Nicotine is the psychoactive drug in tobacco which has direct effects in the central nervous system. About 25 percent of the nicotine inhaled when smoking a cigarette reaches the blood through which the nicotine reaches the brain within 15 seconds.
Nicotine activates the dopaminergic pathways projecting from the tegmental area to the cerebral cortex and the limbic system. It causes an increase in the concentration of the neurotransmitters and hormones norepinephrine, epinephrine, vasopressin,beta-endorphins,adrenocorticotropic hormone(ACTH) and cortisol. Those changes are responsible for the stimulant central nervous system (CNS) effects of nicotine which has a half life of about 2 hours.
The stimulatory effects of nicotine result in improved attention, learning, reaction time, and problem solving ability. The user tobacco also report the effects of decreased tension, lifting of mood lessening of depressive feelings. Studies of the effects of nicotine on the cerebral blood flow suggest that short-term nicotine exposure increases blood flow without changing cerebral oxygen metabolism but that long-term nicotine exposure is associated with a decrease in the cerebral blood flow. In contrast to its central nervous system stimulant effects, nicotine causes skeletal muscle relaxation.
Studies in both humans and animals show that nicotine is a potent psychoactive drug which in high dosed can lead to intoxication and death (WHO-1992).The symptoms of nicotine toxicity include nausea, vomiting, salivation, pallor, weakness, abdominal pain(caused by increased peristalsis),diarrhea, dizziness, headache, increased blood pressure, tachycardia, tremor and cold sweat. Toxicity is also associated with an inability to concentrate, confusion and sensory disturbances. Nicotine is also associated with a decrease in the user’s amount of rapid eye movement (REM) sleep. At doses typically obtained from tobacco products, nicotine is responsible for much of the pleasure and satisfaction obtained by tobacco users. It appears to alleviate various dysphoric states associated with boredom, stress and nicotine withdrawal syndrome. There is no doubt that it produces dependence through activation of nicotine receptors in the central nervous system.
Treatment of smoking cessation/quiting tobacco chewing.
Majority of smokers (and tobacco chewers) wish to quit smoking/chewing, but fail to do so because of nicotine dependence. The most important measure to help smokers quit is counseling and motivation. This may be supplemented by pharmacotherapy. The goals of such pharmacotherapy are:
- To reduce the craving for the satisfying (reward) effects of nicotine.
- To suppress the physical withdrawal symptoms of nicotine.
The drugs currently utilized for the above goals are:
- Nicotine replacement
- Partial agonist of Alpha 4 Beta 2(varenicline)
Nicotine transdermal This patch formulation of nicotine is applied once daily on the hip/abdomen/chest/upper arm as an aid to smoking cessation. It ameliorates the symptoms of nicotine withdrawal, but only partially suppresses the craving, because the intermittent peak nicotine blood levels that occur during smoking are not reproduced by the patch.
Nicotine chewing gum Developed as an alternative to nicotine transdermal, this formulation is found more satisfying by some dependent subjects. The number of gum pieces chewed daily can be adjusted according to the need felt.
Side effects of nicotine replacement therapy are headache, dyspepsia, abdominal cramps, loose motions, insomnia, flu-like symptoms and local irritation. Vasospastic angina may be precipitated. Cardiac arrhythmias and ischaemic heart disease are the contraindications.
Varenicline This alpha 4 beta 2 subtype NR selective partial agonist has been marketed as oral tablets in many countries (UK, USA, Europe, etc) to help smoking cessation. Recent evidence has shown that the reward(reinforcing) action of nicotine is exerted through the alpha 4 beta 2 subtypeof neuronal NRs which are mainly localized in nucleus accumbens and other mesolimbic areas.
Activation of these NRs by nicotine induces DA release which produces feelings of satisfaction/reward and has reinforcing effect. Since varenicline is a partial agonist at these receptors, it provides some level of nicotine substitution, but blocks the reward effects of smoking. Clinically it has been found to reduce craving as well as nicotine withdrawal symptoms in those who stop smoking. Abstinence rates at one year of cessation are comparable to those of nicotine replacement and of bupropion. However, varenicline is not entirely safe. Side effects noted are mood changes, irrational behavior, appetite and test disturbances, sleep disorder and agitation. Warning has been issued that it may promote suicidal thoughts.
Bupropion This atypically antidepressant inhibits reuptake of DA and NA, and has been marketed as a sustained release tablet specifically for smoking cessation. Clinically efficacy has been rated equivalent to nicotine replacement, and it has produced fewer side effects like insomnia, agitation, dry mouth, and nausea, but not sexual side effects.