The active ingredient in cigarettes in nicotine, and its extremely addictive nature is reflected by the fact that it is used by approximately 35% of the US population.1 Nicotine works by binding to one type of acetylcholine receptor in the body.

This nicotinic acetylcholine receptor (nAChR) is endogenously activated by acetylcholine, but is also highly responsive to the drug nicotine. When activated by either acetylcholine or nicotine, the ligand-gated nAChR opens and elicits an immediate response from the effector cells. Cells that have nAChR are found throughout the body, particularly at neuromuscular junctions and in the brain. The immediate effect of nicotine on the cholinergic system is actually a release of epinephrine (which is also known as adrenaline) and a speeding up of the heart. That sensation, however, rapidly subsides and the tobacco user then experiences a state of calm. In addition to activating the body’s cholinergic system, nicotine blocks the release of insulin from the pancreas and causes a brief period of elevated blood sugar and suppressed appetite. Because nAChRs can become less sensitive to the effects of nicotine, repeated use makes the body less responsive to the same dose and people who use nicotine need to use more to get the same effects. In addition, withdrawal from nicotine makes the user feel edgy and agitated, often leading to chain use in order to avoid these negative feelings.

The peripheral effects of nicotine may cause some of the feelings of physical relaxation, but it is the effects on the brain that are responsible for its addictive properties. When nicotine activates nAChrs in the brain, it causes the release of dopamine, the neurotransmitter associated with feelings of comfort and well-being. This pathway of dopamine release has also been called the “reward system” and is activated similarly, but to a greater degree, with other drugs such as cocaine, amphetamines, and alcohol. In addition, the reward system responds to pleasurable activities such as having sex, eating food, or receiving a lot of money. Activation of the reward system involves dopamine release from an area of the brain called the nucleus accumbens and activation of D2 dopamine receptors at target brain regions, resulting in inhibition of cAMP in these target brain regions. With continual stimulation, the reward system becomes more sensitive to the drug, reinforces behaviors of that drug’s use, and motivates the individual to seek out situations in which the drug is available. This combination of factors is what makes addiction especially difficult to combat.

Caffeine functions similarly to nicotine in that it activates the reward system and also binds to a receptor designed for neurotransmitters; in particular, it binds to adeonsine receptors. In the case of caffeine, however, it blocks the adenosine receptors and prevents adenosine from acting on the receptor rather than stimulating the receptor. By blocking the adenosine pathways, caffeine prevents adenosine from calming neural systems and results in arousal. The specifics of these mechanisms have yet to be completely defined, but one place where adenosine has an effect is on dopamine cells. The disinhibition of dopamine cells will prolong their effect and this may be one reason why caffeine makes nicotine more rewarding.

A second mechanism that might play a role in the increased reward experienced by an individual drinking coffee and smoking a cigarette at the same time has to do with the second known mechanism of caffeine. It has a more global effect of altering the metabolic processes of cells throughout the body. Caffeine allows for build up of intracellular energy stores (ATP) by blocking the enzymes that usually breaking them down. This effect is similar to that imparted upon cells by epinephrine, the neurohormone responsible for arousal. Epinephrine is released initially when nicotine is used and the use of caffeine with nicotine may prolong the state of alertness and focus that is experienced in the initial phase of nicotine use.

Ironically, smoking can actually decrease the length of time that caffeine is effective. However, the use of both nicotine and caffeine at the same time initiates an intense feeling of alertness that may help people feel more awake in the mornings. In addition, the use of both drugs together can powerfully activate the brain’s reward system. The reward system will therefore crave continued activation to that degree and other parts of the brain will associate those feelings of well-being with the taste, smell, and situational aspects of nicotine and caffeine consumed with one another, further perpetuating their concomitant use.

1. National Institute of Drug Addiction, National Institutes of Health statistics. Available at: http://www.nida.nih.gov/ResearchReports/Nicotine/nicotine2.html#impact. Accessed: November 29, 2008.

This entry was posted on Sunday, November 30th, 2008 at 6:53 pm and is filed under Ask Dr.Molly . You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.