Modafinil administration improves working memory in methamphetamine-dependent individuals who demonstrate baseline impairment
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Modafinil improves working memory in healthy subjects and individuals diagnosed with schizophrenia and Attention Deficit/Hyperactivity Disorder, though the effects of modafinil have not been evaluated on working memory in methamphetamine‐dependent subjects. This double‐blind, placebo‐controlled study evaluated whether a daily dose of 400 mg of modafinil, administered over three consecutive days, would enhance performance on a measure of working memory relative to test performance at baseline and following 3 days of placebo administration in 11 methamphetamine addicted, nontreatment‐seeking volunteers. The results revealed that participants demonstrating relatively poor performance on the third day of a 3‐day washout period (ie, at baseline), showed significant improvement on measures of working memory, but not on measures of episodic memory or information processing speed. In contrast, for participants demonstrating relatively high performance at baseline, modafinil administration did not affect test scores. The findings provide an initial indication that modafinil can reverse methamphetamine‐associated impairments in working memory. (Am J Addict 2010;00:1–5)
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Modafinil enhances working memory in healthy individuals and individuals with a wide range of psychiatric illnesses, likely due to catecholaminergic actions.
“modafinil enhances working memory in healthy individuals as well as individuals with a wide range of psychiatric illnesses, and this improvement is likely due to modafinil’s catecholaminergic actions (Kalechstein et al 2010, Kalechstein et al 2013, Minzenberg & Carter 2008).”
From Prefrontal cortex executive processes affected by stress in health and disease (2018) · cites this paper as Kalechstein et al 2010, Kalechstein et al 2013, Minzenberg & Carter 2008
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“…previous research has indicated that individuals with low IQ or low baseline performance are the most likely to show cognitive benefi ts with modafi nil (Kalechstein et al., 2010; Randall et al., 2005a), we did not fi nd signifi cant interactions between estimated IQ and response to modafi nil.”
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“Due to its profile as a stimulant and cognitive enhancer, modafinil is being used off label as an anti-relapse medication against METH dependence and other addictive disorders (McGaugh et al., 2009; Kalechstein et al., 2010; Mereu et al., 2013).”
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“Similarly, in a sample of methamphetamine-dependent individuals, administration of 400 mg of modafinil for three days significantly improved response accuracy on measures of working memory in study participants who demonstrated relatively poor performance at baseline (Kalechstein et al., 2010).”
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“For both cocaine and METH users, modafinil was efficacious in improving several domains of cognitive and executive functions (Kalechstein et al., 2013; Ghahremani et al., 2011; Kalechstein et al., 2010; Hester et al., 2010; Finke et al., 2010).”
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“In fact, several reports have shown that modafinil improves cognitive function in healthy volunteers (Turner et al., 2003), adults with ADHD (Turner et al., 2004), and in METH-dependent individuals (Kalechstein et al., 2010; Ghahremani et al., 2011).”
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“Conversely, there is accumulating evidence that modafinil may significantly improve attention and WM in those with SUD (Kalechstein et al., 2010, 2013; Dean et al., 2011; Joos et al., 2013), and may be a useful pharmacological partner for other interventions aiming to improve WM, such as WM…”
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“Modafinil also alleviated meth-induced cognitive impairments during withdrawal (Ling et al., 2006; Minzenberg and Carter, 2008; Vocci and Appel, 2007), improved memory (Ghahremani et al., 2011; Kalechstein et al., 2010), and increased attention (Dean et al., 2011) in meth dependent participants.”
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“Additionally, modafinil improves memory in Meth-dependent participants, indicating efficacy as a cognitive-enhancing drug for Meth addicts (Ghahremani et al. 2011; Kalechstein et al. 2010).”
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“Importantly, METH-associated neurocognitive impairment has been identified as a neglected area of critical concern (Kalechstein et al., 2010; Sofuoglu, 2010; Sofuoglu et al., 2013), particularly given the association between neurocognitive impairment and poor treatment outcomes in other addictive conditions, such as c…”
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“Comparable differential effects of modafinil have also been reported by Kalechstein et al. (2010) in methamphetamine dependent patients, by Finke et al. (2010) in healthy volunteers with high versus low performance on a sustained attention task, by Zack and Poulos (2009) in pathologic gamblers with…”
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“Further, MA use disorder is associated with impairment across a number of cognitive domains, including episodic and working memory [6–11].”
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Enhanced External Counterpulsation Improves Cognitive Function of Persons With Long COVID
Sathyamoorthy, M., Sevak, R. J., Cabrera, J., et al. (2024) · American Journal of Physical Medicine & Rehabilitation · doi:10.1097/phm.0000000000002433 · Cited by 9 · see citing works
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“This finding also has been observed in long-term, high dose methamphetamine users following administration of modafinil for 3 days (Kalechstein et al., 2010).”
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“To date, two studies suggest that modafinil may be able to improve executive function and memory in people with methamphetamine use disorder [95, 96], while appreciating that the evidence does not support modafinil as a pharmacotherapy to reduce meth-amphetamine use per se [97].”
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A Case Report on Modafinil Dependence
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- Authors
- Kalechstein, A. D., De La Garza, II, & Newton, T. F.
- Affiliations
- Baylor College of Medicine (US)
- ORCID
- Newton, Thomas F.
- Venue
- The American Journal on Addictions
- Publisher
- Wiley
- Published
- 2010-06-17
- Volume
- 19
- Issue
- 4
- Pages
- 340-344
- ISSN
- 1055-0496 (ISSN-L)
- 1521-0391
- PMC
- PMC3341927
- OpenAlex
- W1558666780
- Cited by
- 67
- References
- 23
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 4 · 2018: 3 · 2017: 7 · 2016: 4 · 2015: 4 · 2014: 6 · 2013: 7 · 2012: 8
- FWCI
- 3.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal on Addictions (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (R01DA023468, R03DA020591, K24DA017754)
- National Center for Research Resources (RR00865, M01RR000865)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Keywords
- modafinil, methamphetamine dependence, working memory, cognitive impairment, stimulant use disorder, episodic memory, processing speed, cognitive enhancement, placebo response
- MeSH terms
- Modafinil, Adolescent, Adult, Central Nervous System Stimulants, Benzhydryl Compounds, Female, Humans, Memory, Short-Term, Middle Aged, Neuropsychological Tests, Mental Recall, Amphetamine-Related Disorders
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