Nicotine is one of the most widely used drugs of abuse. It is found worldwide, although it only became widespread after the discovery of the New World. After being introduced to Europe, the tobacco habit spread rapidly and widely.
Nicotine is produced by many species of Nicotiana, a genus in the nightshade family, like deadly nightshade, jimpson weed, and tomatoes and potatoes. In particular, Nicotiana tabacum is the cultivated variety. Interestingly, this plant is not found in the wild, and is thought be a deliberate hybrid of other Nicotiana species found in the wild.
A link to the introduction to this series from last week can be found here.
Before we discuss nicotine in particular, we will have to get wonkish for a bit and discuss the central nervous system and the peripheral nervous system and in particular the neurotransmitter acetylcholine. Acetylcholine is one of the most important of dozens of neurotransmitters, and the first to be discovered. Here is a structural diagram of acetylcholine, along with nicotine:
Acetylcholine
Nicotine
The central nervous system basically consists of the brain and spinal cord, both of which are enclosed in bony protective layers due the the critical functions that they perform. There is also the blood/brain barrier, a mechanism that prevents many toxins and drugs from penetrating from the bloodstream into the brain. Nicotine has the ability to cross the barrier with no problem. The central nervous system is responsible for the coordination of all nervous activity in higher animals, and also for cognition in the highest animals, including us.
The peripheral nervous system consists of basically all other nervous tissues, and is the "bus bar" that connects the central nervous system with the target tissues and organs. There is no blood barrier, so toxins have an easier time getting to the peripheral system. Obviously, it by necessity is not encapsulated in bone since those neurons have to reach soft tissue. The peripheral nervous system consists of two major divisions, the autonomic nervous system and the somatic nervous system. The somatic one is generally under conscious control and is responsible for voluntary movement, the senses, and other important functions. The autonomic one, on the other hand, is responsible for little things like respiration, heartbeat, and hundreds of other functions essential for life beyond voluntary control. Sometimes the systems sort of merge, as it is possible to exercise voluntary control over breathing. However, if you hold your breath long enough, you pass out and the autonomic system kicks in and you start breathing again.
The autonomic nervous system is subdivided into three groups: the sympathetic nervous system, the parasympathetic nervous system, and the enteric nervous system. The sympathetic system generally uses norepinephrine as its major neurotransmitter. The parasympathetic system uses acetylcholine as its major neurotransmitter. The enteric system uses both, since it is really an artificial contrivance, being nothing but the combination of the other two systems that control all activities from mouth to anus. There are other neurotransmitters involved with both of these systems as well, such as nitric oxide (the neurotransmitter the concentration of which is increased by the drug Viagra, so you can guess what function nitric oxide serves).
In a broad overgeneralization, one can think of the sympathetic system of being an "excitatory" system, and the parasympathetic system as being an "inhibitory" system. Actually, this is not really correct. In reality, they are opposing systems that, when everything is functioning properly, preserve homeostasis in the organism, that is, a balance required for life. We will focus on the parasympathetic system, since that is were nicotine works.
All nerve impulses are really electrical signals, caused by a gradient of sodium and potassium (amongst other ions) concentrations in a given nerve. When this impulse reaches the end of the nerve, to the synapse, something as to bridge the gap to the next neuron in the chain. That something is a neurotransmitter, and in the case of the parasympathetic system, that neurotransmitter is acetylcholine. Basically, when the impulse gets the the end of the first nerve (the presynaptic neuron), acetylcholine is released and migrates the space (the synaptic junction, or synaptic cleft) between the first neuron and the second one (the postsynaptic neuron). The acetylcholine stimulates the second nerve to propagate the impulse to further neurons. Actually, this is the basic method in which just about all neurotransmitters work.
I know that this is getting very boring, but bear with me just a few more sentences. This is a critical concept for understanding the mechanism of how all drugs of abuse work. After triggering the postsynaptic neuron, the neurotransmitter has to stop working or overload will occur. In some systems, the presynaptic neuron actually reabsorbs the neurotransmitter. In this case, an enzyme (acetylcholine esterase) destroys the neurotransmitter. (The presynaptic neuron makes more pretty quickly for next time). Here is a picture showing the process in graphic form:
It turns out that there are a couple of different parasympathetic receptors, all of which are sensitive to acetylcholine, but some of them are also sensitive to nicotine, which is why you kept on reading. Nicotine mimics acetylcholine for these receptors, and causes the same neural impulse transmission. However, acetylcholine esterase does not have any effect on nicotine, so those nerve impulses continue to fire, and fire, and fire. The result is an artificially high activity of certain effects. This, in turn causes a cascade of other neurotransmitters and hormones to be released.
The effects of nicotine are so complicated that this essay could easily turn into a heavy bound volume, but let us just skim through them (think of Translator as your Cliff Notes version of pharmacology). Almost instantly (nicotine is rapidly absorbed either by smoking or bucchal contact, as in snuff) a release of epinephrine (aka adrenaline), causing a release of glucose to the blood and a feeling of stimulation (paradoxically, some find this to be a calming effect). Then, as the mimic of acetylcholine, parasympathetic pathways are reinforced, causing the pupils to contract somewhat, but more importantly, since nicotine crosses the blood/brain barrier, and mimics acetylcholine, the central nervous system is also stimulated, so alertness increases. How many smokers out there light up another one when they are trying to find the right phrase for their blog, or to study for an exam? Nicotine also seems to promote actual acetylcholine release, further increasing the effect.
Another neurotransmitter that is involved is our old friend, dopamine. Nicotine seems to have a direct effect on increasing the release of dopamine, thus stimulating the reward center in the brain directly. This, in combination of other pleasurable feelings (rising blood glucose is a pleasant thing, because of the energy it gives), causes nicotine to be extremely addictive. People develop a personal relationship with nicotine, like it is an old friend.
On a personal note, I smoke. I have for a long time, and am getting ready to quit for several reasons, not the least of which involve the deleterious health effects. The pocketbook aspect is fairly large as well, and getting ready to increase since both the federal government and the Commonwealth of Kentucky are increasing taxes, starting 01 April, by almost a dollar a pack. I quit once, years ago, for a year and a half, so I can do it again. Saying good-bye to Camel nonfilters will be hard, though. But say good-bye I will, with help from the gum (it works well, and is easier to quit). Unfortunately, I suffer from a family trait of temporal mandibular joint malformation, so I try not to chew more than I need to do. I well remember feeling my grandmum's jaw crunch, and mine does as well. With the nicotine gum, a little chewing goes a long way, and most absorption is bucchal, so you "park" it for a good period of time.
Camel nonfilters have one the highest delivery rates of nicotine of all cigarettes, around 4 mg per fag. I once compared my Camels with the ultra light cigarettes that my brother-in-law's wife smoked, and found that an entire carton of hers contained less that one cigarette of mine. No wonder she became nauseous after smoking one of mine.
It turns out that nicotine acts, in some ways, like nerve agents ("nerve gas") do. Remember the part about acetylcholine esterase destroying the acetylcholine making the synaptic connection? Nicotine is immune from this enzyme, so it intensifies the impulses. Nerve agents inactivate the enzyme that destroys acetylcholine, causing the nerves to fire away without control, leading to what is a really horrible death. I wrote a series about chemical warfare agents a couple of years ago here, so you can hit my profile and find them if you are interested.
This brings up the final point. Nicotine, in itself, does not seem to be carcinogenic, although some of its metabolites may be. Tobacco is replete with many other substances, some of which are definitely carcinogenic. When burnt, polycyclic aromatic hydrocarbons (PAH's) are also formed, and many of them are known carcinogens. I urge all of my readers to join me in quitting, beginning 01 April this year. Perhaps this series can become somewhat of a support group for each other.
As always, all comments, question, corrections, and flames are welcome. Even though I know that you want to light another cigarette to calm down when you hear me say this, I always learn much more than I could possible teach by writing this series because of the feedback that each of you provide.
I think that next week we will discuss alcohol, another very widespread drug of abuse, if there is enough interest. Then we will get into the ones that are illegal.
UPDATE: Folks, I am going to sign off now. The headache is still present and the front has brought in something that has my nose running, and the post nasal drip is sort of making my stomach queasy. I will check comments tomorrow evening before the 24 hour limit for response. Thanks to everyone who read and commented. Next week we shall cover alcohol.
Warmest regards,
Doc
