Nicotine's impact on the brain
This book excerpt ran in Scientific American last year, and there's a lot here that's surprising.
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http://www.scientificamerican.com/ar...arter-excerpt/
On a quest to make his brain work better, a writer delves into the evidence for why the world’s most notorious alkaloid may be the best bet for a true cognitive enhancer
February 9, 2014
From Smarter: The New Science of Building Brain Power, by Dan Hurley. Reprinted by arrangement with Hudson Street Press, a member of Penguin Group (USA), LLC. Copyright © 2013, by Dan Hurley.
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 Parkinson’s, mild cognitive impairment, ADHD, Tourette’s, 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 California’s 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 can’t disassociate the two in their mind, nicotine and smoking. It’s not the general public that annoys me, it’s the scientists. When I tell them about the studies, they should say, ‘Wow.’ But they say, ‘Oh well, that might be true, but I don’t see the point.’ It’s not even ignorance. It’s 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 2 Nicotinic Receptors.”
“A huge literature says that smoking protects against Parkinson’s,”she said. “It started as a chance observation, which is frequently the most interesting kind.”
The first hint of nicotine’s 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, esophagus, larynx—blah, blah, blah. But amid the lineup of usual sus*pects, one oddball jumped out: Parkinson’s 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 nicotine molecule fits into receptors for the neurotransmitter acetylcholine like a key into a lock. By managing to slip through doors marked “Acetylcholine Only,” nicotine revealed a special family of acetylcholine receptors hitherto unknown.
And what a family. Nicotinic receptors turn out to have the extraordinary 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 you’re sleepy, nicotine tends to make you more alert. If you’re 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 Parkinson’s disease, due to its effects on dopamine.
To put the drug to the test, Quik treated rhesus monkeys with Parkinson’s with nicotine. After eight weeks, she reported in a landmark 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 Parkinson’s, nicotine reduced their dyskinesias by an additional one-third. Studies of nicotine in humans with Parkinson’s are now under way, supported by the Michael J. Fox Foundation.
Other research suggests the drug may protect against the early stages of Alzheimer’s 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 aren’t replicated in larger studies, but at least nicotine certainly looks safe. And we’ve seen absolutely no withdrawal symptoms. There doesn’t seem to be any abuse liability whatsoever in taking nicotine by patch in nonsmokers. That’s reassuring.”
--------------
http://www.scientificamerican.com/ar...arter-excerpt/
On a quest to make his brain work better, a writer delves into the evidence for why the world’s most notorious alkaloid may be the best bet for a true cognitive enhancer
February 9, 2014
From Smarter: The New Science of Building Brain Power, by Dan Hurley. Reprinted by arrangement with Hudson Street Press, a member of Penguin Group (USA), LLC. Copyright © 2013, by Dan Hurley.
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 Parkinson’s, mild cognitive impairment, ADHD, Tourette’s, 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 California’s 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 can’t disassociate the two in their mind, nicotine and smoking. It’s not the general public that annoys me, it’s the scientists. When I tell them about the studies, they should say, ‘Wow.’ But they say, ‘Oh well, that might be true, but I don’t see the point.’ It’s not even ignorance. It’s 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 2 Nicotinic Receptors.”
“A huge literature says that smoking protects against Parkinson’s,”she said. “It started as a chance observation, which is frequently the most interesting kind.”
The first hint of nicotine’s 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, esophagus, larynx—blah, blah, blah. But amid the lineup of usual sus*pects, one oddball jumped out: Parkinson’s 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 nicotine molecule fits into receptors for the neurotransmitter acetylcholine like a key into a lock. By managing to slip through doors marked “Acetylcholine Only,” nicotine revealed a special family of acetylcholine receptors hitherto unknown.
And what a family. Nicotinic receptors turn out to have the extraordinary 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 you’re sleepy, nicotine tends to make you more alert. If you’re 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 Parkinson’s disease, due to its effects on dopamine.
To put the drug to the test, Quik treated rhesus monkeys with Parkinson’s with nicotine. After eight weeks, she reported in a landmark 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 Parkinson’s, nicotine reduced their dyskinesias by an additional one-third. Studies of nicotine in humans with Parkinson’s are now under way, supported by the Michael J. Fox Foundation.
Other research suggests the drug may protect against the early stages of Alzheimer’s 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 aren’t replicated in larger studies, but at least nicotine certainly looks safe. And we’ve seen absolutely no withdrawal symptoms. There doesn’t seem to be any abuse liability whatsoever in taking nicotine by patch in nonsmokers. That’s reassuring.”
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