Smoking and Parkinson’s disease

Epidemiologic studies of Parkinson’s disease (PD) that explore the distribution of the disease in various populations, have consistently found, over a number of decades, that cigarette smokers have lower rates of PD than non-smokers. People are taken aback when they first hear this as it is counter-intuitive. Could it be that a habit so clearly linked to poor health can also provide a health benefit?

There are two potential ways to view this association. The first is that smoking has a biological effect that protects a person from PD. The second is that part of the biology of PD makes it less likely that a person would smoke.

(We’re specifically talking about cigarette smoke here. For information on marijuana and Parkinson’s disease, see my previous blog post.) 

Does smoking protect from Parkinson’s disease?

In addition to the numerous studies that demonstrate that PD rates are lower in cigarette smokers than the general population, there are studies that show that the inverse relationship between smoking and PD is dose-dependent. That is, the more a person smokes, the less of a chance that he or she will develop PD. Another study investigated identical twin pairs in which one had PD and the other did not.  The twin without PD tended to smoke more than the twin with PD. Since identical twins share the same DNA and often the same environment, many of the variables normally associated with a difference in risk of PD were removed – except for smoking. The study is therefore cited as evidence that smoking is protective against PD.

Even if this theory is correct, and smoking does protect people from Parkinson’s disease, all physicians and researchers agree, that this does not mean that increasing the rates of smoking among the general population is a desirable strategy to prevent PD. That is because epidemiologic studies have also consistently found that cigarette smoking is a risk factor for a variety of deadly diseases including lung cancer, emphysema, heart disease and stroke. Researchers have therefore tried to harness the possibly protective nature of cigarette smoke in other ways.

Tobacco smoke contains thousands of chemicals, but nicotine is one of the major components. Nicotine stimulates the nicotinic acetylcholine receptor (nAchR), mimicking the brain chemical acetylcholine. It is well known that acetylcholine has effects on the brain circuitry that is involved in PD.  Studies in cell culture and in animals have suggested that nicotine and its receptors are involved in dopamine signaling and that nicotine can protect against cell damage in dopamine neurons in these experimental models. An active area of research, which APDA has played a role in sponsoring, is the exploration of the cellular mechanisms by which nicotine may be protective of dopaminergic neurons.

These findings led to the initiation of clinical trials of nicotine in people with PD to see whether nicotine acts as a neuroprotective medication in PD.  A number of these trials were conducted in a double blinded, placebo-controlled manner, utilizing the nicotine patch in people with PD. None of these trials, however, including the most recent one published in 2017, showed convincing enough results to justify its use as a neuroprotective agent. There are additional studies whose results are not yet known that may weigh in on this question in the future.

Does Parkinson’s disease protect from smoking?

What if cigarette smoking does not actually confer a positive biological effect on the brain to protect from PD, but rather some aspect of PD biology leads to less of a tendency to smoke? Dopamine is the main addiction chemical in the brain, so it stands to reason that in a PD brain, with a reduced amount of dopamine, there will be less of a tendency for addiction. Other hypotheses suggest that people with PD may have alterations in how their brains utilize nicotine, or how the nicotine interacts with the dopaminergic neurons, leading to less of a tendency to become addicted to it.

This possibility was explored in a paper that demonstrated that people with PD who did smoke found it easier to quit smoking as compared to controls, and people with PD utilized reduced amounts of nicotine substitutes in order to quit as compared to controls. This suggested that people with PD have a less intense addiction than controls, leading to the overall decreased smoking rates.

Second-hand smoke

One way to distinguish between the two proposed theories is to investigate people who have been exposed to passive smoke. If cigarette smoke itself is protective, then it should protect those exposed to second-hand smoke. If however, the tendency of people with PD to avoid addiction is the driver of the inverse relationship between PD and smoking, then second-hand smoke should not have any effect on lowering the risk of PD. More than one study has looked at this very question, and results unfortunately, are conflicting, so this angle of research is still up for debate.

All in all, the jury is still out as to whether nicotine, or another component of cigarette smoke, is protective against PD or not. Regardless, cigarette smoking has clear negative effects on health and must be avoided. Rather, researchers are working to determine if there is a neuroprotective agent in cigarette smoke, and if so, how to harness the protective effect without causing harm.

Tips and takeaways

• Rates of PD are lower among cigarette smokers than the general population.
• This may be because a chemical in cigarette smoke is protective against PD or it may be because having PD leads to less of a tendency to smoke.
• Regardless, cigarette smoking is linked to numerous deadly diseases and must be avoided.
• Researchers are trying to understand if a neuroprotective component of cigarette smoking can be harnessed to act as a neuroprotective agent in PD.