Psychostimulants and Cognition: A Continuum of Behavioral and Cognitive Activation

Suzanne Wood; Jennifer R. Sage; Tristan Shuman; Stephan G. Anagnostaras

doi:10.1124/pr.112.007054

Abstract

Psychostimulants such as cocaine have been used as performance enhancers throughout recorded history. Although psychostimulants are commonly prescribed to improve attention and cognition, a great deal of literature has described their ability to induce cognitive deficits, as well as addiction. How can a single drug class be known to produce both cognitive enhancement and impairment? Properties of the particular stimulant drug itself and individual differences between users have both been suggested to dictate the outcome of stimulant use. A more parsimonious alternative, which we endorse, is that dose is the critical determining factor in cognitive effects of stimulant drugs. Herein, we review several popular stimulants (cocaine, amphetamine, methylphenidate, modafinil, and caffeine), outlining their history of use, mechanism of action, and use and abuse today. One common graphic depiction of the cognitive effects of psychostimulants is an inverted U–shaped dose-effect curve. Moderate arousal is beneficial to cognition, whereas too much activation leads to cognitive impairment. In parallel to this schematic, we propose a continuum of psychostimulant activation that covers the transition from one drug effect to another as stimulant intake is increased. Low doses of stimulants effect increased arousal, attention, and cognitive enhancement; moderate doses can lead to feelings of euphoria and power, as well as addiction and cognitive impairment; and very high doses lead to psychosis and circulatory collapse. This continuum helps account for the seemingly disparate effects of stimulant drugs, with the same drug being associated with cognitive enhancement and impairment.

Footnotes

This work was supported in part by the National Institutes of Health National Institute on Drug Abuse [Grants DA026259 (to S.W.) and DA020041 (to S.G.A.)]; a National Science Foundation Fellowship (to S.W.); and a Hellman Fellowship (to S.G.A.).
1 Although some traditional definitions of the term psychostimulant require that the drug increase locomotion in rodents, here we argue that psychostimulants should include drugs that may not produce hyperlocomotion (e.g., caffeine and modafinil). We refer to the more narrow class of psychostimulants that also produce significant hyperlocomotion (e.g., cocaine and amphetamine) as psychomotor stimulants. Moreover, even psychomotor stimulants only do so for a certain range of doses, usually higher than those that produce cognitive enhancement (see Wood and Anagnostaras, 2009; Wood et al., 2007)
2 Sparlon is Cephalon’s trade name for the failed New Drug Application of their modafinil formulation to be used for the treatment of ADHD. Although it never made it to market, it is included here because much clinical trial information was published using this name, and the drug was effective at treating ADHD.
3 http://www.drugs-forum.com/forum/showthread.php?t=9078&highlight=Cocaine+Experiences (retrieved on 9/6/2010).
4 http://www.drugs-forum.com/forum/showthread.php?t=26171&highlight=recreational+amphetamine+dose (retrieved on 9/6/2010). Edited for spelling and grammar. It is common on these forums to use the acronyms “SWIM” (someone who isn’t me) to designate yourself, and “SWIY” (someone who isn’t you) when giving advice to others. For grammatical clarity, these have been edited to match the intent of the writer. See http://www.urbandictionary.com/define.php?term=SWIM (retrieved on 9/6/2010).
5 http://www.erowid.org/experiences/exp.php?ID=15261 (retrieved on 9/6/2010).
6 http://www.dr-bob.org/babble/20080412/msgs/823572.html (retrieved on 7/27/10).
An earlier version of this work served as Chapter 5 of S.W.’s doctoral thesis: Wood S (2013) The Enhancement and Impairment of Learning by Stimulants, Ph.D. thesis, University of California, San Diego, California.
dx.doi.org/10.1124/pr.112.007054.