***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: Throughout the world , drug and alcohol use has a clear adolescent onset ( Degenhardt et al. , 2008 ) . Alcohol continues to be the most popular drug among teens and emerging adults , with almost a third of 12th grade rs and 40 % of college students reporting recent binge drinking ( Johnston et al. , 2009 , 2010 ) , and marijuana ( MJ ) is the second most popular drug in teens ( Johnston et al. , 2010 ) . The initiation of drug use is consistent with an overall increase in risk-taking behaviors during adolescence that coincides with significant neurodevelopmental changes in both gray and white matter ( Giedd et al. , 1996a ; Paus et al. , 1999 ; Sowell et al. , 1999 , 2002 , 2004 ; Gogtay et al. , 2004 ; Barnea-Goraly et al. , 2005 ; Lenroot and Giedd , 2006 ) . Animal studies have suggested that compared to adults , adolescents may be particularly vulnerable to the neurotoxic effects of drugs , especially alcohol and MJ ( see Schneider and Koch , 2003 ; Barron et al. , 2005 ; Monti et al. , 2005 ; Cha et al. , 2006 ; Rubino et al. , 2009 ; Spear , 2010 ) . In this review , we will provide a detailed overview of studies that examined the impact of early adolescent onset of alcohol and MJ use on neurocognition ( e.g. , Ehrenreich et al. , 1999 ; Wilson et al. , 2000 ; Tapert et al. , 2002a ; Hartley et al. , 2004 ; Fried et al. , 2005 ; Townshend and Duka , 2005 ; Medina et al. , 2007a ; McQueeny et al. , 2009 ; Gruber et al. , 2011 , 2012 ; Hanson et al. , 2011 ; Lisdahl and Price , 2012 ) , with a special emphasis on recent prospect i ve longitudinal studies ( e.g. , White et al. , 2011 ; Hicks et al. , 2012 ; Meier et al. , 2012 ) . Finally , we will explore potential clinical and public health implication s of these findings Cannabis use in youth is rising and has been linked to deficits in cognitive functioning . However , cognitive findings have primarily been based on small sample s of users seeking treatment , and few studies have evaluated cognition in occasional cannabis users . Here , we examined 4,568 adolescents and young adults ( ages 14–21 years ) drawn from the Philadelphia Neurodevelopmental Cohort , a prospect i ve , population -based study . Participants were classified as cannabis Non-Users ( n = 3,401 ) , Occasional Users ( twice per week or less ; n = 940 ) , or Frequent Users ( > 3 times per week ; n = 227 ) . Mixed-model analyses examined main effects of cannabis use and interactions between age and cannabis use on cognitive functioning . There was a significant interaction between cannabis group and age such that adolescent ( but not young adult ) Frequent Users performed worse than Non-Users on measures of executive control ( p = .002 ) . Earlier age of cannabis use was associated with worse performance in executive control in Occasional Users ( p = .04 ) . Unexpectedly , Occasional Users exhibited better executive control , memory , and social cognition than Non-Users ( ps < .05 ) . Although mild executive control deficits in adolescent frequent users and a relation between early cannabis initiation and cognitive performance are partially consistent with prior research , cognitive deficits were not found in other hypothesized domains in this community-based sample . Moreover , occasional cannabis users displayed equivalent or even slightly better executive control , social – cognitive , and memory abilities compared with nonusers , suggesting complex relationships between cannabis use and cognition in youth . Longitudinal studies with community sample s are needed to identify variables affecting risk and resilience to cognitive deficits associated with cannabis OBJECTIVE The present study used youth 's in vivo reports of subjective responses to cannabis while smoking in their natural environments to identify real-world mechanisms of topiramate treatment for cannabis misuse . METHOD Participants were 40 cannabis users ( ≥ twice weekly in past 30 days ) , ages 15 - 24 years ( 47.5 % female ) , with at least one cannabis use episode during the final 3 weeks of a 6-week , r and omized clinical trial . Youth reported subjective " high " while smoking , stimulation , sedation , stress , craving , and grams of marijuana used in the natural environment via wireless electronic devices . Bayesian multilevel structural equation modeling ( MSEM ) evaluated mediation via indirect effect tests . RESULTS Significant within ( daily ) and between ( person ) variability and distinctive within and between effects supported the MSEM approach . Subjective high while smoking was significantly reduced for youth in the topiramate condition , relative to placebo , and the indirect effect of reduced subjective high on total grams of cannabis smoked that day was significant . Indirect effects through other subjective responses were not significant . CONCLUSIONS The results of this initial study suggest that altering subjective responses to smoking , specifically subjective high , may be a key target for developing adjunctive pharmacotherapies for cannabis misuse . More generally , this work provides an example for applying ecological momentary assessment and analytic techniques to evaluate mechanisms of behavior change in longitudinal data 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 Objectives : Cannabis is the most commonly used illicit drug ; a substantial minority of users develop dependence . The current lack of pharmacological treatments for cannabis dependence warrants the use of novel approaches and further investigation of promising pharmacotherapy . In this case series , we assessed the use of self-titrated dosages of Sativex ( 1:1 , & Dgr;9-tetrahydrocannabinol [THC]/cannabidiol [ CBD ] combination ) and motivational enhancement therapy and cognitive behavioral therapy ( MET/CBT ) for the treatment of cannabis dependence among 5 treatment-seeking community-recruited cannabis-dependent subjects . Methods : Participants underwent a 3-month open-label self-titration phase with Sativex ( up to 113.4 of THC/105 mg of CBD ) and weekly MET/CBT , with a 3-month follow-up . Results : Sativex was well-tolerated by all participants ( average dosage 77.5 THC/71.7 mg CBD ) . The combination of Sativex and MET/CBT reduced the amount of cannabis use and progressively reduced craving and withdrawal scores . THC/CBD metabolite concentration indicated reduced cannabis use and compliance with medication . Conclusions : In summary , this pilot study found that with Sativex in combination with MET/CBT reduced cannabis use while preventing increases in craving and withdrawal in the 4 participants completing the study . Further systematic exploration of Sativex as a pharmacological treatment option for cannabis dependence should be performed OBJECTIVE The present study examined factors associated with recall error in the measurement of alcohol use onset and whether there was a tendency toward earlier or later self-reported age at alcohol use onset . METHOD This study estimated the effect of predictors on the presence and direction of recall error for age at alcohol use onset . The sample ( n = 1,044 ) was from an existing longitudinal alcohol prevention trial in urban Chicago . Estimates were derived from a series of logistic regression models comparing agreement between a retrospective and a prospect i ve measure of age at alcohol use onset . RESULTS Eligibility for free or reduced-price lunch in 6th grade , alcohol use in 6th grade , cigarette use in 12th grade , and alcohol use in 12th grade were significantly associated with recall error of age at alcohol use onset . Self-reported substance use ( alcohol and tobacco ) in 12th grade was also found to predict a later self-reported age at alcohol use onset when recalled . CONCLUSIONS Those most at risk for the negative outcomes associated with early alcohol initiation are also those most likely to misreport their age at alcohol use onset 
    Output:
    
First , general executive functioning seems to be more impaired in adolescent frequent cannabis users compared to adult frequent cannabis users .
Second , age-effects may be most prominent among very heavy and dependent users .
Third , craving and inhibitory control may not decrease as much post-intoxication in adolescents compared to adults .
Lastly , adolescents ’ vulnerability to reduced learning following cannabis use may not persist after sustained abstinence .