human
***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: Craving is a major motivator underlying drug use and relapse but the neural correlates of cannabis craving are not well understood . This study sought to determine whether visual cannabis cues increase cannabis craving and whether cue-induced craving is associated with regional brain activation in cannabis-dependent individuals . Cannabis craving was assessed in 16 cannabis-dependent adult volunteers while they viewed cannabis cues during a functional MRI ( fMRI ) scan . The Marijuana Craving Question naire was administered immediately before and after each of three cannabis cue-exposure fMRI runs . FMRI blood-oxygenation-level-dependent ( BOLD ) signal intensity was determined in regions activated by cannabis cues to examine the relationship of regional brain activation to cannabis craving . Craving scores increased significantly following exposure to visual cannabis cues . Visual cues activated multiple brain regions , including inferior orbital frontal cortex , posterior cingulate gyrus , parahippocampal gyrus , hippocampus , amygdala , superior temporal pole , and occipital cortex . Craving scores at baseline and at the end of all three runs were significantly correlated with brain activation during the first fMRI run only , in the limbic system ( including amygdala and hippocampus ) and paralimbic system ( superior temporal pole ) , and visual regions ( occipital cortex ) . Cannabis cues increased craving in cannabis-dependent individuals and this increase was associated with activation in the limbic , paralimbic , and visual systems during the first fMRI run , but not subsequent fMRI runs . These results suggest that these regions may mediate visually cued aspects of drug craving . This study provides preliminary evidence for the neural basis of cue-induced cannabis craving and suggests possible neural targets for interventions targeted at treating cannabis dependence 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 BACKGROUND Evidence regarding the association between cannabis use and depression  remain conflicting , especially as studies have not typically adopted a longitudinal design with a follow-up period that was long enough to adequately cover the risk period for onset of depression . METHOD Males from the Cambridge Study in Delinquent Development ( CSDD ) ( N = 285 ) were assessed seven times from age 8 to 48 years to prospect ively investigate the association between  cannabis use and risk of  major depressive disorder ( MDD ) .  A combination of multiple analyses ( logistic regression , Cox regression , fixed-effects analysis ) was employed to explore the strength and direction of effect within different developmental stages . RESULTS Multiple regression analyses revealed that early-onset cannabis use ( before age 18 ) but not late-onset cannabis use ( after age 27 ) was associated with a higher risk and shorter time until a subsequent MDD diagnosis . This effect was present in high-frequency [ ( odds ratio ( OR ) 8.83 , 95 % confidence interval ( CI ) 1.29 - 70.79 ] ; [ hazard ratio ( HR ) 8.69 , 95 % CI 2.07 - 36.52 ) ] and low-frequency early-onset users ( OR 2.41 , 95 % CI 1.22 - 4.76 ; HR 2.09 , 95 % CI 1.16 - 3.74 ) . Effect of increased frequency of cannabis use on increased risk of subsequent MDD was observed only for use during adolescence ( age 14 - 18 ) but not at later life stages , while controlling for observed and non-unobserved time-invariant factors . Conversely , MDD in adulthood ( age 18 - 32 ) was linked to a reduction in subsequent cannabis use ( age 32 - 48 ) . CONCLUSIONS The present findings provide evidence implicating frequent cannabis use during adolescence as a risk factor for later life depression . Future studies should further examine causality of effects in larger sample 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 Worldwide cannabis dependence is increasing , as is the concentration of Δ9-tetrahydrocannabinol ( THC ) in street cannabis . At the same time , the concentration of the second most abundant cannabinoid in street cannabis ,  cannabidiol  ( CBD ) , is decreasing . These two cannabinoids have opposing effects both pharmacologically and behaviorally when administered in the laboratory . No research has yet examined how the ratio of these constituents impacts on the appetitive/reinforcing effects of cannabis in humans . A total of 94 cannabis users were tested 7 days apart , once while non-intoxicated and once while acutely under the influence of their own chosen smoked cannabis on dependence-related measures . Using an unprecedented methodology , a sample of cannabis ( as well as saliva ) was collected from each user and analyzed for levels of cannabinoids . On the basis of CBD : THC ratios in the cannabis , individuals from the top and bottom tertiles were directly compared on indices of the reinforcing effects of drugs , explicit liking , and implicit attentional bias to drug stimuli . When intoxicated , smokers of high CBD : THC strains showed reduced attentional bias to drug and food stimuli compared with smokers of low CBD : THC . Those smoking higher CBD : THC strains also showed lower self-rated liking of cannabis stimuli on both test days . Our findings suggest that CBD has potential as a treatment for cannabis dependence . The acute modulation of the incentive salience of drug cues by CBD may possibly generalize to a treatment for other addictive disorders In light of exp and ing legalization of cannabis and swelling debate about the potential risks , particularly for younger users , underst and ing acute cannabis effects among adolescents and emerging adults is more important than ever . Contemporary models of addiction development identify subjective drug responses as central to the developmental unfolding of drug use disorders . Despite this , surprisingly little is known about cannabis ’s acute subjective effects in human youths . This research utilized ecological momentary assessment ( EMA ) in the natural environment to identify the typical situational context of cannabis use among 85 frequent cannabis users , ages 15–24 years ( M = 19.8 , SD = 2.0 ; 48.2 % female ) . Study aims were to ( a ) characterize momentary changes in several subjective states ( i.e. , stimulation , sedation , tension , craving , and high ) when not using , just before cannabis use , and after use , and ( b ) evaluate whether cannabis responses varied with cannabis use disorder ( CUD ) severity or across the transition from adolescence to emerging adulthood in a correlational manner . Use of cannabis produced measurable reductions in craving and tension , as well as increases in stimulation , sedation , and “ high . ” Participants with more CUD symptoms reported greater relief of craving and increased stimulatory response and high following use . In contrast , emerging adults reported diminished stimulatory response and high following use , relative to adolescents . Results highlight the utility of EMA for characterizing cannabis response as this behavior unfolds in daily life , during a key developmental timeframe in the pathogenesis of cannabis-use pathology BACKGROUND Few effective treatment options exist for cannabis-using youth . This pilot study aim ed to test Approach-Avoidance Training to reduce cannabis use with non-treatment-seeking adolescents . METHODS Eighty cannabis-using non-treatment-seeking adolescents ( average age 19 ) were recruited from San Diego , California and Charleston , South Carolina , and r and omized to complete either six sessions of Cannabis Approach-Avoidance Task Training ( CAAT-training ) design ed to reduce automatic approach biases for cannabis cues or CAAT-sham training . Change in two primary outcome variables was examined : 1 ) cannabis approach bias and 2 ) percent cannabis use days over study enrollment . Change in percent alcohol use days over study enrollment was explored as a secondary outcome . RESULTS A mixed models repeated measures analysis confirmed the group by time interaction effect for approach bias failed to reach statistical significance ( p = .06 ) . Significant group by time interaction effects ( ps < 0.05 ) predicted percent days of cannabis and alcohol use over study enrollment . Participants r and omized to the avoid cannabis condition ( CAAT-training ) reported 7 % fewer days of cannabis use compared to 0 % change for sham ; unexpectedly , those in the avoid cannabis condition reported 10 % percent more alcohol use days compared to 3 % more for sham . CONCLUSIONS Computerized cognitive bias modification paradigms may have utility in reducing  adolescent cannabis use . Future work should consider developing a paradigm that addresses both cannabis and alcohol , as well as alternative computerized approaches for coping with addictive behavior in conjunction with bias modification CONTEXT Cannabis use can both increase and reduce anxiety in humans . The neurophysiological substrates of these effects are unknown . OBJECTIVE To investigate the effects of 2 main psychoactive constituents of Cannabis sativa ( Delta9-tetrahydrocannabinol [ Delta9-THC ] and cannabidiol [ CBD ] ) on regional brain function during emotional processing . DESIGN Subjects were studied on 3 separate occasions using an event-related functional magnetic resonance imaging paradigm while viewing faces that implicitly elicited different levels of anxiety . Each scanning session was preceded by the ingestion of either 10 mg of Delta9-THC , 600 mg of CBD , or a placebo in a double-blind , r and omized , placebo-controlled design . PARTICIPANTS Fifteen healthy , English-native , right-h and ed men who had used cannabis 15 times or less in their life . MAIN OUTCOME MEASURES Regional brain activation ( blood oxygenation level-dependent response ) , electrodermal activity ( skin conductance response [ SCR ] ) , and objective and subjective ratings of anxiety . RESULTS Delta9-Tetrahydrocannabinol increased anxiety , as well as levels of intoxication , sedation , and psychotic symptoms , whereas there was a trend for a reduction in anxiety following administration of CBD . The number of SCR fluctuations during the processing of intensely fearful faces increased following administration of Delta9-THC but decreased following administration of CBD . Cannabidiol attenuated the blood oxygenation level-dependent signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces , and its suppression of the amygdalar and anterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations . Delta9- 
    Output:
    
agent
RESULTS Although causality is unclear , heavy and dependent cannabis use is consistently associated with a high prevalence of comorbid psychiatric disorders and learning and memory impairments that seem to recover after a period of abstinence .
Evidence regarding other cognitive domains and neurological consequences including cerebrovascular events is limited and inconsistent .
Abstinence after treatment is only achieved in a minority of cases ; treatment targeted at reduction in use appears have some success .
Potential moderators of the impact of CUD on the brain include age of onset , heaviness of use , CUD severity , the ratio of ∆9-tetrahydrocannabinol to cannabidiol , and severity of comorbid disorders .
Current evidence of long-term effects of daily cannabis use and cannabis use disorder on brain-related outcomes is suggestive rather than conclusive but use is associated with psychiatric morbidity and with cognitive impairments that recover after a period of abstinence
***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: Craving is a major motivator underlying drug use and relapse but the neural correlates of cannabis craving are not well understood . This study sought to determine whether visual cannabis cues increase cannabis craving and whether cue-induced craving is associated with regional brain activation in cannabis-dependent individuals . Cannabis craving was assessed in 16 cannabis-dependent adult volunteers while they viewed cannabis cues during a functional MRI ( fMRI ) scan . The Marijuana Craving Question naire was administered immediately before and after each of three cannabis cue-exposure fMRI runs . FMRI blood-oxygenation-level-dependent ( BOLD ) signal intensity was determined in regions activated by cannabis cues to examine the relationship of regional brain activation to cannabis craving . Craving scores increased significantly following exposure to visual cannabis cues . Visual cues activated multiple brain regions , including inferior orbital frontal cortex , posterior cingulate gyrus , parahippocampal gyrus , hippocampus , amygdala , superior temporal pole , and occipital cortex . Craving scores at baseline and at the end of all three runs were significantly correlated with brain activation during the first fMRI run only , in the limbic system ( including amygdala and hippocampus ) and paralimbic system ( superior temporal pole ) , and visual regions ( occipital cortex ) . Cannabis cues increased craving in cannabis-dependent individuals and this increase was associated with activation in the limbic , paralimbic , and visual systems during the first fMRI run , but not subsequent fMRI runs . These results suggest that these regions may mediate visually cued aspects of drug craving . This study provides preliminary evidence for the neural basis of cue-induced cannabis craving and suggests possible neural targets for interventions targeted at treating cannabis dependence 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 BACKGROUND Evidence regarding the association between cannabis use and depression  remain conflicting , especially as studies have not typically adopted a longitudinal design with a follow-up period that was long enough to adequately cover the risk period for onset of depression . METHOD Males from the Cambridge Study in Delinquent Development ( CSDD ) ( N = 285 ) were assessed seven times from age 8 to 48 years to prospect ively investigate the association between  cannabis use and risk of  major depressive disorder ( MDD ) .  A combination of multiple analyses ( logistic regression , Cox regression , fixed-effects analysis ) was employed to explore the strength and direction of effect within different developmental stages . RESULTS Multiple regression analyses revealed that early-onset cannabis use ( before age 18 ) but not late-onset cannabis use ( after age 27 ) was associated with a higher risk and shorter time until a subsequent MDD diagnosis . This effect was present in high-frequency [ ( odds ratio ( OR ) 8.83 , 95 % confidence interval ( CI ) 1.29 - 70.79 ] ; [ hazard ratio ( HR ) 8.69 , 95 % CI 2.07 - 36.52 ) ] and low-frequency early-onset users ( OR 2.41 , 95 % CI 1.22 - 4.76 ; HR 2.09 , 95 % CI 1.16 - 3.74 ) . Effect of increased frequency of cannabis use on increased risk of subsequent MDD was observed only for use during adolescence ( age 14 - 18 ) but not at later life stages , while controlling for observed and non-unobserved time-invariant factors . Conversely , MDD in adulthood ( age 18 - 32 ) was linked to a reduction in subsequent cannabis use ( age 32 - 48 ) . CONCLUSIONS The present findings provide evidence implicating frequent cannabis use during adolescence as a risk factor for later life depression . Future studies should further examine causality of effects in larger sample 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 Worldwide cannabis dependence is increasing , as is the concentration of Δ9-tetrahydrocannabinol ( THC ) in street cannabis . At the same time , the concentration of the second most abundant cannabinoid in street cannabis ,  cannabidiol  ( CBD ) , is decreasing . These two cannabinoids have opposing effects both pharmacologically and behaviorally when administered in the laboratory . No research has yet examined how the ratio of these constituents impacts on the appetitive/reinforcing effects of cannabis in humans . A total of 94 cannabis users were tested 7 days apart , once while non-intoxicated and once while acutely under the influence of their own chosen smoked cannabis on dependence-related measures . Using an unprecedented methodology , a sample of cannabis ( as well as saliva ) was collected from each user and analyzed for levels of cannabinoids . On the basis of CBD : THC ratios in the cannabis , individuals from the top and bottom tertiles were directly compared on indices of the reinforcing effects of drugs , explicit liking , and implicit attentional bias to drug stimuli . When intoxicated , smokers of high CBD : THC strains showed reduced attentional bias to drug and food stimuli compared with smokers of low CBD : THC . Those smoking higher CBD : THC strains also showed lower self-rated liking of cannabis stimuli on both test days . Our findings suggest that CBD has potential as a treatment for cannabis dependence . The acute modulation of the incentive salience of drug cues by CBD may possibly generalize to a treatment for other addictive disorders In light of exp and ing legalization of cannabis and swelling debate about the potential risks , particularly for younger users , underst and ing acute cannabis effects among adolescents and emerging adults is more important than ever . Contemporary models of addiction development identify subjective drug responses as central to the developmental unfolding of drug use disorders . Despite this , surprisingly little is known about cannabis ’s acute subjective effects in human youths . This research utilized ecological momentary assessment ( EMA ) in the natural environment to identify the typical situational context of cannabis use among 85 frequent cannabis users , ages 15–24 years ( M = 19.8 , SD = 2.0 ; 48.2 % female ) . Study aims were to ( a ) characterize momentary changes in several subjective states ( i.e. , stimulation , sedation , tension , craving , and high ) when not using , just before cannabis use , and after use , and ( b ) evaluate whether cannabis responses varied with cannabis use disorder ( CUD ) severity or across the transition from adolescence to emerging adulthood in a correlational manner . Use of cannabis produced measurable reductions in craving and tension , as well as increases in stimulation , sedation , and “ high . ” Participants with more CUD symptoms reported greater relief of craving and increased stimulatory response and high following use . In contrast , emerging adults reported diminished stimulatory response and high following use , relative to adolescents . Results highlight the utility of EMA for characterizing cannabis response as this behavior unfolds in daily life , during a key developmental timeframe in the pathogenesis of cannabis-use pathology BACKGROUND Few effective treatment options exist for cannabis-using youth . This pilot study aim ed to test Approach-Avoidance Training to reduce cannabis use with non-treatment-seeking adolescents . METHODS Eighty cannabis-using non-treatment-seeking adolescents ( average age 19 ) were recruited from San Diego , California and Charleston , South Carolina , and r and omized to complete either six sessions of Cannabis Approach-Avoidance Task Training ( CAAT-training ) design ed to reduce automatic approach biases for cannabis cues or CAAT-sham training . Change in two primary outcome variables was examined : 1 ) cannabis approach bias and 2 ) percent cannabis use days over study enrollment . Change in percent alcohol use days over study enrollment was explored as a secondary outcome . RESULTS A mixed models repeated measures analysis confirmed the group by time interaction effect for approach bias failed to reach statistical significance ( p = .06 ) . Significant group by time interaction effects ( ps < 0.05 ) predicted percent days of cannabis and alcohol use over study enrollment . Participants r and omized to the avoid cannabis condition ( CAAT-training ) reported 7 % fewer days of cannabis use compared to 0 % change for sham ; unexpectedly , those in the avoid cannabis condition reported 10 % percent more alcohol use days compared to 3 % more for sham . CONCLUSIONS Computerized cognitive bias modification paradigms may have utility in reducing  adolescent cannabis use . Future work should consider developing a paradigm that addresses both cannabis and alcohol , as well as alternative computerized approaches for coping with addictive behavior in conjunction with bias modification CONTEXT Cannabis use can both increase and reduce anxiety in humans . The neurophysiological substrates of these effects are unknown . OBJECTIVE To investigate the effects of 2 main psychoactive constituents of Cannabis sativa ( Delta9-tetrahydrocannabinol [ Delta9-THC ] and cannabidiol [ CBD ] ) on regional brain function during emotional processing . DESIGN Subjects were studied on 3 separate occasions using an event-related functional magnetic resonance imaging paradigm while viewing faces that implicitly elicited different levels of anxiety . Each scanning session was preceded by the ingestion of either 10 mg of Delta9-THC , 600 mg of CBD , or a placebo in a double-blind , r and omized , placebo-controlled design . PARTICIPANTS Fifteen healthy , English-native , right-h and ed men who had used cannabis 15 times or less in their life . MAIN OUTCOME MEASURES Regional brain activation ( blood oxygenation level-dependent response ) , electrodermal activity ( skin conductance response [ SCR ] ) , and objective and subjective ratings of anxiety . RESULTS Delta9-Tetrahydrocannabinol increased anxiety , as well as levels of intoxication , sedation , and psychotic symptoms , whereas there was a trend for a reduction in anxiety following administration of CBD . The number of SCR fluctuations during the processing of intensely fearful faces increased following administration of Delta9-THC but decreased following administration of CBD . Cannabidiol attenuated the blood oxygenation level-dependent signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces , and its suppression of the amygdalar and anterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations . Delta9- 
    Output:
    