Published in IJCP August 2019
GUEST EDITORIAL
Beneficial Effects of Nicotine – Fact or Fiction
August 16, 2019 | Lynne Dawkins
     


Professor

Centre for Addictive Behaviours Research
London South Bank University

Whether there are any direct ‘positive’ or ‘beneficial’ effects of nicotine on psychological and cognitive functioning remains a topic of debate. This presentation and subsequent write up considered the literature on the effects of nicotine and smoking on three broad areas (cognition, mood and reward) in the general healthy population (rather than in those with specific neurological, developmental or psychiatric disorders).

Nicotine activates receptors in the brain and body known as nicotinic acetylcholine receptors (nAChR). These receptors are usually activated by the endogenous (naturally occurring) neurotransmitter acetylcholine (Ach). Because the receptors are so widespread throughout different parts of the nervous system, their activation produces a variety of effects including on: arousal, respiration, nausea, anxiety, reward, learning, memory and conditioning.

Theories of Nicotine Use

Broadly speaking, the theories of nicotine use through smoking can be classified into two main camps.

Firstly, positive reinforcement theories (which take various forms) state that smokers use nicotine because it offers them various direct beneficial or positive effects.1-3 One variant of this, the self-medication  model, states that smokers use nicotine to relieve neurocognitive deficits associated with a range of psychiatric and neurological disorders (including schizophrenia, mood disorders, attention-deficit hyperactivity disorder [ADHD], Alzheimer’s disease, Parkinson’s disease); others4 suggest that self-medication with nicotine may not be limited to those with a psychiatric diagnosis, but that ‘normal’ smokers may be self-medicating for mild neurocognitive or neurobiological deficits.

Secondly, negative reinforcement models (which again, take various forms) essentially maintain that adverse states experienced during withdrawal promote smoking maintenance – i.e., people smoke to alleviate the negative (affective, cognitive, physical) states associated with nicotine withdrawal.5,6 According to this model, smoking directly causes stress and negative mood states and this would also explain why long-term prospective investigations have found that quitting smoking leads to reduced stress.7,8

Of course, these models are not necessarily mutually exclusive and nicotine may be having both positive and negative reinforcing effects and nicotine may offer direct enhancement effects on some domains and have negative effects on others.

Smokers commonly report that smoking offers a number of beneficial effects including to relax, aid concentration, alleviate negative mood, reduce stress and so on. However, whether these effects are genuinely beneficial or tied to withdrawal relief requires closer scrutiny.

Cognitive Functioning

Cognitive functioning relates to a broad range of processes requiring information processing, learning, memory and higher-order ‘executive’ tasks (such as planning, organizing and creative thinking). There are plenty of studies showing that smokers perform better after smoking (or receiving nicotine in some other form) compared to during abstinence from smoking. For example, in a series of studies, Warburton and colleagues investigated the effects of smoking and oral nicotine on performance on a rapid visual information processing task (RVIP - a classic test of attention and vigilance) during the 1980s. Smokers were tested after overnight (12 hr) abstinence and then after receiving various strengths of cigarettes or doses of oral nicotine and placebo. Vigilance performance was consistently better after receiving moderate to high doses of nicotine compared with no, low or very high doses. The authors interpreted these results as demonstrating that nicotine was acting as a cognitive enhancer – boosting alertness through its actions on the cholinergic system.9

However, it is not clear from these studies whether nicotine is genuinely enhancing performance or whether smokers’ performance is impaired during abstinence and restored to ‘normal’ levels by smoking. More recent studies have therefore tried to determine the effects of nicotine by either using smokers who are not in a state of withdrawal or using non-smokers or occasional smokers (as occasional smokers should not experience withdrawal).

One such study conducted by our group Jansari et al,10 gave nicotine or placebo in lozenge form to both smokers and non-smokers who completed a battery of executive function tests as part of an overall virtual reality task. Smokers were abstinent for 2 hours prior to testing. We found significant differences for smokers across the nicotine and placebo conditions for overall executive functioning, an effect that appears to be driven by worse performance with placebo (2-hr abstinence). For non-smokers, there was no overall performance enhancing effect of nicotine (although some evidence for improved performance on prospective memory). Overall, these findings appear to support a reversal of withdrawal effect for executive functioning rather than a direct enhancing effect of nicotine.

A review carried out by Heishman et al11 examined the effect of nicotine on various aspects of cognitive performance in 41 double-blind placebo-controlled studies between 1994 and 2008 in non-smokers and smokers not experiencing withdrawal. A meta-analysis  revealed significant positive effects of nicotine on 6/9 domains: fine motor abilities, overall accuracy and response times for alerting and orienting attention, working memory response time and accuracy of episodic memory performance. The authors suggest that these capture true performance facilitation effects rather than withdrawal relief due to nicotine’s ability to stimulate the nicotinic receptors normally activated by Ach.

However, whilst there may be enhancing effects of acute nicotine on some areas of cognitive functioning, several longitudinal studies have reported that chronic cigarette smoking is associated with decreased cognitive performance in middle age12,13 and increased risk of cognitive decline and dementia later in life.14 And two reviews have reported that compared with non-smokers, smokers perform worse on a range of cognitive functions (e.g., cognitive flexibility, non-planning impulsivity, attention, auditory verbal learning, visual search and processing speeds, intelligence, short-term memory [STM], long-term memory [LTM], cognitive impulsivity).15,16 It is difficult to determine causality from these cross-sectional studies as groups may have differed prior to the onset of smoking. Longitudinal studies may suggest causality and some of these studies accounted for educational achievement or baseline IQ but of course, they cannot account for all possible sources of influence (e.g., health and lifestyle factors) and there are some studies with negative results too.

Overall, it can be concluded from the studies on cognitive performance that acute nicotine administration can yield performance enhancements in particular areas of attention and memory but that chronic smoking is associated with poorer overall cognitive performance.

Mood and Stress

Smokers often report that smoking helps them to relax and cope with stress and this effect was commonly depicted in early cigarette advertising. There is very little  evidence; however, that smoking does actually help to reduce stress. For example, studies that compare smokers and non-smokers have found generally that smokers report higher levels of stress on a day-to-day basis. Could this be due to self-medication? That is, smokers experienced higher levels of stress even before starting to smoke. Or does smoking cause stress as suggested by Parrott?6

In a study by Parrott and Kaye,17 25 smokers who smoked as usual, 25 smokers who abstained for the day and 25 non-smokers rated their uplifts, hassles, stress and cognitive failures for the day. The ratings of deprived smokers were significantly worse across all measures compared to both non-smokers and smokers who had smoked as usual who did not differ from each other. These findings indicate that abstinence causes deterioration of mood and cognitive functioning and then smoking normalizes (but does not improve) it. The authors concluded that these findings provide evidence to support the negative reinforcement model – that is, “dependent smokers need regular hits of nicotine just to remain feeling normal”.

However, although Parrott concludes that this is due to nicotine dependency (i.e., smoking/nicotine creates a problem that it then fixes), it does not rule out the possibility that smokers were more stressed to begin with and turned to smoking because it helped them, not necessarily that the smoking caused the stress.

For depressed mood, the story is similar. Those with depression are much more likely to smoke, smoke more and are less likely to quit. Amongst clinically depressed individuals, smoking rates are twice as high as in the general population18 and smokers are twice as likely than non-smokers to have suffered depression at some point in their lives.19

However, as with stress, are smokers smoking to help alleviate symptoms of depression (as suggested by the self-medication model)? Or does smoking contribute to the development of depression? One way to help understand this is to look at the sequence of occurrence of depression and smoking, another way is to look at what happens to depressive symptoms when people quit smoking.

In relation to sequencing, Goodman and Capitman20 reported that among 8,704 teenagers, depression was not an antecedent to heavy smoking, but teen smokers who were not depressed at baseline were four times more likely to develop depression after 1 year compared to those who did not smoke. There have been numerous studies demonstrating that depressive symptoms improve after quitting smoking even in those with severe depression.21-23

Overall, the bulk of the evidence on mood, stress and depression indicates that smoking does not improve it and actually may cause or exacerbate negative mood.

Can nicotine enhance the reward value of other reinforcers?

Cigarette company advertisements often linked smoking with other pleasurable activities and smoking certainly does tend to accompany other rewarding activities. Perhaps, this is because it enhances the pleasure or reward value associated with these other activities.

There is plenty of evidence from rodent studies that this may be the case. For example, in one study by Donny et al,24 rats increased their lever-press responses for a visual stimulus when it was paired with nicotine compared to when it was paired with saline or presented alone. Moreover, the lever-pressing for nicotine + visual stimulus was higher than the additive effects of responding for either the visual stimulus or nicotine alone.

In a series of studies in humans in our group, we have also found that responsiveness to a financial incentive on a simple card sorting task is higher after receiving nicotine (smoking or taking a nicotine lozenge) compared to an abstinence state in smokers.25,26 However, the performance of non-smokers on this task more closely resembled the performance of recent smokers (but did not differ statistically from either abstainers or recent smokers). Thus, overall, it appears that the enhanced responsiveness to reward after nicotine compared with abstinence may reflect lowered reward responsivity during abstinence, which is less consistent with the rodent work.

More recently, Perkins’ group have developed a task (Applepicker task) and study procedure designed to closely match those from rodent studies. Participants are required to click on trees to find apples on a Progressive Ratio schedule of reinforcement (i.e., rewards are given for increasing number of apples found and participants can work on the task for as long as they want). In one particular study,27 smokers completed the task under four conditions – with rewards of music, money, a negative reinforcer (stopping an aversive noise) and no reward - on two occasions, once after smoking a nicotine cigarette and once after smoking a denicotinized cigarette (no nicotine).

After controlling for responding under the denicotinized condition, nicotine was associated with a higher rate of responding (more apples earned) compared to no reward and the effect was particularly pronounced for music reward.

A series of studies has shown very similar effects in dependent smokers and non-dependent smokers, particularly for music reward but also video reward. However, all these studies come from the same lab and the task has not been used in non-smokers.

We are in the process of conducting a similar study at London South Bank University (LSBU) with nicotine mouth spray using the Applepicker task to see if there is any evidence that nicotine can enhance the rewarding effects of music reward in non-smokers. These findings will be reported in Autumn 2019.

Overall, there is some evidence that nicotine can enhance the reward value of other rewards; the rodent evidence is strong in this regard and there is reasonably strong evidence in smokers. However, whether this extends to non-smokers is unclear.

References

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