Science’s obsession: The search for a “smart pill” - Salon.com
As for drugs already on the market, he said he shared the perspec.tive of most at the meeting: neither Adderall nor Provigil does much more than keep people awake and working. They might help a stu.dent finish writing a paper, but they wont help him or her write it better. But then he mentioned another cognitive enhancer that he does consider useful, despite its nasty reputation: nicotine.
Nicotine has a legitimate enhancing effect, he said. I self-medicate with it when Im having a difficult time writing something. Ill sit there chewing a cigar when I hit a tough spot. People say to me, Do you ever take any of these drugs youre studying? Nicotine, I find, helps me out.
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Back home in New Jersey, I read through dozens of human and animal studies published over the past five years showing that nicotine freed of its noxious host, tobacco, and delivered instead by chewing gum or transdermal patch may prove to be a weirdly, improbably effective cognitive enhancer and treatment for relieving or preventing a variety of neurological disorders, including Parkinsons, mild cognitive impairment, ADHD, Tourettes, and schizophrenia. Plus it has long been associated with weight loss. With few known safety risks.
Nicotine? Yes, nicotine.
In fact and this is where the irony gets mad deep the one purpose for which nicotine patches have proven futile is the very same one for which they are approved by the Food and Drug Administration, sold by pharmacies over the counter, bought by consumers, and covered by many state Medicaid programs: quitting smoking. In January 2012, a six-year follow-up study of 787 adults who had recently quit smoking found that those who used nicotine replacement therapy in the form of a patch, gum, inhaler, or nasal spray had the same long-term relapse rate as those who did not use the products. Heavy smokers who tried to quit without the benefit of counseling were actually twice as likely to relapse if they used a nicotine replacement product.
I understand that smoking is bad, said Maryka Quik, director of the Neurodegenerative Diseases Program at SRI International, a nonprofit research institute based in Californias Silicon Valley. My father died of lung cancer. I totally get it.
Yet for years Quik has endured the skepticism and downright hostility of many of her fellow neuroscientists as she has published some three dozen studies revealing the actions of nicotine within the mammalian brain.
The whole problem with nicotine is that it happens to be found in cigarettes, she told me. People cant disassociate the two in their mind, nicotine and smoking. Its not the general public that annoys me, its the scientists. When I tell them about the studies, they should say, Wow. But they say, Oh well, that might be true, but I dont see the point. Its not even ignorance. Its their preconceived ideas and inflexibility.
I met Quik at the annual meeting of the Society for Neuroscience held in Washington, D.C. Amid thousands of studies presented in a cavernous exhibition hall, the title of hers jumped out: Nicotine Reduces L-dopa-Induced Dyskinesias by Acting at β2 Nicotinic Re.ceptors.
A huge literature says that smoking protects against Parkinsons,she said. It started as a chance observation, which is frequently the most interesting kind.
The first hint of nicotines possible benefits, I learned, came from a study published in 1966 by Harold Kahn, an epidemiologist at the National Institutes of Health. Using health-insurance data on 293,658 veterans who had served in the U.S. military between 1917 and 1940, he found the kinds of associations between smoking and mortality that even by the mid-1960s had become well known. At any given age, cigarette smokers were eleven times more likely to have died of lung cancer as were nonsmokers and twelve times more likely to have died of emphysema. Cancers of the mouth, pharynx, esoph.agus, larynx blah, blah, blah. But amid the lineup of usual sus.pects, one oddball jumped out: Parkinsons disease. Strangely enough, death due to the neurodegenerative disorder, marked by loss of dopamine-producing neurons in the midbrain, occurred at least three times more often in nonsmokers than in smokers.
What was it about tobacco that ravages the heart, lungs, teeth, and skin but somehow guards against a disease of the brain? Over the course of the 1970s, neuroscientists like Quik learned that the nico.tine molecule fits into receptors for the neurotransmitter acetylcho.line like a key into a lock. By managing to slip through doors marked Acetylcholine Only, nicotine revealed a special family of acetylcho.line receptors hitherto unknown.
And what a family. Nicotinic receptors turn out to have the ex.traordinary capacity to moderate other families of receptors, quieting or amplifying their functioning. According to psychopharmacologist Paul Newhouse, director of the Center for Cognitive Medicine at Vanderbilt University School of Medicine in Nashville, Nicotinic receptors in the brain appear to work by regulating other receptor systems. If youre sleepy, nicotine tends to make you more alert. If youre anxious, it tends to calm you.
The primary neurotransmitter that nicotine nudges is dopamine, which plays an important role in modulating attention, reward-seeking behaviors, drug addictions, and movement. And therein lies the answer to the mystery of why nicotine could prevent a movement disorder like Parkinsons disease, due to its effects on dopamine.
To put the drug to the test, Quik treated rhesus monkeys with Parkinsons with nicotine. After eight weeks, she reported in a land.mark 2007 paper in the Annals of Neurology, the monkeys had half as many tremors and tics. Even more remarkably, in monkeys already receiving L-dopa, the standard drug for Parkinsons, nicotine reduced their dyskinesias by an additional one-third. Studies of nicotine in humans with Parkinsons are now under way, supported by the Mi.chael J. Fox Foundation.
Other research suggests the drug may protect against the early stages of Alzheimers disease. A study involving sixty-seven people with mild cognitive impairment, in which memory is slightly impaired but decision-making and other cognitive abilities remain within normal levels, found significant nicotine-associated improvements in attention, memory, and psychomotor speed, with excellent safety and tolerability.
What we saw was consistent with prior studies showing that nicotinic stimulation in the short run can improve memory, attention, and speed, said Newhouse, who led the study.
As Newhouse sees it, Obviously the results of small studies often arent replicated in larger studies, but at least nicotine certainly looks safe. And weve seen absolutely no withdrawal symptoms. There doesnt seem to be any abuse liability whatsoever in taking nicotine by patch in nonsmokers. Thats reassuring.
Thats not reassuring: its totally bizarre. Nicotine has routinely been described in news accounts as among the most addictive sub.stances known. As the New York Times Magazine famously put it in 1987, nicotine is as addictive as ......, ....... or amphetamines, and for most people more addictive than alcohol.
But thats just wrong. Tobacco may well be as addictive as ......, crack, alcohol, and Cherry Garcia combined into one giant crazy sundae. But as laboratory scientists know, getting mice or other ani.mals hooked on nicotine all by its lonesome is dauntingly difficult. As a 2007 paper in the journal Neuropharmacology put it, Tobacco use has one of the highest rates of addiction of any abused drug. Paradoxically, in animal models, nicotine appears to be a weak rein.forcer.
That same study, like many others, found that other ingredients in tobacco smoke are necessary to amp up nicotines addictiveness. Those other chemical ingredients things like acetaldehyde, anab.asine, nornicotine, anatabine, cotinine, and myosmine help to keep people hooked on tobacco. On its own, nicotine isnt enough.
But what about nicotine as a cognitive enhancer for people with.out Alzheimers, Parkinsons or any other brain disease?
To my knowledge, nicotine is the most reliable cognitive en.hancer that we currently have, bizarrely, said Jennifer Rusted, pro.fessor of experimental psychology at Sussex University in Britain when we spoke. The cognitive-enhancing effects of nicotine in a normal population are more robust than you get with any other agent. With Provigil, for instance, the evidence for cognitive benefits is nowhere near as strong as it is for nicotine.
In the past six years, researchers from Spain, Germany, Switzer.land, and Denmark not to mention Paul Newhouse in Vermont have published over a dozen studies showing that in animals and humans alike, nicotine administration temporarily improves visual attention and working memory. In Britain, Rusted has published a series of studies showing that nicotine increases something called prospective memory, the ability to remember and implement a prior intention. When your mother asks you to pick up a jar of pickles while youre at the grocery store, shes saddling you with a prospective memory challenge.
Weve demonstrated that you can get an effect from nicotine on prospective memory, Rusted said. Its a small effect, maybe a 15 percent improvement. Its not something thats going to have a mas.sive impact in a healthy young individual. But we think its doing it by allowing you to redeploy your attention more rapidly, switching from an ongoing task to the target. Its a matter of cognitive control, shutting out irrelevant stimuli and improving your attention on whats relevant.
Of course, all the physicians and neuroscientists I interviewed were unanimous in discouraging people from using a nicotine patch for anything other than its FDA-approved purpose, as an aid to quit smoking, until large studies involving hundreds of people establish the true range of benefits and risks (even though studies find it doesnt work for that purpose). But with so many studies showing that its safe, and so many suggesting it might well be the most effective cog.nitive enhancer now on the market, I decided to ignore not only their advice but the advice of my personal physician.
I added a nicotine patch to my list.
