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.
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 ,
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 .