Advice for patients,  Pharmacy insights

Drugs that keep you awake: modafinil

Modafinil is the main focus of today’s post. It will be part of posts on prescription drugs that keep you awake and/or affect cognitive performance. I will summarise the mechanism of action of each drug in relation to wakefulness and possible effects on cognitive performance and whether they fall into ‘smart drug’ category.

Smart drugs have been attracting a larger audience in recent years among students, bankers and shift workers. It is a known fact that armies around the world use stimulants to improve performance during a long duration missions (Bower, 2003).

Movies like Limitless contributed to greater interest in smart drugs, particularly modafinil which received a label of NZT-48 drug (the limitless pill), drug which does not exist in real life.

What drugs keep you awake?

With time the following wakefulness promoting drugs will be reviewed:

  • Armodafinil (differences between modafinil and armodafinil)
  • Methylphenidate
  • Amfetamines
  • Cocaine

Modafinil

This prescription only medication (POM) is available in UK for treatment of narcolepsy (excessive daytime sleepiness). It is available as generic medication and under branded name of Provigil. POM status means that you can only get it by having prescription (NHS or private) written by appropriate prescriber. However, modafinil can be purchased online easily from legitimate UK pharmacies who offer private service for supply of this medication.

Comparing with other drugs which promote wakefulness, such as amfetamines, modafinil has lower risks of side effects and is less likely to be abused (Minzenberg & Carter, 2007)

Chemically modafinil exist as enantiomer of L-modafinil and R-modafinil. These enantiomers have same chemical structure (e.g our hands looks the same) but their arrangement in space is different (our left and right hand).

Armodafinil (R-modafinil) exists also as separate drug on its own, available on the market as prescription only drug (not in UK).

Modafinil mechanism of action behind wakefulness

The exact mechanism of action of modafinil is not known. Suggested mechanism of actions based on laboratory experiments include action on dopamine reuptake system, where modafinil binds to dopamine transporter (DAT). Modafinil also showed to bind to norepinephrine (NET) transporter (Minzenberg & Carter, 2007). Actions on both DAT and NET in wake promoting centres are thought to be main drivers of modafinil mechanism of action (Ballas & Dinges, 2009). This is similar effect that modafinil shares with other stimulant drugs such as cocaine, methylphenidate, and the amphetamines (Mereu et al, 2013).

What all of this means?

Dopamine and norepinephrine are neurotransmitters. Number of neurotransmitters promote wakefulness in different areas of the brain. When drug binds to a transporter it prevents this transporter from the reuptake of neurotransmitter back into “synaptic cleft”, prolonging its actions, in case of modafinil it promotes wakefulness.

Modafinil effects on cognition. Is modafinil a ‘smart drug’?

The best evidence on modafinils ability to affects cognitive behaviour comes from systemic review by Dr. Ruairidh Battleday and Dr. Anna-Katharine Brem from the University of Oxford and Harvard Medical School. This systemic review investigated results from 24 studies of modafinil’s effects on cognition in healthy individuals. Half of the studies investigated found that modafinil improves attention and leaning memory. Improved attention and learning were observed when more complex tasks were performed (Battleday & Brem, 2015).  Cognitive benefits of modafinil in investigated studies were more consistent as tasks performed became longer and more complex (ox.ac.uk, 2015).  Professor Guy Goodwin, President of the European College of Neuropsychopharmacology named modafinil as cognitive enhancer, in plain language it can be called a ‘smart drug’, which can help for example with exam preparations (ibid).

Modafinil: commons side effects

Like with all medications taking modafinil comes with risk of side effects. Common side effects experienced with modafinil include:

  • insomnia, nervousness, depression, anxiety, abnormal thinking, confusion
  • dizziness and blurred vision
  • nausea, dry mouth, abdominal pain, diarrhoea, dyspepsia, constipation
  • and more

Rare cases of serious or life-threatening rash, including Stevens-Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) have been reported with use of modafinil.

For full list of modanifil’s side effects read products information leaflet, available online at EMC website.

Although many drugs were labelled as ‘smart drugs’ modafinil is a unique wakefulness agent. Modafinil is the only ‘smart drug’, which is not a stimulant, it has lower risk of side effects as compared with other drugs such as amphetamines. Modafinil has low liability for abuse and dependence making it a good candidate for use as cognitive enhancer. Finally, as Dr Anna-Katharine Brem suggested, a better ways of cognitive performance testing is needed to evaluate benefits of similar drugs.

References:

Ballas & Dinges (2009). Stimulant and Wake-Promoting Substances. Available at:

https://www.sciencedirect.com/topics/neuroscience/modafinil Accessed on 16/04/2019

Battledaya R.M., A.-K.Bremab (2015). Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: A systematic review. Available at: https://www.sciencedirect.com/science/article/pii/S0924977X15002497 Accessed on 16/04/2019

Bower Eric (2003). Use of amphetamines in the military environment. Available at: https://www.thelancet.com/pdfs/journals/lancet/PIIS014067360315060X.pdf 16/04/2019

Maddalena Mereu, Antonello Bonci, Amy Hauck Newman, and Gianluigi Tanda (2013). The neurobiology of modafinil as an enhancer of cognitive performance and a potential treatment for substance use disorders. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3800148/Accessed on 13/04/2019

Minzenberg & Carter(2007). Modafinil: A Review of Neurochemical Actions and Effects on Cognition. Available at: https://www.nature.com/articles/1301534 Accessed on 13/04/2019

Ox.ac.uk, University of Oxford (2015). Review of ‘smart drug’ shows modafinil does enhance cognition. Available at: http://www.ox.ac.uk/news/2015-08-20-review-%E2%80%98smart-drug%E2%80%99-shows-modafinil-does-enhance-cognition# Accessed on 16/04/2019

I am a community pharmacist working in UK. I blog about drugs, health and pharmacy.

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