Psychological effects of ketamine in healthy volunteers. Phenomenological study.
ABSTRACT 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.
Full-textDOI: · Available from: Garry Honey, Nov 18, 2014
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ABSTRACT: Modern neuropsychopharmacology commenced in the 1950s with the serendipitous discovery of first-generation antipsychotics and antidepressants which were therapeutically effective yet had marked adverse effects. Today, a broader palette of safer and better-tolerated agents is available for helping people that suffer from schizophrenia, depression and other psychiatric disorders, while complementary approaches like psychotherapy also have important roles to play in their treatment, both alone and in association with medication. Nonetheless, despite considerable efforts, current management is still only partially effective, and highly-prevalent psychiatric disorders of the brain continue to represent a huge personal and socio-economic burden. The lack of success in discovering more effective pharmacotherapy has contributed, together with many other factors, to a relative disengagement by pharmaceutical firms from neuropsychiatry. Nonetheless, interest remains high, and partnerships are proliferating with academic centres which are increasingly integrating drug discovery and translational research into their traditional activities. This is, then, a time of transition and an opportune moment to thoroughly survey the field. Accordingly, the present paper, first, chronicles the discovery and development of psychotropic agents, focusing in particular on their mechanisms of action and therapeutic utility, and how problems faced were eventually overcome. Second, it discusses the lessons learned from past successes and failures, and how they are being applied to promote future progress. Third, it comprehensively surveys emerging strategies that are (1), improving our understanding of the diagnosis and classification of psychiatric disorders; (2), deepening knowledge of their underlying risk factors and pathophysiological substrates; (3), refining cellular and animal models for discovery and validation of novel therapeutic agents; (4), improving the design and outcome of clinical trials; (5), moving towards reliable biomarkers of patient subpopulations and medication efficacy and (6), promoting collaborative approaches to innovation by uniting key partners from the regulators, industry and academia to patients. Notwithstanding the challenges ahead, the many changes and ideas articulated herein provide new hope and something of a framework for progress towards the improved prevention and relief of psychiatric and other CNS disorders, an urgent mission for our Century. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.European Neuropsychopharmacology 02/2015; 25(5). DOI:10.1016/j.euroneuro.2015.01.016 · 5.40 Impact Factor
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ABSTRACT: Sub-anesthetic doses of the NMDA antagonist ketamine have been shown to model the formation and stability of delusion in human subjects. The latter has been predicted to be due to aberrant prediction error resulting in enhanced destabilization of beliefs. To extend the scope of this model, we investigated the effect of administration of low dose systemic ketamine on memory in a rodent model of memory reconsolidation. Systemic ketamine was administered either prior to or immediately following auditory fear memory reactivation in rats. Memory strength was assessed by measuring freezing behavior 24h later. Follow up experiments were designed to investigate an effect of pre-reactivation ketamine on short-term memory (STM), closely related memories, and basolateral amygdala (BLA) specific destabilization mechanisms. Rats given pre-reactivation, but not post-reactivation, ketamine showed larger freezing responses 24h later compared to vehicle. This enhancement was not observed 3h after the memory reactivation, nor was it seen in a closely related contextual memory. Prior inhibition of a known destabilization mechanism in the BLA blocked the effect of pre-reactivation ketamine. Pre- but not post-reactivation ketamine enhances fear memory. These data together with recent data in human subjects supports a model of delusion fixity that proposes that aberrant prediction errors result in enhanced destabilization and strengthening of delusional belief. Copyright © 2015 Elsevier B.V. All rights reserved.Schizophrenia Research 02/2015; 164(1-3). DOI:10.1016/j.schres.2015.02.009 · 4.43 Impact Factor
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ABSTRACT: Functional Magnetic Resonance Imaging (fMRI) is an effective tool for identifying brain areas and networks implicated in human timing. But fMRI is not just a phrenological tool: by careful design, fMRI can be used to disentangle discrete components of a timing task and control for the underlying cognitive processes (e.g. sustained attention and WM updating) that are critical for estimating stimulus duration in the range of hundreds of milliseconds to seconds. Moreover, the use of parametric designs and correlational analyses allows us to better understand not just where, but also how, the brain processes temporal information. In addition, by combining fMRI with psychopharmacological manipulation, we can begin to uncover the complex relationship between cognition, neurochemistry and anatomy in the healthy human brain. This chapter provides an overview of some of the key findings in the functional imaging literature of both duration estimation and temporal prediction, and outlines techniques that can be used to allow timing-related activations to be interpreted more unambiguously. In our own studies, we have found that estimating event duration, whether that estimate is provided by a motor response or a perceptual discrimination, typically recruits basal ganglia, SMA and right inferior frontal cortex, and can be modulated by dopaminergic activity in these areas. By contrast, orienting attention to predictable moments in time in order to optimize behaviour, whether that is to speed motor responding or improve perceptual accuracy, recruits left inferior parietal cortex.Advances in Experimental Medicine and Biology 01/2014; 829:237-64. DOI:10.1007/978-1-4939-1782-2_13 · 2.01 Impact Factor