Is Adrafinil Safe? | What You MUST Know

Yes, it’s an interesting research chemical—but is adrafinil safe?

The short answer is that according to a review of published clinical studies, adrafinil is well-tolerated by subjects and is not known to cause any serious adverse effects.

But no researcher wants to place their subjects’ health at risk, so it is reasonable to question whether adrafinil is safe.

Adrafinil is an atypical stimulant in that it lacks the adverse effects typically associated with psychostimulants while known to have cognitive-enhancing effects. It remains an interesting reference material for researchers interested in exploring ways to arrest or even reverse neurodegenerative processes.

In this guide, we’ll explore adrafinil’s history, benefits, and documented short-term and long-term side effects.

Let’s get to it.

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What Is Adrafinil?

Adrafinil is a wakefulness agent that was developed in France by scientists at Louis Lafon Laboratories in the 1970s [1]. It was developed specifically to promote vigilance and alertness in elderly patients and was eventually approved in France and released under the brand name Olmifon [2].

When ingested, adrafinil is metabolized into an amide called modafinil (CRL 40476) and an acid (CRL 40467). While little is known about the acid form of adrafinil, modafinil has been widely studied and is believed to account for at least part of adrafinil’s effects [1].

The Lafon Group released modafinil under the proprietary name “Modiodal” in France in 1994, while Olmifon fell into clinical disuse. Modafinil is a far more potent wakefulness agent than adrafinil, and soon became Lafon’s flagship product. The French medical authorities eventually withdrew marketing permission for Olmifon in the early 2000s and the manufacture of the drug, then produced by Cephalon France, ceased in 2011 [3].

Adrafinil is still produced as a research nootropic by a number of companies worldwide, so let’s turn our attention to the compound’s known benefits.

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Adrafinil Benefits

Compared with modafinil, the research on adrafinil is fairly sparse and what little research exists was conducted in France and is published in the French [1]. All studies involved elderly patients showing deficits in vigilance, attention span, behavior, and/or mood. These studies indicate that adrafinil offers multiple benefits, most notably increased vigilance and reduced fatigue when administered to elderly patients.

For example, a 90-day double-blind placebo-controlled study by Israel et al. found that 50 test subjects aged 65 and older who received three tablets of adrafinil per day (900 mg/d), “felt happier, more energetic, and less sleepy by the end of the 3 months.” They were given a set of tests at baseline and day 90, and assessed according to a Dynamic Intellect scale, Sleep Intake Questionnaire, and MacNair scale test. The results showed a “marked improvement” in the subjects’ vigilance, attention span, and power of recall [4].

An open trial by Kohler and Lubin, involving 304 patients aged 45 to 88 years, found that subjects who received 900 mg/d of adrafinil experienced “improvements in vigilance, attention, and concentration.” Their daily activities improved, as did their depression and anxiety levels [5].

These benefits were also observed in other clinical trials including Boyer et al. [7 in 1], Defrance et al. [16 in 1], and Fontan et al. [29 in 1], all of which found that adrafinil produced notable improvements in wakefulness when administered to elderly patients.

We know that adrafinil can be an efficacious vigilance-promoting agent, but what side effects and safety issues have been associated with adrafinil?

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Adrafinil Side Effects and Safety

The clinical trials conducted to date indicate that adrafinil is safe and generally well-tolerated [1, 4, 5]. There is no evidence to suggest that it causes serious adverse events and there is no suggestion that anyone has ever died or even overdosed as a result of taking adrafinil.

There are still some things you should know about the side effects and safety profile of adrafinil before deciding whether to conduct research on it.

Short-term side effects

The majority of studies involving adrafinil have been short-term studies lasting 90 days or less. These studies show that adrafinil can lead to the following short-term side effects [1]:

• Sleeplessness
• Increased stress
• Aggression
• Nausea [4]
• Irregular heartbeat
• Mouth dryness [29 in 1]
• Stomach pain
• Skin irritation
• Liver issues
• Orofacial dyskinesia

Long-term side effects

As of writing, we simply lack the data to conclude on whether adrafinil causes any long-term side effects. There has been virtually no long-term research into adrafinil’s side effects and this remains a clear area for further study.

What we do know is that the French medical authorities withdrew marketing permission for Olmifon, citing a high risk-to-benefit ratio and the risk of adverse effects [6].

Aside from clinical studies, the best source of information about adrafinil’s long-term side effects is an Olmifon Summary of Product Characteristics document published in the French language by Cephalon France [7]. This document lists the possible side effects as:

• Transient episodes of agitation, confusion, aggression or psychic excitement;
• Insomnia;
• Exceptionally, involuntary, or abnormal movements such as oral-facial dyskinesias or tremors of the extremities;
• Mood swings;
• Manic depression;
• Headache, gastralgia, and rashes.

According to this document, “these manifestations resolved spontaneously upon discontinuation of treatment and sometimes, despite continued treatment or by reducing the daily dose”. This suggests that adrafinil may cause long-term conditions—such as oral-facial dyskinesias—even after the end of a treatment regimen.

So is adrafinil safe? Let’s find out!

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Is Adrafinil Safe? | 2022 Guide

Side effects are a big component of safety, but there are a number of other safety considerations you should be aware of before deciding whether to conduct research on adrafinil.

Adrafinil and the liver

As adrafinil is metabolized by the liver, it does place extra strain on this organ and may cause elevated liver enzyme values. It is therefore plausible that over a long period of time, adrafinil could have a damaging effect.

While we have not been able to find any conclusive or direct research linking adrafinil to liver issues, this is largely due to the short-term nature of the studies conducted to date.

The Olmifon Summary document does state, in the section titled “Precautions for Use,” that in cases of “severe hepatic impairment and renal impairment, use a lower dosage (300 to 600 mg, per day)” and “in case of prolonged treatment, it is advisable to monitor alkaline phosphatase” [7].

This suggests that subjects with a history of liver issues, or who are at risk of developing liver issues, should not participate in adrafinil research.

Adrafinil should not be administered to subjects with certain conditions

Referring back to the “Precautions for Use” section in the Olmifon Summary document, the guidelines state that adrafinil should not be administered to the following groups [7]:

• Subjects with epilepsy;
• Subjects with severe hepatic impairment or renal impairment;
• Subjects who are pregnant, regardless of term.

Having discussed the main precautions that researchers should take when selecting adrafinil test subjects, we can discuss the possibility of overdose.

Adrafinil overdose?

In general terms, an overdose occurs any time a subject ingests more of a substance than the recommended dose. Is an overdose of adrafinil dangerous?

According to Cephalon France’s Olmifon Summary document, “no case of adrafinil overdose has been reported” [7]. Note that while the document was dated to 2011, adrafinil by that point had been around for nearly four decades.

Toxicology tests conducted on animals reinforce adrafinil’s safety in this regard. In studies with dogs, fatalities were only seen at doses of 200 mg/kg [49 in 1]. This suggests that a human subject would have to take a vast amount of adrafinil to come anywhere near a fatal dose.

The Summary document states that “in case of overdose, the manifestations expected are of the neuropsychiatric type in relation to the pharmacological action of the product.” Symptoms of overdose include [7]:

• Agitation
• Excitement
• Confusion
• Aggressiveness
• Insomnia
• Mood swings in people with manic depression

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Is It Safe to Take Adrafinil Every Day?

It appears to be, yes.

In the clinical trials out of France, it was common for researchers to give between 300 mg and 900 mg a day to elderly individuals every day for three months [1, 4, 5]. Each of those trials concluded that adrafinil was safe.

It is important to note that these trials lasted less than three months and involved elderly patients. Adrafinil’s safety over the long term is under researched and little understood. In this context, nootropics researchers are well-advised to consider administering adrafinil no more than two to three times per week as a safeguard against the potential for liver damage.

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How to Take Adrafinil Safely | 5 Quick Tips

That was a lot of information—we know. Here is the condensed version of our five tips on how to safely administer adrafinil to test subjects.

1. Administer adrafinil at 300-900 mg/d. Past clinical trials have seen adrafinil dosed at up to 900 mg/d. Doses can be scaled down if test subjects begin to report adverse effects.
2. Advise test subjects to stay hydrated. Several of the side effects, like headaches, dry mouth, and nausea, are related to dehydration. It is prudent to advise test subjects to stay hydrated to minimize the occurrence of these side effects.
3. Administer adrafinil in the morning. One of the main effects of adrafinil is that it increases wakefulness and can cause insomnia. Advise test subjects to take their dose early in the morning to avoid this side effect.
4. Limit short-term studies to 90 days. Most trials have lasted 90 days or less. Limiting experiments to that length of time is advisable, unless you specifically plan to study the long-term effects of adrafinil.
5. Monitor alkaline phosphatase levels in test subjects. In case of prolonged experiments, be sure to monitor alkaline phosphatase in test subjects and consider administering the nootropic no more than two to three times per week.

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Adrafinil Safety Guide | Verdict

The available research suggests that adrafinil lacks the harmful effects seen with other psychostimulants and has a good safety profile. It has not been linked to any fatalities or long-term side effects to date, so long-term trials appear warranted.

Although most nootropics researchers have focused their attention on modafinil, adrafinil remains an interesting research chemical with many possible therapeutic applications including as a cognitive enhancement agent and as a treatment of deficits associated with movement disorders.

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