Adrafinil vs Modafinil: which is better eugeroic?

Adrafinil eugeroic has gained popularity in recent years due to its similarity to modafinil and relative accessibility.

Adrafinil is treated like a dietary supplement in the United States in that you can buy it without a prescription.

In terms of chemical structure, adrafinil is just like modafinil with the addition of an OH (hydroxyl group) to the amide nitrogen, forming a hydroxylamine.

Given the choice between the two wakefulness-promoting drugs, our verdict is to stick with modafinil. Adrafinil is just not very robust in comparison.
Adrafinil is a prodrug for modafinil. This means that it’s converted to modafinil in the body, which is the biologically active agent. Only a fraction of adrafinil is converted to modafinil, with the remainder being metabolized to the inactive modafinil acid. Modafinil acid is also a metabolite of modafinil itself. It’s unclear what percentage of adrafinil gets converted to modafinil. This percentage would be a good indication of adrafinil’s potency relative to modafinil.

We favor modafinil because adrafinil is an inefficient and roundabout way of getting modafinil in the body. Adrafinil also requires higher doses to achieve a similar effect.

adrafinil vs modafinil metabolism in the body

Adrafinil and Liver Toxicity
It’s rumored that adrafinil may be hepatotoxic (injure the liver). The idea is that since the conversion of adrafinil to modafinil (generic Provigil) requires liver enzymes, that adrafinil stresses the liver.

It remains unclear what CYP450 isoform (liver enzyme) converts adrafinil to modafinilic acid and modafinil. But there’s no solid evidence that adrafinil harms the liver.

I drink 1-2 units of alcohol a few times a week. I’m personally more concerned about the effect of alcohol on my liver than adrafinil. Alcohol-induced hepatotoxicity is so well-documented.

When was this rumor about adrafinil and liver damage started? An adrafinil user reported elevated transaminases in a blood test.

Transaminases are liver enzymes that will sometimes become elevated as a result of liver toxicity. But there’s lots of reasons for transaminase elevation.

This isolated report certainly isn’t evidence that adrafinil is worse than modafinil for your liver. Modafinil itself is rarely associated with transaminase elevation (<1%). Since adrafinil is a produg for modafinil, it’s difficult to disentangle the effects of adrafinil vs modafinil on liver function.

Adrafini vs Modafinil Dosage

The standard dosage of eugeroic modafinil is 200 mg. I personally take 100 mg since I’m sensitive to medication.

There was also a recent study demonstrating that taking 400 mg of modafinil in two divided doses was more effective for the treatment of narcolepsy than a single 200 mg dose in the morning1. So perhaps we should say that the range of reasonable modafinil doses is 100 – 400 mg, with 200 mg being a typical dose.

Adrafinil is a precursor to modafinil, and is considerably less potent.

A typical dosage for adrafinil is 600-1,200 mg. As you can see, higher doses of adrafinil are required to achieve the same effects as modafinil. That’s because in the body, not all adrafinil is converted to modafinil (some is directly metabolized to modafinilic acid).

Adrafinil vs Modafinil: Formal Comparison

Prodrug. Adrafinil is a precursor that is converted to modafinil in the body; therefore the effects of the two drugs are nearly identical
Schedule. Adrafinil is unregulated in the US and may be sold as a dietary supplement; modafinil is a schedule IV drug (US), requiring a prescription
Legal status. Adrafinil is marketed online and sold as a nootropic and nutraceutical, whereas modafinil can only be purchased online illegally
Potency. Adrafinil is less potent than Modafinil; therefore, higher doses are usually required to achieve the same effect
Dosage. A typical dose of adrafinil is 300-600mg vs 200mg for modafinil
Half-life. The half-life of adrafinil is about ~5 hours, but the effects last much longer because modafinil is the active metabolite and has a 14 hour half-life
Physical characteristics. Adrafinil is a whitish powder with an orange tint, whereas modafinil is white or off-white
Chemical Differences Between Adrafinil versus Modafinil (generic Provigil)
In terms of chemical structure, adrafinil is modafinil with a single modification: a hydroxyl group (circled in red below) is added to the amine (the functional group containing nitrogen). In the GI tract (due to stomach acidity), the hydroxyl group is protonated and reduced to the amine to form modafinal.

Effects of Adrafinil and Modafinil
Adrafinil is metabolized to Modafinil in vivo (in the body). Functionally speaking adrafinil and modafinil have identical pharmacological effects. These effects include, increased arousal and vigilance, decreased fatigue and possibly enhanced cognitive function in some subjects.

But since modafinil is the active metabolite of adrafinil, and not all adrafinil is converted to modafinil in the body (some is converted to the inactive metabolite, modafinilic acid), adrafinil is less potent than modafinil.

When we ask which is better eugeroic comparing adrafinil vs. modafinil, it is important to recognize that about twice as much adrafinil (in terms of mg) is required to produce the same effects as modafinil.

Drugbank characterizes adrafinil’s pharmacodynamics as follows:

Adrafinil is a prodrug; it is primarily metabolized in vivo to modafinil, resulting in nearly identical pharmacological effects. Unlike modafinil, however, it takes time for the metabolite to accumulate to active levels in the bloodstream. Effects usually are apparent within 45–60 minutes when taken orally on an empty stomach.

Legal Differences between Adrafinil and Modafinil

Adrafinil verses Provigil (modafinil) differ in terms of their legal status.

Modafinil is a prescription drug in the United States (Schedule IV). So modafinil is illegal to possess in the US without a prescription, but prosecutions are rare. A large number of people in the US purchase modafinil overseas ecause it is better in means of strength, dose,and other factors over modafinil; rarely parcels are seized in customs but no legal action seems to be rarely (if ever) pursued.

Adrafinil, despite being essentially a prodrug for modafnil, is unregulated in the US and may be sold as a dietary supplement. Hence, adrafinil is both less expensive and more readily obtainable, due to the legal risks associated with purchasing modafinil online.