Adrafinil and Drug Tests | What You MUST Know

adrafinil and drug tests

Ethan Thorne

Last Updated February 14, 2022

Are you curious about adrafinil and drug tests?

This popular research compound has an interesting history. It was originally prescribed as a vigilance-promoting medicine used to treat elderly patients and has subsequently gained popularity for its cognitive enhancement potential. According to some reports, athletes have used adrafinil to boost focus and improve athletic performance.

But will adrafinil show up on a drug test?

The short answer is that adrafinil is not a regulated pharmaceutical product and most workplace drug tests do not screen for it. However, adrafinil can be screened for and tests administered to certain groups of people, such as athletes, are effective and readily available.

Below, we’ll offer an overview of the types of drug tests that can be used to screen for this compound. We’ll also summarize the efficacy of different testing methods and illuminate areas where further research may be warranted.

Keep in mind that all information presented in this article is general information and should not be relied upon when deciding whether to partake in adrafinil research.

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What is Adrafinil?

Adrafinil is a vigilance-promoting substance that was formerly manufactured in France and sold under the brand name “Olmifon.” Available as a pharmaceutical drug from 1985-2011, Olmifon was mainly prescribed to elderly patients who struggled to stay alert and mentally active during the day [1].

Adrafinil was discovered in 1974 by Louis Lafon Laboratories, a French pharmaceutical company, and underwent clinical trials during the 1970s and early 1980s. It is the “prodrug” of the well-known nootropic modafinil, meaning that it is metabolized (converted) into modafinil in the liver.

These days, adrafinil is less widely known than modafinil primarily because the latter exhibits a far more powerful effect on wakefulness. In 1994, Lafon released modafinil under the brand name “Modiodal” and it soon became the company's flagship product. This caused Olmifon to fall into clinical disuse and its manufacture ended in 2011.

At the time of writing, adrafinil is available in most countries as a reference material and may be purchased by qualified researchers.

Adrafinil benefits

Most of the research into adrafinil’s benefits was conducted by scientists working for Lafon during the 1970s and early 1980s and is published in French. Here is a brief overview of adrafinil’s main known benefits:

  • Increased wakefulness: Adrafinil’s primary benefit is that it acts as a powerful psychostimulant and increases wakefulness in both animals and humans. Animal studies have shown that it significantly increases nocturnal activity in rhesus monkeys [2], while human trials have demonstrated that it helps elderly patients stay awake and mentally active during the day [1] when administered at doses of 300-600 mg per day.
  • Treatment for depression: In clinical trials, adrafinil has shown to be effective in the treatment of depression [1] and was found to be better tolerated than clomipramine.
  • Cognitive benefits: While there is no published data specifically showing that adrafinil offers cognitive benefits in healthy individuals, there is ample evidence to indicate that its active metabolite—modafinil—offers significant cognitive benefits [3]. Modafinil has been shown to improve memory, motivation, and focus when administered to healthy, non-sleep-deprived test subjects [4]. This strongly indicates that adrafinil, which is metabolized in vivo to modafinil, offers similar benefits. However, this has not been directly tested in humans, and data from animal studies remains inconclusive: one study found that adrafinil increased “performance motivation” in canines [5] while a separate study found that it impaired working memory in beagle dogs [6].
  • Enhanced athletic ability: Adrafinil’s supposed ability to increase performance motivation was one factor behind the World Anti-Doping Organization’s decision to add it to their list of banned substances in 2004 [7]. While there is no published data supporting this use of adrafinil, its status as a banned substance, coupled with anecdotal evidence of its use by professional athletes, indicates that it can help enhance athletic performance.

While adrafinil has not been manufactured as a registered pharmaceutical product since 2011 and is currently produced only as a research chemical, interested researchers clearly have a number of angles for further research.


Adrafinil Side Effects and Safety

Little is known about adrafinil’s side effects and safety, especially its long-term safety, outside of the clinical trials conducted by Lafon in the 1970s and early 1980s. Product inserts from boxes of Olmifon (brand-name adrafinil) indicated that data from these trials had linked adrafinil to four main side effects:

  • Stomach pain
  • Headache
  • Skin irritation
  • Inner tension

It’s important to note that these clinical trials involved elderly patients and research involving other age groups or conditions remains lacking. So, what else do we know about adrafinil’s side effects and safety?

Research has linked adrafinil use to “orofacial dyskinesia,” a condition that causes involuntary movements of the nose, mouth, and face [8], and the drug has also been linked to elevated liver enzyme values—neither of which appear to be associated with modafinil [9].

The evident gaps in our understanding of adrafinil’s side effects and safety point to clear opportunities for further investigation of its cognitive and antidepressive effects, especially in non-elderly individuals.

Will Adrafinil Show Up on a Drug Test?

We now turn to our main question: will adrafinil show up on a drug test? As we explained earlier, the short answer is that it is highly unlikely to show up on a standard workplace or employment screening drug test. But this depends on the type of test being conducted and whether adrafinil is screened for.

Below, we’ll explore the different tests that can be used to screen for adrafinil.

Urine testing

Urine testing, or urinalysis, is the most common way to screen for drugs and may be conducted as part of pre-employment screening, following an accident, or randomly, depending upon a person’s occupation or circumstances. It is currently the most popular type of employment drug testing and, in the United States, is the only testing method approved for federally mandated testing.

Urine drug tests typically screen for opiates, PCP, marijuana, cocaine, amphetamines, and methamphetamines. As adrafinil shares no structural similarities with any of these substances, there is very little risk that it would cause a “false positive.” Since most urine drug tests do not screen for adrafinil, it should not show up.

However, a reliable two-step liquid chromatography/tandem mass spectrometry (LC/MS/MS) method from screening adrafinil in urine has been developed [10]. It works in combination with gas chromatography/mass spectrometry (GC/MS) and has been in use since 2008. A scientific paper outlining this method confirms that this test can be “applied to routine analyses and the WADA Proficiency Test” [11]. Therefore, urine tests conducted by athletics departments, athletics associations, or any organization connected with semi-professional or professional sports, may screen for adrafinil.

In summary, the available research suggests that non-athletes who submit to a workplace urine drug test could reasonably expect to not be screened for adrafinil, but professional athletes should expect that adrafinil use would show up if they submit to a urine drug test.

Hair testing

Hair drug testing is regarded by many scientists to be the “gold standard” indicator of repeat drug use as it has a wider “detection window” (90 days) than urinalysis. This method of drug testing requires the collection of a small sample of hair under direct supervision. Like urinalysis, it can be used to screen for opiates, PCP, marijuana, cocaine, amphetamines, and methamphetamines.

An adrafinil user or test subject who submits to a workplace hair test could reasonably expect that it will not show up. Most hair tests do not screen for this substance and it should not create a “false positive” for amphetamine or methamphetamine use.

However, adrafinil can be detected in human hair when analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and drug-tested athletes who submit to hair testing should expect their samples to be screened for adrafinil.

In terms of the capabilities of this test, according to one study a single 200 mg adrafinil dose was detectable up to 10 days after administration [12]. Researchers noted that analysis of a single beard hair “highlighted the presence of adrafinil at 0.8 ng/mg and modafinil at 0.5 ng/mg.” This indicates that both adrafinil and its active metabolite modafinil can be detected via hair testing even after a single consumption at a low dose.

Given the expense of this type of analysis, only professional athletes or those subject to a law enforcement action could ever reasonably expect to have their hair tested using LC-MS/MS. This method is beyond the scope of workplace drug tests and hair drug tests in general. Adrafinil researchers may find it worthwhile to develop a low-cost method of screening for adrafinil in hair samples.

Oral fluid testing

Oral fluid tests, otherwise known as saliva tests or mouth swab tests, are the cheapest type of drug tests with many advantages. They are easy to administer and testers can observe the process, making it difficult to cheat. If an oral fluid test were used to screen for adrafinil, it could detect extremely recent use, up to around 48 hours.

The lack of published research into the detection of adrafinil through oral fluid tests indicates that this may be a fruitful avenue of research for interested researchers.

Adrafinil and “Corporate America”

Research has indicated that adrafinil is used as a cognitive enhancer in “corporate America” [13]. There is clear evidence that adrafinil’s active metabolite, modafinil, improves both “cold” cognition and “hot” cognition, such as emotion recognition and task-related motivation [14]. So, will adrafinil show up on a workplace drug test?

Based on the available evidence, adrafinil should not show up on a standard workplace drug test, nor should it create a false positive for banned substances such as amphetamines or methamphetamines. The lack of an economical, effective, and reliable way of screening for adrafinil use suggests that this could be an interesting direction for researchers to pursue.


Does Adrafinil Show Up On a Drug Test? | The Verdict

If you were curious about adrafinil and drug tests, we hope that you found this informative guide useful.

Despite adrafinil’s ability to act as a cognition-boosting agent, all published evidence suggests that it is not routinely screened for as part of pre-employment screening or random screening. This means that it should not show up on most urine or swab drugs tests.

Our review of the available data has indicated clear areas where further research into adrafinil and drug tests would be warranted.

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  1. Milgram, N.W., Callahan, H. and Siwak, C. (1999), Adrafinil: A Novel Vigilance Promoting Agent. CNS Drug Reviews, 5: 193-212. doi:10.1111/j.1527-3458.1999.tb00100.x
  2. Milhaud CL, Klein MJ. Effets de l'adrafinil sur l'activité nocturne du macaque rhésus (Macaca mulatta) [The effect of adrafinil on the nocturnal activity of the rhesus monkey (Macaca mulatta)]. J Pharmacol. 1985 Oct-Dec;16(4):372-80. French. PMID: 4094435.
  3. Battleday RM, Brem AK. Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: A systematic review. Eur Neuropsychopharmacol. 2015 Nov;25(11):1865-81. doi: 10.1016/j.euroneuro.2015.07.028. Epub 2015 Aug 20. PMID: 26381811.
  4. Minzenberg MJ, Carter CS. Modafinil: a review of neurochemical actions and effects on cognition. Neuropsychopharmacology. 2008 Jun;33(7):1477-502. doi: 10.1038/sj.npp.1301534. Epub 2007 Aug 22. PMID: 17712350.
  5. Siwak CT, Callahan H, Milgram NW. Adrafinil: effects on behavior and cognition in aged canines. Prog Neuropsychopharmacol Biol Psychiatry. 2000 Jul;24(5):709-26. doi: 10.1016/s0278-5846(00)00103-2. PMID: 11191710.
  6. Siwak CT, Tapp PD, Milgram NW. Adrafinil disrupts performance on a delayed nonmatching-to-position task in aged beagle dogs. Pharmacol Biochem Behav. 2003 Aug;76(1):161-8. doi: 10.1016/s0091-3057(03)00211-9. PMID: 13679229.
  7. Ameline A, Gheddar L, Raul JS, Kintz P. Identification of adrafinil and its main metabolite modafinil in human hair. Self-administration study and interpretation of an authentic case. Forensic Sci Res. 2020 Jan 29;5(4):322-326. doi: 10.1080/20961790.2019.1704482. PMID: 33457050; PMCID: PMC7782130.
  8. Thobois S, Xie J, Mollion H, Benatru I, Broussolle E. Adrafinil-induced orofacial dyskinesia. Mov Disord. 2004;19(8):965-966. doi:10.1002/mds.20154
  9. Ballas CA, Kim D, Baldassano CF, Hoeh N. Modafinil: past, present and future. Expert Rev Neurother. 2002;2(4):449-457. doi:10.1586/14737175.2.4.449
  10. Lu J, Wang X, Yang S, Liu X, Qin Y, Shen L, Wu Y, Xu Y, Wu M, Ouyang G. Doping control analysis for adrafinil and its major metabolites in human urine. Rapid Commun Mass Spectrom. 2009 Jun;23(11):1592-600. doi: 10.1002/rcm.4044. PMID: 19399790.
  11. Dubey, S., Ahi, S., Reddy, I. M., Kaur, T., Beotra, A., & Jain, S. (2009). A novel study of screening and confirmation of modafinil, adrafinil and their metabolite modafinilic acid under EI-GC-MS and ESI-LC-MS-MS ionization. Indian journal of pharmacology, 41(6), 278–283.
  12. Ameline A, Gheddar L, Raul JS, Kintz P. Identification of adrafinil and its main metabolite modafinil in human hair. Self-administration study and interpretation of an authentic case. Forensic Sci Res. 2020 Jan 29;5(4):322-326. doi: 10.1080/20961790.2019.1704482. PMID: 33457050; PMCID: PMC7782130.
  13. Dowling G, Kavanagh PV, Talbot B, O'Brien J, Hessman G, McLaughlin G, Twamley B, Brandt SD. Outsmarted by nootropics? An investigation into the thermal degradation of modafinil, modafinic acid, adrafinil, CRL-40,940 and CRL-40,941 in the GC injector: formation of 1,1,2,2-tetraphenylethane and its tetra fluoro analog. Drug Test Anal. 2017 Mar;9(3):518-528. doi: 10.1002/dta.2142. Epub 2016 Dec 29. PMID: 27928893.
  14. Brühl AB, d'Angelo C, Sahakian BJ. Neuroethical issues in cognitive enhancement: Modafinil as the example of a workplace drug? Brain Neurosci Adv. 2019 Feb 15;3:2398212818816018. doi: 10.1177/2398212818816018. PMID: 32166175; PMCID: PMC7058249.

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