Nicotine seems doomed to suffer from its association with smoking. Because it is the most famous constituent of tobacco, it has been accused of causing all the harms of smoking, when in reality just about everything in burning tobacco causes disease and death except nicotine. Not only is nicotine blamed for health problems it doesn’t cause—like cancer and emphysema—but the actual health benefits of nicotine are often ignored or even suppressed.
Wait…benefits? Nicotine has benefits?
Would you be surprised to learn that the drug a majority of Americans believe causes cancer not only doesn’t cause cancer, but may be a breakthrough treatment for neurodegenerative diseases like Parkinson’s? Or that nicotine might help unlock the mysteries of schizophrenia, or be used to create new weight loss therapies? Or that a major federally funded clinical trial is testing nicotine as a treatment for Alzheimer’s disease?
Despite the popularity of nootropics—so-called smart drugs or study drugs—many people don’t realize that nicotine has been proven to enhance memory and improve other cognitive functions. Although it’s widely misunderstood by the public and pilloried in the press, researchers recognize the positive effects of nicotine, and are actively seeking new ways nicotine can help people live better lives.
Nicotine binds with nicotinic acetylcholine receptors (nAChRs) in the brain and other areas of the body, and stimulates various effects. This system of receptors—the cholinergic system, intended to bind with the neurotransmitter acetylcholine—controls muscle contraction, works in the immune system to regulate inflammation, and stimulates the production of other neurotransmitters like norepinephrine, serotonin, glutamate, endorphins, and most famously dopamine.
The rush of dopamine in the brain is what makes nicotine addictive when it’s delivered rapidly, like it is when you smoke a cigarette. It provides a reward of pleasure to the smoker, and some people can’t help but come back again and again for that feeling.
But dopamine does something else too: it can prevent or reduce uncontrolled movement like the palsies experienced by people with Parkinson’s disease. As the disease progresses, neurons that produce dopamine in one part of the brain (the striatum) die. The traditional treatment, a drug called L-dopa (levodopa), itself eventually causes another movement disorder: dyskinesia, the sudden movements of the hands, head and torso commonly seen in Parkinson’s patients.
Researchers have known since the 1960’s that cigarette smokers have a much lower incidence of Parkinson’s than non-smokers. And research on Swedish snus users has confirmed that the protective effect of nicotine doesn’t depend on smoking.
In addition to protecting long-term users, could nicotine also provide the key to effectively treating this brutal disease after the symptoms begin? Animal studies have been promising, and nicotine seems effective in monkeys to reduce dyskinesia in patients already using L-dopa. But trials using nicotine patches to treat Parkinson’s patients haven’t produced conclusive results. The research continues, with the hope that science can identify a way that nicotine can help those with this terrifying condition.
Nicotine seems to be neuroprotective, helping to prevent degenerative brain maladies. And it appears that the same properties that make nicotine a powerful potential weapon against neurological illnesses like Parkinson’s disease can also improve some brain functions for anyone who chooses to use it. Nicotine temporarily improves working memory and visual attention, for example.
“To my knowledge, nicotine is the most reliable cognitive enhancer that we currently have, bizarrely,” Sussex (U.K.) University psychology professor Jennifer Rusted told author Dan Hurley. “The cognitive-enhancing effects of nicotine in a normal population are more robust than you get with any other agent.”
“We’ve demonstrated that you can get an effect from nicotine on prospective memory,” Rusted told Hurley. Prospective memory is the brain function that allows you to remember and complete tasks you’ve set for the future—like reminding yourself to call your sister at a certain time.
“It’s a small effect, maybe a 15 percent improvement. 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, switching from an ongoing task to the target. It’s a matter of cognitive control, shutting out irrelevant stimuli and improving your attention on what’s relevant.”
It’s long been accepted that nicotine acts as a weight suppressant. When smokers quit, they usually gain weight. But a recent study shows how nicotine affects metabolism by triggering the body to burn certain kinds of fat cells through a process called thermogenesis.
Thermogenic (“beige”) fat cells are activated to burn by stimulating a certain nicotinic acetylcholine receptor called CHRNA2—the same receptor that regulates nicotine dependence in brain cells—either naturally by the body with acetylcholine, or with nicotine, which mimics the effect of acetylcholine on the CHRNA2 receptor.
“This pathway is important from a basic research standpoint, but it also has relevance for metabolic and human health research,” said senior author Jun Wu, an assistant professor of molecular and integrative physiology at the University of Michigan Medical School. “The more we can narrow down a precise pathway for activating beige fat, the more likely we are to find an effective therapy for metabolic health that does not carry harmful side effects.”
A 2017 paper by scientists from New Zealand and the U.K. even suggested the idea that “vaping electronic cigarettes with nicotine and flavors could deliver similar appetite and weight control effects as smoking.” The idea deserves exploration, say the researchers.
Research has repeatedly shown that nicotine enhances short-term memory. In fact, it’s among the most widely recognized benefits of nicotine. In a typical nicotine/memory study, University of Surrey (U.K.) researchers gave 10 smokers and 10 non-smokers either nicotine gum or a placebo, and then had them complete short-term memory tasks at set points for four hours.
“The results suggest that nicotine enhanced memory reaction time performance…when subjects were probed for information already present in short-term memory (correct positive responses) but had no effect on reaction time when the information was absent from memory (correct negative responses),” wrote the authors. “It is suggested that nicotine facilitates the processing of stimulus information in short-term memory.”
Nicotine may be as effective as Ritalin for improving attention in people with Attention-Deficit/Hyperactivity Disorder (ADHD), according to Paul Newhouse, director of the Center for Cognitive Medicine at Vanderbilt University School of Medicine.
Newhouse has done a variety of studies using nicotine to treat cognitive and neurological disorders, both at Vanderbilt and previously at the University of Vermont. In a 2004 study with co-author Alexandra Potter, Newhouse administered nicotine with transdermal patches to eight adolescents with ADHD, and compared the results against Ritalin and a placebo.
Newhouse and Potter concluded that “nicotine administration has measurable positive effects on cognitive/behavioral inhibition in adolescents with ADHD. The size of the effect is at least comparable to methylphenidate [Ritalin].” A follow-up study with 15 subjects published three years later confirmed the results.
Multiple studies have shown that nicotine decreases (improves) reaction time when performing experimental tasks. Researchers at the University of London’s Institute of Psychiatry tested 113 smokers, and found that smoking a cigarette “under naturalistic conditions improves the performance of the smoker on an IQ related task.”
In a similar experiment, scientists at the University of Auckland (New Zealand) tested 29 subjects “under non-smoking, sham smoking, and low, medium and high nicotine cigarette conditions,” and found that nicotine reduced (improved) the time to make a decision, and that sham smoking (going through the motions of smoking with an unlit cigarette) increased (worsened) decision time. The effect was seen whether the test subject was a normally heavy or light smoker.
It’s easy to see why athletes might be eager to try nicotine as a performance-enhancing drug. Particularly in complex team sports, better short-term memory and reaction time are valuable commodities. And nicotine is still legal in the eyes of the sporting world’s governing bodies (although some American stadiums are “tobacco-free,” by rule or law).
A 2017 meta-analysis of 10 studies about nicotine and athletic performance found that athletes believe nicotine helps them perform better. Not only is smokeless tobacco use widespread among American football and (especially) baseball players, but snus is very common among elite athletes from Sweden, Finland and Norway. Of more than 400 Finnish athletes funded by their National Olympic Committee in 2002, 25 percent used snus.
The athletes report that use of smokeless tobacco prevents dry mouth, controls weight, helps relaxation, and improves reaction time and concentration.
Almost 90 percent of people suffering from schizophrenia smoke cigarettes. That’s a smoking rate about six times higher than the general population. Scientists have long assumed that this is an example of self-medication.
A study by Uwe Maskos of the Pasteur Institute in Paris and a large international team showed the discovery of a genetic mutation associated with the cognitive problems found in many schizophrenic patients — which may also explain why so many people with schizophrenia smoke. The study describes how nicotine helps normalize brain activity in people with the mutation. The authors hope their research will lead to effective nicotine-based treatments for patients with the mutation.
People with Alzheimer’s disease show signs of the disorder years before the appearance of the severe confusion, paranoia and disorientation that signal the the disease’s later stages. Eventually the patient is trapped in dementia, and may become unable to walk, speak or even swallow.
Researchers are trying to learn if nicotine can effectively treat people with Mild Cognitive Impairment (MCI), possibly delaying or preventing the progression to full-blown Alzheimer’s. Preliminary studies have been encouraging. People with early Alzheimer’s symptoms have damaged cholinergic receptors.The hope is that nicotine can supplement the natural neurotransmitter acetylcholine to stimulate the compromised receptors.
In a clinical trial, Paul Newhouse and colleagues studied 67 people in the early stages of Alzheimer’s and found that the patients (all non-smokers) who were given nicotine patches “showed significant nicotine-associated improvements in attention, memory, and psychomotor speed, and improvements were seen in patient/informant ratings of cognitive impairment.”
Now Newhouse, director of the Center for Cognitive Medicine at the Vanderbilt University School of Medicine, is leading the MIND Study, a large trial that will follow 300 MCI sufferers treated with nicotine at 29 institutions over a two-year period. MIND stands for Memory Improvement through Nicotine Dosing.
“I am convinced that we will find a way to help improve early memory loss and make a real difference in people’s lives, said Newhouse. “In this study, we have an inexpensive, widely available potential treatment.”