What constitutes the main effect of a drug, and what constitutes the side effect? Aspirin relieves headaches, but also thins your blood as a side effect. Unless you are taking aspirin to prevent a heart attack, and then it is the other way around. With psychoactive drugs, that target one or more neurotransmitters, it can be even harder to sort out. It takes complicated research to figure out the complicated effects of many psychoactive medications.
Here is a story about a complicated study that looks at one effect of one well-known drug, bupropion, which is marketed as both Zyban and as Wellbutrin. The patients studied were all ADHD patients, boys and girls, ranging from 9 to 18 years old. Half were given a daily dose of bupropion, and half were given a placebo, and then they were followed for about a year.
Wellbutrin is marketed as an antidepressant. Why give people with ADHD an antidepressant? At first glance, this seems odd at best. Most modern antidepressants, like Prozac, Paxil, and Zoloft are SSRIs (selective serotonin reuptake inhibitors). They primarily target the neurotransmitter serotonin, which helps to regulate mood, among many other functions. Wellbutrin, by contrast, targets dopamine primarily, as well as norepinephrine and serotonin. All three play a role in mood regulation, so Wellbutrin provides an alternative when SSRIs are not very effective. Norepinephrine and serotonin may be at least as important in depression, but it is the dopamine that we focus on here.
Dopamine is another neurotransmitter, one that is associated with motivation, pleasure, rewards, and addiction. Ritalin, the best-known drug which is used to treat ADHD, boosts dopamine levels. According to Nora Volkow, of Brookhaven Laboratories,
“We now know that by increasing the levels of extracellular dopamine, you can activate these motivational circuits and make the tasks that children are performing seem much more exciting. By raising that level of interest, you can significantly increase the ability of the child to focus on the task.”
In other words, a controlled rise in dopamine levels improves motivation and focus in kids who have trouble with both.
Compared to cocaine or amphetamines, which also boost dopamine, ritalin’s action is much slower (when taken in pill form). That probably explains why cocaine and amphetamines are highly addictive, but Ritalin is not. A slow boost in dopamine may also explain why bupropian/Wellbutrin is effective as an ADHD treatment. It is working in a similar fashion to Ritalin, though by a different chemical mechanism.
So one drug, bupropion, is useful in treating both depression and ADHD. But what does this have to do with smoking?
Zyban, which is exactly the same drug as Wellbutrin, is marketed as a helper in stopping smoking. As far as I know, there is no definitive research to show how it works. But I will speculate that since nicotine in cigarette smoke provides a dopamine boost, nicotine withdrawal involves the body expecting that dopamine boost and not getting it. Zyban may relieve that craving by raising dopamine levels, although more slowly and not as much as nicotine does.
Now, back to the complicated study. If bupropion (as Zyban) helps people quit smoking, should it also help adolescents avoid smoking in the first place? Dr. Michael C. Monuteaux and his colleagues (reported in the Journal of Clinical Psychiatry, July 2007) tested this by experimentally manipulating whether patients got bupropion or a placebo. They could not, of course, manipulate whether the patients had ADHD. They all did. Nor did they control whether they were taking Ritalin or another stimulant-based drug, but they carefully tracked this. They had patients of different ages, but the results cited in the news story do not point to any age-related differences. They checked on the outcome variable, whether or not the patients smoked, by looking for a nicotine by-product in their urine.
The result must have been disappointing: The patients in the bupropion group were actually more likely to start smoking than the patients in the placebo group. The drug that works well for stopping smoking was no good at all in preventing these patients from starting to smoke. I don’t know why that was any more than Dr. Monuteaux. I can speculate that maybe starting and stopping reflect different underlying neural mechanisms.
There was another result. Unexpectedly, the patients who were taking stimulant-based drugs, like Ritalin or a generic equivalent, were less likely to smoke. So now Ritalin may turn out to have an unexpected, but beneficial side-effect. As usual, we need more research.
One question lingers with me most of all: Why are kids with an ADHD diagnosis more likely to take up smoking in the first place. Some researchers have suggested that this is an attempt to self-medicate. That raises the interesting possibility that understanding more about nicotine addiction may help us to understand more about ADHD as well. But I promise it will still be complicated.
I am 40 years old, and have been smoking for 28 years. When I quit a year ago, I could no longer function. I could not focus. I was ADD in an extreme way. I had always been ADD, but I always had it under control, till I quit smoking. Self Medicated? You bet! Even after being quit for a year, I craved nicotine. Not to relax, but to think! The moment I started taking Focalin, the desire for nicotine disappeared. I am a firm believer in the connection, but my doctor still denies it exists.
Comment by Ariel — September 20, 2007 @ 2:08 pm
Oh, and let me add this.
My doctor tried anti-depresants before trying ADD drugs. Both Welbutrin and Lexapro sent me into a chemical depression.
Comment by Ariel — September 20, 2007 @ 2:12 pm
The question of whether Zyban helps prevent smoking is related to how the drug interacts with the body. The way I see it there are two possibilities:
A) The drug dulls the effects of the cigarettes.
B) The drug provides some of the stimulants that cigarettes do.
In case A, the drug would work by removing the incentives for smokers to smoke. The disincentives (cost, health, etc.) would then overwhelm the benefits, and people would stop smoking. In case B, smokers would no longer need to smoke to receive the effects, and would refrain from smoking as well. Case B is what was suggested in the main post (Zyban provides a dopamine boost similar to that of nicotine).
According to http://www.quitsmoking.com, “treatment with ZYBAN reduced withdrawal symptoms compared to placebo… treatment with ZYBAN showed evidence of reduction in craving for cigarettes or urge to smoke compared to placebo.” This also supports case B – that Zyban has replaced the active ingredients in cigarettes.
It has been well-documented that first-time smokers often experience a negative reaction to cigarettes. Coughing, nausea, and light-headedness are all common side effects. For non-smokers, case A would probably prevent people from commencing smoking. They would not feel that any of the positive side-effects and would therefore have no incentive to continue.
However, if B were the case, this may serve to promote smoking. When people take Zyban as it is regularly prescribed, they are using it to replace a stimulant that they are already accustomed to. They use it explicitly so that they can refrain from smoking. When non-smokers take Zyban, they are introducing a new stimulant to their body.
The unexpected effect of this might be to dull some of the first-time side-effects that teens feel – they are now accustomed to the active ingredients. Because they don’t have this initial adverse reaction, they may be more inclined to continue. The second unexpected effect is that people who took Zyban under this trial may become addicted to its effects similar to the way people become addicted to cigarettes. When they duplicated the effect by smoking, they were more inclined than others to continue because they were already addicted.
I would be interested in seeing is study replicated with Chantix instead of Zyban. According to http://www.about.com, “if a person smokes during the course of [Chantix] treatment, the drug impedes smoking satisfaction by blocking nicotine from binding with these same receptors.” This seems to fit with case A and may have a better result for the reasons outlined above.
(©2006). Zyban. Retrieved 9/23/07, from http://www.quitsmoking.com/zyban/index.htm
Martin, Terry. (10/23/2006). Smoking Cessation Aids. Retrieve 9/23/07, from http://quitsmoking.about.com/cs/howshouldiquit/a/quitaids.htm
Comment by Paul Brehm — September 23, 2007 @ 3:01 pm
Ariel I’m hearing you. I’m ADHD and have smoked for over 30 years and have had the same profound non-functionality when I stopped.
I have tended to be very irregular with my meds. Sometimes I’d take it, sometimes not. I decided to tackle smoking again and became regular with the meds, since both nicotine and ritalin boost dopamine. I have noticed how reduced my need for nicotine is when the ritalin is active; I can focus and don’t even think about cravings for long periods, only desiring a much reduced dose of nicotine gum. I never tried brupropion.
Comment by Grea — February 20, 2008 @ 5:24 am
I was diagnosed with ADHD when I entered high school. I had always been hyperactive as a child, but not until I was diagnosed with the “condition” did I think something was wrong with me. My psychiatrist recommended that I begin to take Concerta, a Methylphenidate with a timed-release formula (http://www.myomancy.com/2007/04/concerta). When I would go to the doctor as a child, and he/she would prescribe me medicine, I just accepted it without really considering what chemical effect the cough medicine, or ointment, or methylphenidate would have on me. The summer before I entered college, I decided I had had enough of this mind-altering drug that I had so clearly become dependent on. The concerta had a significant impact on my ability to focus, and as a result, on my academic achievments. But I often felt there was a layer of film between me and the rest of the world, mentally removed from the situations I was physically present at.
So I quit. It wasn’t easy. I had an impossible time at-first, randomly deciding to take the concerta, but the result was unpredictable. Then I started smoking. Not only had I never tried a cigarette before the spring of my freshman year, but the idea of smoking had previously been idiotic and repulsive to me. I have not taken Concerta in almost two years, but I suppose I am now “self-medicating” with cigarettes. I did not really want to acknowledge this behavior as medicating, but I suppose after some self reflection that I do at times treat each cigarette as a dose of medication. So, in the short run, it is working for me. Thinking about the future, I am being absolutely foolish. Maybe its part of making stupid decisions in college, but perhaps I am getting myself into a far more grave situation. No pun intended.
Comment by 105 student — March 7, 2008 @ 9:11 pm
Hi, I am 40 years old, was on Ritalin from 1978-1983, after Ritalin my marks fell drastically and I could never really relax, Started smoking in ‘85 tried quitting 2 times with shocking effects on myself, household and family. It is today my third day on Zyban, 1 tablet in the morning, I could not sleep last night, and are very irritable today, I am still smoking as much as always. tomorrow I start with 2 tablets daily!
Comment by Elna — May 4, 2009 @ 9:51 am
I am in my early 20’s and have been smoking for 6 yrs. Was on Zyban in 2006 and quit smoking for 3 months, however getting back to university and stress depended back on the cigerattes. However, I was not consistent with the doses which could have caused my withdrawal symptoms. As many mentioned with Zyban trouble sleeping, jittery were side effects I encountered. I am currently on my 3rd week of Zyban once again, and around the end of the first week I could barely take a puff. So far, I am smoke free!
Comment by Racha — May 17, 2009 @ 3:16 pm
Interesting piece. I have been taking Bupropion for 10 days. I have ADD and suffer from depression. After 25 years smoking, I have not had a cigarette for four days now.
I also stopped taking my daily dose of Dexedrine (for ADD) as I was feeling paranoid and nauseous. As dopamine is involved in learning, maybe an excess of dopamine made everything noteworthy, including the mundane. If everything is significant, paranoia is guaranteed, eventually.
I’m quite impressed with Bupropion. Nothing else has affected my smoking habit like this. Normally, I would be climbing the walls by now. Instead I feel quite at peace. I have also been dusting off half-completed tasks, which is interesting. I am also less impulsive. I’m sure nicotine and ADD are linked in a fundamental way as I have suffered complete meltdown whenever I gave up before.
Comment by Grendel — June 3, 2009 @ 2:47 pm