Since the introduction of tobacco into the civilized world by Columbus' sailors returning from the Americas, nicotine has become the most widespread form of substance dependency in the world. It is legal, encouraged with advertising, and used in any human setting, although it causes more morbidity and mortality than all other drugs combined. Recidivism in individuals who attempt to quit smoking--75%--equals that of recidivism of heroin addicts.
A variety of methods to stop smoking addiction have been tried including hypnotism, psychotherapy, electro-shock aversion, and group counseling. A recent assessment of the success of smoking programs and clinics shows that fewer than half of the smokers participating in such programs quit and less than 25%-30% remain non-smokers 9-18 months later. Evan Richard I., Henderson Allen H., Hill Peter C. and Raines, Betteye: Current Psychological, Social, and Educational Programs in Control and Prevention of Smoking; a Critical Methodological Review. Atherosclerosis Reviews, 1979; 6:201-241.
It is well documented that nicotine has an agonistic action at nicotine receptor sites in the parasympathetic nervous system. Its primary action upon prolonged use is that of a blocking agent. While this activity is less documented in the central rather than the peripheral nervous system, the preponderance of such nicotine receptors appears to be located at the mid-brain level.
With chronic nicotine use, biochemical tolerance and dependency are developed at specific parasympathetic neuro-receptor sites by increased acetylcholine accumulation mediated via enzyme induction and/or de-repression through choline acetyltransferase.
Mammalian studies on the superior cervical ganglia show that chronic nicotine treatment causes acetylcholine increase of about 35%. Marked neuro-transmitter changes occur after withdrawal of nicotine resulting in the reduction of acetylcholine accumulation even to sub-normal levels, normalization of the choline acetyltransferase, and an increase of acetylcholinesterase to about 117% of controls. This activity results from the cessation of nicotine stimulation and an increased release of acetylcholine from nerve axons.
A "tobacco withdrawal syndrome" to nicotine abstinence thus comes about by elimination of the nicotine blockage at specific nicotine-cholinergic synapses. Tolerance and dependency developed by increased acetylcholine synthesis are now replaced by withdrawal, which is brought about by excessive acetylcholine stimulation. The final biochemical interpretation of nicotine withdrawal--i.e., excessive acetylcholine rebound bombardment of lower mid-brain nicotine receptor sites--is through acetylcholine inter-synaptic stimulation of predominently muscarinic cholinergic sites at higher neuronal levels, including the cerebral cortex. Physical effects of cessation of tobacco smoking manifest themselves as a decrease in heart rate and blood pressure, increased irritability, nervousness, gastro-intestinal disturbances, EEG changes and lack of concentration. Similar effects exist through excessive acetylcholine stimulation mediated by di-isoflurophosphate (DFP) poisoning in humans.
In response to tobacco withdrawal symptoms, the dependent smoker resumes his nicotine titration for immediate relief and returns to his prior state of "normality." Glick, Jarvick and Nakamura tested a variety of anti-cholinergic and other drugs and found that only scopolamine and d-amphetamine decreased smoking (puffing pattern) in monkeys. Glick SD, Jarvick ME, and Nakamura NK, Inhibition by Drugs of Smoking Behavior in Monkeys, Nature, Aug. 29, 1970; 227: 969-71.