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.