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This week’s question comes from Joe, who asks “I’ve heard of certain medications, like Adderall and Provigil, that give people a tremendous boost in focus and work ability. Provigil is especially becoming popular with the Wall Street types. How do these drugs work and are there any major negative side effects?”
I think most people have heard of stimulants becoming popular with the big city finance types, starting with cocaine in the 80’s and moving to more sophisticated pharmaceuticals like these as the years progressed. More recently, these types of drugs have become popular with otherwise normal college and even high school students looking to get more done in less time. The military has been using pills like this to keep pilots and other essential personnel awake for days at a time since the early 20th century.
Before we start, one comment: contrary to what some people may believe, no pills as of yet actually make you “smarter” or otherwise enhance your pre-existing function. What they actually do is alter your perception of reality, directly in the brain and/or by systemically suppressing signals of fatigue. The same ability is present no matter what you take, just the drugs can temporarily ease the natural feelings of fatigue that would ordinarily hold back full function.
So to answer the question generally, we can split the drugs into two basic categories. The first category, which most people are familiar with, are stimulants. Stimulants are defined as any chemical that temporarily increases physiological function. Obviously this is a very wide definition that can apply to a wide variety of things. Some drugs we encounter every day are weaker stimulants, like nicotine, than others, like caffeine. Many stimulants are illegal, like cocaine and methamphetamine. Stimulants can and often do cause addiction. Likely the strongest widely available class of stimulants are amphetamines. Adderall is actually a mix of two different types of amphetamine salts, amphetamine and dextroamphetamine. Lets explore how amphetamines work in more detail.
Amphetamines function by causing a large rise in the levels of dopamine and norepinephrine in the brain and prevent their reuptake, allowing these chemicals to continue to exert influence longer than normal. The specifics of this action are not important to this discussion but are described very well in this article. We have already talked about the function of norepinephrine in the brain (here), so I won’t repeat myself. Take a peek at that other article if you need a refresher.
The changes in dopamine are also tremendously important. Dopamine is a neurotransmitter in the brain responsible for a wide variety of functions. One major function is control/ heavy influence over the reward and alertness centers of the brain. So when a substance causes a major release of dopamine, one effect is you feel really good, have a very positive mood, and are very alert. MDMA, the active ingredient in the drug ecstasy, exerts its influence largely by this mechanism (it also happens to be an amphetamine). This is also where amphetamines give us the ability to remain awake. High levels of dopamine can also have an impact on higher level brain functions such as motor control, causing abnormally high motor activity and low threshold for movement. This is possibly the source of the “jitters” people get when they take dopamine releasing drugs like amphetamines. It is also the reason movement is so difficult with Parkinson’s Disease, as the dopamine producing center of the brain is damaged and dopamine levels are lower than normal.
As you might imagine, amphetamines are incredibly addictive due largely to their reward center influencing mechanism of action. They also have negative side effects such as appetite suppression that can cause longer term health effects if left unchecked. As such, their use should be limited only to those instances where their value outweighs the cost.
The second category of drugs are non-stimulants. These are drugs that seek to mimic the individual effects of the stimulant drugs without similar side effects, including addiction potential. For the treatment of ADHD, sometimes SNRIs (selection norepinephrine reputake inhibitors) are used as an alternative method to amphetamines. This seeks to produce the increase in norepinephrine found in amphetamine medication without the associated addiction potential from dopamine-related activity.
The drug you mentioned, Provigil, attempts to do a similar thing by influencing dopamine levels without a massive increase all at once. By upticking the dopamine transporters in the brain, the levels are increased more gradually and causes the desired alertness without the dose of euphoria that underlies the addictive nature of amphetamines and other stimulants. Mind you, amphetamines do a similar thing, but they also cause a massive release and prevent reuptake so it is likely that transporter alteration is the least negative of the three effects. It also has an impact on norepinephrine, serotonin, and histamine levels in various areas of the brain through its impact on neurons in the hypothalamus, though this effect is much less well understood. However, unlike amphetamines, it seems to have some potential for real cognitive enhancement. There have been basic studies that show some value to this end, and as such this drugs and future drugs like it may actually start to approach a “brain pill” rather than simply tricking your body into not being fatigued.
On the face of it, Provigil seems to work for its intended purpose and is well tolerated, however its full mechanism of action is not well understood. Based on its known mechanism of action, it is likely much less addictive than amphetamines and other stimulants. However, because it is also much less well understood it is something that should also be treated with caution and used only as indicated/prescribed.
In sum, these different types of drugs often work as marketed, but each has their own positives and negatives. You should only use these drugs under the regular care of a physician who prescribes them to you for a legitimate condition. But, should you decide to obtain them outside of that, I would advise you tread carefully. While they may seem innocent at the time and certainly useful in many contexts, you may be making a deal with the devil in the process. There are much more beneficial methods of increasing alertness (exercise, meditation, etc.) than taking a potentially dangerous pill. I would suggest trying those before jumping to a pharmaceutical solution.
Hope this helps, Joe! Thank you for the question. As always, feel free to submit questions to me directly at the link above.
Till next time, tread lightly.