Nicotine

The quality of the available research is limited because information on long-term nicotine use in humans comes entirely from the use of tobacco. Our search found:

• 1 Cochrane systematic review and meta-analysis of 136 randomized trials comparing usage of placebo or no treatment to nicotine replacement therapy
• 1 meta-analysis of 41 randomized controlled trials examining cognitive outcomes in healthy adults, along with 2 pilot randomized trials in healthy nonsmokers
• 3 randomized controlled trials in Alzheimer's disease patients
• 2 randomized controlled trials in patients with mild cognitive impairment or age-associated memory impairment
• 3 clinical trials in healthy adults
• Numerous preclinical studies

Smoking tobacco is likely to increase the risk of dementia, and the evidence is mixed on whether nicotine treatment may protect against cognitive decline or dementia. In healthy adult non-smokers, nicotine has improved aspects of fine motor skills, attention, auditory processing, and memory in short clinical trials [1; 2]. However, these effects may be unrelated to the risk of dementia or long-term cognitive decline. For older adults with mild cognitive impairment, nicotine therapy in two small trials led to improvements in some aspects of cognition but not others [3; 4]. A trial is underway with support from the National Institute of Aging and the Alzheimer's Drug Discovery Foundation to more conclusively test the effects of transdermal nicotine patches for patients with mild cognitive impairment [5].

In preclinical research, nicotine worsened some aspects of Alzheimer’s disease [6; 7] and protected against others [8; 9; 10].

APOE4 Carriers:

Nicotine was reported to promote cognition to a greater extent for APOE4 carriers, based on a handful of experiments with healthy adults [11; 12; 13], but older smokers with APOE4 were the most likely to have impaired cognition and low brain metabolism [14]. However, APOE4 status did not alter the association of smoking history on disease progression or biological markers of Alzheimer’s disease [15]. For more information on what the APOE4 gene allele means for your health, read our APOE4 information page.

For Dementia Patients

It is uncertain whether Alzheimer's patients might benefit from nicotine therapy. A handful of clinical trials suggested that they are not likely to benefit but a 2001 meta-analysis by the Cochrane Collaboration, an independent global health network, concluded that these trials were of poor quality [16]. 

Nicotine therapy not provided through tobacco is well-tolerated but there are some safety concerns such as impaired sleep, addiction, interactions with other drugs, gastrointestinal symptoms, and possible cardiovascular effects [17]. Nicotine poisoning or overdose can occur, and children are especially vulnerable [18]. Some individuals may have health conditions that substantially increase the risks of side effects. Most experts agree that nicotine is highly addictive [19], although it is not clear how addictive nicotine gum, patches, spray, or lozenges are for non-smokers. Nicotine interacts with many other drugs so the use of other medications can impact the safety of nicotine treatment.

NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.

Nicotine replacement therapy is marketed to help people stop using tobacco. It is available as patches, gum, and lozenges that can typically be purchased over the counter and as inhalers and nasal sprays that require a doctor’s prescription. In small clinical trials, the dose of nicotine that improved some aspects of cognition ranged from 5 to 15 mg/day [3; 4; 20]. Higher doses likely have greater risk of sleep side effects [21].

Full scientific report (PDF) on Cognitive Vitality Reports

The American Cancer Society Guide to Quitting Smoking

Check for drug-drug interactions and drug-supplement interactions on Drugs.com

1. Heishman SJ, Kleykamp BA, Singleton EG (2010) Meta-analysis of the acute effects of nicotine and smoking on human performance. Psychopharmacology (Berl) 210, 453-469.
2. Sun S, Kapolowicz MR, Richardson M et al. (2021) Task-dependent effects of nicotine treatment on auditory performance in young-adult and elderly human nonsmokers. Sci Rep 11, 13187.
3. Newhouse P, Kellar K, Aisen P et al. (2012) Nicotine treatment of mild cognitive impairment: a 6-month double-blind pilot clinical trial. Neurology 78, 91-101.
4. White HK, Levin ED (2004) Chronic transdermal nicotine patch treatment effects on cognitive performance in age-associated memory impairment. Psychopharmacology (Berl) 171, 465-471.
5. Memory Improvement Through Nicotine Dosing (MIND) Study.
6. Oddo S, Caccamo A, Green KN et al. (2005) Chronic nicotine administration exacerbates tau pathology in a transgenic model of Alzheimer's disease. Proc Natl Acad Sci U S A 102, 3046-3051.
7. Deng J, Shen C, Wang YJ et al. (2010) Nicotine exacerbates tau phosphorylation and cognitive impairment induced by amyloid-beta 25-35 in rats. Eur J Pharmacol 637, 83-88.
8. Brown D, Ramlochansingh C, Manaye KF et al. (2013) Nicotine promotes survival of cells expressing amyloid precursor protein and presenilin: implication for Alzheimer's disease. Neurosci Lett 535, 57-61.
9. Inestrosa NC, Godoy JA, Vargas JY et al. (2013) Nicotine prevents synaptic impairment induced by amyloid-beta oligomers through alpha7-nicotinic acetylcholine receptor activation. Neuromolecular Med 15, 549-569.
10. Xue MQ, Liu XX, Zhang YL et al. (2014) Nicotine exerts neuroprotective effects against beta-amyloid-induced neurotoxicity in SH-SY5Y cells through the Erk1/2-p38-JNK-dependent signaling pathway. Int J Mol Med 33, 925-933.
11. Marchant NL, King SL, Tabet N et al. (2010) Positive effects of cholinergic stimulation favor young APOE epsilon4 carriers. Neuropsychopharmacology 35, 1090-1096.
12. Evans S, Gray MA, Dowell NG et al. (2013) APOE E4 Carriers show prospective memory enhancement under nicotine, and evidence for specialisation within medial BA10. Neuropsychopharmacology 38, 655-663.
13. Evans S, Dowell NG, Tabet N et al. (2013) Nicotine effects on attentional reorienting in mid-age adults, and interactions with apolipoprotein E status. J Psychopharmacol 27, 1007-1014.
14. Durazzo TC, Mattsson N, Weiner MW et al. (2016) Interaction of Cigarette Smoking History With APOE Genotype and Age on Amyloid Level, Glucose Metabolism, and Neurocognition in Cognitively Normal Elders. Nicotine Tob Res 18, 204-211.
15. Sabbagh MN, Tyas SL, Emery SC et al. (2005) Smoking affects the phenotype of Alzheimer disease. Neurology 64, 1301-1303.
16. Lopez-Arrieta JM, Rodriguez JL, Sanz F (2001) Efficacy and safety of nicotine on Alzheimer's disease patients. Cochrane Database Syst Rev, CD001749.
17. Hartmann-Boyce J, Chepkin SC, Ye W et al. (2018) Nicotine replacement therapy versus control for smoking cessation. Cochrane Database Syst Rev 5, CD000146.
18. Nicotine Replacement Therapy to Help You Quit Tobacco.
19. Tobacco, Nicotine, and E-Cigarettes Research Report: Is nicotine addictive?
20. Min SK, Moon IW, Ko RW et al. (2001) Effects of transdermal nicotine on attention and memory in healthy elderly non-smokers. Psychopharmacology (Berl) 159, 83-88.
21. Stolerman IP, Jarvis MJ (1995) The scientific case that nicotine is addictive. Psychopharmacology (Berl) 117, 2-10; discussion 14-20.