Literature-review on cognitive effects of modafinil (my bachelor thesis)

post by David Althaus (wallowinmaya) · 2014-01-08T19:23:47.830Z · LW · GW · Legacy · 42 comments

Contents

  Introduction:
  Overview of effects in healthy individuals:
  Adverse effects:
  Abuse potential:
  Conclusion:
None
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Modafinil is probably the most popular cognitive enhancer. LessWrong seems pretty interested in it. The incredible Gwern wrote an excellent and extensive article about it. 

Of all the stimulants I tried, modafinil is my favorite one. There are more powerful substances like e.g. amphetamine or methylphenidate, but modafinil has much less negative effects on physical as well as mental health and is far less addictive. All things considered, the cost-benefit-ratio of modafinil is unparalleled. 

For those reasons I decided to publish my bachelor thesis on the cognitive effects of modafinil in healthy, non-sleep deprived individuals on LessWrong. Forgive me its shortcomings. 

Here are some relevant quotes:

Introduction:

...the main research question of this thesis is if and to what extent modafinil has positive effects on cognitive performance (operationalized as performance improvements in a variety of cognitive tests) in healthy, non-sleep deprived individuals.... The abuse liability and adverse effects of modafinil are also discussed. A literature research of all available, randomized, placebo-controlled, double-blind studies which examined those effects was therefore conducted.

Overview of effects in healthy individuals:

...Altogether 19 randomized, double-blind, placebo-controlled studies about the effects of modafinil on cognitive functioning in healthy, non sleep-deprived individuals were reviewed. One of them (Randall et al., 2005b) was a retrospect analysis of 2 other studies (Randall et al., 2002 and 2005a), so 18 independent studies remain.

Out of the 19 studies, 14 found performance improvements in at least one of the administered cognitive tests through modafinil in healthy volunteers.
Modafinil significantly improved performance in 26 out of 102 cognitive tests, but significantly decreased performance in 3 cognitive tests.

...Several studies suggest that modafinil is only effective in subjects with lower IQ or lower baseline performance (Randall et al., 2005b; Müller et al., 2004; Finke et al., 2010). Significant differences between modafinil and placebo also often only emerge in the most difficult conditions of cognitive tests (Müller et al., 2004; Müller et al., 2012; Winder-Rhodes et al., 2010; Marchant et al., 2009).

Adverse effects:

...A study by Wong et al. (1999) of 32 healthy, male volunteers showed that the most frequently observed adverse effects among modafinil subjects were headache (34%), followed by insomnia, palpitations and anxiety (each occurring in 21% of participants). Adverse events were clearly dose- dependent: 50%, 83%, 100% and 100% of the participants in the 200 mg, 400 mg, 600 mg, and 800 mg dose groups respectively experienced at least one adverse event. According to the authors of this study the maximal safe dosage of modafinil is 600 mg.

Abuse potential:

...Using a randomized, double-blind, placebo-controlled design Rush et al. (2002) examined subjective and behavioral effects of cocaine (100, 200 or 300 mg), modafinil (200, 400 or 600 mg) and placebo in cocaine users….Of note, while subjects taking cocaine were willing to pay $3 for 100 mg, $6 for 200 mg and $10 for 300 mg cocaine, participants on modafinil were willing to pay $2, regardless of the dose. These results suggest that modafinil has a low abuse liability, but the rather small sample size (n=9) limits the validity of this study.

The study by Marchant et al. (2009) which is discussed in more detail in part 2.4.12 found that subjects receiving modafinil were significantly less (p<0,05) content than subjects receiving placebo which indicates a low abuse potential of modafinil. In contrast, in a study by Müller et al. (2012) which is also discussed in more detail above, modafinil significantly increased (p<0,05) ratings of "task-enjoyment" which may suggest a moderate potential for abuse.

...Overall, these results indicate that although modafinil promotes wakefulness, its effects are distinct from those of more typical stimulants like amphetamine and methylphenidate and more similar to the effects of caffeine which suggests a relatively low abuse liability.

Conclusion:

In healthy individuals modafinil seems to improve cognitive performance, especially on the Stroop Task, stop-signal and serial reaction time tasks and tests of visual memory, working memory, spatial planning ability and sustained attention. However, these cognitive enhancing effects did only emerge in a subset of the reviewed studies. Additionally, significant performance increases may be limited to subjects with low baseline performance. Modafinil also appears to have detrimental effects on mental flexibility.

...The abuse liability of modafinil seems to be small, particularly in comparison with other stimulants such as amphetamine and methylphenidate. Headache and insomnia are the most common adverse effects of modafinil.

...Because several studies suggest that modafinil may only provide substantial beneficial effects to individuals with low baseline performance, ultimately the big question remains if modafinil can really improve the cognitive performance of already high-functioning, healthy individuals. Only in the latter case modafinil can justifiably be called a genuine cognitive enhancer.

You can download the whole thing below. (Just skip the sections on substance-dependent individuals and patients with dementia. My professor wanted them.)

Effects of modafinil on cognitive performance in healthy individuals, substance-dependent individuals and patients with dementia

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