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Cited by 85Psychedelics and Drug StudiesTreatment of Major DepressionSubstance Abuse Treatment and Outcomes

A sub-set of psychoactive effects may be critical to the behavioral impact of ketamine on cocaine use disorder: Results from a randomized, controlled laboratory study

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Dakwar, E., Nunes, E.V., Hart, C.L., Hu, M.C., Foltin, R.W., Levin, F.R.·2018·Neuropharmacology
DOI 10.1016/j.neuropharm.2018.01.005PMC PMC6033686
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Abstract

Efforts to translate sub-anesthetic ketamine infusions into widespread clinical use have centered around developing medications with comparable neurobiological activity, but with attenuated psychoactive effects so as to minimize the risk of behavioral toxicity and abuse liability. Converging lines of research, however, suggest that some of the psychoactive effects of sub-anesthetic ketamine may have therapeutic potential. Here, we assess whether a subset of these effects - the so-called mystical-type experience - mediates the effect of ketamine on craving and cocaine use in cocaine dependent research volunteers. We found that ketamine leads to significantly greater acute mystical-type effects (by Hood Mysticism Scale: HMS), dissociation (by Clinician Administered Dissociative States Scale: CADSS), and near-death experience phenomena (by the Near-Death Experience Scale: NDES), relative to the active control midazolam. HMS score, but not the CADSS or NDES score, was found to mediate the effect of ketamine on global improvement (decreased cocaine use and craving) over the post-infusion period. This is the first controlled study to show that mystical-type phenomena, long considered to have therapeutic potential, may work to impact decision-making and behavior in a sustained manner. These data suggest that an important direction for medication development is the identification of ketamine-like pharmacotherapy that is selectively psychoactive (as opposed to free of experiential effects entirely), so that mystical-type perspectival shifts are more reliably produced and factors lending to abuse or behavioral impairment are minimized. Future research can further clarify the relationship between medication-occasioned mystical-type effects and clinical benefit for different disorders. This article is part of the Special Issue entitled 'Psychedelics: New Doors, Altered Perceptions'.

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Authors
Dakwar, E., Nunes, E. V., Hart, C. L., Hu, M. C., Foltin, R. W., & Levin, F. R.
Affiliations
  • New York State Psychiatric Institute (US)
  • Columbia University (US)
Corresponding author
Dakwar, E.
ORCID
Venue
Neuropharmacology
Publisher
Elsevier BV
Published
2018-11
Volume
142
Pages
270-276
ISSN
0028-3908 (ISSN-L)
DOI
10.1016/j.neuropharm.2018.01.005
PMC
PMC6033686
OpenAlex
W2782003333
Cited by
85
References
47
Citations by year
2026: 10 · 2025: 19 · 2024: 13 · 2023: 12 · 2022: 14 · 2021: 6 · 2020: 5 · 2019: 1 · 2018: 5
FWCI
4.98
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuropharmacology (acceptedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Drug Abuse (DA035472, DA031771)
  • New York State Psychiatric Institute
Topics
  • Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Keywords
ketamine, cocaine dependence, psychedelic therapy, craving, dissociation, near-death experiences, midazolam, abuse liability, psychoactive effects, decision-making
MeSH terms
Dissociative Disorders, Female, Hallucinogens, Hospitalization, Humans, Ketamine, Male, Midazolam, Middle Aged, Mysticism, Treatment Outcome, Cocaine-Related Disorders

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