Remember, Parkinson’s involves a loss of dopamine, a neurotransmitter that regulates not only movement but also addictive behaviors. It has long been observed that people who develop Parkinson’s tend to be more low-key and risk-averse than average, as if their innate dopamine levels have always been on the low side. When they take L-dopa, however, some have been known to swing to the other side of the reward-seeking spectrum, developing gambling or sexual addictions. Boyd hopes nicotine might push such patients back to a middle ground.
He is also the principal U.S. investigator for a randomized trial that began late last year in Germany and is now being conducted here to test the value of nicotine as a therapeutic drug. The study seeks to answer whether ordinary over-the-counter nicotine gum or patches can halt the progression of Parkinson’s. To get at the answer, one component the study will look at is whether the chemical can relieve the writhing, twisting movements that eventually beset almost every Parkinson’s patient taking L-dopa.
While researchers await the results of the Parkinson’s studies, they look beyond to nicotine treatments for other disorders as well.
“Nicotine has separate mechanisms by which it may protect brain cells, aside from its influence on dopamine,” Boyd says. “One of the functions of nicotinic receptors is to moderate the entry of calcium into cells. The presence of nicotine increases the amount of intracellular calcium, which appears to improve cellular survival.”
And nicotine may have an antioxidant effect, serving to mop up the toxic free radicals produced as a byproduct of metabolism, thus protecting the brain. The neuroprotective effects of nicotine were studied in a randomized clinical trial involving 67 subjects in the early stages of Alzheimer’s disease, where memory was slightly impaired but decision-making and other cognitive abilities remained intact. They received either a 15-milligram nicotine patch or placebo for six months. The results found “significant nicotine-associated improvements in attention, memory and psychomotor speed,” with excellent safety and tolerability.
Other studies suggest that nicotine may be as effective at enhancing attention as methylphenidate (Ritalin) and the wakefulness-promoting drug modafinil (Provigil). In 2008, Paul Newhouse, director of the Center for Cognitive Medicine at Vanderbilt University School of Medicine in Nashville, compared performance on a series of cognitive tasks in 15 nonsmoking ADHD patients while wearing either a 7-mg nicotine patch or a placebo patch. After just 45 minutes with the nicotine patch, the young adults were significantly better at inhibiting an impulse, delaying a reward and remembering an image they had seen.
Even people without any diagnosed disorder might benefit from nicotine. Psychologist Jennifer Rusted of the University of Sussex in Britain calls the drug “the most reliable cognitive enhancer that we currently have.” In addition to improving visual attention and working memory, nicotine has been shown by Rusted to increase prospective memory: the ability to remember and implement a prior intention. (When your mother asks you to pick up a jar of pickles at the grocery store on the way home, she’s saddling you with a prospective memory challenge.)
“It’s a small effect, maybe a 15 percent improvement,” Rusted says. “It’s not something that’s going to have a massive impact in a healthy young individual. But we think it’s doing it by allowing you to redeploy your attention more rapidly.” In short, the drug seems to work by helping users shut out irrelevant stimuli so that important information can come to the fore.
The ability to shut out stimuli could also turn nicotine into a treatment for schizophrenia, where afflicted individuals are overwhelmed by sights, sounds and thoughts that most of us would either ignore or quickly dismiss. Studies in the United States, Canada and Germany have shown that nicotine improves the ability of people with schizophrenia to focus their attention and recall recent events. In addition, the potent antipsychotic haloperidol often causes dyskinesia, which Quik’s 2007 study proved nicotine can relieve.
Not the Great Satan
Perhaps most surprising is that, in studies by Boyd and others, nicotine has not caused addiction or withdrawal when used to treat disease. These findings fly in the face of nicotine’s reputation as one of the most addictive substances known, but it’s a reputation built on myth. Tobacco may well be as addictive as heroin, as some have claimed. But as scientists know, getting mice or other animals hooked on nicotine alone 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 it’s almost impossible to get laboratory animals hooked on pure nicotine, though it has a mildly pleasant effect.
The same study found that tobacco smoke itself is necessary to amp up nicotine’s addictiveness. In 2005, for instance, researchers at the University of California, Irvine, found that animals self-administer a combination of nicotine and acetaldehyde, an organic chemical found in tobacco, significantly more often than either chemical alone. In 2009, a French team found that combining nicotine with a cocktail of five other chemicals found in tobacco — anabasine, nornicotine, anatabine, cotinine and myosmine — significantly increased rats’ hyperactivity and self-administration of the mix compared with nicotine alone.
In short, the estimated 45.3 million people, or 19.3 percent of all adults, in the United States who still smoke are not nicotine fiends. They’re nicotine-anabasine-nornicotine-anatabine-cotinine-myosmine-acetaldehyde-and-who-knows-what-else fiends. It is tobacco, with its thousands of chemical constituents, that rightly merits our fear and loathing as the Great Satan of addictiveness. Nicotine, alone: not so much.
Despite the potential benefits and apparent safety, researchers like Boyd want more evidence before they’ll recommend a nicotine patch for anything other than its FDA-approved (but seemingly useless) purpose, smoking cessation. “Nicotine has potential drug interactions. It can interfere with blood pressure medications. To recommend something for which there is no good long-term safety data — it’s just wrong,” Boyd says.
To Quik, the upside is clear. “People have tested all their favorites to help treat Parkinson’s and other neurological disease,” she says. “Now nicotine’s time has come.”