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Modafinil Alternatives: BEST Cognitive Enhancers

Modafinil alternatives - best cognitive enhancers

Modafinil (brand name Provigil) is one of the primary drugs used to manage narcolepsy in the UK. Narcolepsy is a rare condition that affects sleep control and results in daytime sleepiness, often sudden and uncontrollable.

The public’s interest in modafinil comes from the drug’s association with a class of medicines called ‘smart drugs,’ also called nootropics and cognitive enhancers. Many individuals search for cognitive enhancement drugs, and modafinil tends to be one of the primary drugs which always gets mentioned.

Today I will review modafinil alternatives, drugs that promote awakeness and/or improve cognitive functions. I will not check over-the-counter modafinil alternatives or modafinil’s natural alternatives simply because none of the existing supplements or over-the-counter products have the same effect as modafinil.


What is modafinil? What are modafinil alternatives?

If they did, they would not be available over the counter (at least in the UK).

Please read the related post: How to get modafinil? To learn various aspects of modafinil's supply in the UK.

What Is Modafinil?

The Legal Classification Of Modafinil (UK)

Modafinil is classified as a prescription-only medication (POM) in the UK. A doctor or another qualified prescriber can only prescribe POMs.

In the UK, modafinil has narrow licensed use. It is used to manage excessive sleepiness in adults, associated with narcolepsy with or without cataplexy (the sudden muscle weakness).

The second licensed use of modafinil covers individuals who experience excessive sleepiness, defined as difficulty keeping wakefulness and an increased likelihood of falling asleep in inappropriate situations (eMC, 2020).

Well-defined licensed use for modafinil means that an NHS doctor would only prescribe it to treat narcolepsy after an appropriate referral is made to a specialist.

Is Modafinil A Smart Drug?

Smart drug

The mechanism of action of modafinil is not fully understood.

Modafinil increases wakefulness and can potentially be a cognitive enhancing drug ('smart drug').

When studied in patients with excessive sleepiness, modafinil significantly affected wakefulness (Hirshkowitz & Black, 2007).

The available evidence shows a small capability for modafinil to be a cognitive enhancer in people who do not have a sleeping disorder (Kredlow et al., 2019). Based on current evidence, modafinil may produce ‘modest’ benefits in terms of cognitive enhancement.

Individuals who perform poorest (those with lower IQ) may achieve more significant benefits. Improvement in this group of people may be more effective. Taking ‘smart drugs’ in people with a modest level of cognitive function may lead to overconfidence (Nicholson, 2015).

A systemic review on modafinil use by youths aged 12-25 years old suggests that modafinil improves reaction time, problem-solving and logical reasoning (Bagot & Kaminer, 2014).

The wake-promoting properties of modafinil are well known. Although the mechanism underlying the wake-promoting action is fully understood, this effect is similar to other drugs, for example, amphetamines and methylphenidate, but with a distinct pharmacological profile (FDA, 2010).

When studied in animals, modafinil produced psychoactive and euphoric effects changes in mood, thinking, and awareness, all of which are associated with reactions produced by stimulants in people (ibid).

Is Modafinil Addictive?

Studies on modafinil in people indicate that modafinil is less likely to be abused than other ‘stimulating’ drugs, for example, methylphenidate or dexamphetamine (McClellan KJ & Spencer, 1998).

Additionally, compared with alternative medications such as amphetamines, modafinil is considered safe with a small number (‘minimal’) of side effects (Easow et al., 2013).

How To Get Modafinil?

Details on the supply of modafinil in the UK were discussed in one of my previous posts. I discussed the supply of modafinil on NHS through private routes and current restrictions on the supply of modafinil.

Modafinil Alternatives Drugs

Various drugs can be used in the management o narcolepsy, most of which will be used outside their license.

1. Pitolisant: Modafinil Alternative Drug To Treat Narcolepsy

Pitolisant (brand name: Wakix) is the latest drug licensed for narcolepsy in the UK. Pitolisant is a prescription-only medication. Treatment with pitolisant is usually initiated by a doctor who specializes in the treatment of sleeping disorders.

Pitolisant is extremely rarely prescribed in NHS. A quick search on OpenPrescribing.net shows that Pitolisant was prescribed less than 300 times in the last 12 months (OpenPrescribing.net, 2021).

The main reason for this is the drug cost, which is £310 for a 30-day treatment with a lower dose of pitolisant and £620 for a treatment with a higher pitolisant dose (prices as of February 2017, excluding VAT).

Pitolisant Vs. Modafinil: What’s The Difference?

Pitolisant is described as a ‘first in class drug. Pitolisan’s mechanism of action is different from modafinil. Pitolisant acts primarily on histamine receptors in the brain, with a possible effect on noradrenaline (same as modafinil) and dopamine, resulting in increased wakefulness.

Histamine neurons in the brain also control various functions, including memory and attention (Romigi et al., 2018).

When studied in animals, pitolisant was found not to cause dependence or induce ‘abuse’ behavior. Pitolisant enhanced memory performance in animals (ibid).

2. Armodafinil

Armodafinil is closely related to modafinil. Modafinil comes as a 50:50 mixture of two enantiomers, which means a combination of 50% to 50% of two molecules that are mirror images of each other. To put it in a simple context, you could represent enantiomers with your left and right hand; both look the same and are mirror images of each other.

In pharmaceuticals, it is possible to market enantiomers as separate drugs. Common prescription drugs that exist as mirror images of each other are esomeprazole and omeprazole (see Esomeprazole vs. Omeprazole post).

Armodafinil is not available in the UK, but it is used to treat narcolepsy in many countries.

Armodafinil vs. modafinil: which drug is better?

Modafinil alternative - Strattera - contains atomoxetine

When taken, armodafinil results in a higher amount of drug in the body when compared to modafinil.

Thus, it is suggested armodafinil may have a better wakefulness action (Darwish et al., 2009).

3. Atomoxetine

Atomoxetine legal classification

Atomoxetine (brand name: Strattera) is the first drug on the list of modafinil alternatives, especially use Strattera for treating Attention Deficit Hyperactivity Disorder (ADHD) in children and adults. Atomoxetine is a prescription-only medication.

Atomoxetine availability in the UK

Atomoxetine is available as a generic drug (atomoxetine hydrochloride) and branded as Strattera in the UK.

Is atomoxetine a cognitive enhancer?

Atomoxetine is a non-stimulant drug that primarily affects one neurotransmitter in the brain called norepinephrine (noradrenaline). Atomoxetine stops the action of the norepinephrine transporter in the brain and therefore increases the concentration (amount) of norepinephrine in the brain. Noradrenaline plays a role in regulating cognitive function, attention, and stress reactions (Hussain et al., 2020).

Unlike some other drugs discussed in the following paragraphs, atomoxetine does not affect dopamine actions in the brain’s relevant parts associated with pleasure. Therefore, atomoxetine is classified as a non-addictive medication with a low tendency for abuse.

There are a large number of research papers around atomoxetine. When used in the treatment of ADHD, atomoxetine significantly improved visual memory and attention (Shang & Gau, 2012).

Furthermore, atomoxetine enhanced many parts of ‘ executive function’ such as cognitive flexibility, short-term/working memory, attention, and susceptibility to distraction in young adults. Other evidence suggests that atomoxetine may boost other aspects of cognition beyond attention (Callahan, 2019).

4. Modafinil Alternatives: Methylphenidate

Methylphenidate is a prescription-only drug available in the UK to treat ADHD. Methylphenidate is classified as a controlled drug (Schedule 2), bringing additional legal requirements for writing prescriptions and various medicine supply restrictions.

Methylphenidate would only be prescribed for ADHD under a doctor who specializes in behavioral disorders.

Methylphenidate: legal aspects

Despite its classification as a prescription-only medication in the UK, which is also a controlled drug, purchasing methylphenidate is possible from overseas pharmacies.

Unlike with modafinil, possession of a class B controlled drug (not prescribed by a doctor) is an offense that carries imprisonment and fine penalties.

Methylphenidate: availability of different brands and forms

Methylphenidate is available in many forms in the UK. Methylphenidate is broadly available in immediate-release forms, including generic methylphenidate tablets and controlled release (prolong release / modified release) tablets and capsules.

Common brands of methylphenidate prescribed in the UK:

  • Concerta XL prolonged-release tablets
  • Equasym modified-release capsules
  • Medikinet tablets (immediate-release)
  • Medikinet XL prolonged-release capsules
  • Ritalin immediate-release tablets
  • Ritalin XL modified-release capsules
  • Xaggitin prolonged-release tablets

Is methylphenidate a ‘smart drug’?

Methylphenidate became a popular choice as a cognitive enhancer by healthy individuals seeking to improve their concentration, stay awake for longer to study, and increase motivation functioning (Batistela et al., 2016). It is known, for example, that medical students in the UK take cognitive enhancement drugs, including methylphenidate (Lane et al., 2015).

There is no consistent evidence to show that methylphenidate improves cognitive enhancement, although some evidence on memory has been demonstrated in laboratory tests (Nicholson & Wilson, 2017).

Similar to modafinil, individuals whose intellectual processes are ‘below optimal level’ (Batistela et al., 2016).

Methylphenidate vs. modafinil

Methylphenidate has a distinct mechanism of action to modafinil. Methylphenidate is classified as a stimulant, and primarily it affects the release and increases dopamine in the brain.

The end effect of increased dopamine in the brain is similar to one produced by cocaine and amphetamines (not to the same extent), yet the mechanism of action is different (Morton & Stockton, 2000).

Methylphenidate is classified as a stimulant drug, making it a reasonable option for treating narcolepsy. Methylphenidate is not licensed for the treatment of narcolepsy; therefore, other drugs like modafinil would be considered in the first instance.

5. Amfetamines

Two amfetamines used in the UK are dexamfetamine and lisdexamfetamine. Dexamfetamine is licensed for managing narcolepsy and ADHD, whereas lisdexamfetamine is just for ADHD.

Both drugs are prescription-only medicines, classified as controlled drugs Schedule 2 (class B). Both drugs need to be initiated by a specialist, i.e., a doctor is in secondary care rather than GP.

Are amfetamines cognitive enhancers?

Amfetamines positively impact cognitive functioning, as demonstrated by some studies. For example, when investigated in school-aged children, amfetamines improved attention and performance and decreased the number of errors (Rapoport et al., 1978).

Additionally, amfetamines may enhance the attainment of new knowledge, how it is stored in the brain, and retrieve information (Bagot & Kaminer, 2014).

The positive effects of amfetamines on cognitive functioning are overshadowed by negative aspects of the treatment, including psycho-stimulation, which may be characterized by individuals being ‘high,’ potential ‘high’ addictive properties, which all together increases the chances of the abuse.

6. Sodium Oxybate As Modafinil Alternative

Sodium oxybate is a prescription-only medication licensed for narcolepsy in the UK but rarely prescribed in practice. Sodium oxybate is a controlled drug Schedule 2 (class B).

Sodium oxybate comes only in liquid form as a generic medication or branded as Xyrem oral solution. One of the main drivers for the low popularity of this drug in the treatment of narcolepsy in the UK is its price, which stands at £360 per 180ml of oral solution.

Sodium oxybate (known as GHB) has widespread use as an illegal drug. The exact mechanism of sodium oxybate is unknown, but it is believed that sodium oxybate improves sleep at night, which promotes improved alertness the following day (Kothare & Kaleyias, 2010).

Does sodium oxybate affect cognitive performance?

Cognitive functions

The use of sodium oxybate by sleep-deprived, healthy voluntaries demonstrated that this drug improves daytime alertness and attention (Walsh et al., 2010).

Modafinil Alternatives: Conclusion

I revied the main prescription-only drugs, which can be classified as modafinil alternatives. All medicines have some evidence of cognitive enhancement and, most importantly, evidence of being effective in the treatment of narcolepsy due to its significant effect on wakefulness.

I did not cover two fundamental aspects of drug use that I did not cover in this post: potential side effects and interactions with other drugs. Individuals who consider using drugs to improve cognition need to recognize the risk of treatment (side effects) and possible interaction with other medicines they may take.

The legal route of modafinil alternatives/cognitive enhancers in the UK is through a consultation with a doctor (and a specialist), which almost eliminates unlicensed use of the above medicines as cognitive enhancers in healthy individuals.

Purchasing medicines from the Internet carries the additional risk of medication not being genuine with questionable quality.



Bagot, K.S. and Kaminer, Y., 2014. Efficacy of stimulants for cognitive enhancement in non‐attention deficit hyperactivity disorder youth: a systematic review. Addiction109(4), pp.547-557. Available at: https://onlinelibrary.wiley.com/doi/abs/10.1111/add.12460 Accessed on 06/03/2021

Batistela, S., Bueno, O.F.A., Vaz, L.J. and Galduróz, J.C.F., 2016. Methylphenidate as a cognitive enhancer in healthy young people. Dementia & Neuropsychologia10, pp.134-142.Available at: https://www.scielo.br/j/dn/a/J4dxfrMFfrfnKVFNGh84tKk/?lang=en Accessed on 06/03/2021

Callahan, P.M., Plagenhoef, M.R., Blake, D.T. and Terry Jr, A.V., 2019. Atomoxetine improves memory and other components of executive function in young-adult rats and aged rhesus monkeys. Neuropharmacology155, pp.65-75. Available at: https://www.sciencedirect.com/science/article/pii/S0028390819301650  Accessed on 03/03/2021

Darwish, M., Kirby, M., Hellriegel, E.T. and Robertson, P., 2009. Armodafinil and modafinil have substantially different pharmacokinetic profiles despite having the same terminal half-lives. Clinical Drug Investigation29(9), pp.613-623. Available at: https://link.springer.com/article/10.2165/11315280-000000000-00000 Accessed on 01/03/2021