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Bhattacharyya S.,Kings College London | Crippa J.A.,University of Sao Paulo | Allen P.,Kings College London | Martin-Santos R.,Kings College London | And 13 more authors.
Archives of General Psychiatry | Year: 2012

Context: The aberrant processing of salience is thought to be a fundamental factor underlying psychosis. Cannabis can induce acute psychotic symptoms, and its chronic use may increase the risk of schizophrenia. We investigated whether its psychotic effects are mediated through an influence on attentional salience processing. Objective: To examine the effects of Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) on regional brain function during salience processing. Design: Volunteers were studied using event-related functional magnetic resonance imaging on 3 occasions after administration of Δ9-THC, CBD, or placebo while performing a visual oddball detection paradigm that involved allocation of attention to infrequent (oddball) stimuli within a string of frequent (standard) stimuli. Setting: University center. Participants: Fifteen healthy men with minimal previous cannabis use. Main Outcome Measures: Symptom ratings, task performance, and regional brain activation. Results: During the processing of oddball stimuli, relative to placebo, Δ9-THC attenuated activation in the right caudate but augmented it in the right prefrontal cortex. Δ9-Tetrahydrocannabinol also reduced the response latency to standard relative to oddball stimuli. The effect of Δ9-THC in the right caudate was negatively correlated with the severity of the psychotic symptoms it induced and its effect on response latency. The effects of CBD on task-related activation were in the opposite direction of those of Δ9-THC; relative to placebo, CBD augmented left caudate and hippocampal activation but attenuated right prefrontal activation. Conclusions: Δ9- Tetrahydrocannabinol and CBD differentially modulate prefrontal, striatal, and hippocampal function during attentional salience processing. These effects may contribute to the effects of cannabis on psychotic symptoms and on the risk of psychotic disorders. ©2012 American Medical Association. All rights reserved. Source


Patent
Dart Neuroscience Llc | Date: 2014-03-11

The invention provides a chemical entity of Formula (I) wherein R


Patent
Dart NeuroScience LLC | Date: 2014-03-14

Systems and methods for treating patients to improve cognitive or motor abilities are disclosed. One exemplary method comprises receiving a visiting patient at a clinic, administering an augmenting agent to the visiting patient, training the visiting patient to stimulate neuronal activity, and recording augmenting agent administration data and patient training data associated with the visiting patient. The augmenting agent may comprise a phosphodiesterase 4 (PDE 4) inhibitor. The method may further comprise receiving a returning patient at the clinic, administering the augmenting agent to the returning patient, training the returning patient to stimulate neuronal activity, and recording augmenting agent administration data and patient training data associated with the returning patient.


Goren M.A.,New York Medical College | Morizumi T.,University of Toronto | Menon I.,New York Medical College | Joseph J.S.,Scripps Research Institute | And 6 more authors.
Nature Communications | Year: 2014

Opsin, the rhodopsin apoprotein, was recently shown to be an ATP-independent flippase (or scramblase) that equilibrates phospholipids across photoreceptor disc membranes in mammalian retina, a process required for disc homoeostasis. Here we show that scrambling is a constitutive activity of rhodopsin, distinct from its light-sensing function. Upon reconstitution into vesicles, discrete conformational states of the protein (rhodopsin, a metarhodopsin II-mimic, and two forms of opsin) facilitated rapid (>10,000 phospholipids per protein per second) scrambling of phospholipid probes. Our results indicate that the large conformational changes involved in converting rhodopsin to metarhodopsin II are not required for scrambling, and that the lipid translocation pathway either lies near the protein surface or involves membrane packing defects in the vicinity of the protein. In addition, we demonstrate that β2 -adrenergic and adenosine A 2A receptors scramble lipids, suggesting that rhodopsin-like G protein-coupled receptors may play an unexpected moonlighting role in re-modelling cell membranes. Source


Patent
Dart Neuroscience Llc | Date: 2014-03-11

The invention provides a chemical entity of Formula (I) wherein R

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