article http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666055/ and I am curious on your thoughts about the findings. It describes some of the same mixed results I experience on modafinil [legally prescribed].
ReplyDeleteMy concentration and immediate recall improved, short window of time where my eyesight is sharper, frustration tolerance lower, chance to catch errors higher. However, I am more distractable, it doesn't improve my short or long term memory, and the rebound fatigue is punishing. In my case, it only allows me to drive safely and to keep up with those much younger than I at work. There is no competitive advantage in the environment I am in.
I think the paper has some of the same methodological shortcomings of the original commentary nit the least of which is the fact that they claim no benefit and then demonstrate a benefit? There is also the issue I pointed out in my post. If you have a significant attentional problem that for the sake of this argument of independent of motor restlessness to the point that you literally have to reread the same same two pages - how would your academic performance NOT improve if stimulants allowed you to read chapters. These are the students who will have clear improvement with stimulants, although it is a complex effects that can affect other executive functions.
ReplyDeleteIn terms of methodology, the authors point out they did not independently confirm diagnoses and this is problematic given what we know about the number of students seeking cognitive enhancement who do not have a diagnosis. The selection bias involved in looking at ADHD students who have GPAs and SAT score on par with the non ADHD students is considerable. If the diagnosis is confirmed my guess would be that this is an uncharacteristic sample of ADHD students and the generalizability of the data would not he high.
These seem to be general problems studying the issue of cognitive enhancement and the constraints of studying human subjects. One obvious experiment would be to discontinue the stimulants in a group of college students with confirmed diagnoses of ADHD. I can't think of a human subjects committee that would approve that study, but if the subjects have significant ADHD the outcome would be fairly predictable. That results would go against the quotes about a lack of improvement in functional ability in the early part of the article.
I would add it to the accumulating articles on the controversy about cognitive enhancement. In any ways it is similar to the controversy about drug legalization and what happens when you try to look at a complex subject in a a dichotomized manner. The review cited in the original post is a far superior approach.
Wondering if you read the study on valproate and perfect pitch. Probably a less toxic way to get a better result. Still cheating though.
ReplyDeleteHave not seen that study - do you have the reference?
Deletehttp://journal.frontiersin.org/Journal/10.3389/fnsys.2013.00102/full
ReplyDeleteFascinating article - more fascinating if it is true. Because of the relationship between math and music it would be interesting if the researchers looked at acquisition of math skills in the valproate treated group and if it was enhanced.
DeleteIf that panned out - more students would want cognitive enhancement with valproate than with stimulants.
Your headline says "cognitive enhancement is cheating," but your argument is that it's dangerous. These are different things. Cheating is defined in relation to a set of rules. PEDs in sports constitute cheating because they violate the rules. Rules in sports can be arbitrarily restrictive: time-outs, rest breaks, and many other variables can be "performance enhancing" and either allowed or disallowed by the rules. A subset of such restrictions, including those prohibiting PEDs, are imposed for health and safety reasons. In contrast, cognitive enhancement (broadly speaking) in academic studying and test taking is not cheating, as it is clearly allowed. As you acknowledge, there are many cognitive enhancers aside from amphetamines: good sleep, tutoring — and caffeine, the last of which seems to fill the bill as an already-invented "safe cognitive enhancer that can be made widely available."
ReplyDeleteNone of this is to argue that amphetamines should be used for studying or test-taking. I agree that (1) it's dangerously misguided to balance one medication against another and use medications to tolerate a toxic lifestyle or workplace, (2) amphetamines are generally old drugs with bad side effect profiles particularly with respect to the potential for addiction, and (3) that new rules for residency training are a better step in the right direction. But none of this has to do with cheating, it's all about promoting health.
The valproate and perfect-pitch article is indeed fascinating. We may be entering an era when formerly clear distinctions between chemistry and psychology begin to blur — magnifying debates over performance enhancement, "natural" abilities, and the like.
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ReplyDeleteAssuming they want to learn rather than get high. If VPA pans out, and they still prefer stimulants, then that is telling.
The perfect pitch study is amazing. I learned piano at 8 and I can usually only name 4-5 notes out of 12 correctly although I have relative pitch, which is a lot easier to learn (ex. C to F#="Maria" etc.) I think the application for maths and programming would be the next step.
Dogged by chronic insomnia, I think I will be looking for reduced plasticity for at least one area of my brain.
ReplyDeletehttp://www.hopkinsmedicine.org/news/media/releases/researchers_identify_brain_differences_linked_to_insomnia
Thanks for this reference - it is an area of great interest to me. Tononi is a great theorist in this area and I heard him speak about his Synaptic Homeostasis Hypothesis (SHY) at the anniversary of the psychiatry department at UW-Madison. I hope to post some details when I have read it through a few times.
DeleteTononi G, Cirelli C. Sleep and the price of plasticity: from synaptic and cellular homeostasis to memory consolidation and integration. Neuron. 2014 Jan 8;81(1):12-34. doi: 10.1016/j.neuron.2013.12.025. PubMed PMID: 24411729; PubMed Central PMCID: PMC3921176
better learning through plasticity and liberating fluid intelligence seems intuitively like a safer route than better learning by dopamine..but that could be wrong...would love to see a head to head study...
ReplyDeleteHere is an article I recently came across when searching for something else: https://today.duke.edu/2014/02/dendrites
ReplyDeleteEnd run around plasticity or the ultimate plasticity? I don't know; that's why I brought it here.
It is called structural plasticity of dendrites. In other words, experience dependent structural changes rather than changes only at the synapse. There is a good chapter by the same name in "dendrites" by stuart, spruston, and hausser.
ReplyDeleteThis only makes sense if you think that school is about competing, like a sporting event. Then, 'cheating' would be defined as something that gives you an unfair advantage. But if the purpose of school is not to compete, but to learn, then to restrict something that helps you learn better (as measured by test performance or whatever other outcome measures are employed) because it is 'cheating' is outrageous.
ReplyDelete