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(35) hypothesize that Ssociated with increased COMT activity and Henquet et al. (35) hypothesize that this might lead to a mixture of (a) reduced dopamine neurotransmission inside the prefrontal cortex, and subsequently (b) increased levels of mesolimbic signaling that is thought to result in enhanced danger of experiencing delusions and hallucinations. Conversely, the Met/Met genotype is connected with greater prefrontally mediated executive function functionality than the Met/Val and Val/Val genotypes (46). Reasoning that considering that COMT is especially significant inside the prefrontal cortex, and since the prefrontal cortex is establishing during puberty, Barnett et al. (47) investigated the function of COMT genotypes on cognitive functioning through puberty. They located that amongst boys who had already entered puberty, these with all the Met/Met genotype had an average IQ 10 points larger than these with the Val/Val genotype. This relevant to our focus on psychosis and cannabis for two reasons: initially, it supports the neurodevelopmental model of schizophrenia (48) exactly where genetic and environmental liabilities interact with typical brain improvement to enhance danger for the disorder (49); and secondly it supplies a sound neurodevelopmental framework inside which the adolescent use of cannabis can be understood as conferring improved danger for later psychosis.CLINICAL PRESENTATION OF PSYCHOSIS IN CANNABIS Customers ?ARE THERE Distinct Capabilities? If cannabis does certainly play a causal role in psychotic illness and there's differential risk for psychosis in cannabis users, then it is actually pertinent to address the query of whether cannabis is often distinguished clinically as an etiology for psychosis? The view on the Indian Hemp Drug Commission more than 100 years ago was that you will discover no distinguishing clinical capabilities of psychosis on account of CU (aside from perhaps a shorter duration from the episode). Had been these early impressions correct? In answering this question it is actually crucial to keep in mind the issue raised in the starting of this overview, namely: one particular will have to differentiate in between lifetime use and recent/current use of cannabis as these may have fairly distinct effects upon clinical presentation, course and outcome of psychosis. Duration of untreated psychosis (DUP) will be the period among the onset of your initially psychotic symptoms and also the initiation of antipsychotic treatment. DUP has significance in that longer DUP is related with poorer response to remedy, far more frequent relapses and poorer long-term outcome of psychosis (50, 51). Conversely, early detection and intervention improves outcome to aFrontiers in Psychiatry | Addictive Disorders and Behavioral DyscontrolOctober 2013 | Volume 4 | Article 128 |BurnsCannabis and psychosisconsiderable degree. The well-liked hypothesis linking lengthy DUP for the damaging long-term consequences of psychosis relates to proposed neurotoxicity; however, an analysis of the clinical and neurobiological evidence for this hypothesis suggests that it is in truth synaptic plasticity, and not neurotoxicity, that is definitely among the list of most important mediating processes underlying this association (52). The evidence-base supporting a hyperlink amongst DUP and outcome is important enough to have modified clinical practice. There is certainly as a result a very good rationale for thinking about whether or not CU impacts on DUP. A recent systematic critique identified nine studies with data on DUP and CU, and meta-analysis located no significant difference in DUP between cannabis users and non-users (three).