Nicotine and Parkinson's Disease: The Research

Table of Contents

1. The Papers
2. PubMed Topic Searches
3. Connections
4. Featured Videos

The Papers (21)

Newest first. Study types on this page — Human trial: 3 · Review: 5 · Animal study: 12 · Cell study: 1. Each summary is written from the paper’s own abstract; follow the PubMed link for the full record.

The interpeduncular nucleus blunts the rewarding effect of nicotine

Animal study, 2025. This study used genetically modified mice to look at how nicotine acts on a small brain region called the interpeduncular nucleus. Even low doses of nicotine switched on one group of nerve cells there and quieted another, and a specific type of nicotinic receptor (one containing the beta-4 subunit) drove only the switching-on. When the researchers blocked that activation, the brain's reward area responded more strongly and the mice showed a stronger preference for the place where they had received nicotine; silencing this region's connection to a nearby area called the laterodorsal tegmental nucleus had the same effect. The authors conclude that this brain region works as a brake on nicotine's rewarding effect, a finding shown so far only in mice.

Jehl J, Ciscato M, Vicq E et al. (2025). The interpeduncular nucleus blunts the rewarding effect of nicotine. Neuron. — PubMed PMID: 40262615 · doi:10.1016/j.neuron.2025.03.035

Novel Putative Positive Modulators of α4β2 nAChRs Potentiate Nicotine Reward-Related Behavior

Animal study, 2021. Researchers tested a new group of lab-made compounds that block a cold-sensing receptor on nerves, the same receptor that menthol switches on. They wanted to see whether these compounds change how rewarding nicotine is to mice. In mice, the compounds made nicotine more rewarding, not less. In nerve-derived cells grown in the lab, the compounds boosted the activity of a nicotinic receptor (alpha4beta2) that plays an important role in nicotine dependence, so the researchers suggest the compounds may be useful as research tools for studying these receptors.

Cooper SY, Akers AT, Journigan VB et al. (2021). Novel Putative Positive Modulators of α4β2 nAChRs Potentiate Nicotine Reward-Related Behavior. Molecules. — PubMed PMID: 34443380 · doi:10.3390/molecules26164793

Anticataleptic activity of nicotine in rats: involvement of the lateral entorhinal cortex

Animal study, 2021. This study used middle-aged male rats in which a stiff, frozen posture called catalepsy was triggered with a drug injected into the brain. Nicotine injected directly into one brain area, the lateral entorhinal cortex, reduced the catalepsy, but injecting it into two other brain areas did not. The effect was blocked by drugs that block glutamate receptors in that same area, and nicotine also lessened the drug-induced changes in dopamine chemistry in brain regions that control movement. The authors say this may help in developing new treatments for movement disorders such as parkinsonism, but these results come only from rats.

Ionov ID, Pushinskaya II, Gorev NP et al. (2021). Anticataleptic activity of nicotine in rats: involvement of the lateral entorhinal cortex. Psychopharmacology (Berl). — PubMed PMID: 34002247 · doi:10.1007/s00213-021-05870-3

Modulatory Effects of Nicotine on neuroHIV/neuroAIDS

Review, 2018. This review looks at how nicotine, which acts on nicotinic acetylcholine receptors in the brain, may affect the memory and thinking problems linked to HIV infection (HIV-associated neurocognitive disorders), which remain common even with modern antiretroviral treatment. The authors summarise earlier animal and cell studies, including work in a rat model engineered to carry HIV genes, which suggested that nicotine may protect nerve cells, possibly by reducing inflammation, similar to effects seen in Alzheimer's and Parkinson's disease research. They stress that tobacco smoking is harmful, including in people with HIV, and conclude that more research is needed on nicotine's dual effects to see whether nicotine or related compounds could be used medically in a purer, less dangerous form.

Han H, Yang Z, Chang SL et al. (2018). Modulatory Effects of Nicotine on neuroHIV/neuroAIDS. J Neuroimmune Pharmacol. — PubMed PMID: 30215204 · doi:10.1007/s11481-018-9806-5

c-Fos marking of identified midbrain neurons coactive after nicotine administration in-vivo

Animal study, 2018. This study in mice looked at which brain cells in the midbrain switch on after nicotine, using a marker of recent nerve-cell activity. Both a single dose and seven days of daily nicotine strongly activated certain inhibitory (GABA-releasing) nerve cells in two midbrain areas, while a single dose, but not repeated dosing, also activated small percentages of dopamine and other nerve cells in reward-related areas. After 24 hours of withdrawal following daily nicotine, activity in one of these areas was suppressed, and a single dose of cocaine activated a different pattern of cells than nicotine did. The authors say the loss of activation after repeated nicotine is a form of tolerance that may help explain nicotine dependence; these results are from mice only.

Baur K, Hach A, Bernardi RE et al. (2018). c-Fos marking of identified midbrain neurons coactive after nicotine administration in-vivo. J Comp Neurol. — PubMed PMID: 29888787 · doi:10.1002/cne.24471

Chronic nicotine improves cognitive and social impairment in mice overexpressing wild type α-synuclein

Animal study, 2018. This study used mice bred to make too much alpha-synuclein, a human protein closely linked to Parkinson's disease. These mice have memory and social problems, much like the early non-movement symptoms of Parkinson's. A small pump under the skin gave the mice nicotine for 6 months at a low dose (0.4 mg/kg/h) or a high dose (2.0 mg/kg/h). The high dose was toxic to these mice, but both doses improved memory in a maze test, and a month of the low dose in a separate group partly reversed problems with object memory and social behavior. Nicotine did not improve movement problems and did not change protein clumping or other brain-tissue markers. These results are only in mice.

Subramaniam SR, Magen I, Bove N et al. (2018). Chronic nicotine improves cognitive and social impairment in mice overexpressing wild type α-synuclein. Neurobiol Dis. — PubMed PMID: 29859873 · doi:10.1016/j.nbd.2018.05.018

Nicotine suppresses the neurotoxicity by MPP+/MPTP through activating α7nAChR/PI3K/Trx-1 and suppressing ER stress

Animal study, 2017. This study looked at whether nicotine protects nerve cells from MPP+ and MPTP, two toxins used in the lab to mimic Parkinson's disease damage, using rat-derived PC12 cells and mice. In the cells, nicotine reduced the toxin's damage, brought back a protective protein called thioredoxin-1, and lowered markers of cell stress; blocking the α7 nicotinic receptor or the PI3K signalling pathway cancelled these effects. In mice, giving nicotine beforehand improved movement and restored thioredoxin-1 and tyrosine hydroxylase, an enzyme needed to make dopamine, after MPTP exposure. These results come only from cells and mice, not people.

Cai Y, Zhang X, Zhou X et al. (2017). Nicotine suppresses the neurotoxicity by MPP+/MPTP through activating α7nAChR/PI3K/Trx-1 and suppressing ER stress. Neurotoxicology. — PubMed PMID: 28082123 · doi:10.1016/j.neuro.2017.01.002

Optogenetic activation of striatal cholinergic interneurons regulates L-dopa-induced dyskinesias

Animal study, 2016. This mouse study looked at uncontrolled movements called dyskinesias, a common side effect of the Parkinson's drug L-dopa. The researchers used light to switch on acetylcholine-releasing nerve cells in a movement-control area of the brain. Short light pulses made the movements worse through muscarinic receptors. Longer pulses cut them by about 50%, similar to nicotine treatment, and this effect ran through nicotinic receptors. The authors say this supports the idea that nicotine reduces these movements by desensitizing nicotinic receptors, but the result so far comes only from mice.

Bordia T, Perez XA, Heiss J et al. (2016). Optogenetic activation of striatal cholinergic interneurons regulates L-dopa-induced dyskinesias. Neurobiol Dis. — PubMed PMID: 26921469 · doi:10.1016/j.nbd.2016.02.019

Transcriptional regulation by nicotine in dopaminergic neurons

Animal study, 2013. This laboratory study tested how long-term nicotine exposure changes gene activity in dopamine-making nerve cells from the substantia nigra, the brain area that breaks down in Parkinson's disease. The researchers collected twenty of these cells and measured which genes were switched on or off. Nicotine changed the activity of 129 genes, 67 up and 62 down, including genes for clearing damaged proteins, controlling cell division, packaging DNA and regulating RNA. It did not significantly change genes linked to a cell stress response that had been suggested as a possible protective mechanism, nor genes for dopamine or for nicotinic receptors. This work was done in laboratory brain cells, not in people.

Henley BM, Williams BA, Srinivasan R et al. (2013). Transcriptional regulation by nicotine in dopaminergic neurons. Biochem Pharmacol. — PubMed PMID: 23939186 · doi:10.1016/j.bcp.2013.07.031

Nicotine reduces established levodopa-induced dyskinesias in a monkey model of Parkinson's disease

Animal study, 2013. Researchers tested whether nicotine could reduce the involuntary movements, called dyskinesias, that levodopa can cause in Parkinson's disease. They used monkeys given a toxin to produce Parkinson-like symptoms and gave them nicotine in their drinking water. Some started nicotine after levodopa (23 monkeys) and some before it (26 monkeys); in both groups the involuntary movements fell by 60% to 70%, and the benefit lasted through the 17 to 23 weeks of the study. Nicotine did not make the Parkinson-like symptoms worse, but these results come from monkeys, not people.

Quik M, Mallela A, Ly J et al. (2013). Nicotine reduces established levodopa-induced dyskinesias in a monkey model of Parkinson's disease. Mov Disord. — PubMed PMID: 23836409 · doi:10.1002/mds.25594

Is nicotine protective against Parkinson's disease? An experimental analysis

Animal study, 2012. This study used rats with damage to one side of the brain that mimics Parkinson's disease. The rats were given nicotine in their daily drinking water over a long period, to copy how smokers take in nicotine. Nicotine cut one drug-triggered movement problem (circling) by 40% but raised another by 230%, and it changed how dopamine receptors and certain brain cells behaved in the damaged area. The authors concluded that nicotine did not specifically protect brain cells from dying, but changed how the brain's dopamine system works, and suggested it might have a role in treating Parkinson's disease; these results are from rats only.

García-Montes JR, Boronat-García A, López-Colomé AM et al. (2012). Is nicotine protective against Parkinson's disease? An experimental analysis. CNS Neurol Disord Drug Targets. — PubMed PMID: 23131151 · doi:10.2174/1871527311201070897

Nicotine effects on general semantic priming in Parkinson's disease

Human trial, 2011. This small randomized, double-blind, placebo-controlled crossover trial tested a low-dose nicotine skin patch (7 mg over 24 hours) against a placebo patch in 12 non-smokers with Parkinson's disease and 17 matched non-smoking healthy people. The researchers measured semantic priming, which is how quickly the brain connects words that are related in meaning, using one fast automatic task and one slower controlled task. In the slower controlled task, nicotine changed priming in people with Parkinson's disease but not in the healthy volunteers. In the fast automatic task, nicotine did not change priming in Parkinson's disease, but it unexpectedly improved the weaker automatic priming seen in the healthy older volunteers, and the authors conclude that nicotine can improve compromised word-meaning processing in Parkinson's disease.

Holmes AD, Copland DA, Silburn PA et al. (2011). Nicotine effects on general semantic priming in Parkinson's disease. Exp Clin Psychopharmacol. — PubMed PMID: 21480732 · doi:10.1037/a0023117

Acute nicotine enhances strategy-based semantic processing in Parkinson's disease

Human trial, 2011. This double-blind, placebo-controlled crossover study tested a single nicotine skin patch (7 mg over 24 hours) in 10 non-smokers with Parkinson's disease and 16 matched non-smokers without it. Participants did a word task that measures how well people use expectations to guide their thinking, called controlled semantic processing. On placebo, the people with Parkinson's did not show the normal expectation effect, but on nicotine they showed it at a level comparable to the healthy controls. The authors conclude that nicotine can improve this impaired thinking process in Parkinson's disease, possibly by strengthening expectancy or inhibitory mechanisms in the brain.

Holmes AD, Copland DA, Silburn PA et al. (2011). Acute nicotine enhances strategy-based semantic processing in Parkinson's disease. Int J Neuropsychopharmacol. — PubMed PMID: 21281557 · doi:10.1017/S1461145710001665

Nicotine neuroprotection against nigrostriatal damage: importance of the animal model

Review, 2007. This review looks at whether nicotine can protect the brain cells lost in Parkinson's disease, a movement disorder. Tobacco users get Parkinson's disease less often, and in cell studies nicotine consistently protected nerve cells from damage. In animals the results were mixed: studies in mice disagreed with each other, while studies in rats and in monkeys with a condition much like human Parkinson's disease showed protection again and again. The authors conclude that choosing the right animal model and treatment conditions matters when testing possible brain-protecting treatments, and these findings come only from cells and animals, not from people.

Quik M, O'Neill M, Perez XA (2007). Nicotine neuroprotection against nigrostriatal damage: importance of the animal model. Trends Pharmacol Sci. — PubMed PMID: 17412429 · doi:10.1016/j.tips.2007.03.001

Chronic oral nicotine treatment protects against striatal degeneration in MPTP-treated primates

Animal study, 2006. Researchers gave monkeys nicotine in their drinking water for 6 months, which produced blood nicotine levels of 10 to 15 ng/mL, in the range seen in cigarette smokers. They then gave the monkeys low doses of MPTP, a toxin that damages the brain's dopamine system, over several months while the nicotine continued. Compared with monkeys that got the toxin but no nicotine, the nicotine-treated monkeys kept higher levels of several dopamine-related markers and of nicotinic receptors in the striatum, a brain area involved in movement. Nicotine had no effect in monkeys that did not get the toxin, and it did not prevent the loss of dopamine-producing cells in the substantia nigra. This was only in monkeys; the authors say the results support the possibility that nicotine contributes to the lower rate of Parkinson's disease seen in smokers.

Quik M, Parameswaran N, McCallum SE et al. (2006). Chronic oral nicotine treatment protects against striatal degeneration in MPTP-treated primates. J Neurochem. — PubMed PMID: 16882311 · doi:10.1111/j.1471-4159.2006.04078.x

Investigating the receptor-independent neuroprotective mechanisms of nicotine in mitochondria

Cell study, 2005. Nicotine has been linked to a lower risk of Parkinson disease, but no one knows why, so researchers tested it on mitochondria (the energy-producing parts of cells) taken from brains, and on human nerve-like cells grown in the lab. Nicotine reduced the swelling of mitochondria and the release of cytochrome c, a protein that signals a cell to die, when these were exposed to MPP+ (a nerve toxin) or calcium. It did not prevent the mitochondria from losing their electrical charge, but it did reduce electron leakage at a part of the energy chain called complex I. In the lab-grown cells, nicotine still delayed this damage from a mix of nerve toxins when a drug blocked nicotinic receptors, which suggests some of its protective effect does not depend on those receptors. These results come only from isolated mitochondria and cells, not from animals or people.

Xie YX, Bezard E, Zhao BL (2005). Investigating the receptor-independent neuroprotective mechanisms of nicotine in mitochondria. J Biol Chem. — PubMed PMID: 15985439 · doi:10.1074/jbc.M504664200

Regulation of dopamine and MPP+ transport by catecholamine transporters

Review, 2004. This review looks at the proteins that clear dopamine and norepinephrine from the gaps between nerve cells after they are released, and at MPP+, a nerve toxin that causes Parkinson's-like damage and gets into nerve cells through these same transporter proteins. The authors describe how nicotine changes how these transporters move dopamine, norepinephrine and MPP+. They suggest this may explain why some people with depression, schizophrenia or attention deficit hyperactivity disorder may use nicotine to self-medicate, and why nicotine may protect nerve cells against MPP+. Much of the detailed work described was done in laboratory cells made to carry these transporters, and the authors also note that changing single building blocks of the dopamine transporter may point toward new drugs.

Dohi T, Kitayama S, Morioka N et al. (2004). Regulation of dopamine and MPP+ transport by catecholamine transporters. Nihon Shinkei Seishin Yakurigaku Zasshi. — PubMed PMID: 15164608

Transdermal nicotine in PD: a randomized, double-blind, placebo-controlled study

Human trial, 2001. This 12-week randomized, double-blind, placebo-controlled trial tested nicotine skin patches as an add-on treatment in 32 non-smoking people with Parkinson's disease. Patients wore either nicotine patches (17.5 mg of nicotine in the first week and 35.0 mg in the second and third weeks) or placebo patches that looked the same, followed by 3 weeks without patches. Movement, tremor, fine motor skill, walking speed, daily function and depression scores showed no significant difference between the nicotine and placebo groups. Side effects were mild and happened about as often in both groups, and the authors concluded that nicotine patches at this dose and treatment length did not help Parkinson's symptoms.

Vieregge A, Sieberer M, Jacobs H et al. (2001). Transdermal nicotine in PD: a randomized, double-blind, placebo-controlled study. Neurology. — PubMed PMID: 11571330 · doi:10.1212/wnl.57.6.1032

Nicotine prevents experimental parkinsonism in rodents and induces striatal increase of neurotrophic factors

Animal study, 1998. Researchers tested whether nicotine could protect the brain in mice and rats given chemicals that damage dopamine nerve cells and cause Parkinson's-like disease. Nicotine protected against this damage in both models, about as well as a comparison drug that blocks a different brain receptor (NMDA). Nicotine also raised two growth factors that support nerve cells (FGF-2 and BDNF) in the rat striatum, a brain area affected in Parkinson's disease, and a drug that blocks nicotinic receptors stopped the FGF-2 increase. The authors suggest that these growth factors may be one way nicotine protected the animals, but these results come only from rodents.

Maggio R, Riva M, Vaglini F et al. (1998). Nicotine prevents experimental parkinsonism in rodents and induces striatal increase of neurotrophic factors. J Neurochem. — PubMed PMID: 9832142 · doi:10.1046/j.1471-4159.1998.71062439.x

Pharmacology of nicotine: addiction and therapeutics

Review, 1996. This review describes how nicotine works in the body, both as the substance that keeps people addicted to tobacco and as a medicine to help people quit smoking. Nicotine acts on nicotinic receptors in the nervous system, and its effects depend on how fast and by what route it is taken and on tolerance; a few people have been described who break down nicotine unusually slowly and make little cotinine. The authors note that nicotine affects most organ systems, but its contribution to smoking-related disease is still unclear. At the time, nicotine medicines were available as a gum, a skin patch and a nasal spray for quitting smoking, and nicotine was being studied for ulcerative colitis, Alzheimer's disease, Parkinson's disease, Tourette's syndrome, sleep apnea and attention deficit disorder.

Benowitz NL (1996). Pharmacology of nicotine: addiction and therapeutics. Annu Rev Pharmacol Toxicol. — PubMed PMID: 8725403 · doi:10.1146/annurev.pa.36.040196.003121

Beneficial effects of nicotine

Review, 1991. This 1991 review looks at what pure nicotine, apart from tobacco, does in the body. Nicotine attaches to nicotinic receptors throughout the body, which triggers the release of several brain chemical messengers, especially catecholamines and serotonin. The author lists possible effects of long-term use: reinforcing effects that can drive continued use, lower body weight, better performance, and possible protection against Parkinson's disease, Tourette's disease, Alzheimer's disease, ulcerative colitis and sleep apnea. The paper notes that nicotine in tobacco causes illness and death in millions of people, that these effects vary greatly in how reliable they are, and that this justifies further research into possible medical uses.

Jarvik ME (1991). Beneficial effects of nicotine. Br J Addict. — PubMed PMID: 1859921 · doi:10.1111/j.1360-0443.1991.tb01810.x

Back to Table of Contents

PubMed Topic Searches

1. PubMed: Parkinson's Disease and nicotine (the search this page is built from)

Back to Table of Contents

Connections

• Nicotine: The Research
• Dr. Bryan Ardis on this subject — his claims, presented on their own pages and kept separate from this research collection
• The Nicotine Patch, animated
• Nicotinic Acetylcholine Receptors
• Cigarette Smoke — what burnt tobacco adds that nicotine alone does not
• Brain and Memory
• Mood and Mental Health
• Inflammation and Immunity
• Cancer Research
• Heart and Blood Vessels
• Metabolism and Weight
• Addiction and Withdrawal
• Patches, Gum and Delivery

Back to Table of Contents

Featured Videos