***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: OBJECTIVE This study aim ed to evaluate the abuse potential and cognitive effects of nabiximols ( Sativex , GW Pharma Ltd. Salisbury , UK ) , an oromucosal spray primarily containing delta‐9‐tetrahydrocannabinol ( THC ) and cannabidiol ( CBD ) . METHODS This was a single‐dose , r and omized , double‐blind , crossover study comparing nabiximols ( 4 , 8 , and 16 consecutive sprays : 10.8 , 21.6 , and 43.2 mg THC , respectively ) with dronabinol 20 and 40 mg ( synthetic THC : Marinol , Solvay Pharmaceuticals , Brussels , Belgium ) and matching placebos in 23 recreational cannabis users . Subjective and cognitive/psychomotor measures were administered over 24 h post‐dose . RESULTS Dronabinol was significantly different from placebo  on abuse potential measures , thereby confirming study validity . Nabiximols 10.8 mg was not significantly different from placebo  on primary measures but was different on some secondary measures . Nabiximols 21.6 mg was significantly greater than placebo  on some primary / secondary measures , whereas nabiximols 43.2 mg showed significant effects on most measures . Nabiximols 10.8 mg was significantly lower than dronabinol doses on most measures ( p < 0.05 ) . Dronabinol 20 mg effects were numerically higher than nabiximols 21.6 mg but were statistically significant only for some measures . Dronabinol 40 mg and nabiximols 43.2 mg were generally not statistically different . CONCLUSIONS Both dronabinol and nabiximols had significant abuse potential compared with placebo at higher doses . Nabiximols showed similar or slightly less abuse potential compared with dronabinol . Therefore , the abuse potential of nabiximols should be no higher than that of dronabinol BACKGROUND Our previous research suggested the involvement of γ-aminobutyric acid ( GABA ) , in particular the GABAB receptor subtype , in the interoceptive effects of Δ(9)-tetrahydrocannabinol ( Δ(9)-THC ) . The aim of the present study was to determine the potential involvement of the GABAA receptor subtype by assessing the separate and combined effects of the GABAA positive allosteric modulator diazepam and Δ(9)-THC using pharmacologically selective drug-discrimination procedures . METHODS Ten cannabis users learned to discriminate 30 mg oral Δ(9)-THC from placebo and then received diazepam ( 5 and 10 mg ) , Δ(9)-THC ( 5 , 15 and 30 mg ) and placebo , alone and in combination  . Self-report , task performance and physiological measures were also collected . RESULTS Δ(9)-THC functioned as a discriminative stimulus , produced subjective effects typically associated with cannabinoids ( e.g. , High , Stoned , Like Drug ) and elevated heart rate . Diazepam alone impaired performance on psychomotor performance tasks and increased ratings on a limited number of self-report question naire items ( e.g. , Any Effect , Se date d ) , but did not substitute for the Δ(9)-THC discriminative stimulus or alter the Δ(9)-THC discrimination dose-response function . Similarly , diazepam had limited impact on the other behavioral effects of Δ(9)-THC . CONCLUSIONS These results suggest that the GABAA receptor subtype has minimal involvement in the interoceptive effects of Δ(9)-THC , and by extension cannabis , in humans 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 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 Introduction Cannabinoids produce a spectrum of effects in humans including euphoria , cognitive impairments , psychotomimetic effects , and perceptual alterations . The extent to which dopaminergic systems contribute to the effects of Δ-9-tetrahydrocannabinol ( Δ-9-THC ) remains unclear . This study evaluated whether pretreatment with a dopamine receptor antagonist altered the effects of Δ-9-THC in humans . Material s and methods In a 2-test-day double-blind study , 28 subjects including healthy subjects ( n = 17 ) and frequent users of cannabis ( n = 11 ) were administered active ( 0.057 mg/kg ) or placebo oral haloperidol in r and om order followed 90 and 215 min later by fixed order intravenous administration of placebo ( vehicle ) and active ( 0.0286 mg/kg ) Δ-9-THC , respectively . Results Consistent with previous reports , intravenous Δ-9-THC produced psychotomimetic effects , perceptual alterations , and subjective effects including “ high . ” Δ-9-THC also impaired verbal recall and attention .  Haloperidol pretreatment did not reduce any of the behavioral effects of Δ-9-THC . Haloperidol worsened the immediate free and delayed free and cued recall deficits produced by Δ-9-THC . Haloperidol and Δ-9-THC worsened distractibility and vigilance . Neither drug impaired performance on a motor screening task , the Stockings of Cambridge task , or the delayed match to sample task . Frequent users had lower baseline plasma prolactin levels and blunted Δ-9-THC induced memory impairments . Conclusions The deleterious effects of haloperidol pretreatment on the cognitive effects of Δ-9-THC are consistent with the pre clinical literature in suggesting crosstalk between DAergic and CBergic systems . However , it is unlikely that DA D2 receptor mechanisms play a major role in mediating the psychotomimetic and perceptual altering effects of Δ-9-THC . Further investigation is warranted to underst and the basis of the psychotomimetic effects of Δ-9-THC and to better underst and the crosstalk between DAergic and CBergic systems Rationale Δ9-Tetrahydrocannabinol ( THC ) is the main active constituent of cannabis . In recent years , the average THC content of some cannabis cigarettes has increased up to approximately 60 mg per cigarette ( 20 % THC cigarettes ) . Acute cognitive and psychomotor effects of THC among recreational users after smoking cannabis cigarettes containing such high doses are unknown . Objectives The objective of this study was to study the dose – effect relationship between the THC dose contained in cannabis cigarettes and cognitive and psychomotor effects for THC doses up to 69.4 mg ( 23 % ) . Material s and methods This double-blind , placebo-controlled , r and omised , four-way cross-over study included 24 non-daily male cannabis users ( two to nine cannabis cigarettes per month ) . Participants smoked four cannabis cigarettes containing 0 , 29.3 , 49.1 and 69.4 mg THC on four exposure days . Results The THC dose in smoked cannabis was linearly associated with a slower response time in all tasks ( simple reaction time , visuo-spatial selective attention , sustained attention , divided attention and short-term memory tasks ) and motor control impairment in the motor control task . The number of errors increased significantly with increasing doses in the short-term memory and the sustained attention tasks . Some participants showed no impairment in motor control even at THC serum concentrations higher than 40 ng/mL. High feeling and drowsiness differed significantly between treatments . Conclusions Response time slowed down and motor control worsened , both linearly , with increasing THC doses . Consequently , cannabis with high THC concentrations may be a concern for public health and safety if cannabis smokers are unable to titrate to a high feeling corresponding to a desired plasma THC level While the effects of cannabis use on retrospective memory have been extensively examined , only a limited number of studies have focused on the links between cannabis use and prospect i ve memory . We conducted two studies to examine the links between cannabis use and both time-based and event-based prospect i ve memory as well as potential mechanisms underlying these links . For the first study , 805 students completed an online survey design ed to assess cannabis consumption , problems with cannabis use indicative of a disorder , and frequency of experiencing prospect i ve memory failures . The results showed small to moderate sized correlations between cannabis consumption , problems with cannabis use , and prospect i ve memory . However , a series of mediation analyses revealed that correlations between problems with cannabis use and prospect i ve memory were driven by self-reported problems with retrospective memory . For the second study , 48 non-users ( who had never used cannabis ) , 48 experimenters ( who had used cannabis five or fewer times 
    Output:
    
Verbal learning and memory and attention are most consistently impaired by acute and chronic exposure to cannabis .
Psychomotor function is most affected during acute intoxication , with some evidence for persistence in chronic users and after cessation of use .
Associations between poorer performance and a range of cannabis use parameters , including a younger age of onset , are frequently reported .
Little further evidence has emerged for the development of tolerance to the acutely impairing effects of cannabis .