Review: Explaining the influence of ADHD on smoking
behavior
Bauke van der Velde, BSc
Student ID: 5873517
Supervisor: Mieke ter Horst Track: Cognitive neuroscience
MSc Brain and Cognitive Sciences, University of Amsterdam
TABLE OF CONTENTS
1. The influence of ADHD on Smoking Behavior explained 3
2. Influence of ADHD on Smoking Behavior 3
2.1 Initiation of Smoking 6
2.2 Progression From Experimentation to Regular Use 7 2.3 Cessation of Smoking and Withdrawal Symptoms 8
2.4 Severity of Smoking 9
2.5 Section summary 10
3. Explaining ADHD as a risk factor or smoking 11
3.1 Self-medication 11
3.1.1 Direct evidence 12
3.1.2 Inattentivity vs Hyperactivity/Impulsivity 13
3.1.3 ADHD Pharmacotherapy 14
3.1.4 Nicotine pharmacotherapy 15
3.1.5 Neurobiology of ADHD and smoking 16
3.1.6 Self-medication summary 17
3.2 Cognitive and social factors 18
3.2.1 Cognitive factors 19
3.2.2 Social factors 20
3.2.3 Section summary 21
4. Discussion 21
5. Model for the Relationship Between Smoking and ADHD 24
6. Treatment and Prevention possibilities 26
7. Future Directions 27
8. Summary 28
Explaining the influence of ADHD on smoking behavior
ABSTRACT – ADHD is one of the most prevalent psychiatric disorders in western society. One of the most striking components of the ADHD disorder spectrum is its high comorbidity with nicotine abuse. This was previously explained by the lack of inhibition most ADHD patients display. However, a lack of evidence for this theory and a great difference in the rate of nicotine abuse compared to other substances abused in ADHD-patients has led scientists to believe that there might something else driving this connection. This review will mostly focus on the merits and limits of the most common explanation of the link between ADHD and smoking: self-medication. This theory shows great theoretical strength, but lacks severely in direct evidence. Other cognitive and social factors driving this link will therefore be discussed as well. Finally, this is all summarized into a unified model.Attention-deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders, mainly affecting boys. It affects approximately 5.3 percent of children worldwide, with a male-to-female ratio of at least 3:1 (Wilens et al., 2008; Ramtekkar, Reiersen, Todorov & Todd, 2010). The disorder is known to resolve through maturation, but most patients experience some symptoms connected to ADHD throughout their life (Kessler, Adler, Barkley, et al., 2006). ADHD is a genetically heritable disorder, which manifests itself through high levels of inattention, hyperactivity and impulsivity. According to DSM-IV, a patient suffering from ADHD must show at least six of nine
inattention symptoms and at least six out of nine hyperactivity-impulsivity symptoms (see Figure 1 for the list of symptoms). These symptoms must have been present before the age of 7, must impair at least two settings of a patients’ life (e.g. school, work), and cannot be just present during a psychosis.
ADHD has and incredibly high impact on both health care systems and societies. The costs of healthcare and absence from work of treated adults with ADHD and their family members are estimated at 31.6 billion dollars per year in the United States alone (Biederman & Faraone, 2006). But this is not the whole story: ADHD patients are also more susceptible to anxiety, depression, aggression, poor school performance, trouble with the law, difficulties in adult social relationships and substance abuse. This review will focus on one type of substance abuse: smoking.
Figure 1: The list of possible symptoms of ADHD according to DSM-IV. Patients need
In the late 1980s, several studies found ADHD to be an important risk factor for substance abuse in general (Hartsough & Lambert, 1987; DeMilio, 1989). This spurred an abundance of studies to determine to which extent certain substances were abused in the ADHD population. Further studies over the last two decades have implied ADHD as an important risk factor for smoking in particular. It was found that around 40 percent of the adult ADHD population smoked versus 28 percent in a healthy population (Pomerlau, Downe, Stelson & Pomerlau, 1995). Adolescents showed a similar pattern (30 vs. 12 percent; Molina & Pelham, 2003). Adults with ADHD are more likely to smoke, the age of onset of experimentation is earlier in life, the amount of daily smoked cigarettes is higher and the withdrawal symptoms are more severe, leading to a greater difficulty to quit smoking. Even ADHD symptoms present at levels too low for a diagnosis, show a significant association with smoking (Pingault, Côté, Galéra, et al., 2012). Early studies attributed the higher smoking prevalence in patients with ADHD to comorbid disorders (Biedermann, Wilens, Mick, et al., 1995), not ADHD itself. However, it was later found that when correcting for more strictly and psychiatrically defined comorbid disorders, increased smoking rates persisted in the ADHD-population (Milberger, Biedermann, Faraone, Chen & Jones, 1997; Molina & Pelham, 2003). This suggests that ADHD itself is the risk factor for smoking.
Habitual smoking leads in a significant proportion of users to nicotine dependency (Balfour, 1994), which is characterized by repetitive use of nicotine-containing products and withdrawal symptoms following cessation of use. As with most substance dependencies, nicotine dependence starts through an experimentation phase usually during adolescence. After experimentation, most users transition to regular smokers. While some smokers can limit their daily intake, the majority of daily users smoke at high rates (McClernon & Kollins, 2008): currently five trillion cigarettes are sold to 1.1 billion smokers each year, which corresponds to approximately 5000 cigarettes per smoker a year and about 14 cigarettes per smoker a day (Rang et al., 2007). The detrimental health effects caused by smoking are well-known and have been for a long time – in the 17th century King James I of England already initiated the first known anti-smoking campaign (Rang, Dale, Ritter & Flower, 2007). Despite these
known adverse effects, cigarette use rose steadily in the world until it reached its peak in the early 1970s. Since then it has dropped approximately 50 percent, mainly caused by adverse publicity and an increase in price (for the smoking trend of the United States, see figure 2). Still, tobacco use is currently the leading cause of preventable deaths in Western societies (Danaei, Ding, Mozaffarian, et al., 2009). Since ADHD has been found to be an important risk factor for smoking, it is important to determine why this is the case, so in the future measures can be taken in order to prevent habitual smoking in ADHD patients.
It is currently not fully understood why people suffering from ADHD are more likely to suffer from nicotine dependency and this review will try to shine a light on what is known today by summarizing all known research, studying the influence of ADHD on smoking behavior and listing the most common explanations for this relationship: through (1) self-medication, (2) cognitive and (3) social factors. Lastly, all these possible explanations will be summarized into a unified model, to aid future research and treatment possibilities.
2. INFLUENCE OF ADHD ON SMOKING BEHAVIOR
Both ADHD and nicotine dependence are complex and heterogeneous disorders and may interact in an even more complex way. To simplify the analysis of the influence of ADHD on smoking behavior, it will be divided into four parts: The influence of ADHD on (1) the onset of smoking experimentation, (2) the progression from experimentation to regular smoking, (3) the severity of regular smoking, and (4) the cessation of smoking.
2.1 Initiation of smoking
Nicotine dependence starts with a phase of experimentation, usually taking place during adolescence, when behavioral inhibition is limited by development. Evidence suggests that ADHD greatly influences this experimentation phase, causing adolescents to start smoking at a younger age (Milberger et al., 1997; Pomerlau et al., 2003).
A longitudinal study during which 128 boys suffering from ADHD were followed for four years reported that on average individuals with ADHD started smoking at a significantly younger age than healthy controls (15.5 years old vs. 17.3 years old). In addition, at the ages under 15, twenty-five percent of the individuals with ADHD started smoking compared to nine percent of the non-ADHD controls and between the ages of 15 and 16, forty-six percent of the ADHD-subjects started smoking compared to eighteen percent in the control group (Milberger et al., 1997).
A similar study, in which the age of onset was divided into two categories: onset of experimentation and onset of regular smoking, replicated this finding. Both the age of onset form experimentation (12.8 vs. 14.6 years old for ADHD and non-ADHD respectively) and the age of onset for regular smoking (15.6 vs 17 years old for ADHD and non-ADHD respectively) were significantly lower for children suffering from ADHD compared to controls (Pomerlau, Downey, Snedecor, et al., 2003). Lastly and most conclusively, it was found that ADHD-patients not only started smoking earlier in live, but that the severity of their ADHD symptoms strongly correlated with the age of onset of smoking experimentation. Hence, patients suffering from more severe cases of ADHD were more likely to start smoking at a younger age, which suggests a negative
correlation between symptom severity and age of onset of smoking (Kollins, McClernon & Fuemmeler, 2005). Overall, studies repeatedly show that ADHD decreases the age of smoking onset and increases the likelihood of children smoking.
2.2 Progression from experimentation to daily smoking
ADHD also increases the likelihood of an adolescent experimenting with smoking to progress nicotine dependence (Rohde, Kahler, Lewinsohn & Brown, 2004; Fuemmeler, Kollins & McClernon, 2007). A study with a large group of ADHD-adolescents, found that the severity of suffered ADHD-symptoms predicted the likelihood of a patients progression to daily smoking (Rohde, Kahler, Lewinsohn & Brown, 2004). This finding was replicated in detail with a large group of young adults suffering from ADHD. In this study, ADHD symptoms were broadly divided into two categories, hyperactive-impulsive and inattentive symptoms and tested whether they predicted the likelihood of a patient’s progression to daily smoking. Only the hyperactive/impulsive symptoms and not the inattentive symptoms could validly predict the progression, meaning that the more severe a subject reported their hyperactive/impulsive symptoms to be, the more likely this subject was to progress from the experimental phase to daily smoking. Overall, subjects who reported the highest rates of hyperactive/impulsive symptoms were 1.9 times more likely to progress to regular smoking (Fuemmeler, Kollins & McClernon, 2007).
The first study concluded that any ADHD symptom could cause an increased chance of progression to regular smoking, while the second study only underlined the importance of hyperactive-impulsive symptoms. The slight discrepancy between these two studies was explained in a later study, which found that not only the type of symptom has an influence on the progression to regular smoking, but also the age at which a patient started experimenting with smoking. This study found that in adolescents, more severe IN symptoms caused a more likely progression to nicotine dependence, while in young adults, more severe HI symptoms caused a more likely progression to nicotine dependence (Rodriguez, Tercyak & Audrain-McGovern, 2008).
2.3 Severity of smoking
Studies on the influence of ADHD on the severity of daily smoking are mixed. In 2007, one study reported that the severity of ADHD symptoms experienced correlated with the subjects’ smoking severity score on the Fagerstrom Test of Nicotine Dependence (Fuemmeler et al., 2007), which was later expanded by a study that reported that both inattentive and hyperactive-impulsive ADHD symptoms significantly predicted the amount of cigarettes subjects smoked per day (Kollins et al., 2005). These studies however are starkly contrasted to two different studies that have found no relation between daily smoked cigarettes and severity of ADHD (Pomerleau, Downey, Snedecor,
et al., 2003; McClernon, Kollins, Lutz, et al., 2008).
Why there is such discrepancy between these studies is currently not fully understood. McClernon and Kollins (2008) relate the differences in results to a different use of sampling strategies. Studies that found an effect of ADHD on smoking severity were population-based and calculated a continuously measured scale of symptoms connected to ADHD for each participant, while the latter two studies (that did not find an effect) only used specifically diagnosed ADHD patients and smokers. This underlines the importance of distinguishing between ADHD-diagnosis and a continuously measured scale of ADHD symptoms (McClernon & Kollins, 2008). A second explanation might come from a Molina & Pelham study (2001) who found that childhood ADHD was only a risk factor for high daily nicotine intake when combined with a high IQ. An overrepresentation of people with a relatively low IQ in the community-based samples of the last two studies could therefore have diminished any effect of ADHD on daily nicotine intake.
2.4 Cessation of smoking and withdrawal symptoms
Evidence suggests that ADHD-patients have greater difficulty quitting and maintaining their abstinence after quitting. Of 77 questioned adult ADHD-patients, only 29 percent of the once ADHD-smokers successfully quitted compared to a successful quit rate of 48.5 percent in the general population. Surprisingly, this quit rate difference was only found in male subjects, female subjects were equally likely to quit successfully compared to
Table 2:
Summary of the known literature on the influence of ADHD on the different stages of smoking
the general population. This was attributed to the fact that women usually quit smoking once pregnant, which may be such a strong conditioner to stop smoking that it overcomes the greater difficulty quitting (Pomerlau et al., 1995). A later study found that even male subjects who only experienced symptoms of ADHD during childhood (and not during adulthood) showed remarkable lower quit rates compared to controls during adulthood (Humfleet, Prochaska, Mengis et al., 2005).
2.5 Section Summary
ADHD seems to affect multiple factors related to smoking (for summary see Table 2). ADHD-adolescents start experimenting with smoking earlier in life, are more likely to become regular smokers, can be seen as heavier smokers and male ADHD-patients have more difficulty quitting. All these factors contribute to the high smoking prevalence in ADHD. Not only do these studies further expand our understanding of the ADHD-smoking relationship, the discrepancies in studies also underline the importance to distinguish between samples, age groups and symptoms studied
Study Result Sample
Initiation phase
Milberger et al.
(1997) Earlier experimentation ADHD longitudinal
Lambert &
Hartsough (1998) Earlier experimentation ADHD adolescents Pomerlau et al.
(2003) Earlier experimentation and regular smoking ADHD adolescents Kollins et al. (2005)
Correlation severity ADHD and experimentation age ADHD adolescents
Progression to regular smoking
Rohde et al. (2004)
ADHD symptoms predict progression ADHD adolescents
Fuemmeler et al
Severity of Smoking
Kollins et al. (2008)
Symptoms predict daily smoked cigarettes (DSC) Population based adults Fuemmeler et al.
(2007)
Symptoms predict daily smoked cigarettes (DSC) Population based adults
Pomerlau et al.
(2003) No relation between symptoms and DSC ADHD adults
McClernon et al.
(2008) No relation between symptoms and DSC ADHD adults
Cessation of Smoking
Pomerlau et al.
(1995) Lower successful quit rates among men ADHD adults
Humfleet et al
(2004) Lower quit rates even among child ADHD only ADHD adults
Pomerlau et al.
(2003) More severe withdrawal symptoms ADHD adults
Gray et al. (2010) More severe withdrawal symptoms ADHD adults
McClernon et al. (2007)
Worsening ADHD symptoms ADHD adults
3. EXPLAINING WHY ADHD IS A RISK FACTOR FOR SMOKING
The studies mentioned above describe the influence of ADHD on smoking behavior, but fail to address what causes this link. The following section will address studies that provide possible explanations of higher smoking rates among ADHD-patients, starting with the most commonly used explanation: self-medication.
3.1 Self-medication
The self-medication hypothesis is the most thoroughly studied of all explanations for link between ADHD and smoking. The theory states that the stimulating effect of nicotine on the central nervous system can diminish some of the symptoms ADHD-patients experience (Conners, Levin, Sparrow, et al., 1996). Broadly, there are two main reasons
why this explanation is compelling. Firstly, smoking is not only linked to ADHD, but numerous other psychiatric disorders including schizophrenia, depression, bipolar disorder and anti-social personality disorder (Barry, Fleming, Manwell & Copeland, 1997; Tanskanen, Viinamaeki, Koivumaa-Honkanen et al., 1999; Lyon, 1999). This suggests that patients might smoke to alleviate psychiatric disorder symptoms. Secondly, more specific for ADHD and smoking, the cognitive effects of nicotine on healthy subjects seem to improve certain cognitive abilities, which are diminished in ADHD-patients. Nicotine has been implied on numerous occasions to improve attention (Lawrence, Ross & Stein, 2002; Levin, Conners, Sparrow, et al., 1996), calm stressful moods (File, Fluck & Leahy, 2001) and increase responsiveness to future rewards (Barr, Pizzagalli, Culhane, Goff & Evins, 2008).
3.1.1 Smoking improves symptoms related to ADHD
Conners et al. showed in 1996 in a sample of smoking and non-smoking ADHD-patients, that nicotine use through a nicotine patch alleviated attention problems during cognitive tasks (Conners et al, 1996). This result was replicated later that year (Levin et al., 1996). This direct influence of nicotine on inattentive symptoms has only been found while using nicotine patches. Other studies mostly look at the cognitive abilities, similar to ADHD-symptoms, in a general population. In one study, 62 male non-smokers were tested either with a 7mg nicotine patch or a placebo. They showed that low-attentive subjects under the influence of nicotine performed better at the Conner’s Continuous Performance Test than without nicotine, implying better attention under the influence of nicotine, but only in those with low attentional standards. Potter and Newhouse (2004) compared the influence of transdermal nicotine with methylphenidate (most commonly used medicine used to treat ADHD-symptoms) and placebos. They found that in five of eight subjects, nicotine improved performance both in behavioral inhibition and delay aversion tasks (Potter & Newhouse, 2004). They extended this result in 2008, when they showed a significant positive effect of nicotine on the stop signal reaction time and showed that nicotine increases tolerance for delay (Potter & Newhouse, 2008).
self-medicating effect of smoking in ADHD. One study reported no evidence for patients using smoking to alleviate sleeping and mood problems with both controls and ADHD-individuals reporting to be equally likely to use cigarette smoking as a way to alleviate sleeping problems or mood swings (Wilens et al., 2007). Another study researched the link between the severity of ADHD and the rates of nicotine dependence. They found no evidence that severity of ADHD could cause increased smoking or that smokers show less severe ADHD-symptoms (through self-medication; Dinn et al., 2004). It is important to note however, that both studies that fail to find an effect of smoking on ADHD symptoms, strictly used self-reported data from adolescents that in the case of adolescents has been found to be unreliable (Crockett, Schulenberg & Petersen, 1987). Also, the latter study tested the severity of symptoms of current ADHD-smokers. This however, introduces a bias. If patients with more severe types of ADHD smoke more and therefore alleviate some of their symptoms, they may report their symptoms to be less severe, because of their self-medication. This could possibly cause the lack of distinction in severity of ADHD-symptoms between smokers and non-smokers. In short, there is some promising direct evidence for the self-medication theory. Limited subject pools and the use of transdermal nicotine in stead of inhaled nicotine show however, that these results can only be used with caution.
3.1.2 Inattentive symptoms mediate smoking risk in ADHD patients
Stronger evidence for self-medication comes from the literature looking specifically at the two different types of symptoms of ADHD: Hyperactive impulsive symptoms and inattentive symptoms. A number of studies have examined the effect of these two groups of symptoms specifically on smoking behavior. Strong evidence suggests that inattentive symptoms, rather than hyperactive/impulsive symptoms mediate smoking in ADHD.
During one particular study, 177 clinically referred adolescent boys were divided into two groups of high hyperactivity/impulsivity and high inattention. The group scoring high on inattention showed a nicotine dependency 2.2 times higher than either the hyperactive-impulsive group or controls, even when controlling for comorbid disorders
(Burke, Loeber & Lahey, 2001). Later, evidence showed that the amount of inattentiveness an ADHD-patient showed was directly related to risk for smoking, meaning that the more inattentive symptoms someone showed, the more likely he/she was to smoke (Molina & Pelham, 2003). This effect persisted well into adulthood, even if the inattentive symptoms had subsided (Burke, Loeber, White, Stouthamer-Loeber & Pardini, 2007). Lastly, in 2012, Pignut and colleagues tested the connection of ADHD with all possible substance disorders and concluded that almost all substance disorders were completely unrelated to ADHD. All except for one: nicotine. This connection however, was solely mediated by the inattentive symptoms (Pingault et al., 2012).
These studies provide strong evidence that only inattentiveness and not hyperactive/impulsive symptoms mediate the relationship of ADHD and smoking. More specifically, it seems that patients with high levels of inattention are more likely to smoke earlier and at higher rates. This finding is easiest explained through self-medication. Nicotine is a known attention enhancer (Levin et al., 1996). Since ADHD-patients with high attention deficits show higher smoking rates, it is possible that they use the attention enhancing nicotine as a medication against their impaired attention. Impulsivity symptoms, which in a general population greatly influence smoking behavior, are rarely found to be mediating the link between smoking and ADHD. Only one study showed evidence that not only inattentive symptoms, but also hyperactive/impulsive symptoms mediated the link between smoking and ADHD. Kollins and colleagues (2005) reported that among their sample of 15197 adults, both inattentive and hyperactive/impulsive symptoms were strongly linked to nicotine dependence (Kollins et
al., 2005).
So, while most of the literature reports inattentive symptoms as the driving force behind smoking among ADHD-patients, there is some evidence pointing to equal importance for hyperactive/impulsive symptoms. Once again this could be explained by the differences in sampling strategies used. In a healthy sample, impulsivity is a strong risk factor for substance abuse (Bickel, Odum, & Madden, 1999). The latter study used a non-clinical sample of adults with a varying degree of symptoms related to ADHD. It is therefore not unexpected that people with more severe impulsivity traits are more likely
to smoke.
3.1.3 ADHD Pharmacotherapy causes lower smoking rates
Indirect evidence for self-medication has also been found in the pharmacotherapy field of ADHD. At the end of the last century, one of the most prominent theories for the high smoking rates among ADHD-individuals was the gateway theory which stated that the use of psycho-stimulants to manage ADHD symptoms possibly worked as a gateway drug that lead to abuse of other substances including nicotine and alcohol (Biederman
et al., 1995). However, extensive research has shown that for nicotine these claims are
unlikely. No link has been found between the use of psycho-stimulants for the treatment of ADHD and an increased smoking ratio (Biederman, Monetaux, Spencer et al., 2009; Faraone, Biederman, Wilens, Adamson, 2007; Lambert, 2005; Whalen, Jamner, Henker, Gehricke, King, 2003).
On the contrary, several studies have found that treatment with psycho-stimulants actually lowered smoking rates among ADHD-patients. One study followed ADHD-patients for 28 years and reported that subjects medically treated with methylphenidate showed lower rates of smoking and that these rates went up as soon as the medication stopped (Lambert, 2005). This implies smoking as a substitute medication. Similarly, adolescents undergoing pharmacotherapy were found to be less likely to smoke (Whalen et al., 2003). A recent meta-study, summarized the findings of 31 studies on this subject and found a significant association between stimulant treatment of smoking and lower smoking rates. Effect sizes were larger in clinical studies, studies with more women and adolescent studies (Schoenfelder, Faraone & Kollins, 2014). These studies all show that smoking might very well be used as substitute medication for ADHD and that the need for smoking disappears when ADHD is treated.
3.1.4 Nicotine pharmacotherapy influences ADHD symptoms
It has also proven useful to look at approved pharmacotherapy for nicotine dependence and its effects on ADHD, since it sheds more light on the overlap between the
processes underlying ADHD and smoking addiction. The most used smoking cessation aid is nicotine replacement. By using nicotine patches or other forms of nicotine administration subjects will become less reliant on smoking and have a greater possibility of quitting altogether. As mentioned before, there is evidence that nicotine patches might alleviate certain ADHD symptoms (Levin, Conners, Sparrow, et al., 1996; Potter & Newhouse, 2008). This is not a complete surprise considering the aforementioned positive impact of nicotine on ADHD.
What is more interesting however, is the effect of Bupropion on ADHD. Bupropion is approved by the Food and Drug Administration (FDA) as a smoking cessation treatment (Gray & Upadhyaya, 2009) and has shown to be quite effective (Hurt, Sachs, Offord, et al., 1997). Interestingly, there is also evidence of Bupropion being effective at treating ADHD. ADHD-patients treated with Bupropion showed improvements in ADHD symptoms 76% of the cases compared to 37% in the placebo condition. Moreso, 52% of the subjects treated with Bupropion reported to be “much improved” compared to 11% in the placebo condition (Wilens, Spencer, Biederman, et
al., 2001). This indicates that Bupropion might have a positive influence on both
smoking cessation and ADHD, suggesting similar underlying processes. The use of the currently most effective smoking cessation aiding drug, Varenicline (Aubin, Bobak, Britton, et al., 2008), showed clear improvements in overall attention (Rhodes, Hawk Jr., Ashare, Schlienz, Mahoney, 2012). So far however, no studies have been published on the use of Varenicline to treat ADHD. So the exact effect of Varenicline on ADHD is currently unknown. In the future, Varenicline might however prove useful in treating the inattentive symptoms of ADHD. Even more recently, Ispronicline, a highly effective partial agonist of the α4β2 nicotinic acetylcholine receptors, caused diminishing ADHD symptoms in a large group of ADHD-adults (Potter, Dunbar, Mazulla, Hosford & Newhouse, 2014). This shows the undeniable connection between the nicotinic system in the brain and ADHD.
All these studies show the undeniable connection between nicotine dependency and ADHD. From a self-medication perspective, this could be explained through the mechanisms of action of any of these drugs. The drugs discussed here are partial
agonists of the nicotinic α4β2 receptor, therefore partially stimulating the receptor, without producing the full effect (Ferris & Baman, 1983; Mihalak, Carroll & Luetje, 2006). So these drugs mimic the effect of nicotine on the brain. Since these drugs alleviate many symptoms related to ADHD, it could possibly point to nicotine self-medication. Future research on the exact mechanisms of action of these drugs is needed however, to underline the current findings.
3.1.5 Neurobiology of ADHD and smoking show great overlap
Neurobiological evidence for self-medication is currently mixed. This has mostly to do with the limited knowledge of the exact neurobiological background of ADHD. ADHD is hypothesized to arise from a poorly functioning dopaminergic system operating between the striatum and cortical regions important for attention (Dougherty, Bonab, Spencer, et al., 1999).
The cortical higher association areas and the cerebellum are of the utmost importance for attention (Posner & Petersen, 1989). The connection between these areas and the striatum is largely overseen and modulated by the prefrontal cortex through catecholamines, most notably dopamine. The effects of catecholamines on the prefrontal cortex seem to follow an inverted u-model. Under moderate catecholamine availability the prefrontal cortex responsiveness thrives, while both in low (sleepy) and high (stressed) catecholamine state, the prefrontal cortex shuts down, giving way to more primal brain areas like the amygdala (Brennan & Arnsten, 2008).
The notion that ADHD patients might have over or under expressed catecholamine release is echoed by several studies showing differences in dopamine transporter densities in striatal areas in patients suffering from ADHD. While most studies concerning the link between dopamine transporter density and ADHD report higher DAT density in patients suffering from ADHD (Cheon, Ryu, Kim, et al., 2003; Dresel, Krause, Krause et al., 2000; Madras, Miller, Fischman, 2002), some studies report the exact opposite (Jucaite, Fernell, Halldin, et al., 2005; van Dyck, Quinlan, Cretella, et al., 2002). For an extensive review see (Spencer, Biederman, Madras, et al., 2005). So while the exact direction of the abnormal dopamine transporter binding is not
yet fully understood, it is thought to play a critical role in the neurobiology of ADHD. It is clear that both nicotine dependency and ADHD are rooted in problems with the dopaminergic system. It has been implied that this alteration of dopamine functioning might cause a lower tonic dopamine tone in patients with ADHD. This in turn leads to an over reactive phasic dopamine response (Grace, 2000). While smoking, in the brain of the ADHD-patient, two separate things could happen: (1) it could work as a form of self-medication. Evidence showed that nicotine might normalize the dopamine function in the striatum, by increasing the available dopamine. This static dopamine in turn increases the too low tonic dopamine tone in patients with ADHD, which in turn causes ADHD symptoms to become less pronounced (Mihailescu & Drucker-Colín, 2000). (2) On the other hand the over reactive phasic dopamine response could result in a far larger rewarding phasic dopamine boost in ADHD-patients, which in turn results in a higher possibility of dependency (McClernon & Kollins, 2008). It is most likely however a combination of the two. Smoking seems to normalize dopaminergic function in the ADHD-brain, but is also felt as more rewarding through the extra reactive dopamine release.
3.1.6 Section summary
There are compelling theoretical arguments why the self-medication theory can describe the link between ADHD and smoking. The evidence presented here seems to be largely in agreement with the theory. Transdermal nicotine improved ADHD symptoms in patients. Patients not treated with psycho-stimulants for their disorder are more likely to smoke, implying smoking as a substitute medication. Psychopharmaca with their mechanisms of action centered on the acetyl nicotinic receptors seem to positively influence ADHD symptoms and lastly, only inattentive symptoms seem to mediate the role between ADHD and smoking. It is important to note however that this is all mostly indirect evidence. The only studies reporting direct evidence for nicotine improving ADHD-symptoms used transdermal nicotine and had limited subject pools. Furthermore, other studies were completely unable to find any evidence of ADHD-patients using smoking as medication. These studies however, used self-reporting
adolescents and their results are possibly confounded by adolescents successfully medicating their severe ADHD symptoms by smoking. Still, it is important to note that the evidence for self-medication is not as clear cut as it could be. From a neurological point of view, the evidence becomes even more clouded. No known studies have successfully shown how smoking influences the ADHD-brain. The two current theories, (1) Smoking relaxes the aberrant dopamine system and (2) smoking is over rewarded because of the aberrant dopamine system, are not backed with conclusive evidence. More research on this topic is therefore warranted. The differences in findings in these studies show the importance of a clear definition of self-medication and that both population-based and clinical studies are absolutely vital to furthering our understanding of substance abuse in ADHD.
Most evidence presented here certainly points to an important role for self-medication in the relationship between smoking and ADHD. As the one unifying theory however, it seems to fall short. Over the last two decades, numerous studies have therefore focused on cognitive and social factors directly related to ADHD that undeniably influence the likelihood of someone smoking.
3.2 Cognitive and social factors
Some of the cognitive and social deficits of ADHD, like impaired inhibition and problems with executive functioning have been linked repeatedly to an increased risk for substance abuse in a healthy population (Nigg & Casey, 2005). Despite this obvious connection between the cognitive deficits of ADHD and smoking, research on this link specifically for ADHD-patients is currently sparse. Studies on the coping skills, middle school adjustment, novelty seeking and several social problems of ADHD-patients will be discussed here.
3.2.1 Cognitive factors
Coping skills - how well someone can reduce the adverse impact of life stress - are strongly connected to substance abuse (Wills & Hirky, 1996). People using negative
coping tactics (escape/avoidance coping) are more likely to develop a substance disorder (Lyness & Koehler, 2014). Two of the main variants of positive coping, behavioral coping (trying to solve the problem) and cognitive coping (trying to see the problem differently) have been associated with a lower vulnerability to nicotine dependence (Wills & Hirky, 1996). This correlation can also be found in ADHD-patients. In one study, 242 adolescents with and without ADHD were tested on their coping skills and whether it could explain the higher rates of smokers among ADHD-patients. They found that both cognitive and behavioral coping skills partially mediated the relation between smoking and ADHD. They concluded that ADHD patients might be less likely to solve their problems positively and therefore have a higher risk for nicotine dependence (Molina, Marshal, Pelham, & Wirth, 2005).
Other individual cognitive factors have also been implied to influence smoking rates among ADHD-patients. A longitudinal study studied the influence of middle school adjustment on smoking rates among ADHD-adolescents, which was defined as a combination of the student’s perception of school, the parent’s perception of the student at school and overall school performance. Extensive evidence showed that ADHD students with lower middle school adjustment were more likely to smoke and mediated the link between ADHD and nicotine dependence (Flory, Malone & Lamis, 2011). Lastly, Tercyak & Audrain-McGovern tested the adolescents’ personality traits and related them to self-reported ADHD and nicotine dependence symptoms. They found that smoking ADHD adolescents reported higher levels of novelty seeking than non-smoking ADHD adolescents (Tercyak & Audrain-McGovern, 2003).
3.2.2 Social factors
Social factors have been implied to possibly influence the smoking-ADHD link as well. On three different occasions, studies found that ADHD-adolescents were more likely to have friends who smoked (Kalyva, 2007; Tercyak & Audrain-McGovern, 2003; Wilens et
al, 2008). For example, Wilens et al. (2008) found during a longitudinal study that in
adolescents, social smoking factors like having friends who smoke, living with a smoker and having a parent who smokes significantly interacted with ADHD. This underlines the
possibility that ADHD-individuals may be more vulnerable for social smoking. Parent-child communication plays an important role as well: Molina and colleagues (2005) showed that in ADHD-adolescents usually lacked positive parent-child support, which in turn caused them to be more likely to smoke.
3.2.3. Section summary
Overall, the studies described here underline the importance of other factors that mediate smoking in individuals with ADHD. ADHD is inextricably linked to certain cognitive and social capabilities like poor coping skills, low middle school adjustment and a poorly functioning social environment. All these factors directly influence the likelihood an ADHD-patient smoking. The evidence presented here shows promise, but is currently insufficient. More thorough research, specifically designed to understand the influence of these factors on specific smoking behavior is warranted to understand the exact role the cognitive and social factors play. Also, treatment studies, specifically designed to improve the cognitive and social constructs are warranted in order to find direct causal evidence for the mediating role of these factors.
4. DISCUSSION
People suffering from ADHD show higher rates of nicotine dependence than people who do not experience ADHD-symptoms. Why this happens is currently not fully understood. Several explanations were discussed here. In order to get a better grasp on this relationship, the merits and limitations of the most common explanations, self-medication, and cognitive and social factors were discussed here.
The self-medication theory shows great theoretical strength in that the known effects of nicotine have been shown to better cognitive and attentional deficits, which are common to ADHD (Lawrence et al., 2002; Levin et al., 1998). Several studies showed at least some evidence underlining the possibility of self-medication for ADHD-smokers. Three studies discussed here showed a direct link between transdermal nicotine and improvements in ADHD symptoms (Poltavski & Petros, 2006; Potter &
Newhouse, 2004; 2008). It is however, important to note that these studies all suffered from a limited subject pool size and that transdermal nicotine is very different in terms of functionality compared to nicotine inhalation through smoking. The effects found are encouraging, but more thorough research is required to understand the effects of nicotine on ADHD symptoms. More convincing evidence has been found indirectly, longitudinal studies done by Lambert et al (2005) and Whalen et al (2003) showed that patients treated for ADHD by methylphenidate were less likely to smoke, implying smoking as substitute medication.
More evidence for self-medication has been found in the differences in smoking habits linked to specific symptom severity. In general, most of the evidence points to more severe inattentional problems being linked to higher smoking rates. This finding could be explained from a self-medication point of view. Nicotine is known to have a positive influence on attention (Levin et al., 1996). Since more inattentive ADHD-patients seem more likely to smoke, they possibly use this as a way to overcome their inattentiveness.
Other evidence for self-medication is mixed. Two studies failed to find any proof for self-medication (Dinn et al., 2004; Wilens et al., 2007). These studies however, use a poor definition of self-medication based on symptoms related to, but not directly caused by ADHD. Also they rely on self-reporting in order to quantify the severity of the symptoms ADHD-patients were experiencing. This self-reporting introduces a possible bias in the data. The authors expected smokers to report less sever ADHD-symptoms, since the patients would have successfully self-medicated their symptoms, but found no differences in symptoms reported and concluded from this that there was no evidence for self-medication. Previous research however, has shown that ADHD-patients who are experiencing more severe symptoms are more likely to smoke and in greater quantity. If these patients successfully use nicotine as a form of self-medication, their symptoms severity should then return to the mean in stead of being smaller than non-smoking patients. The results of these studies should therefore be noted with interest, but used with caution.
mixed. On the one hand it seems that several processes which are over reactive in an ADHD-brain might be calmed through nicotine intake, which may be interpreted as self-medication (Mihailescu & Drucker-Colín, 2000). On the other hand it has been implied that the direct reward of smoking might be larger because of a badly functioning dopamine system. This would imply that not self-medication, but over rewarding of nicotine causes higher smoking rates among ADHD-patients (Kollins & McClernon, 2008). Also, medication used to treat nicotine dependence show positive effects on ADHD symptoms. Both Varenicline and Bupropion are partial agonists of the nicotinic α4β2 receptor, therefore partially stimulating the receptor, but without producing the full effect (Ferris & Beaman, 1983; Mihalak, Carroll & Luetje, 2006). Since these psychopharmacological drugs partially copy the effect of nicotine on the brain, this could point to the possibility of self-medication. This is gross guesswork so far though and more research into the exact mechanism of action of these drugs on ADHD-symptomatology is needed.
Since evidence for self-medication is undoubtedly mixed, other possible theories were discussed here as well. The main problem is that as it currently stands, no other unified theory has been proposed, the remaining explanations are therefore shattered into factors. The two most notable factors were discussed here: cognitive and social factors. Two methodologically strong studies have found cognitive factors - cognitive coping and middle school adjustment, to mediate smoking in ADHD (Molina et al., 2005; Flory et al., 2010). Social factors might play an important role as well. ADHD-adolescents reported to have significantly more smoking friends and family members. (Wilens et al., 2008; Kalyva et al., 2007). This could cause a social pressure to start smoking. The problem with both the cognitive and social factor studies lies in causality. It is unclear whether the factors described cause the ADHD-adolescent to smoke or whether these factors arise because the ADHD-adolescent is smoking. For example, smoking is usually a social event. It is therefore likely that smokers have more friends who smoke, simply because they got to know certain people through smoking. The causality of smoking parents might also be somewhat mixed since smoking during pregnancy is a known risk factor for ADHD (Langley, Rice, van der Bree & Tapar, 2005).
This smoking might cause in some cases a more severe ADHD subtype (Neuman, Lobos, Reich et al., 2007), which in turn might lead to a higher likelihood to smoke. The results found so far are interesting nonetheless and more research is warranted to understand what the exact role of these factors is.
One major factor that has not been discussed here, since it went beyond the scope of this review was the genetic predisposition of both smoking and ADHD. For a review, please refer to (McClernon & Kollins, 2008). This review showed that genetic substrates of nicotine dependency and ADHD greatly overlap, which is not surprising considering that both nicotine dependency and ADHD are disorders of the striatal dopaminergic system. Genes and SNPs coding for these particular processes in the brain were therefore found to be directly related to both and in some cases even regulated the relationship between ADHD and smoking. For completion’s sake, the genetic overlap is included into the following summarized model.
5. MODEL FOR THE RELATIONSHIP BETWEEN SMOKING AND ADHD
In an attempt to bring all this together a model has been proposed (see figure 2). This part serves as a textual explanation for the model. Smoking is divided into the four factors that are influenced by ADHD in some way: time of initiation, progression of experimentation to regular smoking, the severity of smoking and the success of smoking cessation. ADHD-patients start experimenting earlier, are more likely to progress to regular smoking, show higher rates of smoked cigarettes per day and show more severe withdrawal symptoms, which increases the risk of relapse.
The self-medication theory can explain most of these influences except for one: the earlier experimentation with smoking. That ADHD-patients start experimenting earlier in life with smoking cannot be caused by self-medication, simply because the medicating power of nicotine has then not yet been experienced. Only after the first use, the possibility of self-medication comes into play. It could be that an ADHD-adolescent is advised to use nicotine to overcome ADHD-symptoms by a friend or family member,
but this is in effect more likely to be social pressure than real self-medication. It is therefore more likely that other genetic, cognitive and social factors might play a role in the earlier initiation of smoking in ADHD-patients. The genetics of both smoking and ADHD show great similarities as can be seen in this review. It could therefore be that underlying processes causing ADHD might also cause a greater likelihood of experimentation with nicotine. This is likely to occur in concurrence with the social and cognitive factors mentioned in this review, most notably cognitive coping. Previous research has shown that using negative instead of more positive coping strategies is a strong risk factor for early smoking initiation (Siqueira, Diab, Bodian & Rolnitzky, 1999). The lack of positive cognitive coping abilities in ADHD-patients could therefore cause an earlier onset of experimentation.
Figure 3: Graphical summary of all factors possibly involved in the relationship of smoking and ADHD. Depicted here are the different factors and their influence on smoking behavior mentioned in this review divided into factors of self-medication and others.
This experimentation then leads to regular use. From this moment onwards, the self-medication theory is the most likely theory to explain the effects of ADHD on smoking. How likely one is to go from experimentation to regular use might be largely influenced by the positive effects experienced while smoking. In the case of ADHD, the extra positive effect of smoking might lie in the aid with attentional problems. This could cause the reward an ADHD-smoker experiences from the first cigarette to be larger than a regular smoker. This effect is then amplified through neurological processes. Kollins and McClernon describe that the over reactiveness of and ADHD-patients DA system causes nicotine intake to be more rewarding (Kollins & McClernon, 2008). Therefore, self-medication can explain some of the influence of ADHD on the progression from initiation to regular use, but it is likely that this happens in concurrence with other neurological processes not necessarily connected to self-medication.
The fact that ADHD-patients smoke more cigarettes a day on average is likely an effect of self-medication. Indirect evidence for this can be found in the studies looking at the link of the severity of ADHD-symptoms and daily smoked cigarettes. ADHD-patients showing more severe symptoms smoked on average significantly more daily cigarettes (Molina & Pelham, 2003), which could mean that patients smoke more because they try to medicate against more severe symptoms.
Lastly, self-medication seems to play a large role in the cessation of smoking and the withdrawal symptoms experienced. When a person without ADHD quits smoking, the main withdrawal symptoms reported are sleeping problems, inability to focus, restlessness and irritability (Shiffman & Jarvik, 1976). Coincidentally all these symptoms are also present in ADHD-patients. When a person with ADHD therefore quits smoking, it is likely that he or she will experience more severe withdrawal effects in that the symptoms of his/her ADHD will become a larger burden. In other words, stopping with smoking not only causes the withdrawal symptoms from smoking, but also causes some of the ADHD symptoms to return. This will therefore amplify the withdrawal symptoms, increasing the risk of relapse and with it the difficulty to quit smoking.
This review showed ample evidence for the undeniable link between smoking and ADHD. Understanding this link is a first and important step. More important however, is to prevent this smoking behavior, since tobacco use is the leading cause of preventable deaths in Western societies (Danaei, Ding, Mozaffarian, et al., 2009).
The negative health consequences of smoking have long been studied and from this a wealth of protocols for the prevention and treatment of nicotine dependence have been suggested and used with some success. The usefulness of these protocols relies largely on social influences. Therefore their use might be limited in the case of ADHD-patients. The direct social environment of ADHD-patients, like families and friends, who play a large role in the prevention of smoking, are more likely to smoke, stimulating ADHD patients to start smoking. Prevention therapies should therefore rely more than ever on influencing the direct social environment of ADHD patients, most notably, the family.
While the larger risk for smoking seems to be disheartening, this link also gives us good opportunities for prevention. ADHD is often diagnosed before the age of seven, well before most children start experimenting with smoking. Prevention therapy could therefore possibly be more effective, since the patient and their family can be informed and warned more directly about the risks of early initiation of cigarette use. New found important cognitive factors that play an important role in the mediation of smoking ADHD-patients should be used as well. Treatments focusing on improving a patient’s positive coping abilities could show promising results in preventing children from smoking. Lastly, new drugs, like Bupropion, Varenicline and AZD-3480, could play an important role as well, in that they seem to show efficacy in treating symptoms of both ADHD and nicotine dependency.
7. FUTURE DIRECTIONS
From this review stems that it is not likely that there is one unified theory explaining the high smoking rate among ADHD-patients. ADHD influences several factors of smoking.
All of which can, as it stands, impossibly be unified in one theory. Research trying to find which one specific theory is correct, will therefore be fruitless. This was realized more recently, as studies looking at very specific factors, including neurobiological, social and genetic factors, have become more common. This is not necessarily a bad development, but it does make it more vital to not lose the general overview of all these factors. This review aimed to summarize what is known to date and create a model from this knowledge. It is very much apparent that important pieces of the puzzle are still missing. More research is warranted, specifically to the influence of each factor on each stadium of smoking. For example inattentional symptoms likely mediate smoking in ADHD patients, but do these symptoms mediate all smoking habits equally? The mediating role of inattentive symptoms is thought to be largely caused by self-medicatory processes. It is therefore unlikely that patients with larger inattentional problems will start experimenting with smoking earlier in life than patients without these larger inattentional problems. It is currently unknown however, whether this is the case. The neural mechanisms underlying the relationship between smoking and ADHD are so far also shrouded in mystery. The most notable burning question that arises from the current literature is whether nicotine relaxes or over stimulates the aberrant DA system. Lastly, nicotinic receptor agonists like bupropion, varenicline and ispronicline have shown efficacy ADHD. What role does the nicotinic receptor play in the disorder and how does (partially) stimulating it relieve some of the ADHD-symptoms. All these questions are absolutely vital for furthering the treatment possibilities of nicotine dependence in the ADHD-population.
8. SUMMARY
This review aimed to understand the validity of the self-medication explanation for the heightened abuse of nicotine in ADHD patients. The studies discussed in this review show some support for the theory. However, the complete relationship between smoking and ADHD cannot be fully explained through one single theory. Previous
research found that smoking could improve attention problems in ADHD patients. Also, patients who already use any kind of medication for their ADHD symptoms are less likely to smoke. However, the self-medication theory can not explain all the facets of the nicotine-ADHD relationship. For example, why ADHD-patients start smoking at a younger age than healthy controls. Since the self-medication theory by itself could not account for all the effects of nicotine on ADHD-patients, research to other possible theories was evaluated as well. This research showed support for the importance of social and cognitive factors specific for ADHD-patients, the similarity of the genetic predisposition, and lastly, the great similarities of their DA-system. None of the other theories however, engrossed all possible characteristics of the nicotine-ADHD relationship, making it likely that no such overarching theory exists. It is more likely that the heightened use of nicotine in ADHD-patients is caused by multiple factors. Understanding these factors is of vital importance for future prevention and treatment possibilities, which could hopefully reduce the dangerously high incidence of nicotine abuse among ADHD-patients.
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