29 January 2006

Smart Drugs: What are the Prospects?

We begin with an article from Sciam Mind, by Michael Gazzaniga.
Enhancing intelligence is not science fiction. Many "smart" drugs are in clinical trials and could be on the market in less than five years. Some medications currently available to patients with memory disorders may also increase intelligence in the healthy population. Likewise, few people would lament the use of such aids to ameliorate the forgetfulness that aging brings. Drugs that counter these deficits would be adopted gratefully by millions of people.

Drugs designed for psychotherapy can also be used to enhance certain regular mental functions. Just as Ritalin can improve the academic performance of hyperactive children, it can do the same for normal children. It is commonly thought to boost SAT scores by more than 100 points, for both the hyperactive and the normal user. Many healthy young people now use it that way for that purpose, and quite frankly, there is no stopping this abuse.

... consider the following. In July 2002 Jerome Yesavage and his colleagues at Stanford University discovered that donepezil, a drug approved by the FDA to slow the memory loss of Alzheimer's patients, improves the memory of the normal population. The researchers trained pilots in a flight simulator to perform specific maneuvers and to respond to emergencies that developed during their mock flight, after giving half the pilots donepezil and half a placebo. One month later they retested the pilots and found that those who had taken the donepezil remembered their training better, as shown by improved performance. The possibility exists that donepezil could become a Ritalin for college students. I believe nothing can stop this trend, either.

...Recently geneticists have discovered that even such abstract qualities as personality and intelligence are coded for in our genetic blueprint. Studies of the genetic basis of g are just beginning, and because g most likely arises from the influence of many genes, the hunt will be a long one. Yet one study has already found that a gene on chromosome 6 is linked to intelligence.

So-called genetic brain mapping could help the search. Scientists are looking at the structural features (size, volume, and so on) of the brains of many individuals, including twins, familial relatives and unrelated individuals. By scanning all these brains in magnetic resonance imaging machines and looking at the differences, researchers have been able to determine which areas of the brain are most under the control of genes. These studies have emerged only in the past three to four years. Geneticists hope that once they know which brain areas are most affected by heredity, they can figure out which genes are responsible for those regions. With this kind of reverse mapping, the experts should be able to learn more about the genetics of intelligence.

...Whatever happens, we can be sure that cognitive enhancement drugs will be developed and that they will be used and misused. But just as most people do not choose to alter their mood with Prozac and just as we all reorient our lives in the face of unending opportunities to change our sense of normal, our society will absorb new memory drugs according to each individual's underlying philosophy and sense of self. Self-regulation will occur. The few people who desire altered states will find the means, and those who do not want to alter their sense of who they are will ignore the drug potions. The government should stay out of it, letting our own ethical and moral sense guide us through the new enhancement landscape.
by Michael Gazzaniga

Next we go to Nootropics.com, a Hedweb site. This review of "Smart Drugs 2" by John Morgenthaler and Steven Fowkes, links to discussions of several potential smart drugs, as well as discussions about the underlying neuroscience and pharmacology involved. Here, we are introduced to modafinil, an increasingly prescribed drug that seems to do what it is supposed to do, with few serious side effects.

Modafinil, or Provigil, is a new stimulant with several different indications, and many more off label uses. Modafinil.org lists 45 uses of modafinil, cognitive enhancement being number 45. Modafinil.com is another Hedweb site, full of links to other pages describing the neuropharmacology of provigil, and the underlying neuroscience involved. Modafinil is becoming very popular with young professionals who never seem to have enough time to get everything done. Militaries use it for special ops troops, helicopter pilots, and pilots on long bombing missions. It works for ADD/ADHD, as an adjunct for depression, for cerebral palsy, and many more dysfunctions. Cephalon is coming out with a single isomer formulation of modafinil called "Nuvigil."

Both donazepil and modafinil are available from physicians, and over the internet. The ethics of internet prescribing are a bit shaky, but expect these drugs to become more available, rather than less, with time.

The last stop on today's smart drug train is the Ampakine station. Ampakines have the potential to not only help normal people think more clearly, as Donazepil and Modafinil seem to do, but to also make them "smarter." Ampakines directly affect the basic learning system of the brain.

New Scientist presented an article last May titled "11 Steps to a Better Brain." Gary Lynch, the inventor of ampakines, was cautious but optimistic:
The drug acts only in the brain, claims Lynch. It has a short half-life of hours. Ampakines have been shown to restore function to severely sleep-deprived monkeys that would otherwise perform poorly. Preliminary studies in humans are just as exciting. You could make an elderly person perform like a much younger person, he says.

While donazepil works on the acetylcholine system, and modafinil works on dopamine receptors, ampakines in contrast affect the glutamate receptors, specifically AMPA receptors. From neurotrasmitter.net, here are a few dozen scientific abstracts dealing with potential ampakines and mechanisms of ampakines--if the wikipedia article did not give you enough information.

That is a lot of information to digest, although if you take these drugs it may not be as difficult as you might think. Perhaps a joke, perhaps not? In time, people who choose not to boost their cognition may be less common than those who choose to do so.

The long term goal is to adjust the genes themselves, to do a better job of improving cognition than any one drug, or symphony of drugs, could possibly do. In the meantime, expect smart drugs to be delivered by pill, injection, skin patch, long term implant, and even injector pumps. The intelligence of a population is serious business, more serious than most people understand. For now.

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Blogger Chris Chatham said...

Very nice post.

I have a friend who worked for a defense sleep research lab, before modafinil was available via prescription. They were dosing humans, monkeys, rats, mutant fruit flies, basically everything they could get their hands on just trying to find any possible side-effects. Despite a couple years of research with massive quantities of the stuff, they couldn't find any serious downsides (occasional headaches/nausea aside). There is certainly a lot of interest in cognitive enhancers from the military.

And in fact, a lot of these "smart drugs" have been developed from attempts to treat Alzheimers. In the mid 90's, piracetam could have had an IHOP-esque slogan: it's not just for dementia anymore!

Steven Rose writes about smart drugs in his book "The Future of the Brain" as does Martha Farah in a 2004 issue of Nature Reviews Neuroscience, in the context of neuroethics. But I don't think there's yet reason for either alarmism (or unbridled enthusiasm). I went on an agressive piracetam regimen for about a month in 1999, and got quite depressed very quickly (even with choline supplements) with no noticeable positive effects. Until there are large sample studies demonstrating the efficacy of these drugs, it's difficult to see through the hype.

Monday, 30 January, 2006  
Blogger al fin said...

Thanks, Chris. I agree that the hype about some of these drugs can be depressing in itself.

I believe that you are right about the lack of serious side effects with modafinil. It will be interesting to see, over time, how effective modafinil is in treating Alzheimer's and other conditions of cognitive decline. The single isomer formulation may also hold some surprises.

Modafinil actually works on more than just the dopamine system, as you probably know. Glutamate receptors and norepinephrine receptors are also apparently affected by the drug.

There is a lot to learn, and I for one need all the help I can get.

Monday, 30 January, 2006  

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