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Adr3.4

Adrafinil (Olmifon) Research

Mostly mechanism / observationalLimited safety

6 peer-reviewed studies

What the evidence says

Mostly mechanism / observational

Most Adrafinil (Olmifon) studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.

Most evidence is from medium-quality studies published 2000–2020.

Based on 6 studies

Confidence

Low

By outcome

Cognition & vigilance
Mostly mechanism / observational4 studies
Wakefulness & fatigue
Too few graded studies1 study
Safety profile
Too few graded studies1 study

Older research base

Newest study from 2020

200020102020

1Review2018

Adrafinil, a new molecule identified by a French drug company, L. Lafon Ltd, in 1974 … the kinetics of adrafinil led to the identification of an active metabolite, modafinil.

Billiard, Broughton · Sleep medicine (2018)

Historical review tracing adrafinil (identified by Lafon in 1974) and the discovery of its active metabolite, modafinil
Michel Jouvet prescribed adrafinil to narcoleptic patients as early as 1977–78 but 'without consistent results'
Modafinil was discovered through adrafinil's pharmacokinetics and went on to become the better-characterized drug

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2Review2020

A review of modafinil (and of its prodrug adrafinil and its enantiomer armodafinil) pharmacokinetics, pharmacodynamics and clinical and forensic aspects.

Sousa, Dinis-Oliveira · Substance abuse (2020)

Pharmacokinetic/pharmacodynamic review that frames adrafinil explicitly as the prodrug of modafinil
Wakefulness is driven by the modafinil metabolite acting on catecholamine, orexin, and histamine arousal systems
Covers the clinical and forensic (doping) context in which adrafinil is now mostly encountered

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3Animal2000

Treatment with adrafinil produced significant improvement in learning of a discrimination task in aged beagle dogs.

Milgram, Siwak, Gruet, Atkinson · Pharmacology, biochemistry, and behavior (2000)

Aged beagle dogs trained on size or intensity discrimination 2 h after 20 mg/kg adrafinil or placebo (counterbalanced crossover)
Adrafinil significantly improved acquisition of the discrimination task versus placebo
Among the cleanest direct efficacy signals for adrafinil — but it is an animal model of cognitive aging

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4Animal2000

Dogs were randomly assigned to receive adrafinil … propentofylline … or nicergoline … for 33 days.

Siwak, Gruet, Woehrlé, Muggenburg, Murphey · American journal of veterinary research (2000)

Randomized comparison in 36 aged beagles: adrafinil (20 mg/kg/day) vs propentofylline vs nicergoline over 33 days
Adrafinil increased open-field locomotor and exploratory behavior in aged dogs
Supports a behavioral-activation (vigilance) effect, consistent with its wake-promoting mechanism

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5Animal2003

Adrafinil disrupts performance on a delayed nonmatching-to-position task in aged beagle dogs.

Siwak, Tapp, Milgram · Pharmacology, biochemistry, and behavior (2003)

Aged beagles tested on a delayed-nonmatching-to-position (working-memory) task after 10 or 20 mg/kg adrafinil or placebo
Adrafinil DISRUPTED performance on the memory task rather than improving it
Shows the cognitive effect is not uniformly positive and may impair working memory while activating behavior

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6Case Study2004

We describe the first case of orofacial abnormal movements induced by adrafinil … the dyskinesias did not spontaneously recover despite adrafinil withdrawal for a 4-month period.

Thobois, Xie, Mollion, Benatru, Broussolle · Movement disorders : official journal of the Movement Disorder Society (2004)

Case report of persistent orofacial dyskinesia attributed to adrafinil
The abnormal movements did not resolve after 4 months off the drug; they improved only with tetrabenazine
Documents a real, durable neurological adverse effect in a human user

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View in Research Library

Adrafinil (Olmifon) Research

Mostly mechanism / observational

Modafinil: its discovery, the early European and North American experience in the treatment of narcolepsy and idiopathic hypersomnia, and its subsequent use in other medical conditions.

Pharmacokinetic and pharmacodynamic of the cognitive enhancer modafinil: Relevant clinical and forensic aspects.

Oral administration of adrafinil improves discrimination learning in aged beagle dogs.

Comparison of the effects of adrafinil, propentofylline, and nicergoline on behavior in aged dogs.

Adrafinil disrupts performance on a delayed nonmatching-to-position task in aged beagle dogs.

Adrafinil-induced orofacial dyskinesia.