According to Wikipedia, Nootropics are “drugs, supplements, or other substances that improve cognitive function, particularly executive functions, memory, creativity, or motivation, in healthy individuals.”

There are a few things you should know before wasting your hard earned money on anything that promises to make you smarter, more motivated, or reverses your impending dementia.  If you really are in the beginning stages of dementia, consult a good doctor and don’t buy stuff you see advertised heavily on Fox News Channel. The one that comes to mind is the jellyfish thing. We won’t mention the name because we are adverse to ugly tweets and lawsuits. If you are rich and healthy, give it a shot. Try ingesting strange things into your body to see how it works. You will be doing a clinical study with N=1.

Another word you should know, also defined on Wikipedia, is xenobiotic: “A foreign chemical substance found within an organism that is not normally naturally produced by or expected to be present within.” Drugs are xenobiotics as are many substances from so called natural supplements. Many things in food are xenobiotics. How your body processes these foreign substances and renders them harmless is very complex and not everyone handles them the same. Some people cannot handle gluten or lactose.

The next thing to learn about if you want to mess around with stuff to make you smart is the body’s cytochrome P450 mixed-function oxidase system.  It’s the body’s way of taking care of a lot of stuff the digestive tract, or other mechanisms didn’t handle completely. The P450 system is determined genetically. Something that you can handle well may kill someone else.  You can have genetic testing to see which isoenzymes you produce and how active they are, but it is largely a waste of time and money at this point.  Doctors deal with it empirically by trial and error, trying different drugs and adjusting the doses.

Let’s look at cytochrome P450 1A2, abbreviated CYP1A2. Its activity in the body helps detoxify xenobiotics such as caffeine, and acetaminophen.  Acetaminophen can kill you and you don’t know what a lethal dose is for you until you try it. Even then it may depend on what else you have been eating, if you are dehydrated, or if you eat your vegetables. Caffeine, like acetaminophen, can kill you and the lethal dose will vary. The median lethal dose (LD50) in humans is estimated to be 150-200 mg per kilogram of body mass.  Don’t depend on this number. It only kills half of those who overdose.

Back to nootropics, which we really never left:  Caffeine is a good one- pretty safe and a weak inhibitor and substrate of CYP1A2.  Some people can detoxify the stuff all day long and sleep like a baby. Others handle a cup in the morning. It’s not simply a matter of detoxifying it. Your genes determine sites in your body that it binds to, some well, others not so well. Boys don’t handle it as well as the ladies, generally.

What about modafinil?  It’s an inhibitor of CYP2C19, and inducer of CYP3A4 so if you are taking any drugs for therapeutic reasons you will probably mess up your treatment.  Besides it is a prescription drug and your doctor will need a diagnosis such as shift work-sleep disorder to feel good about giving you the prescription. But if you are old, have high blood pressure and are on a long list of drugs, the doctor will warn you about a myriad of drug interactions and suggest that you quit your night job.  Oh, but we forgot. You are over 50 and retired.  Right?