Cocaine self-administration disrupted by the N-methyl-D-aspartate receptor antagonist ketamine: a randomized, crossover trial
Open accessAbstract
Repeated drug consumption may progress to problematic use by triggering neuroplastic adaptations that attenuate sensitivity to natural rewards while increasing reactivity to craving and drug cues. Converging evidence suggests a single sub-anesthetic dose of the N-methyl-D-aspartate receptor antagonist ketamine may work to correct these neuroadaptations and restore motivation for non-drug rewards. Using an established laboratory model aimed at evaluating behavioral shifts in the salience of cocaine now vs money later, we found that ketamine, as compared to the control, significantly decreased cocaine self-administration by 67% relative to baseline at greater than 24 h post-infusion, the most robust reduction observed to date in human cocaine users and the first to involve mechanisms other than stimulant or dopamine agonist effects. These findings signal new directions in medication development for substance use disorders.
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That effect disappeared after a few days.
“though this effect disappeared after a few days [148]”
From Ketamine in neuropsychiatric disorders: an update (2024) · cites this paper as [148]
The Findings section (‘Cocaine use in the natural ecology’) says ketamine initially reduced cocaine use significantly but ceased to separate from midazolam after several days. That supports the loss of a detectable difference from the control, not that the effect itself disappeared; the Discussion notes that some participants sustained abstinence for at least two weeks. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn a randomized controlled trial of 20 participants with cocaine use disorder, ketamine decreased cocaine self-administration by 67% after 24 h.
“another randomized, controlled trial of 20 participants with cocaine use disorder found that ketamine decreased cocaine selfadministration by 67% after 24 h”
From Ketamine in neuropsychiatric disorders: an update (2024) · cites this paper as [148]
The Findings (Cocaine self-administration) report a 67% reduction from baseline, but the measurement was at 28 hours post-infusion, not 24 hours. The Findings (Participants) give a final sample of 20, of whom 18 were included in the primary self-administration analysis. (LLM, conf=0.90)
Experimental — accuracy not yet measuredEmbedding ketamine administration into a mindfulness-enhancing behavioural training framework successfully extended ketamine's anti-addictive properties, which had previously been reported only transiently.
“This study demonstrated that embedding ketamine administration into a mindfulness-enhancing behavioural training framework successfully extended ketamine's anti-addictive properties, which had previously been reported only transiently, subsiding over several days (138, 139).”
From Examining the Potential Synergistic Effects Between Mindfulness Training and Psychedelic-Assisted Therapy (2021) · cites this paper as [139]
The Discussion reports that a single ketamine dose disrupted cocaine use, with some participants abstinent for at least two weeks. It proposes a behavioral treatment platform as a possible way to sustain effects, but does not report testing a mindfulness-enhancing training framework or show that one extended ketamine’s effects. The Methods describe relaxation and breathing exercises around the infusion, not the claimed training intervention; section labels are available, but page numbers are not. (LLM, conf=0.85)
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References 37 · Cited by 105
Research works printed but not linked: 1
- [24]Stahl S Stahl's Essential Psvchopharmacoloav: Neuroscientific Basis and Clinical Applications 2008 Cambridge University Press New York, NY
- Authors
- Dakwar, E., Hart, C. L., Levin, F. R., Nunes, E. V., & Foltin, R. W.
- Affiliations
- New York State Psychiatric Institute (US)
- Corresponding author
- Dakwar, E
- Venue
- Molecular Psychiatry
- Published
- 2016-04-19
- Volume
- 22
- Issue
- 1
- Pages
- 76-81
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC5435123
- OpenAlex
- W2341144630
- Cited by
- 105
- References
- 37
- Citations by year
- 2026: 11 · 2025: 22 · 2024: 14 · 2023: 10 · 2022: 13 · 2021: 6 · 2020: 9 · 2019: 6 · 2018: 7 · 2017: 4 · 2016: 3
- FWCI
- 3.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (R21DA035472, K24DA029647, K23DA031771)
- 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 › Pharmacology › Treatment of Major Depression
- Keywords
- cocaine self-administration, ketamine, NMDA receptor antagonists, cocaine dependence, neuroplasticity, reward salience, craving, drug cue reactivity
- MeSH terms
- Adult, Central Nervous System Stimulants, Cocaine, Cues, Female, Humans, Ketamine, Male, Middle Aged, Motivation, Self Administration, Receptors, N-Methyl-D-Aspartate, Cross-Over Studies, Cocaine-Related Disorders, Craving
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