Tetrahydrocannabinol (THC) impairs encoding but not retrieval of verbal information Efficacy, tolerability and safety of cannabis‐based medicines for chronic pain management – An overview of systematic reviews Acute effects of THC on time perception in frequent and infrequent cannabis users Cannabidiol Attenuates the Appetitive Effects of Δ9-Tetrahydrocannabinol in Humans Smoking Their Chosen Cannabis Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration. Oral Cannabidiol does not Alter the Subjective, Reinforcing or Cardiovascular Effects of Smoked Cannabis Psychomotor performance in relation to acute oral administration of Δ9-tetrahydrocannabinol and standardized cannabis extract in healthy human subjects Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial Examining the theory‐effectiveness hypothesis: A systematic review of systematic reviews Cannabidiol in Humans—The Quest for Therapeutic Targets Cannabinoids in the management of difficult to treat pain Cannabinoid–Opioid Interaction in Chronic Pain Dietetic guidelines: diet in secondary prevention of cardiovascular disease. Balancing the strengths of systematic and narrative reviews. Naltrexone does not attenuate the effects of intravenous Δ9-tetrahydrocannabinol in healthy humans. Summarizing systematic reviews: methodological development, conduct and reporting of an umbrella review approach Treatment of Tourette Syndrome with Delta-9-Tetrahydrocannabinol (Δ9-THC): No Influence on Neuropsychological Performance Efficiency and Contribution of Strategies for Finding Randomized Controlled Trials: A Case Study from a Systematic Review on Therapeutic Interventions of Chronic Depression The impact of cash transfers on social determinants of health and health inequalities in Sub-Saharan Africa: a systematic review protocol Dose-Related Modulation of Event-Related Potentials to Novel and Target Stimuli by Intravenous Δ9-THC in Humans Energy balance-related behaviours associated with overweight and obesity in preschool children: a systematic review of prospective studies. Outcome Measures of Chinese Herbal Medicine for Hypertension: An Overview of Systematic Reviews Vaporization as a Smokeless Cannabis Delivery System: A Pilot Study
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 Medicinal cannabis has already entered mainstream medicine in some countries . This systematic review ( SR ) aim ed at evaluating the efficacy , acceptability and safety of cannabis-based medicines for chronic pain management . Qualitative systematic review of SRs of r and omized controlled trials with cannabis-based medicines for chronic pain management . The Cochrane data bases of SRs , Data base of Abstract s of Review s of Effects and PubMed were search ed for SR published in the period January 2009 to January 2017 . Assessment of the method ological quality of SR was performed by the AMSTAR checklist . Out of 748 papers identified , 10 SRs met the inclusion criteria . The method ological quality was high in four and moderate in six SRs . There were inconsistent findings of four SRs on the efficacy of cannabis-based medicines in neuropathic pain and of one SR for painful spasms in multiple sclerosis . There were consistent results that there was insufficient evidence of any cannabis-based medicine for pain management in patients with rheumatic diseases ( three SRs ) and in cancer pain ( two SRs ) . Cannabis-based medicines undoubtedly enrich the possibilities of drug treatment of chronic pain conditions . It remains the responsibility of the health care community to continue to pursue rigorous study of cannabis-based medicines to provide evidence that meets the st and ard of 21st century clinical care . SIGNIFICANCE We provide an overview of systematic review s on the efficacy , tolerability and safety of cannabis-based medicines for chronic pain management . There are inconsistent findings of the efficacy of cannabinoids in neuropathic pain and painful spasms in multiple sclerosis . There are inconsistent results on tolerability and safety of cannabis-based medicines for any chronic pain Rationale Cannabinoids have been shown to alter time perception , but existing literature has several limitations . Few studies have included both time estimation and production tasks , few control for subvocal counting , most had small sample sizes , some did not record subjects ’ cannabis use , many tested only one dose , and used either oral or inhaled administration of Δ9-tetrahydrocannabinol ( THC ) , leading to variable pharmacokinetics , and some used whole-plant cannabis containing cannabinoids other than THC . Our study attempted to address these limitations . Objectives This study aims to characterize the acute effects of THC and frequent cannabis use on seconds-range time perception . THC was hypothesized to produce transient , dose-related time overestimation and underproduction . Frequent cannabis smokers were hypothesized to show blunted responses to these alterations . Methods IV THC was administered at doses from 0.015 to 0.05 mg/kg to 44 subjects who participated in several double-blind , r and omized , counterbalanced , crossover , placebo-controlled studies . Visual time estimation and production tasks in the seconds range were presented to subjects three times on each test day . Results All doses induced time overestimation and underproduction . Chronic cannabis use had no effect on baseline time perception . While infrequent/nonsmokers showed temporal overestimation at medium and high doses and temporal underproduction at all doses , frequent cannabis users showed no differences . THC effects on time perception were not dose related . Conclusions A psychoactive dose of THC increases internal clock speed as indicated by time overestimation and underproduction . This effect is not dose related and is blunted in chronic cannabis smokers who did not otherwise have altered baseline time perception 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 BACKGROUND Sativex ( ® ) , a cannabis extract oromucosal spray containing Δ(9)-tetrahydrocannabinol ( THC ) and cannabidiol ( CBD ) , is currently in phase III trials as an adjunct to opioids for cancer pain treatment , and recently received United Kingdom approval for treatment of spasticity . There are indications that CBD modulates THC 's effects , but it is unclear if this is due to a pharmacokinetic and /or pharmacodynamic interaction . METHODS Cannabis smokers provided written informed consent to participate in this r and omized , controlled , double-blind , double-dummy institutional review board-approved study . Participants received 5 and 15 mg synthetic oral THC , low-dose ( 5.4 mg THC and 5.0 mg CBD ) and high-dose ( 16.2 mg THC and 15.0 mg CBD ) Sativex , and placebo over 5 sessions . CBD , THC , 11-hydroxy-THC , and 11-nor- 9-carboxy-THC were quantified in plasma by 2-dimensional GC-MS . Lower limits of quantification were ≤0.25 μg/L. RESULTS Nine cannabis smokers completed all 5 dosing sessions . Significant differences ( P < 0.05 ) in maximum plasma concentrations ( C(max ) ) and areas under the curve from 0 - 10.5 h postdose ( AUC(0→10.5 ) ) for all analytes were found between low and high doses of synthetic THC and Sativex . There were no statistically significant differences in C(max ) , time to maximum concentration or in the AUC(0→10.5 ) between similar oral THC and Sativex doses . Relative bioavailability was calculated to determine the relative rate and extent of THC absorption ; 5 and 15 mg oral THC bioavailability was 92.6 % ( 13.1 % ) and 98.8 % ( 11.0 % ) of low- and high-dose Sativex , respectively . CONCLUSION These data suggest that CBD modulation of THC 's effects is not due to a pharmacokinetic interaction at these therapeutic doses Cannabidiol ( CBD ) , a constituent of cannabis with few psychoactive effects , has been reported in some studies to attenuate certain aspects of Δ9-tetrahydrocannabinol ( THC ) intoxication . However , most studies have tested only one dose of CBD in combination with one dose of oral THC , making it difficult to assess the nature of this interaction . Further , the effect of oral CBD on smoked cannabis administration is unknown . The objective of this multi-site , r and omized , double-blind , within-subject laboratory study was to assess the influence of CBD ( 0 , 200 , 400 , 800 mg , p.o . ) pretreatment on the reinforcing , subjective , cognitive , and physiological effects of smoked cannabis ( 0.01 ( inactive ) , 5.30–5.80 % THC ) . Non-treatment-seeking , healthy cannabis smokers ( n=31 ; 17 M , 14 F ) completed eight outpatient sessions . CBD was administered 90 min prior to cannabis administration . The behavioral and cardiovascular effects of cannabis were measured at baseline and repeatedly throughout the session . A subset of participants ( n=8 ) completed an additional session to measure plasma CBD concentrations after administration of the highest CBD dose ( 800 mg ) . Under placebo CBD conditions , active cannabis ( 1 ) was self-administered by significantly more participants than placebo cannabis and ( 2 ) produced significant , time-dependent increases in ratings of ‘ High ’ , ‘ Good Effect ’ , ratings of the cannabis cigarette ( eg , strength , liking ) , and heart rate relative to inactive cannabis . CBD , which alone produced no significant psychoactive or cardiovascular effects , did not significantly alter any of these outcomes . Cannabis self-administration , subjective effects , and cannabis ratings did not vary as a function of CBD dose relative to placebo capsules . These findings suggest that oral CBD does not reduce the reinforcing , physiological , or positive subjective effects of smoked cannabis Abnormalities in psychomotor performance are a consistent finding in schizophrenic patients as well as in chronic cannabis users . The high levels of central cannabinoid ( CB1 ) receptors in the basal ganglia , the cerebral cortex and the cerebellum indicate their implication in the regulation of motor activity . Based on the close relationship between cannabis use , the endogenous cannabinoid system and motor disturbances found in schizophrenia , we expected that administration of cannabinoids may change pattern of psychomotor activity like in schizophrenic patients . This prospect i ve , double-blind , placebo-controlled cross-over study investigated the acute effects of cannabinoids on psychomotor performance in 24 healthy right-h and ed volunteers ( age 27.9 ± 2.9 years , 12 male ) by comparing Δ9-tetrahydrocannabinol ( Δ9-THC ) and st and ardized cannabis extract containing Δ9-THC and cannabidiol .  Psychomotor performance was assessed by using a finger tapping test series . Cannabis extract , but not Δ9-THC , revealed a significant reduction of right-h and tapping frequencies that was also found in schizophrenia . As to the pure Δ9-THC condition , left-h and tapping frequencies were correlated with the plasma concentrations of the Δ9-THC metabolite 11-OH-THC . These effects are thought to be related to cannabinoid actions on CB1 receptors in the basal ganglia , the cerebral cortex and the cerebellum . Our data further demonstrate that acute CB1 receptor activation under the cannabis extract condition may also affect intermanual coordination ( IMC ) as an index of interhemispheric transfer . AIR-Scale scores as a measure of subjective perception of intoxication were dose-dependently related to IMC which was shown by an inverted U-curve . This result may be due to functional changes involving GABAergic and glutamatergic neurotransmission within the corpus callosum BACKGROUND Multiple sclerosis is associated with muscle stiffness , spasms , pain , and tremor . Much anecdotal evidence suggests that cannabinoids could help these symptoms . Our aim was to test the notion that cannabinoids have a beneficial effect on spasticity and other symptoms related to multiple sclerosis . METHODS We did a r and omised , placebo-controlled trial , to which we enrolled 667 patients with stable multiple sclerosis and muscle spasticity . 630 participants were treated at 33 UK centres with oral cannabis extract ( n=211 ) , Delta9-tetrahydrocannabinol ( Delta9-THC ; n=206 ) , or placebo ( n=213 ) . Trial duration was 15 weeks . Our primary outcome measure was change in overall spasticity scores , using the Ashworth scale . Analysis was by intention to treat . FINDINGS 611 of 630 patients were followed up for the primary endpoint . We noted no treatment effect of cannabinoids on the primary outcome ( p=0.40 ) . The estimated difference in mean reduction in total Ashworth score for participants taking cannabis extract compared with placebo was 0.32 ( 95 % CI -1.04 to 1.67 ) , and for those taking Delta9-THC versus placebo it was 0.94 ( -0.44 to 2.31 ) . There was evidence of a treatment effect on patient-reported spasticity and pain ( p=0.003 ) , with improvement in spasticity reported in 61 % ( n=121 , 95 % CI 54.6 - 68.2 ) , 60 % ( n=108 , 52.5 - 66.8 ) , and 46 % ( n=91 , 39.0 - 52.9 ) of participants on cannabis extract , Delta9-THC , and placebo , respectively . INTERPRETATION Treatment with cannabinoids did not have a beneficial effect on spasticity when assessed with the Ashworth scale . However , though there was a degree of unmasking among the patients in the active treatment groups , objective improvement in mobility and patients ' opinion of an improvement in pain suggest cannabinoids might be clinical ly useful PURPOSE Health interventions based on theory may be more effective than those that are not . This review of review s synthesizes all published r and omized controlled trial ( RCT ) meta-analytic evidence from the last decade to examine whether theory-based interventions were found to be associated with more effective  adult health behaviour change interventions . METHODS Systematic review s including meta-analyses were identified by search ing Medline , CINAHL , PsycINFO , and CDSR . A narrative synthesis was used to summarize and analyse the evidence . Only review s including RCTs of health behaviour change interventions with adults aged 18 + published from 2007 to 2017 were included . RESULTS Of 8,659 articles , nine systematic review s met inclusion criteria . The majority of review s ( n = 8) suggested no increased effectiveness for theory-based compared to non-theory-based interventions for effectiveness of outcomes relating to health behaviour . Less than half of the RCTs included in the review s reported the use of theory ( 85/183 ) . Two review s suggested interventions based on control theory , motivational interviewing , or self-determination theory were associated with greater effectiveness for physical activity and /or dietary interventions and outcomes . Method ological and reporting issues limit the conclusions . CONCLUSIONS Theory-based interventions as currently operationalized in systematic review s were not found to be more effective than non-theory-based interventions . Method ological and reporting issues at study and review level may not reflect the true utility of theory use within health behaviour interventions . The promotion of theory use may benefit from using a multifaceted argument , rather than a narrow focus of increased effectiveness . Statement of contribution What is already known on this subject ? Theory use is regularly promoted by cl aim ing that it will lead to more effective behaviour change interventions . Theory use has been frequently linked to effectiveness within systematic review s of behaviour change interventions . The theory-effectiveness hypothesis has not been systematic ally examined at the systematic review level . What does this study add ? Theory use as operationalized by systematic review authors was not associated with increased effectiveness within systematic review s examining r and omized controlled trials of behaviour change interventions in adults . Interventions based on control theory , motivational interviewing , or self-determination theory were associated with greater effectiveness for physical activity and /or dietary interventions and outcomes . Theory use should be promoted using a multifaceted argument , and assertions for increased effectiveness of theory-based interventions should only be used in domains where specific evidence exists to support this cl aim Cannabidiol ( CBD ) , a major phytocannabinoid constituent of cannabis , is attracting growing attention in medicine for its anxiolytic , antipsychotic , antiemetic and anti-inflammatory properties . However , up to this point , a comprehensive literature review of the effects of CBD in humans is lacking . The aim of the present systematic review is to examine the r and omized and crossover studies that administered CBD  to healthy controls and to clinical patients . A systematic search was performed in the electronic data bases PubMed and EMBASE using the key word “ cannabidiol ” . Both monotherapy and combination studies ( e.g. , CBD + ∆9-THC ) were included . A total of 34 studies were identified : 16 of these were experimental studies , conducted in healthy subjects , and 18 were conducted in clinical population s , including multiple sclerosis ( six studies ) , schizophrenia and bipolar mania ( four studies ) , social anxiety disorder ( two studies ) , neuropathic and cancer pain ( two studies ) , cancer anorexia ( one study ) , Huntington ’s disease ( one study ) , insomnia ( one study ) , and epilepsy ( one study ) . Experimental studies indicate that a high-dose of inhaled/intravenous CBD is required to inhibit the effects of a lower dose of ∆9-THC . Moreover , some experimental and clinical studies suggest that oral/oromucosal CBD may prolong and /or intensify ∆9-THC-induced effects , whereas others suggest that it may inhibit ∆9-THC-induced effects . Finally , preliminary clinical trials suggest that high-dose oral CBD ( 150–600 mg/d ) may exert a therapeutic effect for social anxiety disorder , insomnia and epilepsy , but also that it may cause mental sedation . Potential pharmacokinetic and pharmacodynamic explanations for these results are discussed This article review s recent research on cannabinoid analgesia via the endocannabinoid system and non-receptor mechanisms , as well as r and omized clinical trials employing cannabinoids in pain treatment .  Tetrahydrocannabinol ( THC , Marinol ® ) and nabilone ( Cesamet ® ) are currently approved in the United States and other countries , but not for pain indications . Other synthetic cannabinoids , such as ajulemic acid , are in development . Crude herbal cannabis remains illegal in most jurisdictions but is also under investigation . Sativex ® , a cannabis derived oromucosal spray containing equal proportions of THC ( partial CB1 receptor agonist ) and cannabidiol ( CBD , a non-euphoriant , anti-inflammatory analgesic with CB1 receptor antagonist and endocannabinoid modulating effects ) was approved in Canada in 2005 for treatment of central neuropathic pain in multiple sclerosis , and in 2007 for intractable cancer pain . Numerous r and omized clinical trials have demonstrated safety and efficacy for Sativex in central and peripheral neuropathic pain , rheumatoid arthritis and cancer pain . An Investigational New Drug application to conduct advanced clinical trials for cancer pain was approved by the US FDA in January 2006 . Cannabinoid analgesics have generally been well tolerated in clinical trials with acceptable adverse event profiles . Their adjunctive addition to the pharmacological armamentarium for treatment of pain shows great promise Cannabinoids and opioids share several pharmacologic properties and may act synergistically . The potential pharmacokinetics and the safety of the combination in humans are unknown . We therefore undertook a study to answer these questions . Twenty – one individuals with chronic pain , on a regimen of twice – daily doses of sustained – release morphine or oxycodone were enrolled in the study and admitted for a 5–day inpatient stay . Participants were asked to inhale vaporized cannabis in the evening of day 1 , three times a day on days 2–4 , and in the morning of day 5 . Blood sampling was performed at 12–h intervals on days 1 and 5 . The extent of chronic pain was also assessed daily . Pharmacokinetic investigations revealed no significant change in the area under the plasma concentration – time curves for either morphine or oxycodone after exposure to cannabis . Pain was significantly decreased ( average 27 % , 95 % confidence interval ( CI ) 9 , 46 ) after the addition of vaporized cannabis . We therefore concluded that vaporized cannabis augments the analgesic effects of opioids without significantly altering plasma opioid levels . The combination may allow for opioid treatment at lower doses with fewer side effects AIM To produce dietetic guidelines summarizing the systematic review evidence on dietary advice for secondary prevention of cardiovascular disease . METHODS The Cochrane Library , MEDLINE and EMBASE were comprehensively search ed for systematic review s on aspects of diet and heart health . Review s were included if they search ed systematic ally for r and omised controlled trials relating to diet and secondary prevention of cardiovascular disease . Two members of the UK Heart Health and Thoracic Dietitians Group critically appraised each review . The quality and results of each review were discussed and summarized in a whole group meeting . The guidelines were trialled in seven dietetic departments and modified where necessary . RESULTS Providing evidence -based dietary information ( including increasing omega-3 fat plus fruit and vegetable intake ) to all people after myocardial infa rct ion will save more lives than concentrating dietary advice on those in need of weight loss or lipid lowering . The practice of prioritizing dietetic time to those with raised lipids is out of date since the advent of statin therapy . CONCLUSION There is good systematic review evidence that dietary advice to those with cardiovascular disease can reduce mortality and morbidity as well as modify risk factors .  Dietary advice that does this most effectively should be prioritized The m and ate of Human Reproduction Up date involves several roles : ( i ) to provide a synthesis of evidence that can aid scientists and clinicians in their daily work ; ( ii ) to help reproductive specialists underst and concepts from related disciplines ; and ( iii ) to summarize current knowledge generated by basic science as the foundation of future scientific and clinical advancement . Given that review and synthesis are central to good scientific and clinical practice , and that a grasp of the current state of knowledge is a prerequisite to design ing new studies , it is pertinent to ask which review s are most likely to fulfil the needs of readers . A related question concerns whether systematic review s meet the needs of all review topics and all readers . Summarizing evidence or knowledge is a difficult problem in reproductive medicine , as in other branches of science and medical care ( Eddy et al. , 1992 ) . For each question there may be multiple studies that use different design s and inclusion criteria . For clinical questions , the interventions , outcomes and measures of effect may vary : the effect measures in treatment studies include odds ratios , relative risks and absolute differences . For scientific questions , the experimental species , models and design s may differ . Moreover , it is always uncertain whether all of the relevant evidence has been evaluated . Even when the search has been exhaustive , there are no simple guides on how to interpret conflicting results and whether to accept apparently outlying studies . The choices that the review er makes to address the variable conditions and uncertainties may be conservative , strict and exclusive , or liberal , open and inclusive . The decisions made by the review er may not be consistent throughout and these choices may or may not satisfy the reader who seeks out the review to address a clinical or research question . Faced with uncertainty and doubt , readers nonetheless must form an impression of the evidence and synthesize the state of knowledge in order to address the clinical or research question that stimulated their interest in the review . We argue that the reader is better served when the choices made in the review , regardless of whether they are strict or open , should be explicit , transparent , clearly stated and reproducible by interested readers . This list of objectives for review s is more easily satisfied by systematic review s , which use explicit methods to method ically search , critically appraise and synthesize the available literature on a specific issue . The question or issue need not be clinical : indeed , the concept evolved primarily in psychology studies ( Light and Pillemer , 1984 ) . The systematic review attempts to reduce review er bias through the use of objective , reproducible criteria to select relevant individual publications and assess their validity . A systematic review may include a meta- analysis or statistical summary of the individual study results : the aggregate of effects from several studies yields an average treatment effect that is more precise than the individual study results ( Schlesselman and Collins , 2003 ) . Thus , the systematic review involves explicit , transparent methods which are clearly stated , and reproducible by others . Whether a systematic review of r and omized controlled trials adheres to the guidelines can easily be evaluated by means of a widely used checklist ( the QUORUM statement ) ( Moher et al. , 1999 ) . The strengths of the systematic review include the narrow focus of the question , the comprehensive search for evidence , the criterion-based selection of relevant evidence , the rigorous appraisal of validity , the objective or quantitative summary , and the evidence -based inferences ( Cook et al. , 1997 ) . For some review topics , however , the strengths of the systematic review may turn into weaknesses . The primary problem is that the narrow focus and prescribed methods of the systematic review do not allow for comprehensive coverage . For example , the historical review is an irreplaceable means of tracing the development of a scientific principle or clinical concept , but the narrative thread could be lost in the strict rules of systematic review . As other examples , it would be burdensome to apply systematic methods to a survey on  aneuploidy and fertility in the aging female or to an assessment of mouse knockout models and polycystic ovarian phenotype . Such topics would require the wider scope of a traditional narrative review , in Human Reproduction Up date , Vol.11 , No.2 pp . 103–104 , 2005 doi:10.1093/humupd/dmh058 Advance Access publication December 23 , Although a wealth of pre clinical evidence indicates an interplay between the μ-opioid ( MOR ) and cannabinoid 1 receptor ( CB1R ) systems , the precise nature of the cross modulation in humans is unclear . The objective of this study was to evaluate the effects of pretreatment with the MOR antagonist , naltrexone , on the subjective , behavioural and cognitive effects of the CB1R agonist , Δ9-tetrahydrocannabinol ( THC ) , in healthy human subjects . Healthy human subjects , screened carefully for any medical or psychiatric illness , were administered either placebo or active naltrexone ( 25 mg ) orally on each test day , followed 45 min later by placebo and 165 min later by active i.v . THC ( 0.025 mg/kg ) in a r and omized , fixed-order , double-blind manner . Subjective , behavioural and cognitive effects were assessed before and at several points after each drug administration . THC produced expected effects , including euphoria , anxiety , transient perceptual alterations , transient psychotomimetic effects and cognitive impairments .  However , naltrexone did not produce any effects alone , nor did it attenuate any of THC 's effects . Thus , in healthy human subjects who use cannabis intermittently , MOR antagonism does not modulate the common acute subjective , behavioural and cognitive effects of THC Aims : With the increase in the number of systematic review s available , a logical next step to provide decision makers in healthcare with the evidence they require has been the conduct of review s of existing systematic review s. Syntheses of existing systematic review s are referred to by many different names , one of which is an umbrella review . An umbrella review allows the findings of review s relevant to a review question to be compared and contrasted . An umbrella review 's most characteristic feature is that this type of evidence synthesis only considers for inclusion the highest level of evidence , namely other systematic review s and meta-analyses . A methodology working group was formed by the Joanna Briggs Institute to develop method ological guidance for the conduct of an umbrella review , including diverse types of evidence , both quantitative and qualitative . The aim of this study is to describe the development and guidance for the conduct of an umbrella review . Methods : Discussion and testing of the elements of methods for the conduct of an umbrella review were held over a 6-month period by members of a methodology working group . The working group comprised six participants who corresponded via teleconference , e-mail and face-to-face meeting during this development period . In October 2013 , the methodology was presented in a workshop at the Joanna Briggs Institute Convention . Workshop participants , review authors and method ologists provided further testing , critique and feedback on the proposed methodology . Results : This study describes the methodology and methods developed for the conduct of an umbrella review that includes published systematic review s and meta-analyses as the analytical unit of the review . Details are provided regarding the essential elements of an umbrella review , including presentation of the review question in a Population , Intervention , Comparator , Outcome format , nuances of the inclusion criteria and search strategy . A critical appraisal tool with 10 questions to help assess risk of bias in systematic review s and meta-analyses was also developed and tested . Relevant details to extract from included review s and how to best present the findings of both quantitative and qualitative systematic review s in a reader friendly format are provided . Conclusions : Umbrella review s provide a ready means for decision makers in healthcare to gain a clear underst and ing of a broad topic area . The umbrella review methodology described here is the first to consider review s that report other than quantitative evidence derived from r and omized controlled trials . The methodology includes an easy to use and informative summary of evidence table to readily provide decision makers with the available , highest level of evidence relevant to the question posed Previous studies provide evidence that marijuana ( Cannabis sativa ) and delta-9-tetrahydrocannabinol ( Δ9-THC ) , the major psychoactive ingredient of marijuana , respectively , are effective in the treatment of tics and behavioral problems in Tourette syndrome ( TS ) . It , therefore , has been speculated that the central cannabinoid receptor system might be involved in TS pathology . However , in healthy marijuana users there is an ongoing debate as to whether the use of cannabis causes acute and /or long-term cognitive deficits . In this r and omized double-blind placebo-controlled study , we investigated the effect of a treatment with up to 10 mg Δ9-THC over a 6-week period on neuropsychological performance in 24 patients suffering from TS . During medication and immediately as well as 5–6 weeks after withdrawal of Δ9-THC treatment , no detrimental effect was seen on learning curve , interference , recall and recognition of word lists , immediate visual memory span , and divided attention . Measuring immediate verbal memory span , we even found a trend towards a significant improvement during and after treatment . Results from this study corroborate previous data suggesting that in patients suffering from TS , treatment with Δ9-THC  causes neither acute nor long-term cognitive deficits . Larger and longer- duration controlled studies are recommended to provide more information on the adverse effect profile of THC in patients suffering from TS Background Identifying all existing evidence is a crucial aspect in conducting systematic review s. Since the retrieval of electronic data base search es alone is limited , guidelines recommend the use of additional search strategies . The aim of this investigation was to assess the efficiency and contribution of additional search strategies for identifying r and omized controlled trials in conducting a systematic review on interventions after performing a sensitive electronic data base search . Design and Methods Seven electronic data bases , 3 journals and 11 systematic review s were search ed . All first authors of the included studies were contacted ; citation tracking and a search in clinical trial registers were performed . A priori defined evaluation criteria were calculated for each search strategy . Results A total of 358 full-text articles were identified ; 50 studies were included in the systematic review , wherefrom 84.0 % ( 42 ) were acquired by the sensitive electronic data base search and 16.0 % ( 8) through additional search strategies . Screening reference lists of related systematic review s was the most beneficial additional search strategy , with an efficiency of 31.3 % ( 5 ) and a contribution of 10.0 % ( 5/50 ) , whereas h and - search ing and author contacts contributed two and one additional studies , respectively . Citation tracking and search ing clinical trial registers did not lead to any further inclusion of primary studies . Conclusions Based on our findings , h and - search ing contents of relevant journals and screening reference lists of related systematic review s may be helpful additional strategies to identify an extensive body of evidence . In case of limited re sources , a sensitive electronic data base search may constitute an appropriate alternative for identifying relevant trials . Significance for public health Systematic review s provide the strongest form of evidence synthesis for therapeutic interventions and are of high relevance for decision makers in public health . Preparing high quality systematic review s can be very time-consuming since all existing evidence should be identified , but the retrieval of electronic data base search es is limited and therefore additional search strategies are recommended . However , the time needed for conducting full systematic review s does often not address the need for urgent evidence . Thus , priorities of summarizing all available evidence and providing fast evidence -based recommendations may conflict . So far , no consensus exists regarding which additional search strategies are beneficial and sparsely time-consuming for conducting systematic review s. We examined the efficiency and contribution of additional search strategies performed after a sensitive electronic data base search . Our results provide highly relevant information for research ers conducting systematic review s in various fields of public health research and for establishing guidelines for conducting rapid review Background There is increasing pressure to address the social determinants of health ( SDoH ) and health inequities through the implementation of culturally acceptable interventions particularly in Sub-Saharan Africa ( SSA ) where health outcomes are generally poor . Available evaluation research on cash transfers ( CTs ) suggests that the programs may influence the wider determinants of health in SSA ; yet , there has been no attempt to synthesize the evidence regarding their contribution to tackling the SDoH and health inequalities . To date , nearly all the review s on CTs ' impact on health have predominantly featured evidence from Latin America with limited transferability to the social , cultural , and political environments in SSA . Therefore , the aim of this study is to undertake a systematic review to assess the role of CTs in tackling the wider determinants of health and health inequalities in SSA . Methods / design A systematic review of published and unpublished literature on CTs ’ impact on health and health determinants covering the period 2000–2016 will be undertaken . Studies will be considered for inclusion if they present quantitative or qualitative data , including all relevant study design s. The SDoH conceptual framework will be used to guide the data extraction process . EPPI Review er software will be used for data management and analysis . Studies included in the review will be analyzed by narrative synthesis and /or meta- analysis as appropriate for the nature of the data retrieved . Discussion This review will provide empirical evidence on the impact of CTs on SDoH to inform CT policy , implementation , and research in SSA . The protocol follows the Preferred Reporting Items for Systematic Review and Meta- Analysis Protocol s ( PRISMA -P ) . Systematic review registration This protocol has been registered with the PROSPERO international prospect i ve register of systematic review s , reference CRD42015025015 Cannabinoids induce a host of perceptual alterations and cognitive deficits in humans . However , the neural correlates of these deficits have remained elusive . The current study examined the acute , dose-related effects of delta-9-tetrahydrocannabinol ( Δ9-THC ) on psychophysiological indices of information processing in humans . Healthy subjects ( n=26 ) completed three test days during which they received intravenous Δ9-THC ( placebo , 0.015 and 0.03 mg/kg ) in a within-subject , double-blind , r and omized , cross-over , and counterbalanced design . Psychophysiological data ( electroencephalography ) were collected before and after drug administration while subjects engaged in an event-related potential ( ERP ) task known to be a valid index of attention and cognition ( a three-stimulus auditory ‘ oddball ’ P300 task ) . Δ9-THC dose-dependently reduced the amplitude of both the target P300b and the novelty P300a . Δ9-THC did not have any effect on the latency of either the P300a or P300b , or on early sensory-evoked ERP components preceding the P300 ( the N100 ) . Concomitantly , Δ9-THC induced psychotomimetic effects , perceptual alterations , and subjective ‘ high ’ in a dose-dependent manner . Δ9-THC -induced reductions in P3b amplitude correlated with Δ9-THC-induced perceptual alterations . Lastly , exploratory analyses examining cannabis use status showed that whereas recent cannabis users had blunted behavioral effects to Δ9-THC , there were no dose-related effects of Δ9-THC on P300a/b amplitude between cannabis-free and recent cannabis users . Overall , these data suggest that at doses that produce behavioral and subjective effects consistent with the known properties of cannabis , Δ9-THC reduced P300a and P300b amplitudes without altering the latency of these ERPs . Cannabinoid agonists may therefore disrupt cortical processes responsible for context updating and the automatic orientation of attention , while leaving processing speed and earlier sensory ERP components intact . Collectively , the findings suggest that CB1R systems modulate top-down and bottom-up processing The current review aim ed to systematic ally identify dietary , physical activity and sedentary behaviours in preschool children ( 4 - 6 years of age ) that are prospect ively related to overweight or obesity later in childhood . Prospect i ve studies published between January 1990 and June 2010 were selected from search es in PubMed , EMBASE , PsycINFO , CINAHL and Cochrane Library . Studies examining the prospect i ve association between at least one relevant behaviour measured during preschool period ( children aged 4 - 6 years at baseline ) in relation to at least one anthropometric measurement at follow-up ( age < 18 years ) were included . Harvest plots were used to summarize the results and draw conclusions from the evidence . Of the 8,718 retrieved papers , 23 papers reporting on 15 different study sample s were included in this review . Strong evidence was found for an inverse association between total physical activity and overweight . Moderate evidence was observed for a positive association between television viewing and overweight . Because of the heterogeneity in the assessed dietary behaviours , insufficient evidence was found for an association between  dietary intake or specific dietary behaviours and overweight . These results suggest that interventions aim ing to prevent overweight among preschool children should focus on promotion of total physical activity and limitation of screen time and that further research is needed to establish whether and which dietary behaviours are important for obesity prevention in this age group . However , despite the lack of evidence for dietary behaviours from the present review , future interventions may already target specific dietary behaviours that are highly prevalent and for which there a clear rationale as well as preliminary evidence that these behaviours are associated with overweight Objective . The aim of this overview was to summarize the outcome measures of Chinese herbal medicine ( CHM ) for the treatment of hypertension based on available systematic review s ( SRs ) , so as to evaluate the potential benefits and advantages of CHM on hypertension . Methods . Literature search es were conducted in the Cochrane Data base of Systematic Review s , MEDLINE , and 4 data bases in Chinese . SRs of CHM for hypertension were included . Two independent review ers ( J. Wang and X. J. Xiong ) extracted the data . Results . 10 SRs were included . 2 SRs had primary endpoints , while others focused on secondary endpoints to evaluate CHM for hypertension such as blood pressure ( BP ) and Traditional Chinese Medicine ( TCM ) syndrome . 6 SRs have reported the adverse effects , whereas the other 4 SRs have not mentioned it at all . Many CHM appeared to have significant effect on improving BP , TCM syndrome , and so on . However , most SRs failed to make a definite conclusion for the effectiveness of CHM for hypertension due to poor evidence . Conclusion . Primary endpoints have not been widely used currently . The benefits of CHM for hypertension need to be confirmed in the future with r and omized controlled trials ( RCTs ) of more persuasive primary endpoints and high- quality SRs Although cannabis may have potential therapeutic value , inhalation of a combustion product is an undesirable delivery system . The aim of the study was to investigate vaporization using the Volcano ® device as an alternative means of delivery of inhaled Cannabis sativa . Eighteen healthy inpatient subjects enrolled to compare the delivery of cannabinoids by vaporization to marijuana smoked in a st and ard cigarette . One strength ( 1.7 , 3.4 , or 6.8 % tetrahydrocannabinol ( THC ) ) and delivery system was r and omly assigned for each of the 6 study days . Plasma concentrations of Δ‐9‐THC , expired carbon monoxide ( CO ) , physiologic and neuropsychologic effects were the main outcome measures . Peak plasma concentrations and 6‐h area under the plasma concentration – time curve of THC were similar . CO levels were reduced with vaporization . No adverse events occurred . Vaporization of cannabis is a safe and effective mode of delivery of THC . Further trials of clinical effectiveness of cannabis could utilize vaporization as a smokeless delivery system
Of these , the metabolite produces the greatest psychoactive effects .
Cannabidiol ( CBD ) is not psychoactive but plays a modulating role on cannabis psychoactive effects .
The proportion of 9-THC in plant material is higher ( up to 40 % ) than in other cannabinoids ( up to 9 % ) .
Conclusions Findings reveal that 9-THC contributes the most to cannabis psychoactivity .
Due to lower psychoactive potency and smaller proportions in plant material , other psychoactive cannabinoids have a weak influence on cannabis final effects .
Objective This systematic review aims to summarize current evidence on which naturally present cannabinoids contribute to  cannabis psychoactivity  , considering their reported concentrations and pharmacodynamics in humans .