The Medical Benefits of Nicotine

In 2008, Paul Newhouse, director of the Center for Cognitive Medicine at Vanderbilt University School of Medicine in Nashville, compared performance on a series of cognitive tasks in 15 nonsmoking ADHD patients while wearing either a 7-mg nicotine patch or a placebo patch. After just 45 minutes with the nicotine patch, the young adults were significantly better at inhibiting an impulse, delaying a reward and remembering an image they had seen. Psychologist Jennifer Rusted of the University of Sussex in Britain calls the drug “the most reliable cognitive enhancer that we currently have.

Nicotine, the wonder drug?, Discover Magazine, 2014

… nicotine is not yet considered to be a carcinogen and may, in fact, have therapeutic potential as a neuroprotective and anti-inflammatory agent.

Nicotine and inflammatory neurological disorders, Acta Pharmacology, 2009

The results suggest that nicotine can enhance psychomotor performance to a significant degree in a real-life motor task.

Effects of nicotine chewing gum on a real-life motor task: a kinematic analysis of handwriting movements in smokers and non-smokers, Psychopharmacology, 2004

We conclude that nicotine increases alertness in non-smokers …

Nicotine effects on alertness and spatial attention in non-smokers , Nicotine & Tobacco Research, 2002

Nicotine gum (2mg-4mg) increased vigilance in a visual detection task.

Nicotine chewing gum (2 mg, 4 mg) and cigarette smoking: comparative effects upon vigilance and heart rate., 1989

Both smokers and nonsmokers reacted more quickly to visual cues and did better with word recognition after an injection of 0.3mg — 0.6mg of nicotine.

Cognitive performance effects of subcutaneous nicotine in smokers and never-smokers, 1996.

People who took nicotine better recalled a list of words they’d just read, and also repeated a story word-for-word, making fewer mistakes than people given placebo made.

An investigation into the effects of nicotine gum on short-term memory, and Effects of transdermal nicotine on prose memory and attention in smokers and nonsmokers.

Other miscellaneous benefits

Lower risk for Parkinson’s disease. Decades ago researchers noticed a strong correlation between smoking and a lower risk for Parkinson’s disease. Since then a large body of research has demonstrated nicotine is responsible for this. Some research suggests it may be useful for treating Parkinson’s as well.

Barreto, GE; Iarkov, A; Moran, VE (Jan 2015). “Beneficial effects of nicotine, cotinine and its metabolites as potential agents for Parkinson’s disease”. Front Aging Neuroscience. 9 (6): 340.

For Alzheimer’s treatment Alzheimers results in a loss of nicotinic cholinergenic receptors (which nicotine binds to an activates) and impairs cognitive function, thus nicotine can help counteract some of the symptoms of Alzheimers.

For treatment of depression There are at least two preliminary research studies [N=11 and N=12] suggesting that nicotine administration, through a nicotine patch, may be useful for treating depression. [Science Daily, 2006] “Antidepressant effect of transdermal nicotine patches in nonsmoking patients with major depression.” People with depression are much more likely to smoke than those without, and it is widely believed that they are self-medicating with nicotine. As a side note, one of the main metabolites of nicotine, cotinine, was developed as an antidepressant but never marketed.

Mineur YS, Picciotto MR (December 2010). “Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis”. Trends Pharmacol. Sci. 31 (12): 580–6.

And More … Studies investigating the effects of chronic nicotine on reduction of brain degeneration:

The potential therapeutic benefit of nicotinic ligands in a variety of neurodegenerative pathologies involving the CNS has energized research efforts to develop nicotinic acetylcholine receptor (nAChR) subtype-selective ligands (Bencherif and Schmitt, 2005). In particular, there has been a concerted effort to develop nicotinic compounds with selectivity for CNS nAChRs as potential pharmaceutical tools in the management of these disorders. Clinical and experimental data demonstrate a central role for alpha7 and alpha4beta2 nAChRs in cognitive function, sensory processing, mood, and neuroprotection (Bencherif and Schmitt, 2005; Buccafusco et al., 2005). The development of safe alpha7-selective ligands has been hampered by their lack of discrimination with hERG channels and 5-HT3 receptors. We have developed a number of compounds that display nanomolar affinity to the alpha7 and/or the alpha4beta2 receptor. Investigation of alpha7 functional activity showed a full range of activities from antagonists to full agonists without any significant activity at the human 5-HT3 receptor, P450 isozymes, hERG channels, or in the AMES test. Our findings demonstrate that potent and highly selective nAChR ligands can be designed.

Therapeutic potential of novel selective drugs targeting nicotinic acetylcholine receptors. Bencherif M(1), Hauser TA, Jordan KG, Gatto GJ.

Nicotinic medications may provide beneficial therapeutic treatment for cognitive dysfunction such as Alzheimer’s disease, schizophrenia and attention deficit hyperactivity disorder (ADHD). For development of nicotinic treatments we are fortunate to have a well characterized lead compound, nicotine. Transdermal nicotine patches offer a way to deliver measured doses of nicotine in a considerably safer fashion than the more traditional means of administration, tobacco smoking. We have found that transdermal nicotine significantly improves attentional function in people with Alzheimer’s disease, schizophrenia or ADHD as well as normal nonsmoking adults. To follow-up on this proof of principal that nicotinic treatment of cognitive dysfunction holds promise, it is important to use animal models to determine the critical neurobehavioral bases for nicotinic involvement in cognitive function so that more selective nicotinic analogues that improve cognitive function with fewer side effects can be developed. We have found with local infusion in rat studies that the hippocampus and amygdala are important substrates for nicotinic effects on working memory function. Both alpha7 and alpha4beta2 nicotinic receptors are involved in working memory. Nicotinic interactions with dopaminergic and glutaminergic systems are also important in the basis of cognitive function. Studies of the neural nicotinic mechanisms underlying cognitive function are key for opening avenues for development of safe and effective nicotinic treatments for cognitive dysfunction.

Nicotinic treatment for cognitive dysfunction. Levin ED(1), Rezvani AH.

Injections of quinolinic acid (60, 180, and 600 nmol) in the dorsal hippocampus induced significant neurotoxicity that was evident 1 day after the injection. By day 3, pyramidal as well as granular cells were affected even at the lowest dose of quinolinic acid, an effect that persisted up to 20 days. Consistent with the histological findings, animals with bilateral injections in the dorsal hippocampus were cognitively impaired during acquisition and retention of spatial information in the water maze. A subacute treatment with (-)-nicotine (62 micromol/kg/day) delivered by subcutaneous minipumps prevented the histological and cognitive deficits induced by the bilateral quinolinic acid (60 nmol) injections. These data indicate that quinolinic acid can induce degeneration of both pyramidal as well as granule cells in the hippocampus, leading to cognitive impairments in the rat, and that activation of neuronal nicotinic acetylcholine receptors can prevent the neurodegenerative process induced by quinolinic acid.

Histological and behavioral protection by (-)-nicotine against quinolinic acid-induced neurodegeneration in the hippocampus. O’Neill AB(1), Morgan SJ, Brioni JD.

In both young adult and aged rats, we tested the ability of chronically administered nicotine to rescue neocortical neurons from transneuronal degeneration resulting 5 mo after ibotenic acid (IBO) lesioning of the nucleus basalis magnocellularis (NBM). Young adult (2–3 mo-old) and aged (20–22-mo-old) rats were given unilateral infusions of IBO (5 mu g/1 mu L) at two sites within the NBM. Following surgery, animals began receiving either daily ip injections of nicotine (0.2 mg/kg) or saline vehicle. Treatment continued for 5 mo, at which time all animals were sacrificed and their brains processed histologically. For each brain, computer-assisted image analysis was then used to analyze the unlesioned (left) and lesioned (right) side of five non-consecutive brain sections from parietal cortex Layers II-IV and V. NBM lesioning in both young adult and aged vehicle-treated rats resulted in a significant 16–21% neuronal loss ipsilateral to NBM lesioning in neocortical Layers II-IV. Aged NBM-lesioned rats also exhibited a significant 12% neuronal loss in neocortical Layer V ipsilaterally. By contrast, those NBM-lesioned young adult and aged rats that received daily nicotine treatment postsurgery did not show any ipsilateral neuronal loss in the same parietal cortex areas, indicating that chronic nicotine treatment prevented the transneuronal degeneration of neocortical neurons resulting 5 mo afer NBM lesioning.

Chronic nicotine treatment prevents neuronal loss in neocortex resulting from nucleus basalis lesions in young adult and aged rats. Socci, DJ, Arendash GW

We investigated the possible long-term neuroprotective roles of (-)nicotine and muscarinic agonist, pilocarpine, in the neocortices of rats receiving bilateral nucleus basalis lesions. Ibotenic acid-lesioned animals eventually displayed a 15–20% reduction in the density of neocortical Nissl staining neurons in layers II, III and VI, as well as a 27% loss in high-affinity GABA uptake 8 months post-lesioning. Deficits were not observed at earlier intervals. (-)Nicotine (0.2 mg/kg, i.p.) or (-)nicotine plus pilocarpine (1 mg/kg, i.p.) attenuated these losses when administered once daily to rats from 5–8 months post-lesioning. Pilocarpine alone had no protective effect on neuronal density or GABA uptake. These results suggest that nicotine receptor activation may counteract neocortical neuronal loss/atrophy following loss of ascending basal forebrain neurons.

Effects of chronic nicotine and pilocarpine administration on neocortical neuronal density and [3H]GABA uptake in nucleus basalis lesioned rats, Sjak-Shie NN, Meyer EM.

The effects of smoking cigarettes with differing FTC nicotine deliveries on anxiety and EEG activity were evaluated in 40 smokers who were compared with 40 non-smokers, matched for age and gender. Following smoking (sham-smoking in the case of the non-smokers), the participants viewed a stress-inducing movie. Smoking higher-nicotine delivery cigarettes during the movie, as compared to smoking low-nicotine control cigarettes, was associated with reductions in anxiety and right hemisphere activation, increased heart rate, and enhancement of the ratio of left-hemisphere parietal EEG activation to right-hemisphere activation. These results are interpreted as indicating that the anxiolytic effects of nicotine may be mediated by the right hemisphere. The EEG activity and emotional responses of non-smokers were more like those of smokers who smoked the lower-nicotine cigarettes than those of smokers of the higher-nicotine cigarettes.

Effects of smoking/nicotine on anxiety, heart rate, and lateralization of EEG during a stressful movie. Gilbert DG, Robinson JH, Chamberlin CL, Spielberger CD.