Nicotine and Schizophrenia: The Research

Most people living with schizophrenia smoke, a far higher rate than in any other group, and research on sensory gating and the alpha-7 nicotinic receptor gene asks whether nicotine eases some of the illness's symptoms. This page collects the published research on nicotine and schizophrenia, each paper summarised in plain language with its PubMed record.

This collection is research only: papers found on PubMed, each described as its own abstract reports it. Cell and animal results are labelled as such, and harms are listed beside benefits. It is not medical advice.

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The Papers (17)

Newest first. Study types on this page — Human trial: 1 · Review: 13 · Animal study: 3. Each summary is written from the paper’s own abstract; follow the PubMed link for the full record.

Nicotine Administration Normalizes Behavioral and Neurophysiological Perturbations in the MAM Rodent Model of Schizophrenia

Animal study, 2021. This study used rats with a brain-development disruption that models schizophrenia to test the idea that people with schizophrenia smoke to self-medicate their symptoms with nicotine. Researchers gave the rats nicotine once or over a longer period. They then measured two behaviours known to be impaired in this model, the startle reflex filter and recognition of a new object, and recorded nerve-cell activity in two brain areas. Both single and repeated doses of nicotine improved the behavioural deficits and brought the overactive nerve-cell activity back to normal in these rats, but the results come from animals only and have not been shown in people.

Weeks JJ, Grace AA, Sved AF (2021). Nicotine Administration Normalizes Behavioral and Neurophysiological Perturbations in the MAM Rodent Model of Schizophrenia. Int J Neuropsychopharmacol. — PubMed PMID: 34622270 · doi:10.1093/ijnp/pyab064

Modeling nicotine regulation: A review of studies in smokers with mental health conditions

Review, 2018. This review looks at studies of smokers with mental health conditions who were switched to cigarettes with very low nicotine content. People with these conditions lose about 15 years of life compared with non-smokers without them, and two-thirds of that loss is put down to smoking. In randomized, double-blind studies, these smokers cut down how many cigarettes they smoked, with little or no effect on withdrawal, psychiatric symptoms or compensatory smoking. Some studies found that lowering nicotine worsened performance on thinking tests in smokers with schizophrenia, and giving nicotine replacement at the same time offset this.

Tidey JW, Davis DR, Miller ME et al. (2018). Modeling nicotine regulation: A review of studies in smokers with mental health conditions. Prev Med. — PubMed PMID: 30343684 · doi:10.1016/j.ypmed.2018.07.003

Nicotine reverses hypofrontality in animal models of addiction and schizophrenia

Animal study, 2017. This study used mice carrying a human gene variant in one part of the nicotinic receptor (the alpha-5 subunit), a variant linked in people to a higher risk of both smoking and schizophrenia. The mice had trouble with social interaction and with filtering incoming sensory signals, and the front part of their brain was less active than normal, which resembles the low frontal brain activity seen in schizophrenia and addiction. Brain imaging in awake mice showed that the lower activity came from a shift in the balance between two types of inhibitory nerve cells. Giving the mice nicotine over a long period reversed this low frontal activity, and the authors suggest this may point to a possible treatment approach for schizophrenia and may explain why people with schizophrenia tend to smoke. These results come from mice only.

Koukouli F, Rooy M, Tziotis D et al. (2017). Nicotine reverses hypofrontality in animal models of addiction and schizophrenia. Nat Med. — PubMed PMID: 28112735 · doi:10.1038/nm.4274

Chronic nicotine attenuates phencyclidine-induced impulsivity in a mouse serial reaction time task

Animal study, 2014. This study in mice tested whether nicotine could reduce impulsive behaviour caused by phencyclidine, a drug used to mimic some symptoms of schizophrenia in animals. The mice performed an attention task that measures impulsivity, selective attention and sustained attention. Nicotine given by mouth over a long period reduced the phencyclidine-induced rise in impulsive responses without changing the other attention measures, but single injections of nicotine did not have this effect. The authors suggest this may help explain why people with schizophrenia smoke at high rates, though the result comes only from mice.

Scott D, Taylor JR (2014). Chronic nicotine attenuates phencyclidine-induced impulsivity in a mouse serial reaction time task. Behav Brain Res. — PubMed PMID: 24239695 · doi:10.1016/j.bbr.2013.11.009

Neurocognitive endophenotypes in schizophrenia: modulation by nicotinic receptor systems

Review, 2014. This review looks at why people with schizophrenia smoke much more often than the general population, and whether nicotine and the brain's nicotinic acetylcholine receptors help explain it. Thinking and memory problems affect about 80% of patients with schizophrenia, and the authors describe evidence that these patients' nicotinic receptor system does not work normally. Earlier research, including animal and laboratory studies, found that nicotine affects several brain chemical messengers, including dopamine, glutamate and GABA. In patients with schizophrenia, giving nicotine improved reaction time, spatial working memory, sustained attention and sensory gating (the brain's filtering of repeated sounds or signals). These improvements appeared stronger in patients who smoke, and the authors suggest this may help explain why schizophrenia and tobacco dependence so often occur together.

Mackowick KM, Barr MS, Wing VC et al. (2014). Neurocognitive endophenotypes in schizophrenia: modulation by nicotinic receptor systems. Prog Neuropsychopharmacol Biol Psychiatry. — PubMed PMID: 23871750 · doi:10.1016/j.pnpbp.2013.07.010

Nicotine enhances antisaccade performance in schizophrenia patients and healthy controls

Human trial, 2013. This randomized, double-blind, placebo-controlled crossover trial tested a nicotine patch in 22 people with schizophrenia (12 smokers, 10 non-smokers) and 26 healthy people (14 smokers, 12 non-smokers). Smokers got a 14 mg patch and non-smokers a 7 mg patch. Each person then did an antisaccade task, which means looking away from a spot that suddenly appears, a test of attention and self-control. People with schizophrenia made more errors than the healthy group, and nicotine reduced errors on the standard version of the task but not on the delayed version. The benefit was similar in smokers and non-smokers, so the authors conclude that nicotine itself improved performance rather than just relieving withdrawal in smokers.

Petrovsky N, Ettinger U, Quednow BB et al. (2013). Nicotine enhances antisaccade performance in schizophrenia patients and healthy controls. Int J Neuropsychopharmacol. — PubMed PMID: 23399382 · doi:10.1017/S1461145713000011

Interactions of nicotine and drugs used in the treatment of mental illnesses with respect to cognitive functions

Review, 2010. This review looks at how nicotine interacts with drugs used to treat mental illnesses, such as schizophrenia and depression, and what that means for thinking skills like attention, memory and learning. The authors explain that people with these illnesses may have fewer of certain nicotinic receptors in the brain, which may contribute to their thinking problems, and that some antipsychotic drugs can also worsen these problems. The review reports that nicotine can change these thinking deficits, partly through its effects on the dopamine and glutamate signalling systems when combined with antipsychotics, and that it may ease symptoms of depression by boosting serotonin and noradrenaline activity. The authors conclude that any study of nicotine for thinking problems must take into account its interactions with other medicines and its effects on brain signalling systems.

Burda K, Czubak A, Nowakowska E et al. (2010). Interactions of nicotine and drugs used in the treatment of mental illnesses with respect to cognitive functions. Arzneimittelforschung. — PubMed PMID: 21117496 · doi:10.1055/s-0031-1296322

Why do patients with schizophrenia smoke?

Review, 2010. This review looks at why people with schizophrenia smoke far more than others, with about 70-80% of these patients smoking. An older explanation was that smoking speeds up how the liver clears some antipsychotic drugs and reduces their side effects. More recent work suggests smoking may also ease some symptoms of the illness, especially negative symptoms (such as low motivation) and problems with thinking, through nicotine's effects on the brain's nicotinic system, and these mechanisms are still being studied. The authors conclude that heavy smoking in schizophrenia is not simply a bad habit: self-medicating symptoms and drug side effects appear to play a major role, and that understanding why may help develop new drugs aimed at the nicotinic system and quit-smoking programs designed for these patients.

Winterer G (2010). Why do patients with schizophrenia smoke?. Curr Opin Psychiatry. — PubMed PMID: 20051860 · doi:10.1097/YCO.0b013e3283366643

Cognitive deficits in schizophrenia: focus on neuronal nicotinic acetylcholine receptors and smoking

Review, 2007. This review looks at the thinking problems people with schizophrenia often have, and at why so many of them smoke. It describes nicotinic acetylcholine receptors, the brain receptors that nicotine acts on. It covers how these receptors become less responsive after repeated stimulation and how the brain makes more of them, and how both changes may relate to schizophrenia. The authors look at whether smoking may help with these thinking problems. They also discuss drugs aimed at these receptors as possible future treatments for the thinking problems of schizophrenia.

Ochoa EL, Lasalde-Dominicci J (2007). Cognitive deficits in schizophrenia: focus on neuronal nicotinic acetylcholine receptors and smoking. Cell Mol Neurobiol. — PubMed PMID: 17554626 · doi:10.1007/s10571-007-9149-x

Nicotine for schizophrenia

Review, 2006. This systematic review looked for randomised clinical trials that tested nicotine or related products, alone or alongside other treatment, in people with schizophrenia or similar serious psychotic illnesses. The background is that people with schizophrenia smoke at very high rates, and nicotine is thought to have psychological effects that may ease psychotic symptoms. The reviewers found no trials that met their inclusion criteria, so they could not draw any conclusion about benefits or harms. They called for well-designed randomised controlled trials of nicotine's effects on schizophrenia symptoms and on the side effects of antipsychotic drugs.

Punnoose S, Belgamwar MR (2006). Nicotine for schizophrenia. Cochrane Database Syst Rev. — PubMed PMID: 16437497 · doi:10.1002/14651858.CD004838.pub2

Nicotinic receptors and schizophrenia

Review, 2004. This review looks at the nicotinic receptors in the brain, which nicotine acts on, and how they relate to schizophrenia. It reports that 80% to 90% of people with schizophrenia smoke, compared with 25% to 30% of the general population, and that studies show tobacco use briefly restores some of their thinking and sensory problems, while quitting appears to worsen symptoms. Studies of brain tissue after death found altered levels of two nicotinic receptor types, alpha7 and alpha4beta2, in several brain areas, and genetic studies have linked the alpha7 receptor to schizophrenia. The authors suggest ways this receptor system may take part in causing the disease.

Ripoll N, Bronnec M, Bourin M (2004). Nicotinic receptors and schizophrenia. Curr Med Res Opin. — PubMed PMID: 15265251 · doi:10.1185/030079904125004060

Effects of nicotinic stimulation on cognitive performance

Review, 2004. This review looks at human studies of how nicotine and similar drugs that act on nicotinic receptors in the brain affect thinking and memory. Across these studies, attention was the mental skill most likely to improve when these receptors were stimulated. In people with Alzheimer's disease, Parkinson's disease, attention deficit/hyperactivity disorder or schizophrenia, the studies suggest nicotinic drugs could be useful as treatments, but in healthy non-smokers nicotine tended to make performance worse. The authors explain this difference by each person's starting level of brain function: healthy people are unlikely to benefit except on very demanding tasks, while people with these conditions can benefit.

Newhouse PA, Potter A, Singh A (2004). Effects of nicotinic stimulation on cognitive performance. Curr Opin Pharmacol. — PubMed PMID: 15018837 · doi:10.1016/j.coph.2003.11.001

Nicotine and nicotinic receptor involvement in neuropsychiatric disorders

Review, 2004. This review looks at experimental and clinical research on nicotine and nicotinic receptors, the brain receptors that nicotine acts on, in several brain and mental health conditions. The authors say changes in the number or function of these receptors have been linked to Alzheimer's disease for several years. They describe growing evidence that the receptors may also play an important role in schizophrenia, Parkinson's disease, anxiety disorders and attention deficit-hyperactivity disorder (ADHD). The review aims to identify targets for developing new medicines.

Newhouse P, Singh A, Potter A (2004). Nicotine and nicotinic receptor involvement in neuropsychiatric disorders. Curr Top Med Chem. — PubMed PMID: 14754447 · doi:10.2174/1568026043451401

Cognitive effects of nicotine

Review, 2001. This review looks at research on how nicotine and other substances that act on nicotinic receptors affect thinking skills. The authors report that nicotine has been found to improve performance on attention and memory tasks. They also report that clinical studies using nicotine skin patches showed benefits for thinking problems linked to Alzheimer's disease, schizophrenia and attention-deficit/hyperactivity disorder (ADHD). In animal studies, the improvement in working memory lasted with long-term exposure, and two types of nicotinic receptors in the hippocampus, a memory area of the brain, were found to be key to these effects.

Rezvani AH, Levin ED (2001). Cognitive effects of nicotine. Biol Psychiatry. — PubMed PMID: 11230877 · doi:10.1016/s0006-3223(00)01094-5

Nicotine and brain disorders

Review, 2000. This review looks at the nicotinic receptors in the brain, the docking sites that nicotine acts on. It explains that these receptors matter for memory and thinking, and that they play a part in several brain disorders: Parkinson's disease, Alzheimer's disease, Tourette's syndrome, schizophrenia, depression and attention deficit disorder. The authors write that clinical studies of these same conditions found nicotine had beneficial effects, both as a treatment and as a way to help prevent them. It is a summary of earlier research, not a new study, and the abstract gives no patient numbers.

Mihailescu S, Drucker-Colín R (2000). Nicotine and brain disorders. Acta Pharmacol Sin. — PubMed PMID: 11263271

Development of nicotinic drug therapy for cognitive disorders

Review, 2000. This paper reviews the authors' research on whether nicotine and related drugs that act on nicotinic receptors could help with thinking problems such as those in Alzheimer's disease, schizophrenia and attention deficit hyperactivity disorder (ADHD). The authors report that nicotine skin patches significantly improved attention in people with these conditions and in healthy adults who do not smoke. In rats, they found that the hippocampus, a memory area of the brain, is important for nicotine's effects on working memory, and that two receptor types, alpha7 and alpha4beta2, are involved. They conclude that newer, more selective drugs tested in animals may help in developing safe and effective nicotinic treatments, but those drugs had only been studied in animals at the time.

Levin ED, Rezvani AH (2000). Development of nicotinic drug therapy for cognitive disorders. Eur J Pharmacol. — PubMed PMID: 10771007 · doi:10.1016/s0014-2999(99)00885-7

Nicotine dependence, midbrain dopamine systems and psychiatric disorders

Review, 1995. This review looks at why nicotine is addictive by examining how it acts on the brain's dopamine reward system. It describes research showing that nicotine increases burst firing of dopamine nerve cells in a midbrain area called the ventral tegmental area, which drives dopamine release in the nucleus accumbens. Nicotinic receptors in the ventral tegmental area appear more important for this effect than receptors in the nucleus accumbens itself, since blocking them there stopped the dopamine release and long-lasting release only followed infusion into that area. The authors suggest this effect on dopamine may help explain the very high smoking rates among people with schizophrenia, who often show reduced activity in the front of the brain that feeds into these dopamine cells.

Nisell M, Nomikos GG, Svensson TH (1995). Nicotine dependence, midbrain dopamine systems and psychiatric disorders. Pharmacol Toxicol. — PubMed PMID: 7617539 · doi:10.1111/j.1600-0773.1995.tb00123.x

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