The Effects of Nicotine and Withdrawal on the Brain From Misstray early 2002 Its no wonder our metabolisms are so messed up. (Warning, this is long, but it's the best info on Nicotine I've ever read) From Medbroadcast.com "The Neurology of Addicitons/Nicotine: Addiction is a disorder or disease of the brain. The parts of the brain responsible for reward, pleasure and reinforcement simply don't work well enough in the addicted person. This condition is thought to be either genetically acquired or due to environmental stressors combined with prolonged or excessive ingestion of the addictive substance. Addiction-prone people are said to lack "hedonic tone". This means they spend more time feeling bad and are more likely to experience negative emotions such as dysphoria, anxiety, and feelings of depression. They are unable to comfort or soothe themselves. They discover, usually in their teens, that certain substances, such as alcohol, marijuana, stimulants, sedatives, narcotic analgesics, and nicotine make them feel better, even normal for a while. The problem is that over time the brain adapts, a process called "neuroadaptation", which changes the structure, function and chemistry of the brain. And so tolerance develops: it takes more drug to get the same effect. It becomes nearly impossible to get high. When they try to stop they feel much more dysphoria, anxiety or depression. Some of this neuroadaptation is reversible, but with prolonged, high-dose use of certain drugs, some of it may be permanent. Like all other addictive drugs, nicotine activates the brain's reward circuitry as described in the neurobiology of addictions. But in some ways nicotine is special. Addictive drugs have been classed as "uppers" or stimulant drugs and "downers" or sedating drugs. Nicotine is both, providing both stimulation and sedation. The brain is richly supplied in many regions with receptors responsive to nicotine. As well as activating the pleasure-reward areas in the mesolimbic system, nicotine stimulates much of the cerebral cortex, regions of the brain responsible for emotions, areas responsible for memory, arousal, and parts of the brain that regulate the nerves, hormones and organ systems of the body. It depresses central nervous system areas responsible for fight-flight (locus ceruleus) and appetite (hypothalamus). As with all addictions, during continued ingestion of the drug, changes called "neuro adaptation" occur. These changes result in increased tolerance to the drug and a group of symptoms characteristic of withdrawal if a constant supply of the drug to the brain is interrupted. The impact of nicotine: People will say they use nicotine to soothe their nerves in times of stress, to pick themselves up when feeling low, to reward themselves or to curb their appetites when hungry. They say nicotine increases concentration and lifts their depressed moods. It does these things via different areas of the brain. Experimental studies have shown that the performance enhancement and mood elevation provided by nicotine is more significant in the tolerant and dependent nicotine addict during withdrawal than in non-dependent individuals. The reason nicotine improves function in smokers is because it effectively medicates the mild impairment caused by nicotine withdrawal. The locus ceruleus, that part of the brainstem that releases chemicals similar to adrenaline in order to initiate the fight-flight response, is believed to be suppressed by nicotine. Withdrawal from nicotine in the dependent smoker removes the inhibition from this centre resulting in compensatory overactivity and increased release of noradrenaline, triggering feelings of anxiety and irritability. The withdrawal experience: Nicotine withdrawal can be very uncomfortable. Neuroadaptation in the tolerant nicotine dependent person results in a relative deficiency of dopamine in the reward/reinforcement centres of the brain, resulting in craving, feelings of depression or despair or even temporary anhedonia (anhedonia = inability to experience pleasure). Loss of the normal stimulant activities in various parts of the brain results in poor concentration. Areas important for memory, such as the hippocampus are temporarily impaired, resulting in complaints of short-term memory loss. The locus ceruleus, released from constant inhibition, releases norepinephrine resulting in anxiety, anger and irritability."