 |
| Figure 5 (Mendelson et al., 2008) |
The relation between nicotine and cortisol, as well as other
hormones associated with stress and the hypothalamic-pituitary-adrenal (HPA)
axis, has been examined in the literature.
Early research found cortisol and ACTH levels were increased after
smoking high nicotine cigarettes and were significantly greater than in
individuals who smoked a low nicotine cigarette (Seyler et al., 1986). Xue et al. (2010) reported an increase in
cortisol levels in average nicotine cigarettes compared to low nicotine
cigarettes, however the correlation between plasma nicotine and cortisol was
not as strong as anticipated (r = 0.66).
Despite statistical significance, the clinical significance of the raise
in cortisol level is believed to be minimal. Smokers have higher basal cortisol
levels than non-smokers, and smoking serves to reduce cortisol levels
(Mendelson. Goletiani, Sholar, Siegel, & Mello, 2008). High nicotine cigarettes may act as a greater
stressor than low nicotine cigarettes, explaining why smoking led to a larger
decrease in cortisol among low nicotine consumers. ACTH levels increased after one high nicotine
cigarette, returned to baseline and did not increase with a second cigarette,
but then increased after a third cigarette.
This pattern may relate to a feedback mechanism involving ACTH and cortisol,
yet the exact mechanism is unknown.
Males who smoked low nicotine cigarettes saw no change in ACTH (Figure
5) (Mendelson et al., 2008).
al’Absi, Hatsukami, Davis, and Wittmers (2004) found acute abstinence
from nicotine increased HPA axis activity and cortisol levels. Smokers experience withdrawal at night while
sleeping, and higher morning cortisol levels are associated with more intense
withdrawal symptoms. Nakajima and al’Absi (2013) assessed levels of cortisol in
smokers who are successfully abstinent versus those who relapsed. For 3 weeks following a quit attempt cortisol
levels were relatively stable, but around 4 weeks post-quit the basal cortisol
levels of abstainers started to reduce (Figure 6). It is expected that cortisol levels of
abstainers would continue to decrease and return to levels closer to those of a
nonsmoker on an extended timeline.
 |
| Figure 6 (Nakajima & al'Absi, 2013) |
Chen, Fu, and Sharp (2008) investigated the effect of
chronic nicotine self-administration on HPA hormonal responses to various acute
stressors. Nicotine served as a stressor and stimulated corticosterone and ACTH
release on day 1, but this effect is diminished over time. Chronic administration led to continuous
stimulation of norepinephrine in the PVN and amygdala. Chronic nicotine administration varied HPA
hormonal outcomes depending on the stressor intensity. In low intensity stressors, there was moderate
HPA hormonal activation, which was further increased by nicotine. In high intensity stressors, corticosterone
and ACTH levels were largely increased and nicotine did not increase them
further (Chen et al., 2008). Yu and Sharp (2010) report nicotine
self-administration reduced the intensity and duration of a norepinephrine
response in the PVN to footshock stress.
The stress of chronic nicotine self-administration led to decreased HPA
hormonal activation in similar stressors and increased corticosterone and ACTH
release with non-related stressors.
Looking at the relationship in reverse, Faraday, Blakeman, and Grunberg
(2005) reports on stress altering the effects of nicotine. In males, stress did not modulate outcomes
related to nicotine, such as body weight changes, but it was observed in
females. However, depending on the
strain of rat and dosage, there was much variability in the relationship
between stress and nicotine use and the behavioral outcomes are not always
clear.
Nicotine administration stimulates the HPA axis and cortisol
release, however dosage and frequency of use may modulate this relationship
(Xue et al., 2010). Baseline cortisol
levels are higher in smokers compared to nonsmokers (Mendelson et al., 2008). The effect of nicotine combined with a
stressor on cortisol is dependent on the type as well as intensity of the
stressor. There is evidence that chronic
stress and cortisol modulates expression of nicotinic acetylcholine receptors (Baier
et al., 2014; Hunter, Bloss, McCarthy, & McEwen, 2010) but how this may
influence smoking behavior or the effects of nicotine has not been examined.
