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      Peak experiences and the afterglow phenomenon: When and how do therapeutic effects of hallucinogens depend on psychedelic experiences?

      1 , 2 , 3 , 1 , 4
      Journal of Psychopharmacology
      SAGE Publications

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          Abstract

          Interest in the therapeutic potential of psychedelic substances has recently resumed. During an early phase of human psychedelic research, their therapeutic application in different pathologies had been suggested, and the first evidence for efficacy was provided. The range of recent clinical applications of psychedelics spans from cluster headaches and obsessive-compulsive disorder to addiction and the treatment of fear and anxiety in patients suffering from terminal illness, indicating potentially different therapeutic mechanisms. A variety of approaches in psychotherapy emphasize subjective experiences, such as so-called peak experiences or afterglow phenomena, as differentially mediating therapeutic action. This review aims to re-evaluate earlier and recent concepts of how psychedelic substances may exert beneficial effects. After a short outline of neurophenomenological aspects, we discuss different approaches to how psychedelics are used in psychotherapy. Finally, we summarize evidence for the relationship between subjective experiences and therapeutic success. While the distinction between pharmacological and psychological action obviously cannot be clear-cut, they do appear to contribute differently from each other when their effects are compared with regard to pathologies.

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          A theory of cortical responses.

          This article concerns the nature of evoked brain responses and the principles underlying their generation. We start with the premise that the sensory brain has evolved to represent or infer the causes of changes in its sensory inputs. The problem of inference is well formulated in statistical terms. The statistical fundaments of inference may therefore afford important constraints on neuronal implementation. By formulating the original ideas of Helmholtz on perception, in terms of modern-day statistical theories, one arrives at a model of perceptual inference and learning that can explain a remarkable range of neurobiological facts.It turns out that the problems of inferring the causes of sensory input (perceptual inference) and learning the relationship between input and cause (perceptual learning) can be resolved using exactly the same principle. Specifically, both inference and learning rest on minimizing the brain's free energy, as defined in statistical physics. Furthermore, inference and learning can proceed in a biologically plausible fashion. Cortical responses can be seen as the brain's attempt to minimize the free energy induced by a stimulus and thereby encode the most likely cause of that stimulus. Similarly, learning emerges from changes in synaptic efficacy that minimize the free energy, averaged over all stimuli encountered. The underlying scheme rests on empirical Bayes and hierarchical models of how sensory input is caused. The use of hierarchical models enables the brain to construct prior expectations in a dynamic and context-sensitive fashion. This scheme provides a principled way to understand many aspects of cortical organization and responses. The aim of this article is to encompass many apparently unrelated anatomical, physiological and psychophysical attributes of the brain within a single theoretical perspective. In terms of cortical architectures, the theoretical treatment predicts that sensory cortex should be arranged hierarchically, that connections should be reciprocal and that forward and backward connections should show a functional asymmetry (forward connections are driving, whereas backward connections are both driving and modulatory). In terms of synaptic physiology, it predicts associative plasticity and, for dynamic models, spike-timing-dependent plasticity. In terms of electrophysiology, it accounts for classical and extra classical receptive field effects and long-latency or endogenous components of evoked cortical responses. It predicts the attenuation of responses encoding prediction error with perceptual learning and explains many phenomena such as repetition suppression, mismatch negativity (MMN) and the P300 in electroencephalography. In psychophysical terms, it accounts for the behavioural correlates of these physiological phenomena, for example, priming and global precedence. The final focus of this article is on perceptual learning as measured with the MMN and the implications for empirical studies of coupling among cortical areas using evoked sensory responses.
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            Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance.

            Although psilocybin has been used for centuries for religious purposes, little is known scientifically about its acute and persisting effects. This double-blind study evaluated the acute and longer-term psychological effects of a high dose of psilocybin relative to a comparison compound administered under comfortable, supportive conditions. The participants were hallucinogen-naïve adults reporting regular participation in religious or spiritual activities. Two or three sessions were conducted at 2-month intervals. Thirty volunteers received orally administered psilocybin (30 mg/70 kg) and methylphenidate hydrochloride (40 mg/70 kg) in counterbalanced order. To obscure the study design, six additional volunteers received methylphenidate in the first two sessions and unblinded psilocybin in a third session. The 8-h sessions were conducted individually. Volunteers were encouraged to close their eyes and direct their attention inward. Study monitors rated volunteers' behavior during sessions. Volunteers completed questionnaires assessing drug effects and mystical experience immediately after and 2 months after sessions. Community observers rated changes in the volunteer's attitudes and behavior. Psilocybin produced a range of acute perceptual changes, subjective experiences, and labile moods including anxiety. Psilocybin also increased measures of mystical experience. At 2 months, the volunteers rated the psilocybin experience as having substantial personal meaning and spiritual significance and attributed to the experience sustained positive changes in attitudes and behavior consistent with changes rated by community observers. When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences. The ability to occasion such experiences prospectively will allow rigorous scientific investigations of their causes and consequences.
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              A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression.

              Existing therapies for major depression have a lag of onset of action of several weeks, resulting in considerable morbidity. Exploring pharmacological strategies that have rapid onset of antidepressant effects within a few days and that are sustained would have an enormous impact on patient care. Converging lines of evidence suggest the role of the glutamatergic system in the pathophysiology and treatment of mood disorders. To determine whether a rapid antidepressant effect can be achieved with an antagonist at the N-methyl-D-aspartate receptor in subjects with major depression. A randomized, placebo-controlled, double-blind crossover study from November 2004 to September 2005. Mood Disorders Research Unit at the National Institute of Mental Health. Patients Eighteen subjects with DSM-IV major depression (treatment resistant). After a 2-week drug-free period, subjects were given an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 test days, a week apart. Subjects were rated at baseline and at 40, 80, 110, and 230 minutes and 1, 2, 3, and 7 days postinfusion. Main Outcome Measure Changes in scores on the primary efficacy measure, the 21-item Hamilton Depression Rating Scale. Subjects receiving ketamine showed significant improvement in depression compared with subjects receiving placebo within 110 minutes after injection, which remained significant throughout the following week. The effect size for the drug difference was very large (d = 1.46 [95% confidence interval, 0.91-2.01]) after 24 hours and moderate to large (d = 0.68 [95% confidence interval, 0.13-1.23]) after 1 week. Of the 17 subjects treated with ketamine, 71% met response and 29% met remission criteria the day following ketamine infusion. Thirty-five percent of subjects maintained response for at least 1 week. Robust and rapid antidepressant effects resulted from a single intravenous dose of an N-methyl-D-aspartate antagonist; onset occurred within 2 hours postinfusion and continued to remain significant for 1 week.
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                Author and article information

                Journal
                Journal of Psychopharmacology
                J Psychopharmacol
                SAGE Publications
                0269-8811
                1461-7285
                February 09 2015
                March 2015
                February 09 2015
                March 2015
                : 29
                : 3
                : 241-253
                Affiliations
                [1 ]Clinic for Psychiatry and Psychotherapy, Charité University Medicine, Berlin, Germany
                [2 ]Neurocomputation and Neuroimaging Unit, Freie Universität, Berlin, Germany
                [3 ]Bernstein Center for Computational Neuroscience, Berlin, Germany
                [4 ]Department for Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
                Article
                10.1177/0269881114568040
                25670401
                2070d800-129f-4575-9c1f-b3fffebb9fb2
                © 2015

                http://journals.sagepub.com/page/policies/text-and-data-mining-license

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