***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: INTRODUCTION Cannabis and agonists of the brain cannabinoid receptor ( CB1R ) produce acute  memory impairments in humans . However , the extent to which cannabinoids impair the component processes of encoding and retrieval has not been established in humans . The objective of this analysis was to determine whether the administration of Δ9-Tetrahydrocannabinol ( THC ) , the principal psychoactive constituent of cannabis , impairs encoding and /or retrieval of verbal information . MATERIAL S AND METHODS Healthy subjects were recruited from the community . Subjects were administered the Rey-Auditory Verbal Learning Test ( RAVLT ) either before administration of THC ( experiment # 1 ) ( n=38 ) or while under the influence of THC ( experiment # 2 ) ( n=57 ) . Immediate and delayed recall on the RAVLT was compared . Subjects received intravenous THC , in a placebo-controlled , double-blind , r and omized manner at doses known to produce behavioral and subjective effects consistent with cannabis intoxication . RESULTS Total immediate recall , short delayed recall , and long delayed recall were reduced in a statistically significant manner only when the RAVLT was administered to subjects while they were under the influence of THC ( experiment # 2 ) and not when the RAVLT was administered prior . CONCLUSIONS THC acutely interferes with encoding of verbal memory without interfering with retrieval . These data suggest that learning information prior to the use of cannabis or cannabinoids is not likely to disrupt recall of that information . Future studies will be necessary to determine whether THC impairs encoding of non-verbal information , to what extent THC impairs memory consolidation , and the role of other cannabinoids in the memory-impairing effects of cannabis . CLINICAL TRIAL INFORMATION Cannabinoids , Neural Synchrony , and Information Processing ( THC-Gamma ) http:// clinical trials.gov/ct2/show/ study /NCT00708994 NCT00708994 Pharmacogenetics of Cannabinoid Response http:// clinical trials.gov/ct2/show/NCT00678730 NCT00678730 Rationale Long-term heavy cannabis use can result in memory impairment .  Adolescent users may be especially vulnerable to the adverse neurocognitive effects of cannabis . Objectives and methods In a cross-sectional and prospect i ve neuropsychological study of 181 adolescents aged 16–20 ( mean 18.3 years ) , we compared performance indices from one of the most widely used measures of learning and memory — the Rey Auditory Verbal Learning Test — between cannabis users ( n = 52 ; mean 2.4 years of use , 14 days/month , median abstinence 20.3 h ) , alcohol users ( n = 67 ) and non-user controls ( n = 62 ) matched for age , education and premorbid intellectual ability ( assessed prospect ively ) , and alcohol consumption for cannabis and alcohol users . Results Cannabis users performed significantly worse than alcohol users and non-users on all performance indices . They recalled significantly fewer words overall ( p < 0.001 ) , demonstrating impaired learning ( p < 0.001 ) , retention ( p < 0.001 ) and retrieval ( p < 0.05 ) ( Cohen ’s d 0.43–0.84 ) . The degree of impairment was associated with the duration , quantity , frequency and age of onset of cannabis use , but was unrelated to alcohol exposure or other drug use . No gender effects were detected and the findings remained after controlling for premorbid intellectual ability . An earlier age of onset of regular cannabis use was associated with worse memory performance after controlling for extent of exposure to cannabis . Conclusions Despite relatively brief exposure , adolescent cannabis users relative to their age-matched counterparts demonstrated similar memory deficits to those reported in adult long-term heavy users . The results indicate that cannabis adversely affects the developing brain and reinforce concerns regarding the impact of early exposure Rationale Many neuropsychological studies have documented deficits in working memory among recent heavy cannabis users . However , little is known about the effects of cannabis on brain activity . Objective We assessed brain function among recent heavy cannabis users while they performed a working memory task . Methods Functional magnetic resonance imaging was used to examine brain activity in 12 long-term heavy cannabis users , 6–36 h after last use , and in 10 control subjects while they performed a spatial working memory task .  Regional brain activation was analyzed and compared using statistical parametric mapping techniques . Results Compared with controls , cannabis users exhibited increased activation of brain regions typically used for spatial working memory tasks ( such as prefrontal cortex and anterior cingulate ) . Users also recruited additional regions not typically used for spatial working memory ( such as regions in the basal ganglia ) . These findings remained essentially unchanged when re-analyzed using subjects ’ ages as a covariate . Brain activation showed little or no significant correlation with subjects ’ years of education , verbal IQ , lifetime episodes of cannabis use , or urinary cannabinoid levels at the time of scanning . Conclusions Recent cannabis users displayed greater and more widespread brain activation than normal subjects when attempting to perform a spatial working memory task . This observation suggests that recent cannabis users may experience subtle neurophysiological deficits , and that they compensate for these deficits by “ working harder”—calling upon additional brain regions to meet the dem and s of the task The main objective of this prospect i ve longitudinal study was to investigate bidirectional associations between adolescent cannabis use ( CU ) and  neurocognitive performance in a community sample of 294 young men from ages 13 to 20 years . The results showed that in early adolescence , and prior to initiation to CU , poor short-term and working memory , but high verbal IQ , were associated with earlier age of onset of CU . In turn , age of CU onset and CU frequency across adolescence were associated with ( a ) specific neurocognitive decline in verbal IQ and executive function tasks tapping trial and error learning and reward processing by early adulthood and ( b ) lower rates of high-school graduation . The association between CU onset and change in neurocognitive function , however , was found to be accounted for by CU frequency . Whereas the link between CU frequency across adolescence and change in verbal IQ was explained ( mediated ) by high school graduation , the link between CU frequency and tasks tapping trial and error learning were independent from high school graduation , concurrent cannabis and other substance use , adolescent alcohol use , and externalizing behaviors . Findings support prevention efforts aim ed at delaying onset and reducing frequency of CU Recent reports show that fewer adolescents believe that regular cannabis use is harmful to health . Concomitantly , adolescents are initiating cannabis use at younger ages , and more adolescents are using cannabis on a daily basis . The purpose of the present study was to test the association between persistent cannabis use and neuropsychological decline and determine whether decline is concentrated among adolescent-onset cannabis users . Participants were members of the Dunedin Study , a prospect i ve study of a birth cohort of 1,037 individuals followed from birth ( 1972/1973 ) to age 38 y.  Cannabis use was ascertained in interviews at ages 18 , 21 , 26 , 32 , and 38 y.  Neuropsychological testing  was conducted at age 13 y , before initiation of cannabis use , and again at age 38 y , after a pattern of persistent cannabis use had developed . Persistent cannabis use was associated with neuropsychological decline broadly across domains of functioning , even after controlling for years of education . Informants also reported noticing more cognitive problems for persistent cannabis users . Impairment was concentrated among adolescent-onset cannabis users , with more persistent use associated with greater decline . Further , cessation of cannabis use did not fully restore neuropsychological functioning among adolescent-onset cannabis users . Findings are suggestive of a neurotoxic effect of cannabis on the adolescent brain and highlight the importance of prevention and policy efforts targeting adolescents BACKGROUND Although cannabis use after a first episode of psychosis has been associated with relapse , little is known about the determinants of this most preventable risk factor for relapse of psychosis . Here we aim ed to study whether the effects on outcome vary depending on the type of cannabis consumed and usage pattern . METHODS In this observational study , we prospect ively recruited and followed up patients aged 18 - 65 years who presented with their first episode of psychosis to psychiatric services in south London , London , UK .  Relapse of psychosis within 2 years after onset of psychosis was defined as risk of subsequent admission to hospital . We classified patients into different patterns of cannabis use based on continuity of use after onset of psychosis , potency of cannabis consumed , and frequency of use after the onset of their illness . We used multiple regression analyses ( logistic or binominal ) to compare the different cannabis use groups and propensity score analysis to vali date the results . FINDINGS Between April 12 , 2002 , and July 26 , 2013 , 256 patients presented with a first episode of psychosis . We did follow-up assessment s for these patients until September , 2015 . Simple analyses showed that former regular users of cannabis who stopped after the onset of psychosis had the most favourable illness course with regards to relapse . In multiple analysis , continued high-frequency users ( ie , daily use in all 24 months ) of high-potency ( skunk-like ) cannabis had the worst outcome , indexed as an increased risk for a subsequent relapse ( odds ratio [ OR ] 3·28 ; 95 % CI 1·22 - 9·18 ) , more relapses ( incidence rate ratio 1·77 ; 95 % CI 0·96 - 3·25 ) , fewer months until a relapse occurred ( b -0·22 ; 95 % CI -0·40 to -0·04 ) , and more intense psychiatric care ( OR 3·16 ; 95 % CI 1·26 - 8·09 ) after the onset of psychosis . INTERPRETATION Adverse effects associated with continued use of cannabis after the onset of a first episode of psychosis depend on the specific patterns of use . Possible interventions could focus on persuading cannabis-using patients with psychosis to reduce use or shift to less potent forms of cannabis . FUNDING National Institute for Health Research ( NIHR ) CONTEXT Cannabis sativa use can impair verbal learning , provoke acute psychosis , and increase the risk of schizophrenia . It is unclear where C. sativa acts in the human brain to modulate verbal learning and to induce psychotic symptoms . OBJECTIVES To investigate the effects of 2 main psychoactive constituents of C. sativa , Delta9-tetrahydrocannabinol ( Delta9-THC ) and cannabidiol , on regional brain function during verbal paired associate learning . DESIGN Subjects were studied on 3 separate occasions using a block design functional magnetic resonance imaging paradigm while performing a verbal paired associate learning task . Each imaging session was preceded by the ingestion of Delta9-THC ( 10 mg ) , cannabidiol ( 600 mg ) , or placebo in a double-blind , r and omized , placebo-controlled , repeated- measures , within-subject design . SETTING University research center . PARTICIPANTS Fifteen healthy , native English-speaking , right-h and ed men of white race/ethnicity who had used C. sativa 15 times or less and had minimal exposure to other illicit drugs in their lifetime . MAIN OUTCOME MEASURES Regional brain activation ( blood oxygen level-dependent response ) , performance in a verbal learning task , and objective and subjective ratings of psychotic symptoms , anxiety , intoxication , and sedation . RESULTS Delta9-Tetrahydrocannabinol increased psychotic symptoms and levels of anxiety , intoxication , and sedation , whereas no significant effect was noted on these parameters following administration of cannabidiol .  Performance in the verbal learning task was not significantly modulated by either drug . Administration of Delta9-THC augmented activation in the parahippocampal gyrus during blocks 2 and 3 such that the normal linear decrement in activation across repeated encoding blocks was no longer evident . Delta9-Tetrahydrocannabinol also attenuated the normal time-dependent change in ventrostriatal activation during retrieval of word pairs , which was directly correlated with concurrently induced psychotic symptoms . In contrast , administration of cannabidiol had no such effect . CONCLUSION The modulation of mediotemporal and ventrostriatal function by Delta9-THC may underlie the effects of C. sativa on verbal learning and psychotic symptoms , respectively Regions in the medial temporal lobes ( MTL ) have long been implicated in the formation of new memories for events , however , it is unclear whether different MTL subregions support different memory processes . Here , we used event-related functional magnetic resonance imaging ( fMRI ) to examine the degree to which two recognition memory processes-re collection and familiarity-were supported by different MTL subregions . Results showed that encoding activity in the rhinal cortex selectively predicted familiarity-based recognition , whereas , activity in the hippocampus and posterior parahippocampal cortex selectively predicted re collection . Collectively , these results support the view that different subregions within the MTL memory system implement unique encoding processes that differentially support familiarity and re collection BACKGROUND The relationship between cannabis use and cognitive function in mid-life has rarely been examined despite verbal learning deficits in young adults . METHOD A longitudinal cohort study of 1,897 Australians recruited at 40 - 46 years of age and followed up 4 years ( 94 % ) and 8 years 
    Output:
    
Memory performance studies showed CU performed worse particularly during verbal memory tasks .
Longitudinal studies suggest that cannabis use may have a causal role in memory deficits .
Pre clinical studies have not provided conclusive evidence of memory deficits following cannabinoid exposure , although they have shown evidence of cannabinoid-induced structural and histological alteration .
Memory performance deficits may be related to cannabis use , with lower performance possibly underpinned by altered functional activation .
Memory impairments may be associated with the level of cannabis exposure and use of cannabis during developmentally sensitive periods , with possible improvement following cessation of cannabis use