Psychological effects of ketamine in healthy volunteers: Phenomenological study

Benito Menni CASM, Barcelona, Spain.
The British Journal of Psychiatry (Impact Factor: 7.99). 09/2006; 189(2):173-9. DOI: 10.1192/bjp.bp.105.015263
Source: PubMed


The psychosis-inducing effect of ketamine is important evidence supporting the glutamate hypothesis of schizophrenia. However, the symptoms the drug produces have not been described systematically.
To examine the effects of ketamine in healthy people using a structured psychiatric interview.
Ketamine (200 ng/ml) or placebo was administered by continuous infusion to 15 healthy volunteers. Symptoms were rated using the Present State Examination, the Thought, Language and Communication Scale and the Scale for Assessment of Negative Symptoms.
Ketamine induced a range of perceptual distortions, but not hallucinations. Referential ideas were seen in nearly half the sample. There were only mild and infrequent ratings on the thought disorder scale. Affective flattening and alogia were seen in some volunteers.
Ketamine does not reproduce the full picture of schizophrenia. The main point of similarity concerns referential thinking. Phenomena resembling negative symptoms are also seen, but the distinction of these from the drug's sedative effects requires further elucidation.

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Available from: Garry Honey, Nov 18, 2014
    • "Together these findings indicate NMDAR autoantibodies might play a causal role in some cases of psychosis. An association between NMDAR antibody and schizophrenia is biologically plausible; NMDAR blockade with ketamine produces psychotic symptoms in healthy volunteers (Pomarol-Clotet et al. 2006). Since a variety of infections, atopic disorders and autoimmune conditions are associated with schizophrenia, it is possible that they share a common underlying pathway most likely involving the inflammatory immune response. "
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    Psychopharmacology 06/2015; DOI:10.1007/s00213-015-3975-1 · 3.88 Impact Factor
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    • "The commonest feature was referential thinking of a delusional nature, together with a range of perceptual abnormalities perhaps best described as dissociative. However, it did not induce hallucinations, and the authors were doubtful about its ability to cause thought disorder; furthermore, although negative-like symptoms resulted they could not exclude the possibility that this was simply due to its anesthetic effects [Pomarol-Clotet et al., 2006]. In a similar vein, Morgan and Curran [2012] who reviewed the literature, noted that ketamine users sometimes reported psychotic symptoms but concluded that " there is little evidence of any link between chronic heavy use of ketamine and a diagnosis of a psychotic disorder. "
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    ABSTRACT: When drug-induced psychoses were first identified in the mid-20th century, schizophrenia was considered a discrete disease with a likely genetic cause. Consequently, drug-induced psychoses were not considered central to understanding schizophrenia as they were thought to be phenocopies rather than examples of the illness secondary to a particular known cause. However, now that we know that schizophrenia is a clinical syndrome with multiple component causes, then it is clear that the drug-induced psychoses have much to teach us. This article shows how the major neuropharmacological theories of schizophrenia have their origins in studies of the effects of drugs of abuse. Research into the effects of LSD initiated the serotonergic model; amphetamines the dopamine hypothesis, PCP and ketamine the glutamatergic hypothesis, while most recently the effects of cannabis have provoked interest in the role of endocannabinoids in schizophrenia. None of these models account for the complete picture of schizophrenia; rather the various drug models mimic different aspects of the illness. Determining the different molecular effects of those drugs whose pharmacological effects do and do not mimic the various aspects of schizophrenia has much to teach us concerning the pathogenesis of the illness. © 2013 Wiley Periodicals, Inc.
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    • "A role for glutamate, the primary excitatory neurotransmitter in the brain, has long been evidenced from observations that drugs such as ketamine and phencyclidine (PCP) that primarily block iontropic n-methyl-d-aspartate receptors (NMDARs) and are capable of causing negative and positive symptoms that resemble those seen in psychotic disorders such as schizophrenia (Luby et al., 1962; Vollenweider and Geyer, 2001; Pomarol-Clotet et al., 2006). This observation led to the NMDA hypofunction hypothesis of schizophrenia (Olney and Farber, 1995) with the involvement of the glutamatergic system in psychosis stemming from neuroimaging, genetic, and postmortem investigations. "
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