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Query: UNIPROT:P21554 (cannabinoid receptor)
 3,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cognitive impairments during psychotic episodes are assumed to be caused not only by one single putative classical neurotransmitter dysfunction but also by an impaired equilibrium of the interaction between different neurobiological generators of cognitive processes. Herein, the perceptual abnormalities induced by psychotogenic agents play a major role as tools for the understanding of model psychoses. The recently discovered cannabinoid receptor system with its endogenous ligand anandamide can be regarded as an extremely relevant regulator system, a dysfunctionality of which may explain at least one subtype of endogenous psychoses. Neuropsychological results (three-dimensional inversion illusion) in delta 9-tetrahydrocannabinol-intoxicated normal volunteers exhibit strong similarities with data acquired from patients suffering from productive schizophrenic psychoses, regarding disturbances in internal regulation of perceptual processes. The relevance of this finding to a general cognitive dysfunction concept of schizophrenic psychosis is discussed.
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PMID:Towards a cannabinoid hypothesis of schizophrenia: cognitive impairments due to dysregulation of the endogenous cannabinoid system. 913 Mar 8

Cognitive impairments during psychotic episodes are assumed to be caused not only by one single putative classical neurotransmitter dysfunction but also to be due to an impaired equilibrium of the interaction between different neurobiological generators of cognitive processes. Here, the perceptual abnormalities induced by psychotogenic agents play a major role as tools for understanding model psychoses. The recently discovered cannabinoid receptor system with its endogenous ligand anandamide can be regarded as an extremely relevant regulation system, a dysfunctionality of which may explain at least one subtype of endogenous psychoses. The present paper discusses the possible associations between the endogenous anandamide/cannabinoid system and schizophrenic psychoses. Neuropsychological experiments with the 3-D inversion paradigm were performed in healthy volunteers intoxicated with delta9-Tetrahydrocannabinol (delta9-THC). The 3-D inversion paradigm represents a visual illusion of binocular depth perception. Such an inversion occurs in many cases, especially when objects with a higher degree of familiarity (e.g. photographs of faces) are displayed. It is assumed that cognitive factors override the binocular disparity cues of stereopsis. We tested the hypothesis that, during psychotic and related prepsychotic states, the human CNS is unable to correct implausible perceptual hypotheses. Our study provides evidence of strong similarities between data acquired from patients, suffering from productive schizophrenic psychoses and delta9-THC-intoxicated healthy volunteers, as concerns disturbances in the internal regulation of perceptual processes.
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PMID:Cannabinoid/anandamide system and schizophrenia: is there evidence for association? 975 42

Rare but striking individual differences in responsiveness to cannabinoids have been observed that might involve mutations in the gene encoding the brain-expressed cannabinoid receptor. In a preliminary study, the human CB1 cannabinoid receptor coding region was comparatively sequenced in different groups of individuals: one group showed acute psychotic symptoms after cannabis intake, while another group did not develop any psychopathology after long-term heavy cannabis abuse. No evidence for structural mutations was obtained, which might provide some insight into the molecular basis of individually different responsiveness to cannabinoids. Comparison of CB1 cannabinoid receptor amino acid sequences between species substantiated evidence that the protein sequence is relatively well conserved.
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PMID:Comparative sequencing of the human CB1 cannabinoid receptor gene coding exon: no structural mutations in individuals exhibiting extreme responses to cannabis. 1132 42

Schizophrenia is a devastating psychiatric disorder with a high prevalence worldwide. There is therefore a need for animal models allowing the development of new therapeutic interventions and reliable diagnostic tests. In the temporal domain, cannabinoid receptor gene (CB1) knockout mice exhibit behavioural alterations, which parallel symptoms in schizophrenia, cannabis intoxication and dopamine D2 activation. While a specific nucleotide homology between CB1 and D2 accounts for the pathophysiology, pre-inserted spirochaetal DNA on the polyadenylation signal of CB1 reveals the aetiology of schizophrenia. If, in analogy to thalassaemia, mutations occur within this 3' regulatory domain, the genetic expression of CB1 is disrupted and sequential information lost in time. CB1, previously unrecognized as a candidate gene, thus unifies the different aspects of schizophrenic psychosis: cannabis-induced model psychosis, disrupted information processing, spatio-temporal distortions and other psychotic symptoms, disturbed neuronal migration, schizophrenic brain disorder, familial transmission, and prenatal infection by Borrelia burgdorferi.
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PMID:Are cannabinoid receptor knockout mice animal models for schizophrenia? 1139 12

There has been considerable debate about the reasons for the association observed between cannabis use and psychosis in both clinical and general population samples. Among the hypotheses proposed to explain the association are the following: 1) common factors explain the co-occurrence; 2 cannabis causes psychosis that would not have occurred in the absence of cannabis use; 3) cannabis precipitates psychosis among persons who were vulnerable to developing the disorders; 4) cannabis use worsens or prolongs psychosis among those who have already developed the disorder; and 5) that persons with psychosis are more likely to become regular or problematic cannabis users than persons without psychosis. This article evaluates the evidence on each of these hypotheses, including recent research on the role of the cannabinoid receptor system in schizophrenia. The evidence suggests that common factors do not explain the comorbidity between cannabis use and psychosis, and it is unlikely that cannabis use causes psychosis among persons who would otherwise not have developed the disorder. The evidence is more consistent with the hypotheses that cannabis use may precipitate psychosis among vulnerable individuals, increase the risk of relapse among those who have already developed the disorder, and may be more likely to lead to dependence in persons with schizophrenia.
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PMID:Cannabis and psychosis. 1200 81

Ontogenetic brain-asymmetry and its reversal in schizophrenia constitute special cases of a more fundamental principle of sensory-motor integration. Transmitted through an immature optical system, asymmetric inputs from the left visual field induce the infant's right hemispheric preference for lower spatial frequencies during early mother-child interaction. The emerging classical features of hemispheric specialisation later in life can be accounted for by a transformation law of the neuronal reference frames based on relativistic non-linear information processing. Accordingly, the asymmetric distributions of the cannabinoid receptor CB1 in the right basal ganglia and the left area of Wernicke reflect the preferences for lateralised posture, positioning, and speech. Epigenetic development of brain asymmetry thus unifies the different aspects related to cradling and breast-feeding, speech- and visuospatial processing, the dimensional conversion of spatiotemporal information and, in the case of a dysbalanced cannabinoid system, its psychotic reversal. The predicted right hemispheric shift and the inverse relationship between Kolmogorov entropy and its dimensional embedding (Shannon entropy) has ultimately been confirmed by non-linear EEG analysis of a fluoro-methyl-anadamide induced model psychosis splitting conscious from unconscious mental processes.
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PMID:The origin of brain asymmetry and its psychotic reversal. 1261 2

Recent advances in the understanding of brain cannabinoid receptor function have renewed interest in the association between cannabinoid compounds and psychosis. In a 3-day, double-blind, randomized, and counterbalanced study, the behavioral, cognitive, and endocrine effects of 0, 2.5, and 5 mg intravenous delta-9-tetrahydrocannabinol (Delta-9-THC) were characterized in 22 healthy individuals, who had been exposed to cannabis but had never been diagnosed with a cannabis abuse disorder. Prospective safety data at 1, 3, and 6 months poststudy was also collected. Delta-9-THC (1) produced schizophrenia-like positive and negative symptoms; (2) altered perception; (3) increased anxiety; (4) produced euphoria; (5) disrupted immediate and delayed word recall, sparing recognition recall; (6) impaired performance on tests of distractibility, verbal fluency, and working memory (7) did not impair orientation; (8) increased plasma cortisol. These data indicate that Delta-9-THC produces a broad range of transient symptoms, behaviors, and cognitive deficits in healthy individuals that resemble some aspects of endogenous psychoses. These data warrant further study of whether brain cannabinoid receptor function contributes to the pathophysiology of psychotic disorders.
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PMID:The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. 1517 44

In the last decade, a large number of studies using Delta9-tetrahydrocannabinol (THC), the main active principle derivative of the marijuana plant, or cannabinoid synthetic derivatives have substantially contributed to advance the understanding of the pharmacology and neurobiological mechanisms produced by cannabinoid receptor activation. Cannabis has been historically used to relieve some of the symptoms associated with central nervous system disorders. Nowadays, there are anecdotal evidences for the use of cannabis in many patients suffering from multiple sclerosis or chronic pain. Following the historical reports of the use of cannabis for medicinal purposes, recent research has highlighted the potential of cannabinoids to treat a wide variety of clinical disorders. Some of these disorders that are being investigated are pain, motor dysfunctions or psychiatric illness. On the other hand, cannabis abuse has been related to several psychiatric disorders such as dependence, anxiety, depression, cognitive impairment, and psychosis. Considering that cannabis or cannabinoid pharmaceutical preparations may no longer be exclusively recreational drugs but may also present potential therapeutic uses, it has become of great interest to analyze the neurobiological and behavioral consequences of their administration. This review attempts to link current understanding of the basic neurobiology of the endocannabinoid system to novel opportunities for therapeutic intervention and its effects on the central nervous system.
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PMID:Role of endocannabinoid system in mental diseases. 1532 60

Delta9-tetrahydrocannabinol (Delta9-THC), the major psychoactive component of marijuana, induces catalepsy-like immobilization and impairment of spatial memory in rats. Delta9-THC also induces aggressive behavior in isolated housing stress. These abnormal behaviors could be counteracted by SR141716A, a CB1 cannabinoid receptor antagonist. Also Delta9-THC inhibited release of glutamate in the dorsal hippocampus, but this inhibition could be antagonized by SR141716A in an in vivo microdialysis study. Moreover, NMDA and AMPA-type glutamate receptor enhancers improved the Delta9-THC-induced impairment of spatial memory. On the other hand, Delta9-THC markedly inhibited the neurodegeneration in experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis and reduced the elevated glutamate level of cerebrospinal fluid induced by EAE. These therapeutic effects on EAE were reversed by SR141716A. Taken together, our results demonstrate that the inhibition of glutamate release via activation of the CB1-cannabinoid receptor is one mechanism involved in Delta9-THC-induced impairment of spatial memory, and the therapeutic effect of Delta9-THC on EAE, and a Delta9-THC analog might provide an effective treatment for psychosis and neurodegenerative diseases.
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PMID:New perspectives in the studies on endocannabinoid and cannabis: abnormal behaviors associate with CB1 cannabinoid receptor and development of therapeutic application. 1559 3

Cannabis consumption may induce psychotic states in normal individuals, worsen psychotic symptoms of schizophrenic patients, and may facilitate precipitation of schizophrenia in vulnerable individuals. Recent studies provide additional biological and genetic evidence for the cannabinoid hypothesis of schizophrenia. Examinations using [3H]CP-55940 or [3H]SR141716A revealed that the density of CB1 receptors, a central type of cannabinoid receptor, is increased in subregions of the prefrontal cortex in schizophrenia. Anandamide, an endogenous cannabinoid, is also increased in the CSF in schizophrenia. A genetic study revealed that the CNR1 gene, which encodes CB1 receptors, is associated with schizophrenia, especially the hebephrenic type. Individuals with a 9-repeat allele of an AAT-repeat polymorphism of the gene may have a 2.3-fold higher susceptibility to schizophrenia. Recent findings consistently indicate that hyperactivity of the central cannabinoid system is involved in the pathogenesis of schizophrenia or the neural mechanisms of negative symptoms.
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PMID:New perspectives in the studies on endocannabinoid and cannabis: cannabinoid receptors and schizophrenia. 1561 77


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