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Subanaesthetic ketamine and altered states of consciousness in humans.

ABSTRACT: BACKGROUND:Despite its designation as a 'dissociative anaesthetic,' the dissociative and psychoactive effects of ketamine remain incompletely understood. The goal of this study was to characterise the subjective experiences and accompanying EEG changes with subanaesthetic doses of ketamine. METHODS:High-density EEG was recorded in 15 human volunteers before, during, and after subanaesthetic ketamine infusion (0.5 mg kg-1 over 40 min), with self-reported measures of altered states of consciousness obtained after ketamine exposure. Sensor- and source-level EEG changes were analysed with a focus on spectral power and regional changes. RESULTS:Ketamine-induced altered states were characterised predominantly by dissociative experiences such as disembodiment and ego transcendence; sensory disturbances were also common. Ketamine broadly decreased low-frequency power, with mean reductions largest at alpha (8-12 Hz) in parietal (-0.94 dB, P<0.001) and occipital (-1.8 dB, P<0.001) channel clusters. Significant decreases in alpha were identified in the precuneus and temporal-parietal junction. CONCLUSIONS:Ketamine induces altered states of consciousness during periods of reduced alpha power in the precuneus and temporal-parietal junction. Modulation of these temporal-parietal loci are candidate mechanisms of the psychoactive effects of ketamine, given that this region is involved in multisensory integration, body representation, and consciousness.

SUBMITTER: Vlisides PE

PROVIDER: S-EPMC6200112 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Subanaesthetic ketamine and altered states of consciousness in humans.

Vlisides P E PE Bel-Bahar T T Nelson A A Chilton K K Smith E E Janke E E Tarnal V V Picton P P Harris R E RE Mashour G A GA

British journal of anaesthesia 20180413 1

<h4>Background</h4>Despite its designation as a 'dissociative anaesthetic,' the dissociative and psychoactive effects of ketamine remain incompletely understood. The goal of this study was to characterise the subjective experiences and accompanying EEG changes with subanaesthetic doses of ketamine.<h4>Methods</h4>High-density EEG was recorded in 15 human volunteers before, during, and after subanaesthetic ketamine infusion (0.5 mg kg<sup>-1</sup> over 40 min), with self-reported measures of alte ...[more]

PMID: 29935579

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Project description:The OAV questionnaire has been developed to integrate research on altered states of consciousness (ASC). It measures three primary and one secondary dimensions of ASC that are hypothesized to be invariant across ASC induction methods. The OAV rating scale has been in use for more than 20 years and applied internationally in a broad range of research fields, yet its factorial structure has never been tested by structural equation modeling techniques and its psychometric properties have never been examined in large samples of experimentally induced ASC.The present study conducted a psychometric evaluation of the OAV in a sample of psilocybin (n = 327), ketamine (n = 162), and MDMA (n = 102) induced ASC that was obtained by pooling data from 43 experimental studies. The factorial structure was examined by confirmatory factor analysis, exploratory structural equation modeling, hierarchical item clustering (ICLUST), and multiple indicators multiple causes (MIMIC) modeling. The originally proposed model did not fit the data well even if zero-constraints on non-target factor loadings and residual correlations were relaxed. Furthermore, ICLUST suggested that the "oceanic boundlessness" and "visionary restructuralization" factors could be combined on a high level of the construct hierarchy. However, because these factors were multidimensional, we extracted and examined 11 new lower order factors. MIMIC modeling indicated that these factors were highly measurement invariant across drugs, settings, questionnaire versions, and sexes. The new factors were also demonstrated to have improved homogeneities, satisfactory reliabilities, discriminant and convergent validities, and to differentiate well among the three drug groups.The original scales of the OAV were shown to be multidimensional constructs. Eleven new lower order scales were constructed and demonstrated to have desirable psychometric properties. The new lower order scales are most likely better suited to assess drug induced ASC.

Project description:BackgroundThe interest in psychoactive agents for treating mental disorders has gathered a growing body of scientific interest. However, research on the relationship between altered states of consciousness (ASCs) and ketamine's antidepressant properties is still limited. Likewise, approaches to sustain early treatment success for the long-term are needed. Taking both aspects into account, the question arises whether the persistence of recurrent ASCs during the subsequent infusion sessions is crucial for the preservation of antidepressant effects during prolonged continued ketamine therapy.AimIn this case study we explored whether recurrent ASC experiences across a large number of infusions are associated with improved antidepressant effects in a single case study.MethodsA 62-year-old patient with treatment-resistant depression, who has been suffering from depressive episodes for over 20 years, was observed for 12 consecutive infusions across 16 weeks. ASCs during ketamine sessions were measured with the 5D-ASC, and pre/post-infusion depression scores with the BDI-II questionnaire. To emphasize psychoactive experiences a personalized antidepressant dose regimen was used.ResultsWe found a strong correlation between the experienced ASCs during ketamine infusions and the antidepressant effect: the stronger the ASCs overall, the stronger the resulting antidepressant effect. This correlation was consistently observed throughout the infusion series, independent of the number of ketamine sessions completed before. However, despite a personalized dose regimen, neither peri-infusion ASCs nor antidepressant effects could be established on a regular basis, leading overall to no improvement in treatment outcome.ConclusionMaintaining psychoactive effects over repeated ketamine infusions may be key to facilitate long-lasting antidepressant effects. However, for some depressed individuals maintenance of antidepressant effects and/or peri-infusion ASCs might not be achieved, even when personalized dosing is used.

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Subanaesthetic ketamine and altered states of consciousness in humans.

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Subanaesthetic ketamine and altered states of consciousness in humans.

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