The Illuminated Brain

A weblog on neuroscience

What You Ought To Know About Cognitive Enhancement

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Introduction

For thousands of years the wish to experience altered states of consciousness has been an integral part of the human experience. In the twenty-first century the wish to increase efficiency and productivity is paramount; in the western world people are striving towards better and faster results. We keep striving for perfection, and the only way to achieve more productivity is to work with the resources we have available to the best of our ability.

Today, with modern science and psychopharmacology, we are slowly making progress in a hugely interesting field spanning the entire human experience. This is called cognitive enhancement.

The wish for a panacea, an all-encompassing solution unlocking the potential of our nervous system, is something shared by millions of people. The futuristic movie Limitless based on the book The Dark Fields written by Alan Glynn examines the prospect of such a panacea. In the movie we meet Eddie, a writer trying to finish writing a book to no avail. He is depressed and has an extremely hard time completing the task. Luckily he meets his brother in-law Vern, who introduces him to the pill NZT-48. The pill allows him to finish the book in three days and Eddie is hooked. We follow him in the footsteps of this cognitively enhancing NZT-48 and experience the glory and doom of the drug’s potential.

The movie is interesting because of two things; it touches on the subject of cognitive enhancement directly, and it primes our brains for the ethical dilemmas that could arise from the use of such a drug.

This article tries to describe what cognitive enhancement actually entails by distilling some of the current thoughts and research on cognitive enhancers, looking into non-pharmacological approaches to cognitive enhancement, and evaluating some of the possible ethical and societal implications.

Cognitive Enhancement: What’s All This Fuss About?

Cognitive enhancement is about improving one’s mental state and intellectual performance, be it either by psychological or psychopharmacological means. Intellectual performance can be subdivided into many different categories, as there is no straightforward or uniform way of defining exactly what intelligence implies. When talking about intelligence it is best to define it as the complex and holistic brain processes which include creative insight, linear and divergent thinking, and the ability to contemplate different solutions to any particular problem. One current problem in the research of cognitive enhancers and their effects on healthy individuals is that our understanding of intelligence and the cognitive examinations and tests used in scientific studies have to be subdivided and specific in order to standardize the subsequent results. However, in real life, as with everything, intelligence and cognitive performance is an extremely hard concept to define. Is the person good with words not as intelligent as a person good with numbers? Do we define the rate of learning as intelligence? If we do, then we must realize that the rate of learning of that particular person depends upon their cognitive framework and past experiences. As cognitive neuroscience dives into the aspect of learning it becomes more difficult to define optimal learning particularly due to the innate individual differences that exist.

An article published last year (2011) in Pharmacology Biochemistry and Behavior called ‘The likelihood of cognitive enhancement’ examined the current body of knowledge surrounding cognitive enhancement. One problem that the authors aptly notes is the fact that there is an enormous difference between increasing the efficiency of cognitive processing (mostly through improving activity in the prefrontal cortex; the area of the brain especially involved in attention, working-memory and executive functions) and improving actual complex cognitive processing.

The problem with the widely used cognitive enhancers, especially by students in the 21st century, is the fact that the drug’s ability to improve cognition lies in their psycho-stimulatory nature. The psycho-stimulants available today, despite increasing the efficiency of cognitive processing, cannot be truly classified as cognitive enhancers as they – as far as the research has shown – only increase the activity of the prefrontal network, improving attention and executive functions, but do not allow for more complex targeted activity. Moreover, most of the psycho-stimulants have a lot of side effects such as appetite suppression, anxiety, insomnia, jitteriness, and often quite significant withdrawal effects. Not the ideal conditions for a cognitive enhancer taken for an extended period of time.

The psycho-stimulants that I speak of here are the amphetamine-based products such as Adderall, Dexedrine, Dexosyn and methylphenidate-based products such as Ritalin, Concerta, Daytrana, and the atypical psycho-stimulant modafinil-based product Provigil.

Most of these drugs are extremely well known to most college students, especially in the United States of America, as most of these drugs, Ritalin and Adderall in particular, are used for the treatment of attention deficit hyperactivity disorder (ADHD). All of these drugs help people afflicted with ADHD by improving prefrontal activity, which improves executive functions such as planning, processing speed, attention and working-memory. As the college and university scene has become increasingly more competitive, especially with an emphasis on standardized testing, the wish for cognitive enhancement becomes increasingly evident. Students both with and without ADHD make use of these drugs to study for extended periods of time in order to improve their grades and test performance.

However, these drugs are only a small subgroup of drugs that require a prescription from a doctor to acquire. Other drugs such as caffeine and nicotine are actually also, despite what you might have thought, cognitively enhancing. Like the psycho-stimulants they also have the potential for side effects. Nicotine, mainly acquired through cigarettes, is especially addicting. Caffeine and nicotine, having been used for thousands of years have been such an engrained part of culture that it is surprising to see the actual results of the drugs in healthy individuals in terms of cognitive enhancement.

Actually, one could argue that nicotine in particular is more cognitively enhancing than the highly regarded amphetamine or methylphenidate-based products as more and more studies show that nicotine has far-reaching neural effects and improves not only processing speed and attentive faculties, but also IQ-scores [1], handwriting [2] and memory [3].

Caffeine, being the psycho-stimulant that it is, improves cognition in largely the same way as Adderall and Ritalin by improving activity in brain areas associated with working-memory and attentive faculties. A study published in the Journal Human Psychopharmacology: Clinical and Experimental in 2010, examined the effects of caffeine and glucose on cognitive performance in healthy volunteers. Using a technique that shows brain activity by looking at regional changes in blood flow (functional magnetic resonance imaging) they found that: “[…] the combination of the two substances improves cognitive performance in terms of sustained attention and working memory by increasing the efficiency of the areas of the brain responsible for these two functions” [4]

Cognitive Enhancement: A Look Into The Future

The scene of more modern cognitive enhancement looks slightly different. Many pharmaceutical companies are currently working at finding cognitive enhancers with minimal side effects that can be used to treat conditions such as ADHD, narcolepsy, chronic fatigue syndrome, Alzheimer’s disease, and more.

In the late 60s a Belgian doctor Corneliu E. Giurgea coined the term ‘nootropic’ after his team from the Belgian pharmaceutical company UCB synthesized a drug called Piracetam that happened to have cognition enhancing properties, no toxicity and largely non-existent side-effects.

The body of research relating to the effects of Piracetam on healthy individual is extremely lacking, but the few studies that do exist suggests that it improves short and long-term memory (verbal learning, in particular), improves reading comprehension in individuals with dyslexia and increases scores on perceptual-motor tasks. A single dose of piracetam was found to decrease the global complexity of brain activity, suggesting, according to one study “an increased cooperativity of functional processes.” [5]

Due to the highly limited research on Piracetam and cognitive enhancement in healthy individuals, many people have used anecdotal reports to determine its efficacy. Most anecdotal reports are highly hit or miss with some people reporting absolutely astounding effects and others reporting minimal, but noticeable effects and yet others impervious to the any effects. The problem with anecdotal reports is of course the lack of a control group, and the implications of both the placebo and nocebo effect. After piracetam researchers synthesized analogs based on the structure of piracetam and a whole range of racetams were synthesized including oxiracetam, aniracetam, pramiracetam, levitiracetam, nefiracetam, phenylpiracetam. The research of these drugs and cognition enhancements is thoroughly lacking although many anecdotal reports swear by their efficacy.
Due to the fact that the racetams have virtually no toxicity and minimal side effects, they are used by many people interested in the scene of cognitive enhancement and with much success.

Currently, the development of cognitive enhancers is focused on improving a phenomenon in the brain called long-term potentiation (LTP). This phenomenon and process is based on basic neuroscientific Hebbian theory: neurons that fire together, wire together, and is hugely involved in the process of learning and long-term memory. It is one of the most important aspects of synaptic plasticity, which is intricately involved in cognitive enhancement.

The current research on cognitive enhancers is focused on drugs called ampakines, affecting long-term potentiation (LTP) by modulating the most abundant neurotransmitter in the central nervous system called glutamate. Through glutamergic modulation (by modulating receptors called AMPA) synaptic transmission is hugely affected, where positively modulating these receptors results in increased cognition in mice and primate studies. Most of the pharmaceutical companies currently working with ampakines are going through the Food and Drug Administration process of drug-development ensuring their safety and actual efficacy. One of these drugs, developed by Cortex Pharmaceuticals, is the drug CX717, which has shown promising results in primates. One study showed that CX717 alleviated the negative effects of sleep deprivation on cognitive tests in monkeys. Furthermore, when looking at the brain activity of the monkeys when sleep deprived, the activity in the prefrontal cortex of the brain was decreased which corresponded with the decreased scores in attention and working-memory tests. However, after administering CX717 to the monkeys the brain activity returned to normal. This is just one of many studies revolving around this highly interesting class of drug, and one should definitely expect to hear and see more research relating to these drugs within the next couple of years.

Cognitive Enhancement: Do You Really Need Drugs?

As the scene of modern cognitive enhancement may seem solely based on psychotropic enhancement, it should be noted that there are other non-pharmacological approaches to improving cognition and psychological states that can allow for improved cognitive performance.

Dual-N-Back

One of these tools is the cognitively enhancing game or program called Dual-N-Back. Neuroscientists were interested in whether computerized cognitive training could actually improve cognition or whether one would simply become better at that specific cognitive task. That is, would the computerized cognitive training only allow for task-specific performance improvement, or would there be improvement in other unrelated tasks? Researchers Jaeggi et al created this program called Dual-N-Back and found that its effects on working-memory it actually improved fluid-intelligence scores. Fluid intelligence relates to one’s ability to solve problems independent of specialized knowledge in novel situations. Raven’s progressive matrices are one of the tools used to test fluid-intelligence. Jaeggi et al found that cognitive Dual-N-Back training improved performance on Raven’s progressive matrices and thus improved fluid-intelligence scores.

At this point in time this was an astounding research result because fluid-intelligence had previously been thought as to be a completely fixed aspect of one’s cognition.

Lumosity

Another computerized cognitive training program is offered by Lumosity.com a site specializing in games targeted to improve cognition. They claim that the results are highly significant and that they actually improve overall cognition. The anecdotal reports seem to support their claims, but without control groups it is hard to say whether there is any actual improvement in cognition or whether it simply improves your ability to play the games that they offer.

Mindfulness Training

A different kind of cognitive training is mindfulness training, which not only improves depression and anxiety scores, but also improves attention, impulsivity, executive control and problem solving. Studies suggest that mindfulness training actually changes regional gray matter density in areas of the brain relating to learning and memory processes. [6]

Cognitive Enhancement: What Possible Ethical and Societal Implications Exist?

Returning to the movie Limitless, one of the interesting things about the movie and – of course – the book, as well, is that it touches base on some of the ethical dilemmas that could arise from using such a drug. If you took a pill and it helped you achieve more than you could possibly do without it, is it the drug, or you that accomplished those feats?

Shortcuts are often just that: shortcuts. You may lose a lot of experience that can teach you the value of hard work and persistence. But on the other hand, one could argue that we have used shortcuts our entire lives and since the brink of humanity. With increased intelligence and the more inventions, it became a question of improving efficiency and performance, so we started optimizing. Work smart, not hard. So if there’s something that can allow us to work smarter and get more done, in a positive direction, why should we limit ourselves? If we dive into the argument that we shouldn’t use any of these drugs because they’re unnatural, need I remind you that most of the things we eat on a daily basis are filled with preservatives that are completely and utterly unnatural? The increased efficiency and mass-market production means that we deviate more and more from our natural roots and need to cope with the unnatural products that have become so engrained in our modernized culture.

How are drugs then not a coping mechanism to reduce the negative side effects that diet may have had on our mental states? It is a negative spiralling effect; we are trying to solve the problems we ourselves have created by masking the underlying problems. The problem with fixing the underlying problems is that it would require a complete metamorphosis in ideology, and such a change is not at all easy, and maybe not even possible in the 21st century.

Moreover, there’s the problem of the split in class that would inevitably occur with such a powerful cognitive enhancer on the market. Who would control and be able to join the market? It would be the people with enough money to actually buy the pill, and if they, and nobody else, could afford such a pill, an elitist group would be created and further emphasize the split between rich and poor (e.g. academic and non-academic.)

We must however also be realistic about society in general. Most people are against drugs, but for the wrong reasons. They associate them with addictions and picture addicts hooked on heroin and crystal meth. However, what we are talking about here is a futuristic scenario with drugs of a non-toxic, non-addicting nature, that work simply by amplifying natural brain processes without – hopefully – perturbing the neurochemical equilibrium.

However one ought to realize that we as a population are horribly addicted to drugs in general. We are a culture of pill-popping, caffeinated Starbucksians, hooked on coffee, cigarettes and alcohol. These drugs are the three major drugs that are used by the entire world and all of them are toxic, highly addictive and have significant withdrawal effects. Moreover, alcohol in particular, is extremely deleterious for cognition and causes thousands of accidents every single day, yet it is still an engrained part of our culture and therefore accepted.

With new technological development comes new drugs and with those new drugs, new cultural movements. Culture is always developing, and I would personally argue that inhibiting the natural development would be detrimental to our future as increasingly globalized societies.

In conclusion, the scene of cognitive enhancement is an extremely interesting field of study at the moment, and more and more people, students in particular, are becoming interested in how to change their conscious experience and improve their intellectual performance.

What we should hope for is that the cognitive enhancement, and thus enhancers we will see in the future will use a holistic approach, and not only be limited to psychotropic drug use, but also behavioural interventions that will allow not only better processing speed, but also wide-brain complex synchronized cognition improvement. Ultimately what we would to see is that people get the possibility of improving their own lives and being happier, whilst also improving the advancements in the Sciences and Arts alike.

References

1: http://www.springerlink.com/content/f43533n81707641r/
2: http://www.springerlink.com/content/w4r53b9cglwt8jqp
3: http://www.springerlink.com/content/mrn6232427w6269q/
4: Josep M Serra Grabulosa, Ana Adan, Carles Falcón, Núria Bargalló. “Glucose and caffeine effects on sustained attention: an exploratory fMRI study”. Human Psychopharmacology: Clinical and Experimental. DOI: 10.1002/hup.1150 (2010).
5: http://www.ncbi.nlm.nih.gov/pubmed/10555876

Connecting The Dots: The Magic of Psilocybin

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See the magic?

After reading psychedelic information theory, I’ve become more and more interested in the molecules behind so-called ‘spiritual’ phenomena occurring in the brain. The fact that DMT, a neurotransmitter which is released during dreaming, evokes the question: Why do we dream? The main hypothesis is that dreaming (and here characterized by both non-REM and REM sleep) somehow processes all subconscious material and emotional content that we have been experiencing on the day of the dream. As of here arises the theories surrounding dream theory and dream analysis (as per e.g. Freudian analysis).

So if DMT is the main molecule released during sleep (along with acetylcholine; a neurotransmitter associated with memory-processes) why is it in plants too? Do plants dream? And if they dream, what do they dream about?

The pineal gland is thoroughly implicated  in dreaming and has been characterized as the brain’s Third Eye by e.g. Hinduism. The pineal gland controls the release of melatonin, which is the main hormone released which induces sleep. The pineal gland also stimulates the release of DMT under strong meditative experiences or otherwise transcendental experiences.

Interestingly, the transcendental experiences and the subsequent enlightenment experienced by people who have meditated for several years can be accelerated or achieved by continual use of magic mushrooms.

Psilocybin

Several scientists such as Richard Feynman, Francis Crick, Kary Mullis and others have used psychedelics and other means of altering one’s state of consciousness (Feynman was a fan of sensory deprivation) to look at things from a new perspective.

Psilocybin, the active ingredient in ‘Magic Mushrooms’, or Psilocybe mushrooms has profound effects in people.

A study published in 2011 by Rácz J., et al., in the Journal of Psychoactive drugs, writes: “The autognostic use of psychedelic drugs may be thus hypothesized as a “training situation” that promotes self-enhancement by rehearsing personal coping strategies and by gaining self-knowledge. However, to assess the actual efficiency and the speculated long-term benefits of these deliberately provoked exceptional experiences, further qualitative investigations are needed.

More interestingly however, are the studies published from John Hopkins University where a controlled set (people) and setting (environment) was used to achieve the best results using psilocybe mushrooms. They called the study: “Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness.”, where 18 healthy adults (avg. age: 46) got to experience a five to eight hour experience with either psilocybin (at different doses) or placebo. All of the participants were interested in spiritual experience and were open to the experience coming their way.

The effects of this study were profound, especially because the participants of the study were asked fourteen months after the experience and asked a number of questions relating to their quality of life, levels of spirituality. Accordingly, 94% of the participants described the experience as one of the most meaningful experiences in their lives, 39% of which said it was the most meaningful.

The effect of the experience didn’t only relate to the individual however, but also had glowing effects on friends, family, co-workers, all of whom reported the participants as less stressed, more calm and happier. As per the abstract: “Consistent with participant claims of hallucinogen-occasioned increases in aesthetic appreciation, imagination, and creativity, we found significant increases in Openness following a high-dose psilocybin session. In participants who had mystical experiences during their psilocybin session, Openness remained significantly higher than baseline more than 1 year after the session. The findings suggest a specific role for psilocybin and mystical-type experiences in adult personality change.

The experience itself is described as being part of a whole, as of relating to a higher state of being, as of seeing the Universe in a new light. Ayahuasca used by the tribes in the Amazonian Colombia have used combination of plants containing DMT (which isn’t orally active) and a monoamine oxidase inhibitor naturally found in Caapi (a plant), which when taken orally (in the form of a drink) allows for a highly transcendental experience. The shamanistic movements believe that only by using these forms of enlightening combinations of being exposed to nature, meditation and of deep insight can revelations of the Self be explored. The reason that some people have bad trips is mostly related to the fact that most people do not like the loss of control that is experienced under the influence of psychedelic drugs. Psychedelic drugs can induce a phenomenon known in parapsychology as the death of one’s ego, or egodeath – as described by the author Eckhart Tolle:

I couldn’t live with myself any longer. And in this a question arose without an answer: who is the ‘I’ that cannot live with the self? What is the self? I felt drawn into a void. I didn’t know at the time that what really happened was the mind-made self, with its heaviness, its problems, that lives between the unsatisfying past and the fearful future, collapsed. It dissolved.

It is reported that the day after this experience he was peaceful and even saw peace in the traffic in the streets of London.

And for the record: I am in no way condoning the use or misuse of psychedelic drugs (as they can have highly detrimental effects in those susceptible, and requires both preparation in terms of set and setting) – magic mushrooms and other psychedelics as e.g. LSD and DMT are tools for enlightenment and not toys.


The SSRI Placebo Myth

Written by Anders on 3 comments

SSRIs are selective serotonin re-uptake inhibitors, commonly referred to as antidepressants, and they are some of the most widely prescribed pharmaceuticals in the world. One of the first SSRIs and most well known is called Prozac (chemical: fluoxetine) marketed by Eli Lily And Company. Another two well-known SSRIs are Lexapro (chemical: escitalopram) and Zoloft (chemical: sertraline) marketed by Lundbeck and Pfizer. This post wants to take a look at one of the biggest myths that surrounds the use of antidepressants (most commonly SSRIs).

The Placebo Myth

There are an increasing number of people re-iterating the same point about SSRIs over and over again. “They are not much better than placebo”. Let’s actually take a look at the evidence. When people say stuff like that, it is either because they a) don’t know anything about the drug, and have a very negative outlook on pharmaceuticals as whole, and therefore makes grand-assumptions with no evidence, or b) they have read one of the many news articles featured in even highly respected newspapers such as the New York Times, who indirectly refers to a meta-analysis done by the Cochrane group. Moreover journalists love to write about controversial findings, such as any preliminary evidence suggesting a widely prescribed class of drug could be ineffective. That said, meta-analyses look at the plethora of studies available on a specific topic of interest, and use various statistical methods to derive a conclusion as to what the majority of evidence suggests. The meta-analysis (1) by the Cochrane group suggested that SSRIs and TCAs (tetra-cyclic antidepressants) were only minimally (and not clinically significantly) better than placebo in the treatment of mild depression.

Interestingly, this meta-analysis has been criticized wildly by a number of other researchers due to methodological flaws. Several papers have been sent in return. Let’s take a look at some of them and their conclusions.

  • In the first letter (2) Glassman et al, found that several other studies suggest that it is not only the severity of the depression that predicts the outcome of medication treatment, but also duration of treatment. Several studies are cited showing significant antidepressant effect in dysthymia (a chronic form of mild depression), and another cohort of studies showing significant results in cohorts with mild depression. “The authors’ observation about depression severity is almost certainly correct, but their conclusion concerning antidepressant medication use is not.”
  • In the second letter (3) Suzuki et al, suggests that there is a bias towards studies with a limited time frame, with approximately 6 weeks, which could compromise the outcome of the subjective rating of depression. This is due to the fact that there is an adaptation period to SSRIs, and depending on the subcategory of depression, some patient may not see immediate improvement, and need more than 6 weeks. This phenomenon is also seen in anxiety disorders treated with antidepressants.  Another point the author points out is that the studies referenced do not include remission rates, but merely depression scale. Furthermore this author references another study showing that antidepressants have significant effect in mild-depression. “First, antidepressants may exert their effects earlier in the course of treatment than previously thought. If so, the exclusion of short-term studies (less than 6 weeks) would have significantly minimized the clinical pertinence of their findings that focused on acute phase treatment. Second, patient-level data on antidepressants vs. placebo could have been analyzed in terms of response and remission rates, as well as their maintenance over time (as is exemplified in a study of schizophrenia treatment), instead of pre-post comparison of the mean values alone.”
  • In the third letter (4) Hicks et al, notes that mild depression only was evaluated in 1 of 6 studies, (with a score in the Hamilton Depression Rating Scale (HDRS) 8-13), and in that one study the HDRS score was not above 14, equivalent to moderate depression. Moreover, the author criticizes the sample sizes because drug-discontinuation occurs in up to 25% patients, and that there is a 3% dropout rate. The question as to whether the patients in the two studies are representative of the general depression population is posed.
  • In the fourth letter (5) Gøtzche draws attention to a very important observation. The linear fit in the model used in the meta-analysis was poor and that the statistics shouldn’t have been based on the HDRS scores, but rather remission rates, and the meta-analysis’ statistic method may exaggerate the negative results. “The meta-analysis of antidepressants by Mr. Fournier and colleagues is important for clinical practice, but I have 3 reservations. First, although the authors had access to individual patient data, they used last observation carried forward for patients who dropped out. This method of imputation is likely to overestimate the effect of antidepressants.”
  • In the fifth letter (6) DeRubeis et al, notes that mild depression was only evaluated in 1 of 6 of the studies in the meta-analysis, making the sample size questionable. The author also points out the problem with heterogeneity in the study population.
  • Besides being quoted multiple studies in the several letters in response to the Cochrane study, here is a large (7) meta-analysis, which shows that SSRIs have shown efficacy in many studies. This meta-analysis showed that antidepressants were significantly more effective than placebo in the treatment of dysthymia.

There is so much evidence in favor of antidepressants, but because a handful of people do not respond favorable to them, they are demonized by a number of people. Conspiracy theories saying that pharmaceuticals are evil and trying to put “hand-cuffs” on people, and steal their money, should really look at the evidence. Depression is a worldwide phenomenon and negatively affects society as a whole. Treatment options shouldn’t be limited for people who need help.

References

1.   Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC, Fawcett J. Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA 2010 Jan;303(1):47-53.[cited 2011 Jul 22 ]

2. Glassman AH. Depression severity and effect of antidepressant medications. JAMA 2010 Apr;303(16):1598; author reply 1599.[cited 2011 Jul 22 ]

3. Suzuki T, Uchida H, Nakajima S. Depression severity and effect of antidepressant medications. JAMA 2010 Apr;303(16):1597-1598; author reply 1599.[cited 2011 Jul 22 ]

4. Hicks P, Hicks XP. Depression severity and effect of antidepressant medications. JAMA 2010 Apr;303(16):1598; author reply 1599.[cited 2011 Jul 22 ]

5. Gøtzsche P. Depression severity and effect of antidepressant medications. JAMA 2010 Apr;303(16):1597; author reply 1599.[cited 2011 Jul 22 ]

6. DeRubeis RJ, Fournier JC, Fawcett J. Depression Severity and Effect of Antidepressant Medications—Reply. JAMA: The Journal of the American Medical Association 2010 Apr;303(16):1599.[cited 2011 Jul 22 ]

Productivity In A Pill? Adderall Part 1

Written by Anders on 6 comments

You may have heard about it, because ever since its use boomed in colleges and high-schools, it has gained a massive attention from the public media. Not only anecdotes and success stories, but also ethical debates about whether it should be allowed to enhance mental functions through chemical means. The drug I am talking about is of course the notorious Adderall. Some people call it speed for the mind or productivity in a pill, where others — namely ADHD patients — sees it as a way to be able to function in society, overcome personal struggles and and getting on with their lives .

What is Adderall?

Adderall is a FDA approved drug for the treatment of attention-deficit hyperactivity disorder or ADHD, and narcolepsy. Adderall is a sympathomimetic drug, meaning that it increases sympathetic tone, making us more alert, focused, and motivated. Adderall is an amphetamine. It is a combination of several amphetamine salts. It consists of 75% dextroamphetamine and 25% levoamphetamine. The majority of the Adderall consists, as you can see, of dextroamphetamine. Dextroamphetamine is sold under the brand-name Dexedrine in the US, and was first synthesized in 1887. It wasn’t before the 1970s that the drug was turned into a prescription-drug, and was no longer available as an over the counter drug.

It is very important to note that Adderall is a combination of amphetamine salts, and does not refer to the widely abused drugs such as Esctasy (MDMA) and Crystal meth (methamphetamine). Although the drugs are chemical cousins, the difference is both dosage and the chemicals effects in the brain. The media sometimes demonize use of “amphetamine” in general because they do not know the difference between the chemicals. There is a big difference between MDMA, methamphetamine and pure amphetamine. Because of that demonization it is now very difficult to procure a script for Adderall, even as an ADHD patient, which is a terrible shame since they are the most efficacious for the treatment of ADHD. Adderall was created by the drug company Shire Pharmaceuticals, and was available since 1996.

Uses

ADHD

First, what are the effects of mixed amphetamine salts in ADHD individuals? Since it is FDA approved and indicated for the disorder, it would only be natural that Adderall reduced symptoms of ADHD, and that is indeed what the literature is telling us. There are a ton of articles indicating that the efficacy rates of Adderall for the treatment of ADHD and adult ADHD are very, very high, and [1] is an example of  treatment of adult ADHD with Adderall, with very high efficacy rates. It reduces symptoms of inattention, impulsiveness and hyperactivity. The Adderall used in the study is one of two forms of Adderall. There is the slow released, or extended release (called XR) and the instant released, or immediate released (called IR). In the study they used the extended release, which is also preferable for full day coverage of ADHD symptoms.

Cognitive Enhancement

What about Adderall and healthy individuals? There are a tons and tons of anecdotal stories about people’s use of Adderall both for the treatment of ADHD as well as for cognitive enhancement in healthy individuals. The problem with such anecdotes, is that they are just that, anecdotes, and do not allow to look at things objectively. But, just for the sake of it, looking at things subjectively, the anecdotes are very positive as to the effects of Adderall on human cognition. Because of many people’s response to Adderall is has became a common smart-drug in intellectually demanding communities such as colleges and universities, where focus is of crucial importance to one’s performance. A post in the New Yorker [2] called The Underground World of Neuroenhancing Drugs also takes a look at several cognitive enhancers, whereas Adderall is one of those drugs. The anecdotes and subjective reports are very promising, from “I went from a C-average student to an A+ student” and “I could focus incessantly on any subject at hand, and I liked it” and many more, makes us believe that perhaps pills can make us smarter. The fact is, though, that they don’t enhance your baseline intelligence, as I suggested in my latest post here. One noteworthy example where amphetamine salts really showed its potential is in the mathematician Paul Erdös, who when his mother died in 1971 started Dexedrine (dextroamphetamine) for the treatment of depression. He became even more productive than before, and is believed to be the most productive mathematician in the history of mathematics, producing over 1525 papers [3].

References

1.    Thomas J Spencer et al., “Efficacy and safety of mixed amphetamine salts extended release (Adderall XR) in the management of attention-deficit/hyperactivity disorder in adolescent patients: a 4-week, randomized, double-blind, placebo-controlled, parallel-group study,” Clinical Therapeutics 28, no. 2 (February 2006): 266-279.
2.    “The underground world of neuroenhancing drugs : The New Yorker”, n.d., http://www.newyorker.com/reporting/2009/04/27/090427fa_fact_talbot?currentPage=all.

3. http://www.oakland.edu/enp/pubinfo/

Limitless: A Look Into The Scene of Cognitive Enhancement

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The advances in neuroscience and pharmacology today are so vast that perhaps one day — in the future — we might be able to selectively enhance certain aspects of our intelligence and/or personality.

The past ten years have brought booming attention to “cognition-enhancing” drugs such as Ritalin, Adderall and Provigil, the first two used for attention deficit disorder, and the latter for narcolepsy and excessive daytime sleepiness. The prospect of such drugs were vast. People want drugs that can enhance their ability to focus at information at hand and learn at greater speeds. An ideal pill for a student enrolled in a demanding program, wouldn’t you say?

The thing is, though, cognitive enhancement per se is very, very difficult. A review-article presented in the journal Pharmacology, Biochemistry, and Behavior January [1] this year looks at different aspects of cognitive enhancement and deliberately critiques the current drugs ability to do so.

First, the article tries to draw attention to how we define a cognitive enhancer. In neuroscience several different parts of the brain need to work in harmony before an efficient state is achieved. Does a cognitive enhancer improve all aspects of intelligence, that is, cross-cortical and even cross-hemispheric communication? Looking at the brain as a network of electric potentials, might upping the voltage allow for faster and better transmission of signals?

How do drugs that we — today — denote cognitive enhancers, actually work? This article is a reflection of my take on cognitive enhancers, while also including my personal conjecture  in regards to future cognitive enhancers; what is to be expected?

Efficiency vs. Capability?

One question of importance when speaking about cognitive enhancement is the question of whether a proposed pharmacological agent enhances the efficiency or the capabilities of our current mental abilities? In one scenario, a cognitive enhancer may just enhance the efficiency by which we learn, that is, reduce errors and or the time needed to learn the given material. In another scenario, a cognitive enhancer may actually enhance our current mental capabilities, thereby making it easier for us to actually relate to the material. Say we are given a novel to read and analyze, and we wish to really understand it. Enhancing the cross-hemispheric connectivity and turning the activity in our visual cortex up a notch may be just what we need to really, really understand what we are reading. Being able to see the scenes played out in our head, in such vivid detail, that we become it with the book and time simply passes without us even noticing. Is that what cognitive enhancers does? Warp the time-space continuum, and make us completely entrenched in the task at hand? It may be that by enhancing the very specific areas   we use for specific tasks, our ability may be significantly enhanced.

Cognitive Enhancers Available Today?

Ritalin, a notorious drug for hyper-kinetic disorder or ADHD,  has become a very, very well-known drug because of its purported effects on human cognition. Drugs such as Ritalin or Adderall (another drug used in the treatment of ADHD) are very popular amongst students enrolled in challenging curricular. The idea is simple. A drug that enhances one’s ability to work for extended periods of time, focused at a task at hand, may effectively enhance all aspects of human cognition, right? Well, that is the purported effects, but what does the evidence tell us?

Given the fact that our performance in mental tasks follows an inverted U-curve  relationship response between arousal levels and performance, (see my post on this phenomenon here) the fact that a psycho-stimulant , such as Ritalin or Adderall increases our performance shouldn’t be surprising. The surprising thing is, though, that while the active constituent of Ritalin, methylphenidate may enhance our ability to focus on simple tasks it may not be able to enhance our ability to solve problems requiring selective attention. Most striking, however, was that tests showed that methylphenidate didn’t improve learning or IQ-dependent tests such as Raven’s progressive matrices, but merely enhanced arousal for a given task without affecting underlying neurobiological cortical networks underpinning intelligent problem-solving.

Provigil, another potential cognitive enhancer, indicated for treatment of narcolepsy and excessive daytime sleepiness have shown some efficacy in improving sustained attention in healthy individuals, but nothing really conclusive have come up. The literature on modafinil (the active constituent of Provigil) and cognitive enhancement is conflicting. Some studies shows increased performance, whereas others don’t. One reason for such discrepancies is that we all have different neurological milieu, and therefore also react differently to drugs. Moreover, the problem with drugs such as Provigil, Ritalin and Adderall is that we know almost nothing about their exact mechanism of action, and therefore we cannot say anything conclusive.

Limitless, Is This To Be Expected?

A novel by Alan Glynn The Dark Fields, which also examines the aspect of cognitive enhancement, has now been made to a movie Limitless by Neil Burger. It is about a young copywriter, who in his path to become a successful writer, stumbles upon a top-secret drug which gives him godlike mental abilities. His life changes dramatically from barely being able to write a word in his book to finishing it in three days. Not only his ability to learn has been transformed, but his whole identity. He can now do what he wants because he has the energy, power and mental ability to do so. All that from a tiny pill.

The movie is a perfect example of what sort of ethical dilemmas such a drug instills. Being able to accomplish such great feats in such minimal amount of time is what we all wish for; the panacea over all panaceas. I do not believe that there is such a magic pill or panacea pill out there, and I do not believe that there is going to be — for now. But in time, our ability to understand the underpinning of human intellect may evolve and become more advanced that such a drug may become the future. I can’t say how reality will pan out, but one thing is for sure: only our imagination is the limit.

That said, I think we are going to see some pretty awesome results with histamine H3 receptor antagonists along with ampakine glutamergic modulators, showing theoretically promising results for sleep disorders, memory consolidation, spatial-memory, social-recognition, working-memory capacity and attention.

References

  1. Gary Lynch, Linda C Palmer, and Christine M Gall, “The likelihood of cognitive enhancement,” Pharmacology, Biochemistry, and Behavior (January 6, 2011), http://www.ncbi.nlm.nih.gov/pubmed/21215768