Adrafinil

6.7

Energy

7.0 /10

Motivation

6.0 /10

Focus

7.0 /10

Adrafinil

Boost Energy
Cognitive
Improve Focus
Improve Memory
Longevity
Mental Health
Nootropics
Mood Support

Description

Summary

Developed in France, in the late 1970s by Louis Lafon Laboratories, Adrafinil is considered a novel pharmaceutical which contains several behaviour-activating effects [1]. Broadly, Adrafinil has to be involved with, and used for treating deficiencies in arousal or vigilance [2]. In addition, adrafinil is known to be used for treating attention difficulties, sleep, memory and mild depression [2]. Adrafinil was originally sold under its trade name, Olmifon, in France, where it was employed to counter the side effects of mood, wakefulness and other factors in the elderly [3]. In this regard, adrafinil was utilised in 1986, experimentally, to treat narcolepsy [4].

 

 

Figure 1: Adrafinil carries its IUPAC name: 2-benzhydrylsulfinyl-N-hydroxyacetamide.

These days, Adrafinil is marketed through biopharmaceutical company, Cephalon under the brand name Olmifon [5]. It acts as a central nervous system stimulant, where it is used for preventing fatigue, along with increasing energy and wakefulness [6].

How Adrafinil works

Pharmacology

As a prodrug, adrafinil is metabolised – in the body – to modafinil, which is the primary metabolite of adrafinil [7,8]. Taken orally, Adrafinil on an empty stomach, once broken down and accumulated in the blood stream, has noticeable effects within between 45-60 minutes [7]. Adrafinil is a solid, light pink white coloured substance. It is metabolised in the liver [23], where the final metabolite produced is modafinil (see Adrafinil and modafinil section).

 

Figure 2: Adrafinil is yielded through several step-wise reactions using NaOH, chloroacetic acid, hydrochloric acid amine and hydrogen peoxide [8]. From this point, Adrafinil undergoes metabolism to modafinil.

Benefits, safety & side effects of Adrafinil

Adrafinil has been found to be effective in counteracting the problems associated with vigilance, attention, concentration, learning, memory and depressive manifestations [1]. In animals, Adrafinil has been documented to increase locomotor activity in mice, monkeys and dogs. [9, 10]. Adrafinil is very similar to modafinil and Armodafinil [20], and, classed as a stimulant, increases alertness minus the addictive nature, having minimal impact on sleep structure [24].

Adrafinil and modafinil

Modafinil is a psychostimulant [11] with effects similar to adrafinil – alertness, mitigating fatigue. Adrafinil is considered as an alternative to Modafinil [Dowling et al., 2016]. It is considered an exclusive medicine in that it can only be prescribed to shift workers, or those suffering from narcolepsy or sleep apnea. It has been reported as being well tolerated with little or no side effects [11]. When compared to modafinil, adrafinil has no adverse side effects [9]. Modafinil’s half-life has been described as ranging from 12 – 15 hours, and as it consists of a ‘mix’ of two modafinil ‘versions’ it is the R-enantiomer version which has the longer waking effect [11]. When compared to traditional stimulants, modafinil has less known side effects. Lastly, Modafinil’s action in the brain has yet to be fully characterised; however, it has been proposed that Modafinil modifies areas of the brain involved in regulating the sleep/wake cycle [24].

 

 

Figure 3. Taken from Kim, 2012, this illustration clearly demonstrates the four categories of psychoactive drugs – tranquilisers, depressants, stimulants and hallucinogens. Modafinil can be seen as an [upper] stimulant [11]. As Modafinil is very similar to adrafinil, it too belongs in this ‘upper [stimulants] class.

Prior research into the effects of modafinil on hypersomnia and narcolepsy showed that besides modafinil producing no side effects – even when administered over a period of 2-3 years – it significantly reduced the number of drowsiness and sleep episodes during the day [18]. Standard therapeutic dose of modafinil, in adult patients, has been described as a daily dose of between 200-400mg [23]. On the subject on whether Adrafinil is as good as, or effective as Modafinil has yet to be established; this is due to that fact that Adrafinil is very similar to Modafinil, and, more obviously Adrafinil is metabolised to Modafinil in the liver.

 

Figure 4a. The structures of both Modafinil (left) and adrafinil (right). Both psychostimulants possess a stereogenic sulfoxide group, and both have been suggested to be effective treatments for ADHD and opioid-induced sedation [19]. The only difference between the two structures, is the absence of an amide hydroxyl group on modafinil – otherwise present on the terminal group of adrafinil [22].

Adrafinil-Induced Orofacial Dyskinesia

Orofacial dyskinesia is classified as a hyperkinetic movement disorder [12], where signs of this disorder manifest as repetitive chewing movements, lip smacking, tongue protrusions or lip puckering [12]. This type of dyskinesia is irreversible [13], and has been associated with, and resulting from, antipsychotic drugs, antidepressants, calcium channel blockers and other agents [14]. Orofacial dyskinesia has been reported in 2% of patients who have been treated with modafinil.

Case study: A 75-year-old man was administered a 900mg/D of adrafinil to alleviate excessive daytime sleepiness. After ten months of treatment, the individual developed orofacial dyskinesia, in which his treatment was stopped two months later. A later investigation, after ruling out other drugs, such as digoxin, showed that adrafinil had induced this person’s orofacial dyskinesia [14]. This case study can provide vital information on the long-term side effects of taking adrafinil.

Adrafinil and vyvanse

Vyvanse, also known clinically as lisdexamfetamine dimesylate, is an FDA-approved medication that is used to treat ADHD [15,16]. Results investigating the effects of vyvanse in treating attention deficit disorders – resulting from traumatic brain injury (TBI) – revealed positive outcomes involving selective measures of sustained attention, working memory, along with positive effects in executive functioning [15]. Little is known that vyvanse was in fact the first chemically formulated prodrug stimulant, and its biological mechanism utilises enzymatsic hydrolysis to ‘cut’ the original chemical into two new chemicals: L-lysine and d-amphetamine [16].

 

Figure 4b: Structure of Vyvanse (left), and structure of adrafinil (right). Both structures are great examples of prodrugs; that is, they are become active once metabolised into a pharmacologically active drug [17].

Adrafinil and phenibut

Phenibut, or 3-phenyl-4-aminobutyric acid, is a psychotropic drug that carries nootropic properties, and is widely used as a mood elevator and tranquilizer [25]. Desired effects reported from use of Phenibut include the elimination of social anxiety, hypnosis, along with a feeling of euphoria [26]. Differences between Phenibut and Adrafinil can be gained from dose and toxicity. Side effects from phenibut intoxication – which can occur from as little as 3g daily over 4 days, to a 30g single dose – include lethargic altered mental status, muscle ‘spasms’, described as dystonia, and, low body temperature (hyperthermia) [26]. However, previous reports have suggested that Phenibut in fact produces anti-aggressive effects, without the depressing effects [27]. In terms of its use, Phenibut is widely used in Russia to alleviate tension, anxiety, as well as to improve sleep in psychosomatic or neurotic patients [28]. From the literature, Adrafinil has not been reported to induce muscle spasms, or changes in body temperature.

Adrafinil and Adderall

The immediate difference between Adrafinil and Adderall, is that Adderall is a commonly abused prescription drug among college students [29], and is used for the treatment of ADHD [30]. For this reason, Adderall has been listed as a Schedule II substance by the Drug Enforcement Administration (DEA).

Stimulation

The first and most important benefit is that it acts as a stimulant and increases a person’s concentration, stamina, and energy levels. Adrafinil for studying allows students to continue reading through the night. It is also great for employees who have to work late shifts.

Increases Productivity

By boosting a person’s energy levels, it helps to increase your overall productivity through motivation increase. This is perfect not only for students but for people who work in competitive fields such as sales and marketing. It allows them to continue working with as much vigor and energy in the evening as they had in the morning.

Enhanced Memory and Learning Abilities

If you are wondering how you can grasp more information faster, adrafinil is a great choice. It boosts your energy levels, thus triggering your brain’s ability to want to keep learning and discovering new things. As such, it allows you to remember more and learn faster. This is great for people who need to remember a lot of information.

Regulates Your Mood

During stressful situations, it is normal for a person’s emotions to be all over the place. Adrafinil works directly with the adrenergic system to stimulate the central nervous system. Thus, your body gets some excitement, and your mind experiences more concentration. It also mildly triggers dopamine, which plays a huge role in regulating your moods. By breaking down the chemical in the body, it enhances your mood and reduces stress.

Adrafinil Appetite Suppressant

Adrafinil is a great appetite suppressant and can be used for weight loss. If you have been experiencing hunger pangs shortly after having meals, you may want to find the best place to buy adrafinil to help you lose weight and keep your appetite in check.

Adrafinil for Studying

While adrafinil is great on its own, you might find yourself in need of a boost. Caffeine with adrafinil increases your wakefulness and pramiracetam with adrafinil improves your body’s choline uptake. This, in turn, increases your recall memory. 5 mg of L-Theanine helps to reduce stress and anxiety during your study sessions. It is critical to note that these combinations are not recommended for new nootropic users.

Adrafinil and Athletic Performance

Some athletes substitute a preworkout powder with adrafinil because of its stimulating effects. Using adrafinil one to two times weekly instead of a preworkout powder is an excellent way to cycle. Cycling is necessary with stimulants as the body will otherwise build a tolerance to them, meaning they lose their effectiveness.

Dosage

As Adrafinil is effective in memory, concentration, learning, along with depressive manifestations, these activities, influenced through Adrafinil, have been characterised as dose-dependent [9]. Studies have documented the oral administration of 20mg/kg Adrafinil to rats; this dosage was monitored for a duration of 12 hours – Figure 5 illustrates the effect of dosage over time [31]. Similarly, Modafinil has been reported as having a low level of toxicity: higher than 1g/kg, and around 400mg/kg in canines. In further studies assessing the impact of Adrafinil on learning in Beagle dogs, a dosage of 20mg/kg was orally delivered in capsules. This dose was shown to enhance cognition in non-human subjects [10]. In measuring locomotor activity in ages canines, Adrafinil at doses between 20-40mg/kg reliably increased over a month of daily treatment (Figure 6) [2]. Results from animal studies looking at how long Adrafinil lasts in the ‘system’ – seen below – shows a gradual decline of Adrafinil (metabolism) at around ~10-12 hours.

 

Figure 5. Left: Duration of Adrafinil at 20mg/kg – fed to rats – was sown to peak after 4 hours upon ingestion. ‘Kick-in time’ of Adrafinil seems to occur just before one hour of ingestion. Right: A single, 20mg/kg dose of Adrafinil given to rats shows a similar serum concentration over time profile; peak Adrafinil is observed at around 4-6 hours [9]. Adrafinil seems to last for around 10-12 hours.

 

 

Figure 6. (Left): Graphical representation of Adrafinil in its effect in locomotor activity. As previously demonstrated, this relationship is dose-dependent [2].

Reviews

Reports on the effects of Adrafinil use have been described through various open-access online social media platforms. Reddit posts discussing Adrafinil outline the effects and dose of Adrafinil as a nootropic. Also, reviews discuss at length how long Adrafinil lasts, as well as its use to aid studying and what it feels like. Equally important, customers share their negative and positive experiences using Adrafinil, which report Adrafinil working and not working.

Regulatory and legal status

Is Adafinil legal?

In the US, adrafinil has not been FDA approved, and is therefore unregulated. Adrafinil does not fall under the category of a controlled substance, this translates to adrafinil not being illegal to possess without a prescription [1]. As mentioned earlier, Adrafinil is prescribed in the treatment of narcolepsy. Its legal status in the UK, for example, is also thoroughly discussed through online social media platforms, such as Quora.

In 2004, The World Anti-Doping Agency announced and implemented adrafinil to its list of substances prohibited for athletic competition [1]. The use of Adrafinil and Modafinil are banned in sports; stipulated by the WADA from their Central Nervous System stimulating effects [21].

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Sources

Sources

 

[1] Norton W. Milgram, Heather Callahan and Christina Siwak, 1999. Adrafinil: A Novel Vigilance Promoting Agent.

 

[2] Christina T. Swiak, Heather Callahan and Norton W. Milgram, 2000. Adrafinil: Effects on Behaviour and Cognition in Aged Canines.

 

[3] https://en.wikipedia.org/wiki/Adrafinil

 

[4] http://enacademic.com/dic.nsf/enwiki/616907

 

[5] http://www.chemeurope.com/en/encyclopedia/Adrafinil.html

 

[6] Mosstafa Kazemi, Sami Sajjadifar, Abdelkarim Aydi, Mohammad Mirzaei Heydari, 2018. Biological and Pharmaceutical Organosulfur Molecules.

 

[7] https://pubchem.ncbi.nlm.nih.gov/compound/adrafinil#section=Pharmacology-and-Biochemistry

 

[8] https://www.lookchem.com/Adrafinil/

 

[9] R. Nageswara Rao, Dhananjay D. Shinde, M.V.N. Kumar Talluri, Sachin B. Agawane, 2008. LC-ESI-MS determination and pharmacokinetics of adrafinil in rats.

 

[10] Norton W. Milgram, Christina T. Swiak, Philippe Gruet, Patricia Atkinson, Frederique Woehrle and Heather Callahan, 2000. Oral Administration of Adrafinil Improves Discrimination Learning in Aged Beagle Dogs.

 

[11] Dongsoo Kim, 2012. Practical Use and Risk of Modafinil, A Novel Waking drug.

 

[12] MV Solbrig, GF Koob and WI Lipkin, 1999. Orofacial dyskinesias and dystonia in rats infected with Borna disease virus; a model for tardive dyskinetic syndromes.

 

[13] Ronald M. Kobayashi, 1976. Orofacial Dyskinesia. Clinical Features, Mechanisms and Drug Therapy.

 

[14] Stephane Thobois, Jing Xie, Helena Mollion, Isabelle Benatru and Emmanuel Broussolle, 2004. Adrafinil-Induced Orofacial Dyskinesia.

 

[15] Michael G. Tramontana, Ronald L. Cowan, David Zald, Jonathan W. Prokop, and Oscar Guillamondegui, 2014. Traumatic brain injury-related attention deficits: Treatment outcomes with lisdexamfetamine dimesylate (Vyvanse).

 

[16] David W. Goodman, 2010. Lisdexamfetamine Dimesylate (Vyvanse), A Prodrug Stimulant for Attention-Deficit/Hyperactivity Disorder.

 

[17] https://en.wikipedia.org/wiki/Prodrug

 

[18] Helene Bastuji and Michel Jouvet, 1988. Successful Treatment of Idiopathic Hypersomnia and Narcolepsy with Modafinil.

 

[19] Antonio Osorio-Lozada, Thomas Prisinzano and Horacio F. Olivo, 2004. Synthesis and determination of the absolute stereochemistry of the enantiomers of adrafinil and modafinil.

 

[20] https://www.drugsand.me/en/modafinil/

 

[21] Dubey S, Ahi S, Beotra A, Reddy IM, Kaur T, Jain S, 2008. A novel study of mass spectrometric fragmentation of adrafinil, modafinil and their metabolite modafilinic acid under ESI-LC-MS/MS and EI-GC-MS.

 

[22] https://psychonautwiki.org/wiki/Adrafinil

 

[23] Geraldine Dowling, Pierce V. Kavanagh, Brian Talbot, John O’Brien, Gary Hessman, Gavin McLaughlin, Brendan Twamley, and Simon D. Brandt, 2016. 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 Testing and Analysis.

 

[24] K. Deventer, K. Roels, F.T Delbeke, P. Van Eenoo, 2011. Prevelance of legal and illegal stimulating agents in sports.

 

[25] Solveiga Grinberga, Liga Zvejniece, Edgars Liepinsh, Maija Dambrova and Osvalds Pugovics, 2008. Quantitative analysis of phenibut in rat brain tissue extracts by liquid chromatography-tandem mass spectrometry.

 

[26] Seth Sankary, Peter Canino, Jennifer Jackson, 2016. Phenibut Overdose. American Journal of Emergency Medicine.

 

[27] V.V. Bagmetova, A.N. Krivitskaya, and I.N. Tyurenkov, 2015. Effects of Phenibut and Citrocard on Non-Competitive and Competitive Behaviour during Provoked Aggression in Animals. Bulletin of Experimental Biology and Medicine.

 

[28] Izyaslav lapin, 2001. Phenibut (beta-Phenyl-GABA): A Tranquilizer and Nootropic Drug.

 

[29] Carl L Hansen, Scott H. Burton, Christophe Giraud-Carrier, Josh H. West, Michael D. Barnes, and Bret Hansen, 2013. Tweaking and Tweeting: Exploring Twitter for Nonmedical Use of a Psychostimulant Drug (Adderall) Among College Students.

 

[30] Rohini R. Vanga, Bikram Bal, and Kevin W. Olden, 2013. Adderall Induced Acute Liver Injury: A Rare Case and Review of the Literature.

Also known as:Olmifon, CRL-40028
Type:Nootropic
Good for: , , , , , , , ,
Stacks well with: Noopept,Phenylpiracetam,Piracetam
Typical dose:300mg
Half Life :4.95 Hours