Psychostimulants and Cognition: A Continuum of Behavioral and Cognitive Activation
Open accessAbstract
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.
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Both cognitive enhancement and drug addiction are highly associated with pharmacokinetic properties.
“Several studies have revealed that both cognitive enhancement and drug addiction are highly associated with pharmacokinetic properties (9, 10).”
Stimulants act broadly and non-specifically on dopamine and norepinephrine reuptake throughout the brain, effectively reducing symptoms for a large proportion of individuals with ADHD.
“This problem has been somewhat elided in current practice, given that stimulants, the current cornerstone of ADHD therapy, act broadly and non-specifically on dopamine and norepinephrine reuptake throughout the brain [73], effectively reducing symptoms for a large proportion of individuals with ADHD.”
From Linking ADHD to the Neural Circuitry of Attention (2017) · cites this paper as [73]
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“001, treatment × arm interaction: F(10,108) = 1.”
BackgroundInfluential
- Authors
- Wood, S., Sage, J. R., Shuman, T., & Anagnostaras, S. G.
- Affiliations
- University of California San Diego (US)
- Venue
- Pharmacological Reviews
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 66
- Issue
- 1
- Pages
- 193-221
- ISSN
- 0031-6997 (ISSN-L)
- PMC
- PMC3880463
- OpenAlex
- W2090108889
- Cited by
- 259
- References
- 20
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 16 · 2023: 21 · 2022: 16 · 2021: 25 · 2020: 18 · 2019: 30 · 2018: 28 · 2017: 19 · 2016: 29 · 2015: 30 · 2014: 10
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Pharmacological Reviews (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Science Foundation
- National Institutes of Health
- National Institute of Mental Health (T32MH018870)
- National Institute on Drug Abuse (F31DA026259, DA020041, DA026259, R01DA020041)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neuroethics, Human Enhancement, Biomedical Innovations
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Keywords
- psychostimulants, cognitive enhancement, cognitive impairment, cocaine, amphetamine, methylphenidate, modafinil, caffeine, dose-response relationship, arousal, attention, addiction, psychosis, stimulant abuse, individual differences
- MeSH terms
- Modafinil, Central Nervous System Stimulants, Animals, Benzhydryl Compounds, Caffeine, Cocaine, Cognition, Humans, Methamphetamine, Methylphenidate
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