Nicotine and Parkinson's: the smoking link explained

The smoking pattern

In 2002, Hernan and colleagues pooled 48 studies of smoking and Parkinson's, 44 case-control studies and 4 cohort studies, in the Annals of Neurology. Compared with people who had never smoked, current smokers had a relative risk of 0.39, about 60% lower, and past smokers a relative risk of 0.80. The more pack-years a person had smoked, the lower the risk ran.

A pattern that strong, repeated across dozens of studies, is rare in this field. It is also what makes Parkinson's different from almost every other condition linked to tobacco, where smoking raises the risk rather than lowering it.

Following people forward: the 2019 European cohort

Looking back at people who already have a disease can mislead, so Gallo and colleagues followed people forward in time instead. Their 2019 study in the International Journal of Epidemiology used the NeuroEPIC4PD cohort, 220,494 people across Europe, among whom 715 developed Parkinson's. Compared with never smokers, former smokers had a hazard ratio of 0.79 and current smokers 0.49, about half the rate.

The authors also tested a common objection, that people in the earliest, undiagnosed stages of Parkinson's simply lose interest in smoking, and their analysis argued against it. They say it is still unclear which compound in tobacco is responsible, and they name nicotine among the candidates.

Why nicotine is the leading candidate

Parkinson's destroys the dopamine-producing cells of a small region deep in the brain called the substantia nigra. These cells carry nicotinic receptors, which is one reason researchers have looked so closely at nicotine rather than at the thousands of other compounds in tobacco smoke.

Animal work has backed that interest. In a 2023 study in Frontiers in Pharmacology, mice were given MPTP, a toxin that damages the same dopamine cells, and some were first given nicotine. Pretreatment with nicotine reduced the loss of those neurons and increased the activity of tyrosine hydroxylase, the enzyme that makes dopamine. It also reduced phosphorylated alpha-synuclein, the protein that builds up in Parkinson's, in the substantia nigra and striatum.

What Dr Ardis has said

Dr Bryan Ardis has made nicotine a recurring subject, and he has discussed nicotine and the brain, Parkinson's among the conditions, in several talks. Some of these clips have been posted by other channels under their own titles. His broader argument, set out in talks such as "They Lied to You About Nicotine. Here's the NIH Proof", is that nicotine has been blamed for harms that belong to the rest of the cigarette, and the Parkinson's pattern is one of the findings that argument draws on.

Dr Ardis has no connection to our store and does not endorse our patches.

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One of his clips on nicotine and nerve conditions, posted by another channel.

The trials so far

In 2007, Villafane and colleagues gave six patients with advanced Parkinson's transdermal nicotine in an open trial, raising the dose over 17 weeks to as much as 105 mg a day. Five of the six reached the target dose, motor scores improved during the plateau phase, and the authors called for a randomised trial to follow.

A randomised phase 2 trial followed in 2018, with 40 patients, half given high-dose nicotine. Raters who did not know each patient's group scored motor function from video, and at week 39 the scores were 19.4 in the nicotine group and 21.5 in the control group, a difference that was not statistically significant. The secondary measures, which were scored without blinding, improved in the nicotine group, and the authors asked for larger placebo-controlled trials to confirm them.

The largest trial so far is NIC-PD, published in NEJM Evidence in 2023, which gave one year of transdermal nicotine or a placebo to people diagnosed within the previous 18 months. Its authors concluded that one year of nicotine did not slow the progression of early Parkinson's. Every trial to date has tested nicotine in people who already have the disease, while the smoking data concerns who develops it in the first place, and no trial of nicotine for prevention has reported.

Nicotine patch safety basics

Nicotine patches can harm an unborn baby, so they are not for use in pregnancy. Keep used and unused patches out of reach of children and pets, because the nicotine left in a used patch can still poison a child or an animal. Do not smoke or use other nicotine products while wearing a patch, as MedlinePlus, the US National Library of Medicine's drug information service, advises.