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  • calculator cbd appraisal dosage
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    Surprisingly, MDMA-induced DA terminal loss was only observed in animals housed at warm but not at room temperature, and this neurotoxic effect was reversed by THC administration.

    Our results indicate that THC protects against MDMA neurotoxicity, and suggest that these neuroprotective actions are primarily mediated by the reduction of hyperthermia through the activation of CB 1 receptor, although CB 2 receptors may also contribute to. The purpose of this report REV04 is to document the thermal-hydrologic-chemical THC seepage model, which simulates the composition of waters that could potentially seep into emplacement drifts, and the composition of the gas phase.

    This report has been developed in accordance with ''Technical Work Plan for: Near-Field Environment and Transport: The technical work plan TWP describes planning information pertaining to the technical scope, content, and management of this report. The plan for validation of the models documented in this report is given in Section 2.

    The TWP Section 3. The THC seepage model is a drift-scale process model for predicting the composition of gas and water that could enter waste emplacement drifts and the effects of mineral. The THC seepage model is a drift-scale process model for predicting the composition of gas and water that could enter waste emplacement drifts and the effects of mineral alteration on flow in rocks surrounding drifts.

    The selection has been conducted in accordance with ''Technical Work Plan for: The post-processing analysis for THC seepage THC -PPA documented in this report provides a methodology for evaluating the near-field compositions of water and gas around a typical waste emplacement drift as these relate to the chemistry of seepage, if any, into the drift.

    The relationship between the post-processing analysis and other closely related models, together with their main functions in providing seepage chemistry information for the Total System Performance Assessment for the License Application TSPA-LA , are illustrated in Figure The data selection methodology of the post-processing analysis Section 6. Biogenic non-methane hydrocarbons NMHC. Terrestrial vegetation provides an important source of volatile hydrocarbons, especially isoprene, monoterpenes and in addition possibly sesquiterpenes as well as oxygenated compounds.

    Although there exist considerable uncertainties in the estimation of the magnitude of these biogenic NMHC emissions, it is generally accepted that the majority of global NMHC release is from natural and not from anthropogenic sources.

    Taking into consideration the high reactivity of the mostly unsaturated biogenic emissions, their impact on tropospheric processes can be assumed to be of great importance. Their oxidation in the atmosphere and the subsequent gas-to-particle conversion of the products lead to the formation of organic aerosols.

    Because of the formation of phytotoxic compounds, the interaction of the biogenic hydrocarbons with ozone inside or outside the leaves and needles of plants has been suggested to play a role in forest decline. Students completed a 3-page survey during regularly scheduled class times.

    Results indicated students reported using synthetic THC for curiosity, to get…. The proteins in this family were originally recognized to play prominent roles in floral development. Recent findings, especially with regard to the regulatory roles of the AGL17 subfamily in root development, have greatly broadened their known functions.

    In this study, a gene from soybean Glycine max [L. The activation of expression was first examined in leaves and roots, followed by shoot apexes. Gm NMHC 5 expression levels rose sharply when the plants were treated under short-day conditions SD and started to pod, whereas low levels were maintained in non-podding plants under long-day conditions LD.

    Furthermore, overexpression of Gm NMHC 5 in transgenic soybean significantly promoted lateral root development and nodule building. These results indicate that Gm NMHC 5 can sense the sucrose signal and plays significant roles in lateral root development and nodule building. Calculating the pharmacokinetic parameters according to the C-t curv, and then use the Phoenix WinNonlin software for data analysis.

    The calibration curves were linear over the range 9. The limit of detection LOD was 0. T max , were 60 and 15 min, AUC 0-t were 44 The results of the experiment shows that the precision, accuracy, recovery and applicability were found to be adequate for the pharmacokinetic studies. After oral administration to mice, the relative bioavailability of THC -solid dispersion show significant improvement compared to THC. A theoretical study for thorium monocarbide ThC. It is shown that calculated equilibrium structural parameters of ThC are in agreement with the experimental results.

    It is seen from calculated single-crystal elastic constants that ThC with NaCl-type structure is mechanically stable. And from calculated density of states and band structure, it is observed that ThC is metallic. After the properties at 0 GPa are clarified, pressure dependency of the structural parameters, the elastic properties and related mechanical properties, density of states DOS and hardness are studied.

    Furthermore, the thermodynamic properties of ThC are obtained from the quasi-harmonic Debye model QHM over high pressure and temperature ranges for three functionals. The results are compared to each other, and the available experimental and theoretical data. Repeatability of oral fluid collection methods for THC measurement. The study objective was to determine the influence of sample collection for two different collection methods on THC concentrations and to compare THC concentrations collected by both methods.

    A total of pairs of oral fluid samples from subjects who had recently smoked Cannabis were obtained by. Black-Right-Pointing-Pointer The obtained results agree with the other available values. Houwing, Sjoerd; Smink, Beitske E.

    To determine the influence of sample collection for two different collection methods on THC concentrations and to compare THC concentrations collected by both methods.

    A total of pairs of oral fluid samples from subjects who had recently smoked Cannabis were obtained. Contrary to other urban areas, natural gas is not the main fuel used in MCMA, neither for domestic and industrial heating, nor for transportation. Therefore, there is a great uncertainty about who is the main contributor of CH4 emissions. The lack of agreement between CH4 and CO indicates these species do not come from the same sources. The results suggest that vehicular emissions are not significant contributors to atmospheric CH4 and that the background methane concentration has not change significantly in 25 years.

    Unlike current methods based on the silylating agent [N,O-bis trimethylsilyl trifluoroacetamide] added in an anhydrous environment, this new proposed method allows the addition of the derivatizing agent propyl chloroformate, PCF directly to the deproteinized blood and recovery of the derivatives by liquid-liquid extraction.

    This novel method can be also used for hydrolyzed urine samples. It is faster than the traditional method involving a derivatization with trimethyloxonium tetrafluoroborate. The analytes are separated, detected and quantified by gas chromatography-mass spectrometry in selected ion monitoring mode SIM. The method was validated in terms of selectivity, capacity of identification, limits of detection LOD and quantification LOQ , carryover, linearity, intra-assay precision, inter-assay precision and accuracy.

    This method was applied to 35 urine samples and 50 blood samples resulting to be equivalent to the previously used ones with the advantage of a simpler method and faster sample processing time. We believe that this method will be a more convenient option for the routine analysis of cannabinoids in toxicological and forensic laboratories. Self-report, task performance and physiological measures were also collected. Several publications have suggested increasing cannabis potency over the last decade, which, together with lower amounts of cannabidiol CBD , could contribute to an increase in adverse effects after cannabis smoking.

    This study aimed to investigate the relationship between THC - and CBD concentrations in blood samples among cannabis users, and to compare cannabinoid concentrations with the outcome of a clinical test of impairment CTI and between traffic accidents and non-accident driving under the influence of drugs DUID -cases. Seizure sample analysis did not reveal high potency cannabis products, and while CBD content appeared high in hashish, it was almost absent in marijuana. Published by Elsevier B.

    Effectiveness in improving acute hospital utilization. Full Text Available Background: Organizing care into integrated practice units IPUs around conditions and patient segments has been proposed to increase value. THC -IPU patients received a comprehensive assessment within two weeks of discharge; medication reconciliation; education using standardized action plans and a dedicated nurse case manager for up to 90 days after discharge.

    Patients who rejected enrolment into THC -IPU received usual post-discharge care planned by their attending hospital physician, and formed the control group.

    The primary outcome was the proportion of patients with at least one unscheduled readmission within 30 days after discharge.

    We found a statistically significant reduction in day readmissions and emergency department visits in patients on THC -IPU care compared to usual care, even after adjusting for confounders. Delivering transitional care to patients with functional dependence in the form of home visits and organized into an IPU reduced acute hospital utilization in this patient segment.

    Extending the program into the pre-hospital discharge phase to include discharge planning can have incremental effectiveness in reducing avoidable hospital readmissions.

    Tetrahydrocannabinol THC impairs encoding but not retrieval of verbal information. Cannabis and agonists of the brain cannabinoid receptor CB 1 R 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.

    Healthy subjects were recruited from the community. Subjects received intravenous THC , in a placebo-controlled, double-blind, randomized manner at doses known to produce behavioral and subjective effects consistent with cannabis intoxication.

    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.

    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.

    Published by Elsevier Inc. Recommendations for interpretation of analysis values in medical-psychological assessments regranting of driver's licenses, Germany include threshold values for the free, unconjugated THC -COOH. The automation was carried out by an x-y-z sample robot equipped with modules for shaking, centrifugation, and solvent evaporation. This method was based on a previously developed manual sample preparation method.

    Validation guidelines of the Society of Toxicological and Forensic Chemistry GTFCh were fulfilled for both methods, at which the focus of this article is the automated one.

    Limits of detection and quantification for THC were 0. Real and external control samples were analyzed, and a round robin test was passed successfully. To date, the method is employed in the Institute of Legal Medicine in Giessen, Germany, in daily routine. Automation helps in avoiding errors during sample preparation and reduces the workload of the laboratory personnel.

    Due to its flexibility, the analysis system can be employed for other liquid-liquid extractions as. The technical work plan TWP describes planning information pertaining to the technical scope, content, and management of this Model Report in Section 1. Except for variations in acceptance criteria Section 4. The THC Seepage Model is a drift-scale process model for predicting the composition of gas and water that could enter waste emplacement drifts and the effects of mineral alteration on flow in rocks surrounding drifts.

    The DST THC model is a drift-scale process model relying on the same conceptual model and much of the same input data i. These models provide the framework to evaluate THC coupled processes at the drift scale, predict flow and transport behavior for specified thermal-loading conditions, and predict the evolution of mineral alteration and fluid chemistry around potential waste emplacement drifts.

    Adolescent deltatetrahydrocannabinol THC exposure fails to affect THC -induced place and taste conditioning in adult male rats. The current study examined the effects of adolescent THC exposure on THC -induced place preference rewarding effects and taste avoidance aversive effects conditioning in adulthood. Forty-six male Sprague-Dawley adolescent rats received eight injections of an intermediate dose of THC 3.

    Animals were given four trials of conditioning with intervening water-recovery days, a final CPP test and then a one-bottle taste avoidance test. THC induced dose-dependent taste avoidance but did not produce place conditioning. None of these effects was impacted by adolescent THC exposure. The failure to see an effect of adolescent exposure was addressed in the context of other research that has assessed exposure of drugs of abuse during adolescence on drug reactivity in adulthood.

    Importance of data comparability for multi-year trends and source apportionment of NMHC concentrations observed in France. Non Methane Hydrocarbon Compounds NMHCs are of interest due to their potential health impact and their key role in atmospheric processes as precursors of secondary pollutants such as ozone O3 and secondary organic aerosols SOA. Hourly measurements of 31 non-methane hydrocarbons NMHCs were carried out at three urban sites in France over the period of a decade.

    Concentrations of long-lived species such as ethane and propane which are known as tracers of distant sources and natural gas remained constant. These trends are consistent with those recently described at urban and background sites in the northern mid-latitudes and with emission inventories.

    A year per year source apportionment study using PMF was also conducted for 2 of the urban sites over the period Using source fingerprints, five common anthropogenic sources were identified for Paris and Strasbourg: Along the presentation, the robustness of these results will be discussed regarding the site representativeness, the data comparability, and the temporal variation of the data quality.

    Mathematical models calculating time of last exposure from whole blood concentrations typically employ a theoretical 0. Ten male chronic, daily cannabis smokers received escalating around-the-clock oral THC mg daily for 8 days.

    Cannabinoids were quantified in whole blood and plasma by two-dimensional gas chromatography-mass spectrometry. Maximum whole blood THC occurred 3. Predictive models estimating time since last cannabis intake from whole blood and plasma cannabinoid concentrations were inaccurate during abstinence, but highly accurate during active THC dosing.

    THC redistribution from large cannabinoid body stores and high circulating THCCOOH concentrations create different pharmacokinetic profiles than those in less than daily cannabis smokers that were used to derive the models. Published by Elsevier Ireland Ltd. Strong increase in total delta- THC in cannabis preparations sold in Dutch coffee shops.

    The total concentration of THC has been monitored in cannabis preparations sold in Dutch coffee shops since This annual monitoring was issued by the Ministry of Health after reports of increased potency.

    The level of the main psychoactive compound, Delta9-tetrahydrocannabinol THC , is measured in marijuana and hashish. A comparison is made between imported and Dutch preparations, and between seasons.

    Hashish derived from Dutch marijuana Nederhasj contained The average THC percentage of Dutch marijuana, Dutch hashish and imported hashish was significantly higher than in previous years.

    It nearly doubled over 5 years. During this period, the THC percentage in imported marijuana remained unchanged. A higher price had to be paid for cannabis with higher levels of THC. Whether the increase in THC levels causes increased health risks for users can only be concluded when more data are available on adjusted patterns of use, abuse liability, bioavailability and levels of THC in the brain.

    How cannabis causes paranoia: Paranoia is receiving increasing attention in its own right, since it is a central experience of psychotic disorders and a marker of the health of a society. Paranoia is associated with use of the most commonly taken illicit drug, cannabis. A randomized, placebo-controlled, between-groups test of the effects of intravenous THC was conducted. A total of individuals with paranoid ideation were randomized to receive placebo, THC , or THC preceded by a cognitive awareness condition.

    Paranoia was assessed extensively via a real social situation, an immersive virtual reality experiment, and standard self-report and interviewer measures. Putative causal factors were assessed. Principal components analysis was used to create a composite paranoia score and composite causal variables to be tested in a mediation analysis. THC significantly increased paranoia, negative affect anxiety, worry, depression, negative thoughts about the self , and a range of anomalous experiences, and reduced working memory capacity.

    The increase in negative affect and in anomalous experiences fully accounted for the increase in paranoia. Working memory changes did not lead to paranoia. Making participants aware of the effects of THC had little impact. In this largest study of intravenous THC , it was definitively demonstrated that the drug triggers paranoid thoughts in vulnerable individuals.

    The most likely mechanism of action causing paranoia was the generation of negative affect and anomalous experiences. Phenotypic assessment of THC discriminative stimulus properties in fatty acid amide hydrolase knockout and wildtype mice.

    In the present study, we compared transgenic mice lacking fatty acid amide hydrolase FAAH , the enzyme primarily responsible for anandamide catabolism, to wildtype counterparts in a THC discrimination procedure. Population pharmacokinetics model of THC used by pulmonary route in occasional cannabis smokers.

    Cannabis is the most widely used illegal drug in the world. Deltatetrahydrocannabinol THC is the main source of the pharmacological effect. Some studies have been carried out and showed significant variability in the described models as the values of the estimated pharmacokinetic parameters. The objective of this study was to develop a population pharmacokinetic model for THC in occasional cannabis smokers. Twelve male volunteers age: After ad libitum smoking cannabis cigarette according a standardized procedure, 16 blood samples up to 72h were collected.

    Demographic and biological data were investigated as covariates. A three-compartment model with first-order elimination fitted the data. The model was parameterized in terms of micro constants and central volume of distribution V 1. Normal ALT concentration 6. We have developed a population pharmacokinetic model able to describe the quantitative relationship between administration of inhaled doses of THC and the observed plasma concentrations after smoking cannabis.

    In addition, a linear relationship between ALT concentration and value of k 10 has been described and request further investigation. This report documents the development and validation of the mountain-scale thermal-hydrologic TH , thermal-hydrologic-chemical THC , and thermal-hydrologic-mechanical THM models.

    The purpose and validation criteria for these models are specified in ''Technical Work Plan for: Model results are used to support exclusion of certain FEPs from the total system performance assessment for the license application TSPA-LA model on the basis of low consequence, consistent with the requirements of 10 CFR The mountain-scale TH simulations provide predictions for thermally affected liquid saturation, gas- and liquid-phase fluxes, and water and rock temperature together called the flow fields.

    The TH model captures mountain-scale three-dimensional flow effects, including lateral diversion and mountain-scale flow patterns. THC alters alters morphology of neurons in medial prefrontal cortex, orbital prefrontal cortex, and nucleus accumbens and alters the ability of later experience to promote structural plasticity.

    Psychoactive drugs have the ability to alter the morphology of neuronal dendrites and spines and to influence later experience-dependent structural plasticity. If rats are given repeated injections of psychomotor stimulants amphetamine, cocaine, nicotine prior to being placed in complex environments, the drug experience interferes with the ability of the environment to increase dendritic arborization and spine density.

    To determine if drugs other than psychomotor stimulants will also interfere with later experience-dependent structural plasticity we gave Long-Evans rats THC 0. THC altered both dendritic arborization and spine density in all three regions, and, like psychomotor stimulants, THC influenced the effect of later experience in complex environments to shape the structure of neurons in these three regions. We conclude that THC may therefore contribute to persistent behavioral and cognitive deficits associated with prolonged use of the drug.

    These models provide the framework to evaluate THC coupled processes at the drift scale, predict flow and transport behavior for specified thermal loading conditions, and predict the chemistry of waters and gases entering potential waste-emplacement drifts. The intended use of this AMR is to provide input for the following: The work scope for this activity is presented in the TWPs cited above, and summarized as follows: Continue development of the repository drift-scale THC seepage model used in support of the TSPA in-drift geochemical model; incorporate heterogeneous fracture property realizations; study sensitivity of results to changes in input data and mineral assemblage; validate the DST model by comparison with field data; perform simulations to predict mineral dissolution and precipitation and their effects on fracture properties and chemistry of water but not flow rates that may seep into drifts; submit modeling results to the TDMS and document the models.

    The model development, input data, sensitivity and validation studies described in this AMR are. GW Pharmaceuticals is undertaking a major research programme in the UK to develop and market distinct cannabis-based prescription medicines [ THC: The cannabis for this programme is grown in a secret location in the UK. It is expected that the product will be marketed in the US in late The company is investigating their use in three delivery systems, including sublingual spray, sublingual tablet and inhaled but not smoked dosage forms.

    The technology is protected by patent applications. GW is also developing a specialist security technology that will be incorporated in all its drug delivery systems. This technology allows for the recording and remote monitoring of patient usage to prevent any potential abuse of its cannabis-based medicines.

    GW plans to enter into agreements with other companies following phase III development, to secure the best commercialisation terms for its cannabis-based medicines. The drug will be marketed under the Sativex brand name. This agreement also provides Bayer with an option to expand their license to include the European Union and certain world markets.

    GW was granted a clinical trial exemption certificate by the Medicines Control Agency to conduct clinical studies with cannabis-based medicines in the UK. The exemption includes investigations in the relief of pain of neurological origin and defects of neurological function in the following indications: Diazepam alone impaired performance on psychomotor performance tasks and increased ratings on a limited number of self-report questionnaire items e.

    Plant material was dried, homogenized and extracted with methanol by ultrasonication. Analytes were detected and quantified using a Waters photo diode array detector. Since no thermal decarboxylation of THCA-A occurs, the method is highly reproducible for different cannabis materials. Full Text Available We applied the positive matrix factorization model to two large data sets collected during two intensive measurement campaigns summer and winter at a sub-urban site in Beirut, Lebanon, in order to identify NMHC non-methane hydrocarbons sources and quantify their contribution to ambient levels.

    Six factors were identified in winter and five factors in summer. PMF-resolved source profiles were consistent with source profiles established by near-field measurements. The NMHC emissions from road transport are estimated from observations and PMF results, and compared to local and global emission inventories.

    When combining emission inventory to our results, there is strong evidence that control measures in Lebanon should be targeted on mitigating the NMHC emissions from the traffic-related sources. From a global perspective, an assessment of VOC volatile organic compounds anthropogenic emission inventories for the Middle East region as a whole seems necessary as these emissions could be much higher than expected at least from the road transport sector.

    Previous in vitro studies suggest that, with successive puffs from a marijuana cigarette, delta THC becomes concentrated in the remaining uncombusted portion of the cigarette. These observations are consistent with the common practice of smoking marijuana cigarettes to a smaller butt length than that to which tobacco cigarettes are smoked. The purpose of the present study was to compare the delivery of delta THC , as well as total insoluble smoke particulates tar and carbon monoxide, from the distal "first" versus the proximal "second" halves of a standard marijuana cigarette during "natural" smoking of marijuana.

    A previously described smoking apparatus 20 was used for measurement of puff volume and inhaled tar. Puff volume and number were allowed to vary spontaneously provided that the specified length of cigarette was consumed , while inhaled volume 1.

    Blood samples were withdrawn prior to smoking and serially after completion of smoking for analysis of blood carboxyhemoglobin COHb and serum delta THC. Heart rate was measured before and 5 min after smoking. Subjects rated their level of "high" 20 min after completion of smoking. Compression of ThC to 50 GPa. Thorium monocarbide crystallizes in the NaCl type structure space group Fmanti 3m at room temperature and atmospheric pressure.

    Very little has been published on the structural high-pressure behaviour of this compound. No phase transformation was observed in contrast to the case of the corresponding uranium compound UC, which transforms to an orthorhombic structure at about 27 GPa. It has been suggested that the B 0 value might be too low, considering the bulk modulus scaling with specific volume for thorium and uranium compounds.

    Thus it should be useful to confirm the B 0 value for ThC and to look for structural phase transformations in an extended pressure range. Oral fluid specimens were collected for These data indicate that OF cannabinoid monitoring can document compliance with Sativex pharmacotherapy, and identify relapse to smoked cannabis during oral THC medication but not Sativex treatment, unless samples were collected shortly after smoking.

    Does cannabidiol protect against adverse psychological effects of THC? Full Text Available The recreational use of cannabis can have persistent adverse effects on mental health. Deltatetrahydrocannabinol THC is the main psychoactive constituent of cannabis, and most, if not all, of the effects associated with the use of cannabis are caused by THC. Recent studies have suggested a possible protective effect of another cannabinoid, cannabidiol CBD.

    Based on the titles and abstracts, an initial selection was made. The reference lists of the publications identified in this manner were examined for additional references. Cannabis is not a safe drug. Depending on how often someone uses, the age of onset, the potency of the cannabis that is used and someone's individual sensitivity, the recreational use of cannabis may cause permanent psychological disorders.

    Most recreational users will never be faced with such persistent mental illness, but in some individuals cannabis use leads to undesirable effects: However, the question remains of how the laboratory results translate to the types of cannabis that are encountered by real-world recreational users. Obesity is one of the highest preventable causes of morbidity and mortality in the developed world [1]. It has been well known for a long time that exposure to cannabis produces an increase of appetite a phenomenon referred to as the 'munchies'.

    This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome. This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile [2].

    Despite being efficacious, Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market. We recently discovered that the prevalence of obesity is paradoxically much lower in cannabis users as compared to non-users and that this difference is not accounted for by tobacco smoking status and is still present after adjusting for variables such as sex and age.

    Effects of varying marijuana potency on deposition of tar and delta9- THC in the lung during smoking. To determine whether smoking more, compared to less, potent marijuana MJ cigarettes to a desired level of intoxication "high" reduces pulmonary exposure to noxious smoke components, in 10 habitual smokers of MJ, we measured respiratory delivery and deposition of tar and delta9-tetrahydrocannabinol THC , carboxyhemoglobin COHb boost, smoking topography, including cumulative puff volume CPV and breathholding time, change in heart rate deltaHR and "high" during ad lib smoking of 0, 1.

    At each session, subjects had access to only a single MJ cigarette. The model development, input data. Congruent vaporization and congruent effusing compositions were defined explicitly and their characteristics brought out. Conversely, the metabolically stable anandamide analog O fully substituted in both groups, but was more potent in knockouts. Quantification of brain endocannabinoid levels revealed expected elevations in anandamide in FAAH knockout mice compared to wildtypes and equipotent dose-dependent elevations in 2-AG following JZL administration.

    Around-the-clock oral THC effects on sleep in male chronic daily cannabis smokers. Human laboratory studies of oral THC have not shown consistent effects on sleep. We prospectively evaluated self-reported sleep parameters during controlled oral THC administration to research volunteers.

    Mary's Hospital Sleep Questionnaire was completed every morning. Changes in sleep characteristics over time and associations between sleep characteristics and plasma cannabinoid concentrations were evaluated with repeated measures mixed linear regression. Higher evening THC and OH- THC concentrations were significantly associated with shorter sleep latency, less difficulty falling asleep, and more daytime sleep the following day.

    In contrast, the duration of calculated and self-reported nighttime sleep decreased slightly 3. These findings suggest that tolerance to the somnolent effects of THC may have occurred, but results should be considered preliminary due to design limitations. Somnolence from oral THC may dissipate with chronic, high-dose use. This has implications for patients who may take chronic oral THC for medicinal purposes, including cannabis dependence treatment.

    Am J Addict ; In this Model Report, any reference to ''repository'' means the nuclear waste repository at Yucca Mountain, and any reference to ''drifts'' means the emplacement drifts at the repository horizon.

    The TH simulations provide predictions for thermally affected liquid saturation, gas- and liquid-phase fluxes, and water and rock temperature together called the flow fields. The THM Model addresses changes in permeability due to mechanical and thermal disturbances in. Maternal substance abuse is an ongoing concern and detecting drug use during pregnancy is an important component of neonatal care when drug abuse is suspected.

    Meconium is the preferred specimen for drug testing because it is easier to collect than neonatal urine and it provides a much broader time frame of drug exposure. The samples are then extracted with an organic solvent mixture as part of a sample "cleanup.

    Following extraction with a second organic mixture, the organic layer is removed and concentrated to dryness. Delta-9 tetrahydrocannabinol THC inhibits lytic replication of gamma oncogenic herpesviruses in vitro.

    Full Text Available Abstract Background The major psychoactive cannabinoid compound of marijuana, delta-9 tetrahydrocannabinol THC , has been shown to modulate immune responses and lymphocyte function. After primary infection the viral DNA genome of gamma herpesviruses persists in lymphoid cell nuclei in a latent episomal circular form.

    In response to extracellular signals, the latent virus can be activated, which leads to production of infectious virus progeny. Therefore, we evaluated the potential effects of THC on gamma herpesvirus replication. Methods Tissue cultures infected with various gamma herpesviruses were cultured in the presence of increasing concentrations of THC and the amount of viral DNA or infectious virus yield was compared to those of control cultures. Inhibition of the immediate early ORF 50 gene promoter activity was measured by the dual luciferase method.

    Importantly, concentrations of THC that inhibit virus replication of gamma herpesviruses have no effect on cell growth or HSV-1 replication, indicating selectivity. The major psychoactive cannabinoid compound of marijuana, delta-9 tetrahydrocannabinol THC , has been shown to modulate immune responses and lymphocyte function.

    Tissue cultures infected with various gamma herpesviruses were cultured in the presence of increasing concentrations of THC and the amount of viral DNA or infectious virus yield was compared to those of control cultures. These studies may also provide the foundation for the development. Marijuana is a widely used illicit drug and its consumption during pregnancy has been associated with adverse reproductive outcomes.

    The pathological characteristics and distribution of cannabinoid receptors in placenta were observed by immunohistochemical IHC staining. Cell migration in response to THC was measured by transwell assays. We found the placenta expressed two main cannabinoid receptors, suggesting that THC induced biological responses in placental cells.

    Supporting this hypothesis, we observed dramatic alterations of placental morphology in marijuana users. Using THC and inhibitors of cannabinoid receptors, we demonstrated that THC impaired trophoblast cell migration and invasion partly via cannabinoid receptors. Additionally, pregnant mice injected with THC showed adverse reproductive events including reduced number of fetuses, lower maternal and placental weights. Mechanistically, STAT3 signaling pathway was involved in the THC -induced suppression of trophoblast cell motility and pregnancy outcomes.

    Central nervous system effects of haloperidol on THC in healthy male volunteers. In a double-blind, placebo-controlled, partial three-way crossover ascending dose study the effects of THC , haloperidol and their.

    The Toronto Harbour Commissioners THC have developed a soil treatment train designed to treat inorganic and organic contaminants in soils. THC has conducted a large-scale demonstration of these technologies in an attempt to establish that contaminated soils at the Toronto Port Full Text Available Aims: Agonist replacement treatment is a promising strategy to manage cannabis-use disorders.

    Subjects completed the multiple-choice procedure to assess drug reinforcement, and self-report, task performance and physiological measures were collected. Nabilone alone also elevated heart rate. These results replicate a previous study demonstrating that nabilone shares agonist effects with the active constituent of cannabis in cannabis users, and contribute further by indicating that nabilone would likely be safe and well tolerated when combined with cannabis.

    These data support the conduct of future studies to determine if nabilone treatment would produce cross-tolerance to the abuse-related effects of cannabis and reduce cannabis use. For engines certified under Full Text Available Synthetic cannabinoids are functionally similar to delta9-tetrahydrocannabinol THC , the psychoactive principle of cannabis, and bind to the same cannabinoid receptors in the brain and peripheral organs. From , synthetic cannabinoids were detected in herbal smoking mixtures sold on websites and in head shops under the brand name of Spice Gold, Yucatan Fire, Aroma, and others.

    Although these products also known as Spice drugs or legal highs do not contain tobacco or cannabis, when smoked they produce effects similar to THC. Intoxication, withdrawal, psychosis and death have been recently reported after consumption, posing difficult social, political and health challenges. More than different Spice products have been identified to date. An escalating number of compounds with cannabinoid receptor activity are currently being found as ingredients of Spice, of which almost nothing is known in terms of pharmacology, toxicology and safety.

    Since legislation started to control the synthetic cannabinoids identified in these herbal mixtures, many new analogs have appeared on the market. New cannabimimetic compounds are likely to be synthesized in the near future to replace banned synthetic cannabinoids, leading to a dog chasing its tail situation. Spice smokers are exposed to drugs that are extremely variable in composition and potency, and are at risk of serious, if not lethal, outcomes. Social and health professionals should maintain a high degree of alertness for Spice use and its possible psychiatric effects in vulnerable people.

    Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex. Current concepts suggest that exposure to THC during adolescence may act as a risk factor for the development of psychiatric disorders later in life. However, the molecular underpinnings of this vulnerability are still poorly understood. To analyze this, we investigated whether and how THC exposure in female rats interferes with different maturational events occurring in the prefrontal cortex during adolescence through biochemical, pharmacological and electrophysiological means.

    We found that the endocannabinoid system undergoes maturational processes during adolescence and that THC exposure disrupts them, leading to impairment of both endocannabinoid signaling and endocannabinoid-mediated LTD in the adult prefrontal cortex. Finally, adolescent THC exposure altered cognition at adulthood. All these effects seem to be triggered by the disruption of the physiological role played by the endocannabinoid system during adolescence.

    Indeed, blockade of CB1 receptors from early to late adolescence seems to prevent the occurrence of pruning at glutamatergic synapses. These results suggest that vulnerability of adolescent female rats to long-lasting THC adverse effects might partly reside in disruption of the pivotal role played by the endocannabinoid system in the prefrontal cortex maturation.

    Clinical experience with THC: CBD oromucosal spray in patients with multiple sclerosis-related spasticity. Over a month timeframe, THC: CBD spray was initiated in patients. Mean follow-up was 9 months. CBD spray was used as add-on therapy in 95 patients and as monotherapy in 25 patients to achieve best-possible therapeutic results. CBD spray for less than 60 days. Main reasons for treatment discontinuation were: No new safety signals were noted with THC: CBD spray during the evaluation period.

    CBD spray was effective and well tolerated as add-on therapy or as monotherapy in a relevant proportion of patients with resistant MS spasticity. In humans, long-term marijuana use is associated with impaired impulse control and attentional capacity, though it has been difficult to distinguish pre-existing cognitive deficits from possible consequences of prolonged marijuana exposure.

    If present in humans, these disruptions may impact academic and professional performance. Effect of oral THC pretreatment on marijuana cue-induced responses in cannabis dependent volunteers. Cannabis dependent participants 7 males and 7 females, who smoked on average 5.

    During each session, participants completed a baseline evaluation and were first exposed to neutral cues then marijuana cues while physiological measures and subjective ratings of mood, craving, and drug effect were recorded. Following placebo oral THC pretreatment, marijuana vs. Males also reported feeling more "Down" during marijuana cues relative to females. Oral THC produced statistically but not clinically significant increases in heart rate and decreases in diastolic blood pressure, independent of cues.

    These marijuana-cue findings replicate earlier results and further demonstrate that oral THC can attenuate selected effects during marijuana multi-cue exposure, and that some of these effects may be sex-related.

    Results of this study suggest oral THC may be effective for reducing marijuana cue-elicited conditioned effects. Further study is needed to determine whether females may selectively benefit from oral THC for this purpose. Cognitive and psychomotor effects in males after smoking a combination of tobacco and cannabis containing up to 69 mg deltatetrahydrocannabinol THC.

    Delta 9 -Tetrahydrocannabinol THC is the main active constituent of cannabis. Acute cognitive and psychomotor effects of THC among. FH - Neurology Impact factor: Effects of chronic delta THC treatment on cardiac beta-adrenoceptors in rats. This study was designed to determine if chronic treatment with deltatetrahydrocannabinol THC alters cardiac beta-adrenoceptors in the rat.

    These results suggest that the tolerance to cardiovascular effects of THC which develops during chronic exposure in the rat is not associated with alterations in cardiac beta-adrenoceptors as monitored by radiolabeled antagonist binding. The Soil Recycle Treatment Train, which consists of s Previous studies suggest that there are sex differences in endocannabinoid function and the response to exogenous cannabinoids, though data from clinical studies comparing acute cannabinoid effects in men and women under controlled laboratory conditions are limited.

    Responses on a drug-discrimination task, subjective effects questionnaire, psychomotor performance tasks, and physiological measures were assessed. Sex differences on VAS items emerged as a function of dose. Rapid elimination of Carboxy- THC in a cohort of chronic cannabis users. These tests, often termed historical data, can be used to identify potential chronic cannabis users who may present occupational health and safety risks within the workplace.

    Conversely, the data can also be used to support employee claims of previous regular, rather than recent, cannabis use. This study aimed at examining the mean elimination of Carboxy- THC in 37 chronic users undergoing voluntary abstinence over a 2-week period. Urine specimens were collected prior to the study and after 1 and 2 weeks of abstinence.

    Carboxy- THC levels in urine were measured by gas chromatography-mass spectrometry GC-MS following alkaline hydrolysis, organic solvent extraction and derivatisation to form its pentafluoropropionic derivative. The study further highlights the value of historical urinary Carboxy- THC data as a means of identifying potential occupational health and safety risks among chronic cannabis users.

    The balance between detrimental, pro-aging, often stochastic processes and counteracting homeostatic mechanisms largely determines the progression of aging. There is substantial evidence suggesting that the endocannabinoid system ECS is part of the latter system because it modulates the physiological processes underlying aging. The activity of the ECS declines during aging, as CB1 receptor expression and coupling to G proteins are reduced in the brain tissues of older animals and the levels of the major endocannabinoid 2-arachidonoylglycerol 2-AG are lower.

    However, a direct link between endocannabinoid tone and aging symptoms has not been demonstrated. This behavioral effect was accompanied by enhanced expression of synaptic marker proteins and increased hippocampal spine density. THC treatment restored hippocampal gene transcription patterns such that the expression profiles of THC -treated mice aged 12 months closely resembled those of THC -free animals aged 2 months.

    The transcriptional effects of THC were critically dependent on glutamatergic CB1 receptors and histone acetylation, as their inhibition blocked the beneficial effects of THC. Thus, restoration of CB1 signaling in old individuals could be an effective strategy to treat age-related cognitive impairments.

    Cannabinoids and metabolites in expectorated oral fluid after 8 days of controlled around-the-clock oral THC administration. Oral fluid OF is an increasingly accepted matrix for drug testing programs, but questions remain about its usefulness for monitoring cannabinoids. THC was detected in only The highest THC concentrations were obtained at admission median 1. A total of 2. THC is currently the only analyte for monitoring cannabis exposure in OF; however, these data indicate chronic therapeutic oral THC administration and illicit oral THC use are unlikely to be identified with current guidelines.

    Delta 9 -tetrahydrocannabinol THC , the main psychoactive constituent of cannabis, accumulates in adipose tissue where it is stored for long periods of time.

    Here we investigated whether conditions that promote lipolysis can liberate THC from adipocytes to yield increased blood levels of THC. In vitro studies involved freshly isolated rat adipocytes that were incubated with THC before exposure to the lipolytic agent adrenocorticotrophic hormone ACTH. Lipolysis promoted by ACTH or food deprivation was indexed by measurement of glycerol levels.

    The present study shows that lipolysis enhances the release of THC from fat stores back into blood. This suggests the likelihood of 'reintoxication' whereby food deprivation or stress may raise blood THC levels in animals chronically exposed to the drug.

    Further research will need to confirm whether this can lead to functional effects, such as impaired cognitive function or 'flashbacks'. Detection time for THC in oral fluid after frequent cannabis smoking. The use of oral fluid for detecting drugs of abuse has become increasingly more frequent.

    Few studies have, however, investigated the detection times for drugs of abuse in oral fluid, compared with that of in urine or in blood.

    Cannabis is the world's most widely used drug of abuse, and the detection times for cannabis, in different types of matrixes, are therefore important information to the laboratories or institutions performing and evaluating drugs of abuse analyses. It is well known that frequent use of high dosages of cannabis, for longer periods of time, might lead to prolonged detection times for THC -COOH in urine.

    Cannabis intake is detected in oral fluid as THC , and a positive finding is considered to be a result of recent smoking, although some studies have already reported longer detection times. The aim of this study was to investigate the detection time for THC in oral fluid, collected from drug addicts admitted for detoxification.

    Findings in oral fluid were compared with findings in urine, among 26 patients admitted to a closed detoxification unit. The study, being the first in doing so, describes the concentration-time profiles for THC in oral fluid among chronic cannabis users, during monitored abstinence, using the Intercept collection kit.

    The study also includes the concentration-time profiles for creatinine-corrected THC -COOH ratios in urine samples, included to monitor for the possibility of new intakes. THC was detected in oral fluid collected from 11 of the 26 patients in the study.

    The elimination curves for THC in oral fluid revealed that negative samples could be interspersed among positive samples several days after cessation, whereas the THC -COOH concentrations in urine were decreasing. THC was, in this study, detected in oral fluid for up to 8 days after admission. The study shows that frequent use of high dosages of cannabis may lead to prolonged detection times, and that positive samples can be interspersed among negative samples.

    Morphine decreases social interaction of adult male rats, while THC does not affect it. Occurrence and time spent in specific patterns of social interactions SI and non-social activities locomotion and rearing was video-recorded for 5 min and then analyzed.

    MOR in doses of 1 and 2. Detailed analysis of specific patterns of SI revealed decrease in mutual sniffing and allo-grooming after all doses of MOR. Rearing activity was increased by lower doses of MOR 1 and 2. THC , in each of the tested doses, did not induce any specific changes when compared to matching control group ethanol. The evidence has been of very low quality, meaning that it does not provide a reliable indication of the likely effect, and the likelihood that the effect will be substantially different is high [ ].

    This remains an area of research and at present no clinical recommendation can be given for routine use in cancer pain [II, D]. Surgical or oncological treatment of cancer can be effective in controlling cancer-related pain but can also be the cause of pain. Interventional techniques include nerve blocks, neurolytic blocks including spinal neurolytic blocks and cordotomy and intrathecal i. Two prospective comparative trials between oral and spinal morphine have compared the analgesics and tolerability of morphine administered orally or by epidural [ , ].

    An improvement in pain control as well as in adverse effects was shown by switching from oral to epidural infusion of morphine [ ]. However, Kalso et al. The authors concluded that the co-administration of local anaesthetic agents, alphaadrenergic agonists or NMDA antagonists may significantly improve the quality of epidural analgesia compared with the s. Spinal opioids work by binding to the mu receptor in the substantia gelatinosa and can be administered epidurally or by the i.

    Generally, this direct delivery to the i. The fully implanted systems offer less risk of infection and need lower maintenance than the percutaneous route, but the positioning is more complex [ ]. These interventional strategies are not appropriate in patients with infections, coagulopathy or very short life expectancy. Many authors [ , ] support the use of a trial of intraspinal analgesia using a temporary epidural or spinal catheter or even single shot bolus to determine efficacy before pump implantation.

    When compared with epidural, i. In addition, it gives better pain control and decreased risk of infection. Limited evidence supports the use of subanaesthetic doses of ketamine, an NMDA antagonist, in intractable pain.

    Management of refractory pain by i. Intraspinal techniques delivered and monitored by a skilled team should be included as part of the cancer pain management strategy [II, B]. Peripheral nerve blocks or plexus blocks can be used when pain occurs in the field of one or more peripheral nerves, or if pain is caused by complications such as pathological fracture or vascular occlusion [ ].

    However, a peripheral nerve block as the principal pain treatment is very rare, and they are always used together with systemic combined analgesia and in combination with the multimodal approach applied to all cancer pain.

    The use of neurolytic agents on peripheral nerves can lead to neuritis; therefore, for patients with good prognosis, this can result in symptoms more difficult to control than the original pain [ ]. These blocks can be used for the sympathetic system as well as for spinal neurolytic purposes for somatic pain. This technique is used for the superior hypogastric plexus block or ganglion impar block, when pelvic pain or perineal pain of visceral origin is present, respectively.

    Coeliac plexus block CPB is useful when pain is of visceral aetiology only, and due to cancer in the upper abdomen or pancreas; it leads to pain control and, frequently, to a decrease in the total amount of systemic drugs and their side effects [ ]. The technique used to carry out CPB anterior or posterior approach; amount and concentration of neurolytic agent and time may affect the results and the duration of the analgesic effect. One new way to carry out this kind of CPB is represented by echo-endoscope guidance, placed in the stomach just below the cardia [ ].

    CPB should be carried out in the presence of visceral pain and only if the clinical condition of the patient is not poor. Previous studies have suggested that when there is evidence of disease outside the pancreas, such as coeliac or portal adenopathy, or both, the success rate of this block decreases significantly [ ].

    Spinal neurolytic blocks are very helpful for focal pain in a small number of dermatomes. For example, it is useful in patients with perineal pain with pelvic cancer e. Spinal neurolytic blocks should also be considered for deafferentation pain, such as that seen in peripheral nerve plexus tumour infiltration and destruction. Spinal neurolytic technique is a highly skilled pain intervention which has been described in various cancer pain management textbooks [ ].

    Informed consent, explaining the side effects of this neuroablative technique including numbness or dysaesthesia, is a key when considering spinal neurolytic or any other neuroablative block. Epidural neurolytic blocks have been described in the literature; however, the benefit is limited and difficult to predict [ ]. It may be applicable only to those patients in the terminal stages of cancer-related pain. Spinal cord stimulation is a well-established neuromodulation technique for chronic NP, for example, for failed back surgery syndrome and complex regional pain syndrome.

    There has been significant improvement in the technology hardware and the programming algorithm including electrical wave forms and frequency and it is now applicable to alleviate severe NP of either malignant or non-malignant causes.

    For cancer-related pain, especially if the cancer is slow growing, there is potential benefit from spinal cord stimulation if pain is difficult to control with pharmacological options. The concern with spinal cord stimulation in cancer-related pain is related to the possible extension of the pain to other areas not covered by the stimulator and the possibility of neurological deficit.

    There are many published case series suggesting significant benefit, but a recent Cochrane systematic review suggested need for further high-quality studies in this field [ ]. Spinal cord stimulation should be included as part of the overall pain management strategy, to be managed by a multidisciplinary team MDT with skill in this type of intervention. It is expected that it will be applicable in only a very small number of cases. Cordotomy for cancer-related pain has been described in the literature from the early s, initially as an open surgical technique, but from the s as a percutaneous technique.

    The technique has been further refined with the evolution of technology involving X-ray imaging facilities and radiofrequency machines, allowing a reliable heat lesion in the spinothalamic tract. High cervical cordotomy is effective for unilateral cancer-related pain below the C4 fourth cervical dermatomes, i.

    Another good indication is incident pain movement-related pain , for example related to pathological fractures in the long bone, pubic rami or pelvis related to local metastatic disease. Surgical treatment is often preferred for these fractures, but some patients have had surgical treatment including RT and still have ongoing intractable pain. This type of pain does not respond well to opioids, as patients have very little or no pain at rest. However, no RCTs were included in this systematic review.

    This review advised setting up a national cordotomy registry that was set up in and now has more than cases prospectively recorded post-cordotomy in the UK. The registry demonstrated the safety and efficacy of this technique, and the data should be published soon.

    Cordotomy should be offered in a MDT setting with palliative medicine, oncology and pain medicine teams to support the care pathway. In the case of patients who are unable to tolerate percutaneous cervical cordotomy because of the intractable nature of pain and the incapacity to lie supine in theatre, surgical cordotomy remains an option. This is carried out by neurosurgeons and is likely to be helpful [ ]. Cordotomy has very rarely been reported to help intractable pain unrelated to cancer in a terminally ill patient [ ].

    Cordotomy should be available to patients with otherwise poorly controlled cancer-related pain [V, C]. On some occasions, as patients are nearing death, pain is perceived to be refractory. Pain is often accompanied by other symptoms such as dyspnoea, agitation, delirium and anxiety, any of which can exacerbate underlying central pain mechanisms.

    A careful assessment of physical and non-physical suffering underpins decisions about the most appropriate therapeutic intervention s. In deciding that pain is refractory, the clinician must, after careful assessment of physical pain and total suffering, perceive that the further application of standard interventions including appropriate simple interventional techniques as described above is either:.

    In this situation, sedation may be the only therapeutic option capable of providing adequate relief. The justification of sedation, which should be a rare intervention for pain, is that it is an appropriate and proportionate goal. However, before administering sedative drugs, all possible causes of suffering must be carefully assessed and evaluated by means of a multidisciplinary specialist approach which includes also psychiatric, psychological and pastoral care personnel.

    Commonly used agents include opioids, neuroleptics, benzodiazepines, barbiturates and propofol. Irrespective of the agent or agents selected, administration initially requires dose titration to achieve adequate relief, followed subsequently by provision of ongoing therapy to ensure maintenance of effect. Patients should be monitored continuously for pain during the sedation process.

    If the team frequently uses sedation for pain relief, procedures should be reviewed to ensure that all other options are being considered first. If sedation is used frequently by a team, then the team should review practices. Some patients with end-of-life pain have been misdiagnosed with having refractory or total pain, when in fact the pain has been induced by opioids, known as OIH [ ]. OIH can be associated with a general sensitivity to a simple light touch as well as a marked increase in pre-existing pain.

    These Clinical Practice Guidelines reviewed the published data and showed the lack of high-quality RCTs in the setting of cancer-related pain. This highlights the necessity for improved study design and a consensus approach to reporting of outcomes.

    Such improvements should lead to more robust evidence to determine appropriate level of evidence LoE and grade of recommendation GoR. The relevant literature has been selected by the expert authors. A summary of recommendations is provided in Table 5. LoE and GoR have been applied using the system shown in Table 6. Statements without grading were considered justified standard clinical practice by the experts and the ESMO Faculty.

    This manuscript has been subjected to an anonymous peer review process. The assessment of all components of suffering such as psychosocial distress should be considered and evaluated [II, B]. Principles of pain management Patients should be informed about pain and pain management and should be encouraged to take an active role in their pain management [II, B].

    The onset of pain should be prevented by means of ATC administration, taking into account the half-life, bioavailability and duration of action of different drugs [II, B]. Treatment of mild pain Analgesic treatment should start with drugs indicated by the WHO analgesic ladder appropriate for the severity of pain [II, B]. Treatment of mild to moderate pain For mild to moderate pain, weak opioids such as tramadol, dihydrocodeine and codeine can be given in combination with non-opioid analgesics [III, C].

    As an alternative to weak opioids, low doses of strong opioids could be an option but is not included in WHO guidance [II, C]. Strong opioids The opioid of first choice for moderate to severe cancer pain is oral morphine [I, A]. Scheduling and titration Individual titration, e. Management of opioid side effects Laxatives must be routinely prescribed for both the prophylaxis and the management of OIC [I, A]. BTcP Immediate-release opioids should be used to treat BTcP that is opioid-responsive and for which background cancer pain management has been optimised [I, A].

    Targeted therapy and bone pain In castrate-resistant prostate cancer patients, radium is effective in reducing SREs, decreasing pain and improving survival [I, A]. Cancer-related NP Cancer-related NP can be treated using opioid combination therapies and carefully dosed adjuvants, when opioids alone provide insufficient pain relief [II, B].

    By permission of the Infectious Diseases Society of America [ ]. The authors thank Emanuela Dell'Aquila for her help with the graphic representation of the tables and figures. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Close mobile search navigation Article navigation. Principles of pain management.

    Treatment of mild pain. Treatment of mild to moderate pain. Treatment of moderate to severe pain. Cancer-related NP Figure 5. Invasive management of refractory pain.

    Management of cancer pain in adult patients: View large Download slide. IR morphine 5 mg every 4 h in opioid-naive patients, 10 mg in patients already on weak opioids Rescue dose: Follow the same scheme Rescue dose: December , last update April This publication supersedes the previously published version— Ann Oncol ; 23 Suppl 7: Prevalence of pain in patients with cancer: Quality of cancer pain management: Is pain in patients with haematological malignancies under-recognised?

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    The use of opioids in cancer patients with renal impairment—a systematic review. A systematic review of the use of opioid medication for those with moderate to severe cancer pain and renal impairment: Therapeutic challenges in cancer pain management: Methadone is superior to fentanyl in treating neuropathic pain in patients with head-and-neck cancer. Switching from morphine to oral methadone in treating cancer pain: Rapid switching from morphine to methadone in cancer patients with poor response to morphine.

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    Comparison of sustained-release morphine with sustained-release oxycodone in advanced cancer patients. No pain relief from morphine? Individual variation in sensitivity to morphine and the need to switch to.

    Opioid rotation from oral morphine to oral oxycodone in cancer patients with intolerable adverse effects: Comparative clinical efficacy and safety of a novel controlled-release oxycodone formulation and controlled-release hydromorphone in the treatment of cancer pain.

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    Systematic review of the role of alternative application routes for opioid treatment for moderate to severe cancer pain: Starting step III opioids for moderate to severe pain in cancer patients: Rapid titration with intravenous morphine for severe cancer pain and immediate oral conversion.

    Immediate- or sustained-release morphine for dose finding during start of morphine to cancer patients: European Palliative Care Research collaborative pain guidelines. Laxatives or methylnaltrexone for the management of constipation in palliative care patients.

    Naloxegol for opioid-induced constipation in patients with noncancer pain. Randomized phase III and extension studies of naldemedine in patients with opioid-induced constipation and cancer. A randomised controlled trial with prolonged-release oral oxycodone and naloxone to prevent and reverse opioid-induced constipation.

    Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC: Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: Sativex oromucosal spray as adjunctive therapy in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy: Results of a double-blind, randomized, placebo-controlled study of nabiximols oromucosal spray as an adjunctive therapy in advanced cancer patients with chronic uncontrolled pain.

    A European association for palliative care research network expert Delphi survey toward a common terminology and classification of transient cancer pain exacerbations.

    Prevalence of breakthrough cancer pain: Development and validation of the breakthrough pain assessment tool BAT in cancer patients. The management of cancer-related breakthrough pain: Efficacy and safety of sublingual fentanyl orally disintegrating tablet at doses determined by titration for the treatment of breakthrough pain in Japanese cancer patients: Efficacy and safety of fentanyl sublingual spray for the treatment of breakthrough cancer pain: Efficacy of rapid-onset oral fentanyl formulations vs.

    A network meta-analysis of the efficacy of opioid analgesics for the management of breakthrough cancer pain episodes. Fentanyl buccal tablet for the treatment of cancer-related breakthrough pain.

    Efficacy and safety of oral or nasal fentanyl for treatment of breakthrough pain in cancer patients: Fentanyl buccal tablet vs. Fentanyl pectin nasal spray versus oral morphine in doses proportional to the basal opioid regimen for the management of breakthrough cancer pain: Fentanyl sublingual tablets versus subcutaneous morphine for the management of severe cancer pain episodes in patients receiving opioid treatment: Palliative radiation therapy for bone metastases: Efficacy of single fraction conventional radiation therapy for painful uncomplicated bone metastases: Palliative radiotherapy for bone metastases: Single- versus multiple-fraction radiotherapy in patients with painful bone metastases: Single versus multiple fractions of repeat radiation for painful bone metastases: Short-course versus split-course radiotherapy in metastatic spinal cord compression: A updated systematic review and clinical practice guideline for the management of malignant extradural spinal cord compression.

    Dose escalation of radiotherapy for metastatic spinal cord compression MSCC in patients with relatively favorable survival prognosis. Effect of radium dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: Evidence on the analgesic role of bisphosphonates and denosumab in the treatment of pain due to bone metastases: A multicenter randomized trial of ibandronate compared with single-dose radiotherapy for localized metastatic bone pain in prostate cancer.

    Decreased occurrence of osteonecrosis of the jaw after implementation of dental preventive measures in solid tumour patients with bone metastases treated with bisphosphonates.

    The experience of the National Cancer Institute of Milan. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: Pain and health-related quality of life in patients with advanced solid tumours and bone metastases: American Society of Clinical Oncology clinical practice guideline update: Confirming neuropathic pain in cancer patients: Prevalence and aetiology of neuropathic pain in cancer patients: Pregabalin for the management of neuropathic pain in adults with cancer: Pharmacotherapy for neuropathic pain in adults: Opioids combined with antidepressants or antiepileptic drugs for cancer pain: Pharmacological treatment of pain in cancer patients: Effectiveness of antiepileptic or antidepressant drugs when added to opioids for cancer pain: Oral ketamine vs placebo in patients with cancer-related neuropathic pain: Opioid treatment for radiating cancer pain: Epidural and subcutaneous morphine in the management of cancer pain: Treatment of cancer-related pain: Polyanalgesic consensus conference EUS-guided celiac plexus neurolysis for pain due to chronic pancreatitis or pancreatic cancer pain.

    A meta-analysis and systematic review. Opioid pharmacotherapy in the management of cancer pain: Oxford; Oxford University Press Percutaneous cervical cordotomy for the management of pain from cancer: Open thoracic cordotomy as a treatment option for severe, debilitating pain.

    Percutaneous cervical cordotomy for non-cancer pain in a patient with terminal esophageal carcinoma. Summary of the guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. For permissions, please email: Email alerts New issue alert. Receive exclusive offers and updates from Oxford Academic. More on this topic Are strong opioids equally effective and safe in the treatment of chronic cancer pain?

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    Searching for the needle in the haystack: The immune profile of small HER2-positive breast cancers: Oral morphine to t. The same dose every 1 h max. Median morphine dosage to achieve pain relief i.

    Assessment The intensity of pain and the treatment outcomes should be assessed regularly and consistently using the VAS or NRS and the worst pain question [V, D] Observation of pain-related behaviours and discomfort is indicated in patients with cognitive impairment to assess the presence of pain [V, C] The assessment of all components of suffering such as psychosocial distress should be considered and evaluated [II, B].

    Treatment of mild pain Analgesic treatment should start with drugs indicated by the WHO analgesic ladder appropriate for the severity of pain [II, B] There is no significant evidence to support or refute the use of paracetamol alone or in combination with opioids for mild to moderate pain [I, C] There is no significant evidence to support or refute the use of NSAIDs alone or in combination with opioids for mild to moderate pain [I, C].

    Treatment of mild to moderate pain For mild to moderate pain, weak opioids such as tramadol, dihydrocodeine and codeine can be given in combination with non-opioid analgesics [III, C] As an alternative to weak opioids, low doses of strong opioids could be an option but is not included in WHO guidance [II, C] There is no evidence of increase in adverse effects from the use of low-dose strong opioids instead of the standard step 2 approach with weak opioids [II, C].

    Treatment of moderate to severe pain Strong opioids The opioid of first choice for moderate to severe cancer pain is oral morphine [I, A] The average relative potency ratio of oral to i. Titration schemes for both types of formulation should be supplemented with immediate-release oral opioids, prescribed as required for BTcP [III, B] The regular dose of slow-release opioids can be adjusted to take into account the total amount of rescue morphine [IV, C].

    BTcP Immediate-release opioids should be used to treat BTcP that is opioid-responsive and for which background cancer pain management has been optimised [I, A] Transmucosal fentanyl formulations oral, buccal, sublingual and intranasal have a role in unpredictable and rapid-onset BTcP [I, A] There are indications for standard normal-release oral opioids e.

    Targeted therapy and bone pain In castrate-resistant prostate cancer patients, radium is effective in reducing SREs, decreasing pain and improving survival [I, A] Radioisotope therapy with strontium, samarium or rhenium can be effective in some cases but may cause bone marrow toxicity [II, C] BPs may be considered as part of the therapeutic regimen for the treatment of patients with bone metastases in patients with a good prognosis [II, C] BPs should be considered especially when pain is not localised or RT is not readily accessible [II, C] Preventive dental measures are necessary before starting BP administration [III, A] Denosumab is indicated as an alternative to BPs for the treatment of patients with metastatic bone disease from solid tumours and myeloma [I, A] Denosumab is effective in delaying bone pain recurrence [II, C] Preventive dental measures are necessary before starting denosumab administration [III, A].

    Evidence from at least one large randomised, controlled trial of good methodological quality low potential for bias or meta-analyses of well-conducted randomised trials without heterogeneity. Small randomised trials or large randomised trials with a suspicion of bias lower methodological quality or meta-analyses of such trials or of trials demonstrated heterogeneity.

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    Comments

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