The international journal of neuropsychopharmacology
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Int. J. Neuropsychopharmacol. · Aug 2021
Psychedelics and Consciousness: Distinctions, Demarcations, and Opportunities.
Psychedelic substances produce unusual and compelling changes in conscious experience that have prompted some to propose that psychedelics may provide unique insights explaining the nature of consciousness. At present, psychedelics, like other current scientific tools and methods, seem unlikely to provide information relevant to the so-called "hard problem of consciousness," which involves explaining how first-person experience can emerge. ⋯ In this review, we discuss common meanings of the term "consciousness" when used with regard to psychedelics and consider some models of the effects of psychedelics on the brain that have also been associated with explanatory claims about consciousness. We conclude by calling for epistemic humility regarding the potential for psychedelic research to aid in explaining the hard problem of consciousness while pointing to ways in which psychedelics may advance the study of many specific aspects of consciousness.
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Ketamine appears to have a therapeutic role in certain mental disorders, most notably unipolar major depressive disorder. However, its efficacy in bipolar depression is less clear. This study aimed to assess the efficacy and tolerability of ketamine for bipolar depression. ⋯ There is some preliminary evidence supporting use of intravenous racemic ketamine to treat adults with bipolar depression. There is a need for additional studies exploring longer-term outcomes and alterative formulations of ketamine.
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Int. J. Neuropsychopharmacol. · Mar 2021
The Microbiota-Gut-Brain Axis in Mental Health and Medication Response: Parsing Directionality and Causality.
There is increasing evidence for the role of the microbiome in various mental health disorders. Moreover, there has been a growing understanding of the importance of the microbiome in mediating both the efficacy and side effects of various medications, including psychotropics. In this issue, Tomizawa and colleagues report on the effect of psychotropic drugs on the gut microbiome of 40 patients with depression and/or anxiety disorders. ⋯ The health consequences of these microbiome alterations remain to be fully understood. In this commentary, we will discuss such findings through the lens of several recent studies on the microbiota-gut-brain axis. We also use the paper as a backdrop to discuss directionality and, by extension, causality in relation to microbiota-gut-brain-brain signaling.
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Int. J. Neuropsychopharmacol. · Jan 2021
Esketamine Nasal Spray for Rapid Reduction of Depressive Symptoms in Patients With Major Depressive Disorder Who Have Active Suicide Ideation With Intent: Results of a Phase 3, Double-Blind, Randomized Study (ASPIRE II).
Patients with major depressive disorder (MDD) having active suicidal ideation with intent require immediate treatment. ⋯ This study confirmed rapid and robust reduction of depressive symptoms with esketamine nasal spray in severely ill patients with MDD who have active suicidal ideation with intent. Trial Registration: Clinical Trials.gov identifier: NCT03097133.
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Int. J. Neuropsychopharmacol. · Dec 2020
Effects of Mu-Opiate Receptor Gene Polymorphism rs1799971 (A118G) on the Antidepressant and Dissociation Responses in Esketamine Nasal Spray Clinical Trials.
At ketamine and esketamine doses at which antidepressant doses are achieved, these agents are relatively selective, noncompetitive, N-methyl-D-aspartate receptor antagonists. However, at substantially higher doses, ketamine has shown mu-opioid receptor (MOR-gene symbol: OPRM1) agonist effects. Preliminary clinical studies showed conflicting results on whether naltrexone, a MOR antagonist, blocks the antidepressant action of ketamine. We examined drug-induced or endogenous MOR involvement in the antidepressant and dissociative responses to esketamine by assessing the effects of a functional single nucleotide polymorphism rs1799971 (A118G) of OPRM1, which is known to alter MOR agonist-mediated responses. ⋯ Variation in rs1799971 (A118G) did not affect the antidepressant response to esketamine + antidepressant. Antidepressant response to antidepressant + placebo was increased in G-allele carriers, compatible with previous reports that release of endorphins/enkephalins may play a role in mediating placebo effect.