💊 How Can You Know How Well You Will Respond to Modafinil?

How Can You Know if and How Modafinil Will Work for You?

So, this blog post is all about how your genes control or determine how you might react to modafinil. Yes, genes do affect how we metabolize drugs. Genetic variations in our genes (but also in regions between genes), which we also call genetic mutations, make us different individually, and those mutations determine how we react to drugs and medications. If you want to learn more about this field focused on the link between genes and drugs, you can check my intro post here.

In this blog post, I will show you how to leverage your 23andMe or Ancestry DNA data for free to learn more about how you might react to modafinil.

This is the first blog post in a series I will write in try to popularize genetic testing, more specifically, pharmacogenetic testing that you can do by just browsing your 23andMe or Ancestry DNA data. You don’t have to pay anything extra, you have a wealth of information already available in your genotype datasets that you can download from 23andMe or Ancestry DNA if you did those tests.

In this concrete blog post, I will present the gene and genetic mutations that affect the metabolism of modafinil, and if you have 23andMe or Ancestry DNA data, you can quickly check your data and see how modafinil will affect you, or you can ask me I will help you for free. You can contact me here.

How Does DNA Determine How We React to Drugs We Take?

Here, I will try to explain it quickly, and for those interested in more detail, please check my post here, which focuses explicitly on this topic.

Short and simplified, genes code for proteins, and among many proteins, there are very large numbers of enzymes, and specific enzymes are involved in the processing of drugs and medications we take.

So, specific changes in our genes (those we call genetic mutations [INSERT LINK]) result in changes in enzymes, which are further reflected in how efficient those enzymes are in processing drugs.

As I mentioned, a whole scientific field in genomics called pharmacogenomics focused on researching how genetic variations in our genes affect how we process drugs and medications we take. If you want to learn more, you can read my large blog post about pharmacogenomics and pharmacogenetics here.

What Is Modafinil?

Modafinil is a medication mainly used to treat excessive sleepiness and promote wakefulness. Modafinil is often prescribed to individuals with conditions such as narcolepsy, sleep apnea, and shift work sleep disorder, which can cause extreme drowsiness and difficulty staying awake during the day.

The exact mechanism of action of modafinil is not fully understood, but it is thought to work by affecting certain neurotransmitters in the brain. Specifically, it appears to increase the release of dopamine, a neurotransmitter that plays a role in wakefulness and motivation. Modafinil may also influence neurotransmitters, such as norepinephrine and histamine, which can contribute to wakefulness and alertness.

Simply, modafinil helps you stay awake and alert by altering the balance of chemicals in the brain that regulate your sleep-wake cycle. It is considered a wakefulness-promoting agent rather than a stimulant like caffeine or amphetamines, and it tends to have fewer side effects and less potential for abuse than traditional stimulants.

Modafinil as a Smart Drug

It is important to mention that modafinil is sometimes called a "smart drug" or a nootropic because it has been associated with cognitive-enhancing effects. Some people use it off-label to improve their focus, concentration, and overall cognitive performance, especially when they need to stay awake and alert for extended periods of time, such as during long work or study sessions.

What Is Narcolepsy

Narcolepsy is a chronic neurological condition that affects a person's ability to control their sleep-wake cycle. Simply, narcolepsy causes unexpected and uncontrollable episodes of extreme daytime sleepiness, which can lead to sudden and irresistible bouts of sleep, even in inappropriate or dangerous situations. People with narcolepsy may also experience symptoms like sudden muscle weakness or loss of muscle control, sleep paralysis, and vivid dream-like hallucinations when falling asleep or waking up. These symptoms can significantly disrupt a person's daily life and activities.

How to Quickly Check if This Drug Is for You Using 23andMe or Ancestry DNA Data?

Now, let’s go back to the main topic of this blog post, which is how we can check how one may react to modafinil if one has narcolepsy based on the genetic data available in 23andMe and Ancestry DNA data sets.

Here, I will focus on the most important genetic variants that have been reported in the relevant peer-reviewed scientific studies:

The genetic mutations you want to check for are the following:

1. Genetic variant/mutation located in the ABCB1 gene with ID code rs1045642

2. Genetic variant/mutation located in the ABCB1 gene with ID code rs1128503

3. Genetic variant/mutation located in the ABCB1 gene with ID code rs2032582

The above-listed three mutations have specific alleles that have been directly associated with modafinil's effect among individuals with narcolepsy. I will provide detailed explanations for those in the next paragraph.

Effect of rs1045642 Located in the ABCB1 Gene on Response to Modafinil

Individuals with rs1045642 genotype AG and narcolepsy may have an increased response to modafinil compared to individuals with genotype AA or GG. However, it is important to note that other clinical and genetic factors can also affect one’s response to modafinil.

Effect of rs1128503 Located in the ABCB1 Gene on Response to Modafinil

Individuals with rs1128503 AG genotype and narcolepsy may have an increased response to modafinil compared to individuals with AA or GG genotype. Again, it is important that other clinical and genetic factors can affect one’s response to modafinil.

Effect of rs2032582 Located in the ABCB1 Gene on Response to Modafinil

Individuals with the rs2032582 AC genotype and narcolepsy can have an increased response to modafinil compared to individuals with the CC genotype. Here again, other genetic and clinical factors can also influence one’s response to modafinil.

Figure 1: Genetic variants and corresponding genotypes associated with response to modafinil among individuals with narcolepsy

Important Note

It is very important to note this is not medical advice. I urge you to use your genetic information for the above three mutations (rs1045642, rs1128503, and rs2032582) and consult a medical professional.