Monthly Archives: August 2022

A series of analyses were undertaken to identify items most pertinent for a brief risk indicator

As evidence for adverse consequences of marijuana use during adolescence on brain functioning accumulates,such research has the potential to improve prevention and intervention efforts through better education,thus reducing marijuana use and associated negative consequences.To guide recruitment,the Adolescent Brain Cognitive Development Study required a method for identifying children at high risk for early-onset substance use that may be utilized during the recruitment process.In this context,childhood risk refers to characteristics identified at ages 9 or 10 years that predict adverse outcomes in adolescence,and “high risk” refers to a categorical classification of some children as having increased risk compared to others.The construction of a brief measure for childhood substance use risk involves the identification of characteristics that predict early-onset substance use in mid to late adolescence.The identification and evaluation of optimal items for a brief childhood measure to serve as a high-risk screener ideally involves data from several large prospective studies with assessments initiated prior to the typical age of onset of substance use.To inform ABCD Study recruitment,secondary analyses are needed with datasets collected prior to ABCD Study initiation.In this context,a set of analyses with available data focused on a specific substance use outcome was determined to be most likely to be informative and feasible.While other substance use outcomes are also important,early-onset marijuana use is a relevant target.Marijuana is the most commonly used illicit drug by adolescents,and regular marijuana use identifies youth likely to develop cannabis use disorder.In these secondary data analyses,the definition of early-onset marijuana use was defined by the initiation of regular use as indicated in the available datasets.The studies contributing datasets were the Center for Education and Drug Abuse Research,cannabis drying the Pittsburgh Youth Study,the Pittsburgh Girls Study,and the Michigan Longitudinal Study.

In the studies contributing data to the secondary analyses described here,the definitions of regular marijuana use differed by sample due to measurement variations.The variations in the definitions of regular marijuana use were as follows: ; five or more use occasions in the past year and; six or more occasions in the past year.By efficiently identifying children at high risk for early-onset marijuana use,a brief and effective measure of childhood risk measure could be utilized as a screen to identify high risk children in prevention research,primary medical care,and mental health clinic settings.The present analyses were specifically undertaken to inform the development a childhood high risk screen for use in the ABCD Study.The ABCD Study is the National Institute of Healths’ large-scale prospective population study of the biological and environmental factors that influence young people’s ability to successfully navigate adolescence.The study has a special emphasis on the risk and protective factors that influence marijuana and other substance use,and subsequent health problems including substance use disorders.Utilizing data from previously conducted studies,the present study was thus undertaken to develop and establish the efficiency of a short measure to identify youth at high risk for early-onset marijuana use with optimal features for use in the ABCD Study.To achieve this goal,the risk level of a potential participant needs to be determined at the time of recruitment and prior to their scheduling for the extensive ABCD Study assessment protocol.Consequently,the optimal ABCD Study high risk screen has several characteristics: extreme brevity,including less than ten items; lack of sensitive items that may raise confidentiality concerns at this early stage of considering participation; consistency with prior research.These characteristics were taken into consideration in the analyses that follow.Historically,studies focusing on mental disorders such as schizophrenia,alcohol use disorder,and major depressive disorder,have used positive family history as a risk marker.Family history has been demonstrated to identify children at high risk of later substance use disorders in many prospective studies.However,a detailed family history may involve the parent being asked to disclose their own socially undesirable,embarrassing or,in some cases,illegal behavior.

There have been alternative strategies to acquire this information,such as the use of publicly available records of drunk driving or other drug offenses,or the use of hospital records to identify parental diagnosis.Obtaining such records would not be feasible in the initial recruitment phase of the ABCD Study.Regardless of the method for obtaining this information,requesting this information at the point of introducing the ABCD Study raises the real possibility that the parent will decline study involvement.Few longitudinal studies have formulated and tested measures for identifying high risk children likely to exhibit early-onset marijuana use.There have been several approaches developed for predicting substance use disorders,but relatively few have targeted the adolescent developmental period.One of the risk measures developed to identify high risk children is the SUD Transmissible Liability Index developed by Vanyukov,Tarter,Clark and colleagues,using longitudinal data from the CEDAR study.Although the TLI is sophisticated in its development,it is long,uses different portions of existing instruments,and is under copyright.In addition,the TLI did not focus on the age 15 outcome of marijuana use,and the publications did not use Receiver Operating Characteristic Area Under the Curve analyses to determine an optimal threshold score.Another screening instrument,the DSM Guided Cannabis Screen has unknown predictive value because it was constructed using cross-sectional data from a small clinical sample aged 14–59.Therefore,the current study fills a significant gap in the empirical literature.This report describes the process and results of secondary data analyses to prospectively identify a brief screening measure applicable to age 9–10-year-old children that would predict early-onset marijuana use in the 5–7 years following the initial screening measurement.To acquire data useful for developing this screening measure,we needed to identify population-based prospective studies which began assessments in late childhood,had been continued at least through ages 14–17,included marijuana use variables at both age periods,measured domains previously identified in the literature as predictive of adolescent substance use disorder outcomes,and had a sufficient number of measures in these domains that were shared across these studies so that screening validation could be replicated across different demographic groups.

The objectives of these secondary data analyses were as follows: To develop a brief screener for 9–10-year-old boys and girls to predict early-onset marijuana and other substance use in mid adolescence with demonstrated predictive utility across four longitudinal data sets; To dichotomize the outcome variable,which will reduce shrinkage,improve replicability and practical utility.; To replicate findings across construction and validation samples.The advantage of this dual analysis approach is that we could construct a screener that considers shrinkage that typically happens between construction of a screener and subsequent validation in another sample.In summary,the objective was to develop a brief and feasible approach to the identification of children at increased risk for early onset marijuana use that may inform the ABCD Study recruitment procedures.To ascertain replication of results,we used four existing longitudinal data sets.These data sets were utilized to build construction and validation samples for each sex,resulting in nine independent analyses.The four longitudinal data sets were from the CEDAR,PYS,PGS,and MLS.Where possible,we used both parent and child as informants,which is particularly important for externalizing behavior that is concealing in nature,because parents usually have less knowledge of the behavior compared to the child.The overall sample consisted of 882 boys and 368 girls.At the initiation of the study,81.3% of the boys were White,and 18.7% Non-White,and 74.7% of the girls were White,25.3% Non-White.Sample selection: Families were ascertained through two methods.The first involved recruitment through all district courts of fathers living in the area convicted for drunk driving with a biological son between the ages of 3 and 5 years old.Fathers were also required to be living with the boy and his biological mother.The second group were required to have the same family composition,but were ascertained through the same neighborhoods as the court-recruited families.Door to door canvassing was carried out to recruit two subgroups: families where neither parent met a lifetime substance use disorder diagnosis ; families where father met criteria for an alcohol use disorder but were not involved with the court.In addition to the original 3-5-year-old son and his biological parents,a female sibling within the range of 3–11,when present,was also recruited.If other siblings in the 3-11-year age range were also present in the home,they were recruited as well.Assessment at T1 for this study : average ages: 10.55 for boys and 10.61 for girls.

Where possible,we used both parent and child as informants,which is particularly important for the externalizing behaviors that are concealing in nature,because parents often are not aware of this type of child behavior.The outcome of interest was child self-report of marijuana use at about age 14.Attrition was 10%.The potential items for analyses were identified by examining prior research,prior analyses with the available datasets,greenhouse benches particularly the extensive analyses with CEDAR data,identifying pertinent items available in the four longitudinal projects used in these secondary analyses,and deliberations on the acceptability of areas of inquiry for potential participants during the recruitment process.Based on these considerations,the constructs represented by the pool of items to be considered included child externalizing behaviors,child internalizing behaviors,and parent tobacco smoking.Child externalizing behaviors.In the case of the ABCD Study design,we are projecting from ages 9–10,when marijuana use typically is minimal and not a viable risk item for screening purposes.Therefore,for candidate items on child externalizing behaviors,we considered non-substance use characteristics that other studies have found to predict early-onset substance use in mid adolescence,particularly child externalizing behaviors.Potential externalizing behaviors considered were vandalism,lying,and disobedience at school.Child internalizing behaviors.In addition,we examined whether selected internalizing behaviors augmented predictions.After examining potential internalizing items’ correlations with both the tentative screener and with the outcome variable,we initially focused on the following items : unhappy,sad or depressed; too fearful or anxious; secretive or keep things to oneself; self-conscious or easily embarrassed.After considering which internalizing items correlated with the externalizing screener at that point,we finally focused on: unhappy,sad or depressed; too fearful or anxious.Parent smoking.For candidate items on parent behaviors,parent smoking was also considered a viable candidate.This candidate item for the screener was available in the 4 study data sets.The predicted outcome was marijuana use by ages 14–15 with a frequency that indicated greater than experimental use.The available outcome categories varied across the studies,including monthly use in CEDAR,use at five times or more in the past year in the PYS and PGS,and 6 or more times during the past year in the MLS.The presence of marijuana use at or above these thresholds for the depicted ages defined “early-onset marijuana use” in these secondary analyses.The evaluations of individual items and their combinations in relations to early-onset marijuana use were undertaken with Receiver Operating Characteristic statistics.This approach is typically used in evaluating screening for diseases,with several examples in the prior literature focusing on substance use frequency in relation to adolescent substance use disorders.Using ROC statistics,the evaluation of the prediction power of a screen is usually based on a 2 by 2 table,as illustrated in Fig.1.The quality of a screen is indicated by four parameters: Sensitivity and specificity,which refer to True Positives/,and True Negatives/,respectively,and Positive predictive value and negative predictive value,which refer to True Positives/True Positives + False Positives and True Negatives/True Negatives + False Negatives,respectively.

Area Under the Curve analyses were used to establish whether the prediction is better than chance; and what the optimal cut-off is to minimize false negative and false positive errors.AUC can range from 0.5 to 1.0,when sensitivity and specificity are considered equally important.In practice,AUC tends to be lower than 1.0,meaning that one cannot correctly classify all future marijuana users or correctly classify all future non-marijuana users.The general rule is that the higher the sensitivity,the lower the specificity.Lowering the cut-off score can increase sensitivity,but with the consequence that there will be more false positives.Where sample sizes from study sites were sufficient,we created two subgroups,labeled “construction” and “validation” samples,using a randomization method,the SPSS random variable generation function.This partitioning of the samples was done to avoid idiosyncratic findings.Sufficient sample sizes were available to take this approach for CEDAR boys,PYS,and PGS,but not for CEDAR girls,MLS boys,or MLS girls.To support scale construction yet allow for validation in these limited samples,weightings were applied so that there were more subjects assigned to the construction sub-sample than to the validation sub-sample.We searched for equivalent predictor items of interest in each dataset.This is very important because we needed construct convergence among the four longitudinal datasets.We used prorating in cases where there were missing items so that we would maximize the numbers of participants.Note that sample sizes varied somewhat due to missing cases for each analysis.

The loss of energy is found out on the reading obtained from the impact testing machine

The raw banana and hemp fibers used in for fabrication of composite laminates are presented in Fig.1 and Fig.2.The fabricated composite laminates are given Fig.3 and Fig.4.The tensile test specimens are prepared and testing of the composite laminates are carried out as per ASTM D638 standards and procedures.There are three specimen are used from each laminates for testing tensile behavior of hybrid laminates.The test has been carried out on the universal testing machine,by means of applying load on the specimen until its get failure and the results are observed.These methodologies are followed for remaining specimen in the same composite laminate and other laminate specimens to get the mean tensile strength and corresponding stresses for the comparison of results.The tensile test specimen before and after fracture of bananahemp-glass fibers reinforced epoxy composites are presented in Fig.5 and Fig.6.The use of natural and manmade fibers reinforced hybrid composite materials are growing day by day due to its characteristics like eco-friendly,recyclable,bio-degradable and user friendly in nature.Many researchers are working in this field to make the composites hybrid and to replace metals and alloy materials in the field of engineering and technology without affecting the load carrying capabilities and cost aspects.In the present experimental study,the banana and hemp fibers are hybridized with glass fiber and prepared hybrid composite laminates.Then the test specimen are prepared from the composite laminates as per ASTM standards and testing of materials has been carried out under tensile,pot for growing marijuana flexural and impact loading conditions by using universal testing machine and impact testing machine.The experimental results on mechanical properties of the tested composite specimen are observed and presented in Table.2.

The composite samples are tested in the universal testing machine and the typical force vs.stroke curve generated directly from the machine during tensile loading for the hybrid composites is presented in Fig.11.The tensile strength comparison of different hybrid composites is presented in Fig.12.From the figure it can be observed that the banana-glass fiber reinforced composites are performing better than the other composites tested which can withstand the tensile strength of 39.5MPa followed by hemp-glass fiber reinforced composites can hold the strength of 37.5MPa.The flexural properties of the hybrid composite samples are tested and the experimental values are presented in Table.2.The force vs.stroke curve generated directly from the machine during flexural loading for the hybrid composites is presented in Fig.13.The flexural strength comparison of different hybrid composites is presented in Fig.14.From the figure,it is asserted that the flexural load carrying capacity of banana-hemp-glass fiber reinforced composites is better than banana-glass fiber reinforced composites and hemp-glass fiber reinforced composites.The impact test is carried out for evaluating the impact load carrying capability of the different hybrid composite specimens and the charpy impact test is used in the present investigation.The impact strength comparison of different hybrid composite samples is presented in Fig.15.The results indicated that the maximum impact strength is obtained for banana hemp-glass fibers reinforced hybrid composites which hold the impact strength of 8.66Joules.The banana-glass fiber reinforced composites and hemp-glass fiber reinforces composites are performing in the same level can withstand the impact strength of 5.33Joules.The failure morphology of the hybrid composite samples tested in the present experiment is examined through scanning electron microscopy analysis.The SEM micro-graphs of the hybrid composite samples subjected to tensile loading are presented in Fig.16.

From the images,it can be seen that the fracture of the fiber and matrix due to the applied tensile load.The SEM micro-graphs of the hybrid composite samples subjected to flexural loading are presented in Fig.17 and the samples subjected to the impact loading are presented in Fig.18.The fiber breakage and fiber pull out due to flexural loading are clearly in observed in Fig.17.Fig.18 indicated that the fractured edges of the fibers in the specimen and also the dislocation of fibers due to impact loading.The permanent growing of the world population within the next two to three decades by round about 2.5 billion will result in an additional demand for food of 43 % and for textile fibers of more than 80 %.In contrast to the increasing demand arable land is more and more limited and the cropland area per capita will shrink.This situation will result not only in a food crisis,but also in a “cellulose gap” because cotton production is predicted to be stagnant in the future and the history of man-made fibers shows that approximately one third of all textile fibers have to be cellulosic fibers because of particular properties like absorbency and moisture management.The outcome of this is a disproportionately high demand for man-made cellulosic fibers in the coming years and for dissolving pulp,the most used raw material for fibers manufacturing,too.Dissolving pulps are usually manufactured from several kind of hard or soft wood by an intensive material and energy consuming cooking procedure,which is required for separation of pulp fibers,hemicelluloses and lignin.For those reasons an increase of pulp production will require a lot of time for growth of the trees and money for erection and implementation of new pulp mills.In contrast,pulp raw material based on annual plants like bast fibers offers the options to increase much more quickly the available pulp volume,because of the faster rate of crop growth and lower energy consumption for degumming and fiber separation.Nevertheless,new process steps for pulp purification are required.

Furthermore,pulp quality will have to be adapted to the intended fiber manufacturing and processing line.Here new approaches are needed and have to be developed by the R&D activities.For that purpose a project consortium was installed,consisting of partners from organic farming,agricultural machine development,pulp and fiber manufacturing and fiber and fabrics processing.Moreover,as present in figure 1 it was the target of the team to develop an integrated process chain for the manufacturing of innovative fabrics produced of man-made Lyocell type fibers made of dissolving pulp based on OG hemp.Bast fiber material almost free of wooden shives and dried HBS was delivered by Bast & Faser GmbH and was used as delivered.Dried HBS and mechanical pre-processed hemp fiber tow were typically treated by aqueous caustic soda at 160 °C for about one hour.A mixture of caustic soda and surface active additives was applied as cooking liquor.Reduction of Kappa number was used for process time and DP adjustment.Alternative,a fiber bleaching sequence could be applied for adjustment of cellulose pulp DP at 450 up to 700 using subsequently hydrogen peroxide and sodium hypochlorite at 55 °C for 120 minutes,each.Within of pulping procedures suitable sequestrants were added for elutriation of high metal ion contents.The resulting pulp was finally dried to a solid content of 80 % and was used without any further treatment for dope preparation.For dope preparation about 15 % of delivered pulp was redispersed in 85 % aqueous dissolution of NMMO comprising about 20 % of water and transferred into a discontinuous laboratory scaled stirring and kneading reactor.The pulp was dissolved by evaporation of excess water as well as elevated temperatures of 100 °C,decreased pressure of in minimum and a rotational speed of 20 rpm.At the moment when excess water was fully evaporated and a mixture of one mole of water per mole of NMMO was achieved the pulp dissolved immediately and a transparent,brownish,viscous spinning dope was generated.The shearing was continued another 20 minutes at 10 rpm for dope homogenization.Within the project activities the major part of HBS should be converted into dissolving pulp suitable for solution spinning of cellulose man-made fibers.For that purpose a feasibility study was ordered as subcontract from OP Papirna s.r.o.,Olšany,Czech Republic.Because bast fibers commonly offer higher alpha cellulose content,it is not so difficult to adjust required pulp purities of more than 92 % alpha-cellulose content.

But for an application in solution spinning the primary DP of hemp is too high and should be reduced either by a pulp cooking or a pulp bleaching process.At first both approaches were pre-tested in laboratory scale using flax fibers.In the end,the conducted cooking trials generally confirmed,container for growing weed that the increase of cooking liqueur concentration and/or of cooking time could acceptably increase polymer degradation down to the intended pulp DP.However,the cooking process lowered the overall pulp yield.Therefore also the adaptation of bleaching sequences was investigated in a second step.Conventional bast fiber pulp bleaching procedures for paper manufacturing use successively hydrogen peroxide,chlorine dioxide.They end up with an extraction sequence at presence of hydrogen peroxide.For the intended DP reduction an additional sequence was required using sodium hypochlorite as bleaching agent.Also this approach worked well,but only the cooking approach should be further investigated in the running project,because of the environmental toxicity of chlorine containing agents.To conclude from figure 5: At lower caustic soda concentration the Kappa number is different in case of hemp tow control from those of HBS because of its higher amount of lignin in contained hurds.Nevertheless,the Kappa numbers of both hemp samples could become equal,if the optimal caustic soda concentration and process duration were chosen.From these results the conclusion could be drawn that the lignin of hurds was also fully separated from hemp tow control at the properly chosen concentration and time.Table 1 summarizes the typical properties found in crude and purified pulp.Another challenge,also arising from high metal salt contents,is the chemical sensivity of the solvent NMethylmorpholine-N-oxide.Especial,the pulp immanent heavy metal complexes based on iron and copper ions,might generate serious solvent decomposition,what could be autocatalytic pushed on by means of addressed ions.For that reason crude pulps were washed with de-ionized water in order to isolate most of the included hazardous metal ions.After washing of the pulp the iron and copper metal ion content decreased down to no longer relevant amounts.Ongoing problems arise from the extremely high Ca2+ and Mg2+ ions concentration,even in purified pulp samples.But problems could be solved when cooking was transferred into commercial scale and pulp manufacturing was combined with pulp purification by means of aqueous solution containing suitable sequestrants.

The sequestrants might irreversibly bind the ions by formation of complex compounds,even under caustic and/or oxidative conditions.In the end Ca2+ ion concentration dropped down below 200 and Mg2+ ion concentration was found below 50 ppm.Finally,of cooking process investigation a 5.3 metric ton OG hemp tow sample should be converted into dissolving pulp applying the identified process parameter.Five different cooking batches were performed in commercial scale equipment.Intrinsic viscosity of the produced five pulp samples was in the range of 370 dl/g up to 450 dl/g,what correlates with pulp DP’s of about 500 up to 650,respectively.The accepted iron ion concentration in semi-technical scale was appointed below 10 ppm.Unfortunately the content of iron ion was nearly twice the number.The so-called onset-temperature,that temperature at what thermal induced solvent decomposition occur,has to be measured,if the iron ion content is higher than allowed.In case of dope derived from OG hemp it was determined at the same temperature as of dopes prepared of wooden pulp and was located at higher temperatures than 170 °C.That temperature is high enough to release the prepared pulp for further processing of man-made cellulose fibers.In the last step the pulp was dried to solid content of 80 % and was handed over for further investigation of direct dissolution in NMMO monohydrate.Spinning dopes were manufactured as described in material and method section.After finishing dissolution and homogenization dopes were characterized by daylight microscopy,laser light scattering,particle analysis and rotation/oscillation rheometry.Incomplete pulp dissolution as present in figure 6,what even could be detected by daylight microscopy,might occur whenever fibrous particles are insoluble in case of high molecular cellulose shares or unsuitable pulp is used or solid particles are formed in case of higher amounts of inorganic impurities.Bad solution state as shown in fig.6a could be caused by extreme high Ca2+ and Mg2+ ions concentration.Visible particles are generated by calcium and magnesium salts,which are precipitated at low concentration of excess water in dopes.Because those particles are incompressible danger arises for clogging of spinning holes,if dopes are extruded through the spinneret.Fig.6b demonstrates the effect when OPP Hanf HP pulp is well dissolved and separated from the inorganic contamination at application of sequestrants.Such kind of purified pulp could be easily shaped into cellulose man-made fibers by dry-wet spinning procedure.Adolescence is a unique developmental period characterized by major physiological,psychological,and neurodevelopmental changes.These changes typically coincide with escalation of alcohol and marijuana use,which continues into early adulthood.

Agricultural measures tend to increase the crop yields and to enable a multipurpose exploitation of the crop

With a growing interest in sustainable issues and ecofriendliness,the textile industry is now faced with the challenges of developing eco-friendly textile products with enhanced sustainability.Efforts have been made in the field of wet processing of textile products.However,another equallyimportant aspect of producing more sustainable textile product is to select eco-friendly and low-cost raw materials,as well as to control the textile manufacturing processes in regard to energy and labour savings.An increasing recognition of hemp as more sustainable cellulose fibres has to be accompanied by an improvement in some comfort performances,aesthetics and,last but not least,by cost effectiveness.Apart from the environmental benefits of hemp in comparison to cotton,which is elaborated in the introduction section,the average prices of hemp fibre are 1.0e2.1 US$/kg while the cotton prices are between 2.1 and 4.2 US$/kg.However,the approximate prices for plain hemp textiles range from 5 to 13 US$/kg.In addition to these aspects,modern consumers expect high standard of performance even after a number of care cycles.Low cost and efficient production of synthetic fibres,together with their easy care and shape-retention properties can contribute to hemp based textiles to fulfil these requirements.In this context,acrylic fibres offer some benefits one of which is low specific gravity that allows yarns and fabrics to be made with a high bulk to weight ratio enabling improved softness.Other one is the simple and effective on-line coloration capability of acrylic fibre technology by which any further wet processing for finishing fabrics and garments does not need.This is not only extremely cost-effective,but very environmentally competitive route to market.In addition,avoiding any chemical treatment of hemp based fabrics with softeners to improve the tactile comfort performance is important from both economic and ecological aspects of sustainability.This elaboration,along with the results obtained and references given in the introduction section,clearly indicate that the use of hemp instead of cotton,mobile vertical rack and the use of acrylic to integrate with hemp yarn during knitting offer possibility of improving several sustainability aspects for cellulose based textiles.

However,some efforts are continuously made to achieve the reduction in cost and environmental impact in the range from the crop stage to the hemp product development stage.A new approach to a decrease in the environmental impact involves a reduction in eutrophication in the crop production.In fibre processing step,the research is aimed at improving fibre extraction processes so as to increase fibre quality and reduce labour requirements and price.Attempts have been made to improve hemp yarn production by developing new and more productive equipment and reducing energy costs.The avoidance of additional chemical treatments in this project is extremely important bearing in mind that a large amount of energy,water and chemicals are used for processing,finishing and dyeing of fibres,yarns and fabrics.The current trend towards improving sustainability of these processes goes in a direction of using eco-friendly substances and dyes.The recyclability and degradability of enzymes has stimulated research into their application to hemp fibre processing.Dyeing by natural dyes extracted from various plants,as well as agricultural wastes utilization for dyeing of textile fabrics,have been investigated in recent studies in order to meet the challenges of improving sustainability of production processes.In addition to production technology,new products development is also very important so as to meet market demand.We believe that hemp based textile product developed in our project presents a useful contribution to up to-date hemp textile product range,offering the textile engineers,designers and decision makers in textile companies the way to balance the cellulose based product performance,environmental concerns and costs at the current level of technological development.The utilisation of wood resources for energy production makes up the demand for the development of new technologies in the area of the chemical processing of agricultural residue.

The increasing demand for products derived by the chemical industry also increases the demand for furfural,which is exclusively produced from hemicelluloses-containing biomass.There is no synthetic route available for furfural production in the chemical industry.The production of furfural belongs to environmentally friendly technologies,although it has chemical properties similar to those of petrochemicals.It is used for the production of a wide range of important non-petroleum derived chemicals such as furan,tetrahydrofuran and furfuryl alcohol.It is also used as an extractive,a fungicide,in oil refineries,as well as in the plastics,food,pharmaceutical and agricultural industries.For example,it can be introduced during fibril formation to enhance the thermal and mechanical stability of collagen.At the moment,in the European Union,furfural is an imported products,although potential raw material resources are in a sufficient amount.During hydrothermal pre-treatment,the dehydration of xylose to furfural in water typically proceeds at 150–220 °C,and the reaction rate is small under neutral conditions,increases during autocatalysis by acetic acid,which originates from the biomass,and is accelerated further by the addition of catalysts,especially strong acids such as sulphuric acid or solid acid catalysts such as H-Beta zeolite.The costs and inefficiency of separating these catalysts from the products make their recovery impractical,resulting in large volumes of acid waste,which must be neutralised and disposed of.Other drawbacks include corrosion and safety problems.Al23 as a hydrolysis catalyst has been considered in some publications related to obtaining levulinic acid from biomass,but there are no scientific publications about the use of Al23 in furfural production from lignocellulosic biomass by hydrothermal pre-treatment.Furfural production from hemp shives has not been investigated until now as well,while the high content of hemicelluloses shows that the hemp fibre production byproduct has great potential.Also,this valuable raw material is concentrated in one place at the fibre production manufacturer’s site.The hemp species are an approved and rapidly expanding crop in Latvia,with a yield from 150 ha in 2009 to 1200 ha in 2013.Hemp shives are the woody inner part of the hemp stalk separated from the fibres,making up to 75 % of the oven dry stalk.

The chemical components of the hemp variety “Bialobrzeskie” shives used for experiments testify that the material also has the potential for the production of composites.Up until now,however,the main utilisation of hemp as a crop has been for its bast fibres.To utilise the leftover lignocellulose after obtaining furfural,binder-less panels could be made without the use of any additional adhesives during the panels’ production process.The panels made from the shives after the catalysed pre-treatment may have improved water resistance of the panel because hemicelluloses are the most water absorbing component and,after pre-treatment,their content is significantly diminished.Furthermore,steam explosion treatment transforms the lignin structure in the plant matrix and promotes the binder-less composite moulding in the following hot-pressing process.The objective of the study was to investigate the preliminary technological parameters of obtaining furfural and binder-less panels depending on the hydrothermal pre-treatment temperature,steam explosion treatment and pressing conditions.The pre-treatment process reference criteria for optimal parameters were chosen by the furfural yield and cellulose destruction degree in the leftover lignocellulose,which affects the obtained panel’s mechanical properties.The panel’s evaluation criteria were the panel quality and the maximal values of the tested properties – modulus of rupture and modulus of elasticity.The holocellulose content in the raw material was 75.5 wt% and,after the pre-treatment process,it decreased to 34.2 wt% at 160 °C and 27.7 wt% at 180 °C,calculated on the oven dry hemp shives’ mass.This means that,during the catalytic pre-treatment in the presence of Al23,not only is hemicelluloses converted to furfural,but also some part of cellulose has started to degrade.By increasing the hydrothermal pre-treatment process temperature up to 180 °C,the cellulose content significantly decreased from 31.4 wt% to 22.2 wt%,calculated on the oven dry raw material,vertical grow rack taking into account the yield of lignocellulose.The leftover lignocellulose after the hydrothermal pre-treatment contained ~ 50 wt% moisture content; therefore,it was dried to a 10–15 wt% moisture content at 25°C.

With increasing temperature of the pre-treatment process,the moisture content of residual lignocellulose was higher at the drying stage.This can be explained by the increasing of the surface of the raw material particles due to the degradation of cellulose at elevated temperatures in the presence of the Al23 catalyst.The obtained panels are very different from the outside.The Ref 1 and Ref 2 panels are light enough in colour like the raw shives and similar to conventional OSB panels.The panels from the shives after the catalysed hydrothermal pre-treatment process are slightly darker in colour,compared to the reference panels.The panels from the pre-treated and steam-exploded shives are very dark in colour,with an apparent degraded morphology of shives on the surface.Most of the panels from the pretreated and steam-exploded shives have gaps on the surface and on the inside parallel to the surface.These observations allow concluding that the lignocellulosic material after the steam explosion treatment is significantly degraded.However,the degradation level of lignocelluloses depends on both pre-treatment and treatment,and the treatments conditions should be optimised.Cutting edges are another property of the panel quality that was observed,although only qualitatively.The panels made of untreated shives at 160 °C have unstable edges,which drop off.However,the cut edges of the panels made at 200 °C are stable enough.The panels made of pre-treated shives have cut edges similar to those of the untreated ones,although look more stable.Generally,the cut edges of the obtained panels are poor in quality.This is probably due to the too high moisture content of the pressing material and due to the too high steam explosion temperature that results in the too high severity factor of the material and degradation of cellulose.However,we believe that this could be improved by optimising the panel moulding process that is the next goal of the research.Some studies state that it is possible to make a high quality binder-less panel from agricultural species.The density range of all panels obtained was from 800 kg/m3 to 1250 kg/m3.85 % of the differences in density are explained by the panel’s thickness,which varies from 6 to 8 mm as shown in Fig.4.On the other hand,such different thickness obtained means that the same pressure used at pressing for all samples shows that the samples are different as materials,and different pressures should be used for each of them to obtain the same density.

The MOR values of the panels vary from 2 to 12 N mm-2,depending on all included factors.However,the strength difference is not significant.The low MOR values could be explained by the high enough severity factor of the lignocelluloses and,possibly,the fact that the pressing temperature was too low to achieve the lignin flowing and then the glass transition necessary to form a rigid material.The MOE values of the panels vary from 141 to 3250 N mm-2,also depending on the same factors as in the MOR performance.The obtained maximal MOE value is high enough and demonstrates that the material can be used for panel production.However,the MOR values are too low and should be improved by optimising the panel moulding conditions.In spite of the low mechanical properties,an excellent correlation was obtained between the MOE and MOR values,which means that the strength of the composites could be predictable.Temperature and relative humidity are important parameters influencing perceived indoor air quality and human comfort.High moisture levels can damage construction and inhabitant’s health.High humidity harms materials,especially in case of condensation and it helps moulds development increasing allergic risks.Consequently,several researchers have studied the use of various hygroscopic materials to moderate indoor humidity levels.The material that absorbs and desorbs water vapor can be used to moderate the amplitude of indoor relative humidity and therefore to participate in the improvement of the indoor quality and energy saving.Vegetal fiber materials are an interesting solution as they are eco materials and have low embodied energy.Hemp concrete is one of these materials which is more and more recommended by the eco-builders for its low environmental impact.The physical properties of hemp concrete has been measured by many authors.It is highlighted that the one presents high moisture buffering capacity and a good compromise between insulation and inertia materials.To investigate the hygrothermal behavior of building envelope,a simulation should be done because it is cheaper and more detailed than the test in situ.For this to be done,many simulation tools have been developed.Hygrothermal properties are required for all Heat,Air and Moisture transfer models.Many models and simulation tools for predicting the hygrothermal behavior of building envelope are represented in the Annex 41 of the International Energy Agency’s.For the building envelope,the main difference in HAM-transfer modeling is made by the dimension of represented phenomena and they can be classed by the granularity and complexity†.

The relationship between marijuana smoking and asthma is somewhat complex

Water pipes have become more popular in North America in recent years due to the belief that it is a safer alternative to cigarettes .This is a common misconception in young adults,as a water pipe smoking session can contain over 100 times the amount of smoke in comparison to a single cigarette .In Ontario,the rate of trying water pipes in adolescents has more than doubled from 6% in 2006 to 14% in 2013.Water pipe smoking is linked to several adverse health outcomes such as cancer,cardiovascular disease and decreased lung function.While the causal effect of water pipe smoke and asthma has not been demonstrated,exposure to tobacco smoke was shown to exacerbate asthma symptoms.Since water pipes produce tobacco smoke,it can be assumed that it will be harmful especially for those with asthma.Marijuana has been used as a forbidden medicine to treat asthma symptoms for years as it may have bronchodilator properties,while long term marijuana smoking has also been associated with increased respiratory symptoms.Overall,the relationship between marijuana and lung health is somewhat mixed and the connection may not be the same as tobacco smoke.Previous research has suggested that adolescents with asthma smoked significantly more marijuana than those without asthma.However,the number of adolescents who smoked marijuana in Canada has decreased from 32.7% in 2008 to 24.4% in 2013.Electronic cigarettes are battery powered devices that vaporise nicotine and/or other flavouring mixes,cannabis grow lights but do not burn tobacco.These products have become popular in recent years and they are perceived as a safer alternative to tobacco cigarettes.

While preliminary studies suggest that they may be less harmful than cigarettes,the long term health effects and how e-cigarettes relate to asthma symptoms or severity are unknown.The Canadian Tobacco,Alcohol and Drug Survey reported that as many as one in five adolescents aged 15e19 tried e-cigarettes,however,the absolute trend of usage is still unknown as these products are relatively new.The purpose of this paper is to examine whether adolescents with asthma smoke cigarettes,water pipes,marijuana or e-cigarettes more or less than those without asthma.This study adds to the current literature by examining all smoking habits for youth with asthma,rather than focusing just on cigarettes.The 2013 Ontario Student Drug Use and Health Survey is a population based survey conducted every two years and completed by grade 7e12 students at publically funded schools in Ontario,Canada.Ontario is the largest province in Canada with a population of over 13 million residents.Ontario includes major urban centres such as Toronto and Ottawa,several smaller cities and an abundance of rural lands.The OSDUHS is designed to collect information about drug use and other health related behaviours among students in Ontario.All parents and students gave consent prior to participation.To examine the association between smoking and asthma,we limit our study sample to high school students in 109 schools.These schools were selected with probability proportional to size,to obtain a representative sample within the province.The survey included questions that captured information on self-reported doctor diagnosed asthma and data on tobacco,alcohol and drug use.The survey used a random split-ballot design where some of the questions change on each of the surveys.The sample is randomly divided into 2 groups to maximize questions included and minimize burden on students,but it reduces the sample size for some questions.In the OSDUHS,approximately half of the full sample answered questions pertaining to asthma and all types of smoking reducing the sub-sample to 2,840.

Data are representative of students in Grades 9 to 12 attending publicly funded schools in Ontario.Ages for respondents range from 12 to 19 years of age.In Ontario,the majority of children attended publically funded schools,5% attended private schools,and another 3% were either home schooled,institutionalized for correctional or health reasons,schooled on a First Nation reserve,military base or lived in remote northern region.This study was approved by the research ethics board at the Research Institute of The Hospital for Sick Children.The primary outcome variables in this study are smoking status with regard to cigarettes,water pipes,marijuana and e-cigarettes.Self-reported frequency and intensity of cigarette,water pipe,marijuana and e-cigarette smoking in the last 12 months and lifetime use were measured in the survey.Cigarette non-smokers were classified as those who never smoked a cigarette or smoked less than one cigarette in the last 12 months,while cigarette smokers were those who smoked more than one cigarette in the past 12 months.Similarly,smoking status for water pipe was also classified as a binary outcome variable.Respondents were asked how often they smoked a water pipe in the last 12 months.Those who smoked a few puffs,never smoked,haven’t smoked in the past 12 months or didn’t even know what it was were considered non-water pipe smokers.Those who smoked one or more times were defined as smokers.Marijuana smoking is also defined in a similar manner.Students were asked how often they smoked cannabis in the past 12 months.If they smoked 1 or more times in the past year they were classified as a marijuana smoker.Respondents who have never or not smoked in the last 12 months were considered to be non-marijuana smokers.Finally,respondents were classified as e-cigarette smokers if they smoked an e-cigarette with or without nicotine in it,while those who have never smoked or never heard of e-cigarettes were considered non-smokers.The primary risk factor of interest is the presence of asthma which is captured by the response to the question “has a doctor or nurse ever told you that you have asthma”.Other potential confounding variables include: grade,sex and socioeconomic status.

SES was measured by a 10-point social ladder.Students were asked to imagine that the ladder represents how Canadian society is set up,where the people at the top of the ladder are the “best off”,meaning they have the best jobs,make the most money and have the highest education.Those at the bottom of the ladder are the “worst off”,with no job,or a job no one wants,little education and the least money.Respondents reported what best represents their family on a 10-point scale,which was further grouped into three levels based on the interquartile ranges.The percent distributions of demographic characteristics and other co-variates were compared between smokers and nonsmokers of each type and the any smoking variable.The chi-square test was used to measure statistical significance between the respondents with and without asthma.Each type of smoking was modelled separately using a binary logistic regression.In addition to doctor diagnosed asthma,all co-variates outlined above were included in the regression models.All interactions of smoking types were examined but no significant relationships were found so this study focussed on the four individual models,plus the combined any smoking outcome.The following was used as the reference group in the logistic regression models: grade 9,female and high SES.Given the OSDUHS used a probability stratified cluster sampling design,all analyses were conducted with the sampling weights and utilized Taylor series methods within Stata 14 v14.1 to derive unbiased standard errors and point estimates.Results of the regression models were presented in adjusted odds ratios with 95% confidence intervals.Goodness of fit tests were completed with the F-adjusted mean test.While cigarette smoking may aggravate symptoms and severity for adolescents with asthma,some work on the topic suggests that the prevalence of cigarette,water pipe and marijuana smoking was actually higher in adolescents with asthma than those without.These studies,however,are not conclusive as at least one reported that adolescents with asthma were less likely to smoke cigarettes.It is reasonable to suppose that adolescents with asthma will not smoke as it will aggravate their asthma severity and symptoms,but this unfortunately may not be the case.

Our study showed that students in grades 9e12 with asthma in Ontario,had a higher odds of smoking e-cigarettes or any substance than their peers who do not have asthma.The odds of smoking ecigarettes for adolescents with asthma,was nearly twice as high as those without asthma after adjusting for age,sex and SES.Given the cross-sectional design of the survey,we cannot infer the causal relationship between smoking and asthma.Previous studies suggest that smoking for adolescents with asthma may relate to the desire to obtain social status among one’s peers,and not wanting asthma to interfere with their social status.Of all demographic characteristics studied,student’s grade was most significantly associated with smoking cigarettes,water pipes and marijuana.A longitudinal study in the United States found that rates of cigarette smoking increased from 1.8% at the age of 9 to 22.5% by age 16.Findings suggest that rates for smoking cigarettes and water pipes among grade 9 students were relatively low,but doubled in grade 10,tripled by grade 11 and quadrupled by grade 12.Cigarette and water pipe smoking became more popular in grade 10 and the trend continued as they aged.E-cigarette smoking on the other hand only marginally increased from grade 9 to 12.For adolescents with asthma,rates of e-cigarette smoking were similar to that of the entire sample,cannabis grow tent ranging from about 10% in grade 9 to 16.7% in grade 12.Our study also showed that cigarette,marijuana and any smoking rates were inversely related to SES,where lower SES was associated with higher odds of smoking.Our finding is consistent with the literature that suggests an inverse relationship between individual SES or parental education and cigarette smoking in adolescents.It has been suggested that lower SES households may have a poorer attitude towards health,fewer opportunities or more stressful situations which make them more likely to smoke.Results from our study emphasise the need for tailored interventions for youth from lower SES households.This study had many strengths which relate to the size and generalizability of the survey sample and the fact that it examined how all types of smoking related to asthma prevalence.That being said,there are also some limitations.The primary purpose of this survey is to examine health risk behaviours of adolescents in Ontario and not asthma.As such,the number of respondents with asthma was low and this may have contributed to some of the insignificant findings.

Despite the low number of asthma respondents,the self-reported asthma prevalence rate of adolescents in this study was similar to that reported by the Ontario Asthma Surveillance Information System,which uses a validated health administrative data case definition to capture asthma with 84% sensitivity and 76% specificity.Secondly,the cross-sectional design of the survey is a major study limitation in assessing causal relation of asthma and smoking.It is unknown from this study whether adolescents with asthma smoked e-cigarettes more often or if smoking e-cigarettes contributed to the risk of asthma.Thirdly,asthma was self-reported and it not clinically confirmed.Self-reported asthma may over or under represent actual prevalence of asthma.Furthermore,many studies that examined the relationship between asthma and smoking did not separate severe or “uncontrolled” asthma from those with well-controlled mild to moderate asthma.The effect of smoking on adolescents with severe or uncontrollable asthma may be different than on those with mild to moderate asthma.The definition of smoking used may influence the study findings.We classified smoking for cigarettes,marijuana and water pipes as smoking one or more time over the past 12 months or ever for e-cigarettes.This definition includes those who smoke regularly but also adolescents who experiment with the various types of smoking.This classification of smoking has been used previously in studies using the OSDUHS dataset.We conducted additional analyses using another method of classifying smokers reported by Wong and colleagues.In this method a regular smoker is defined as smoking more than 100 cigarettes in their lifetime and any cigarettes in the past month.Using this method the results and point estimates remained very similar.Given this method of classification was only available for cigarettes,we opted to retain the ‘any cigarettes over the past 12 months’ method to ensure measurement correspondence with the other types of smoking.Nevertheless,results suggest that adolescents with asthma are at least experimenting with e-cigarettes or any type of smoking more often than their peers without asthma,which may lead to higher smoking rates later in life.Finally,we were unable to adjust for parental smoking or parental history of asthma as these data were not collected by the survey.Having a parent who smokes may relate to the respiratory health of children,but it also increases the odds of smoking for adolescents.While information on parental smoking is not available in our data,further research should examine the association between parental smoking and asthma for all types of smoking.This paper adds discussion to the question of whether adolescents with asthma would be less likely to smoke cigarettes,water pipes,marijuana or e-cigarettes.

Three RT-PCR pathway specific arrays were used to validate the expression of specific micro-array genes

Mainstream smoke was passed through a 92 mm glass fiber filter disc for particulate matter collection.To prepare the condensate samples,the respective filter pads were placed in a flask containing dimethyl sulfoxide and shaken on a wrist-action shaker for 20 min.Each condensate sample was standardized to a concentration of 30 mg total particulate matter per ml of DMSO.Cytotoxicity of the smoke condensates was determined using the lactate dehydrogenase assay and the XTT assay.The LDH assay was performed using a kit according to manufacturer’s instructions.Briefly,FE1 cells were grown in 12-well plates and exposed to 8 concentrations of 1.5–30 g/ml of MSC or 3–90 g/ml of TSC in serum free medium for 24 h r.After plates were centrifuged,an aliquot was transferred to flat-bottomed plates and the LDH Assay Mixture was added.Plates were covered with aluminum foil and incubated at room temperature for 20–30 min.1 N HCl was added and the absorbance was measured at 490 nm,with the background measured at 690 nm.The XTT assay was also performed using a kit according to manufacturer’s instructions.Briefly,FE1 cells were grown in 12-well plates and exposed to 8 concentrations of 1.5–30 g/ml of MSC or 3–90 g/ml of TSC in serum free media for 24 h.The XTT reagent was added and the plates were incubated for 2 h at 37 ◦C.The plates were mixed and the absorbance was measured at 450 nm.Absorbance at the reference wavelength of 690 nm was also read and subtracted from the 450 nm value.A reference design with arrays as blocks of size 2 was used to analyze the median signal intensities of the two-color micro-array data.The experiment included main effects of dose,time and dose-by-time interaction.Five biological replicates per condition were used for each of the eight conditions,for a total of 80 micro-arrays.Six MSC and four TSC “outlier” micro-arrays were removed based on quality control checks,cannabis vertical farming leaving a minimum of 3 replicates per group.

The background signal intensity for each array was estimated using the 1533xSLv1 negative controls present on each array.All pre-processing of the data was conducted using R.The data were normalized using the LOWESS normalization method in the R library “MAANOVA”.Differential expression between the control and exposed samples for each of the three dose levels at each of the two time points was tested using the MAANOVA library.The ANOVA model was fitted to include the main effects of dose and time,with a dose by time interaction term and the array as a blocking variable.The Fs statistic,a shrinkage estimator,was used for the gene-specific variance components,and the associated p-values for all the statistical tests were estimated using the permutation method.These p-values were then adjusted for multiple comparisons using the false discovery rate approach.The least squares mean,a function of the model parameters,was used to estimate the fold change for each pairwise comparison of the six pairwise comparisons of interest among the eight treatment-by-time groups.The micro-array data for this experiment has been submitted to the Gene Expression Omnibus repository and can be accessed under record number GSE44603.Visualization and analysis of significantly changing genes was performed using Gene Spring GX 7.3.Important pathways containing significantly expressed genes were identified using Ingenuity Pathway Analysis.Genes were assigned to functional categories using gene ontology in the Database for Annotation,Visualization and Integrated Discovery.BMD Express was used to calculate benchmark doses from gene expression data.Analyses were performed on genes that were identified as statistically significant by one-way ANOVA using four models: Hill,Power,Linear and 2◦ Polynomial.Models that described the data with the least complexity were selected.A nested chi-square test,with cutoff of 0.05,was first used to select among the linear and 2◦ polynomial model,followed by comparison of Akaike information criterion,which measured the relative goodness of fit of a statistical model,between nested models and the power model.The model with the lowest AIC was selected as the best fit.A maximum of 250 iterations and a confidence level of 0.95 were selected.For functional classifications and analyses,the resulting BMD datasets were mapped to KEGG pathways with promiscuous probes removed.BMDs that exceeded the highest exposure dose were removed from the analysis.

Eight nanograms of total RNA,from the same samples that were used for the micro-array study,were reverse transcribed to cDNA using an RT2 First Strand Kit.cDNA was mixed with the RT2 qPCR Master Mixes and aliquoted into 96-well plates containing primers for 84 pathway specific genes.Expression levels were evaluated using a CFX96 real-time Detection System.Relative gene expression was normalized to the Gapdh housekeeping gene,which remained unaffected under experimental conditions.Fold changes and statistical significance were calculated using the REST method for statistical significance.For the micro-array study,FE1 cells were exposed to 2.5,5 and10 g/ml of MSC and 25,50 and 90 g/ml of TSC.Exposed samples were compared to their matched controls,and genes were considered significantly differentially expressed if they had a fold change ≥2 with an FDR-adjusted p-value ≤0.05.A total of 1020 unique probe identifiers were significantly differentially expressed following exposure to MSC,and of these,979 were deemed “present”.Following exposure to TSC,557 probes were significantly differentially expressed and 527 were deemed “present”.Of these,356 were common to both MSC and TSC exposures.The number of significantly up- and down-regulated genes at each time point and concentration is shown in Table 1.Overall,there was an increase in the number of differentially expressed genes with increasing concentration of condensate,and there were more genes changing after the four hour recovery.At the highest concentration for both time points,cells exposed to MSC had a greater number of changing genes as compared to cells exposed to TSC.Gene expression was most altered for cells exposed to the highest concentration of MSC at the 6 + 4 h time point.Whether separated by dose or considered all together,Venn diagrams show considerable overlap in the genes that are significantly expressed at each time point following MSC or TSC exposure.Hierarchal clustering using all genes that were statistically significant revealed that the controls and the marijuana high concentration clustered independently from the rest of the samples.The remaining samples clustered first by concentration,then by condensate type,with the last branching resulting from time.When cells exposed to TSC and MSC were analyzed separately,samples clustered first by concentration and then by time point,suggesting that concentration has the largest overall effect on gene expression.For MSC,the high concentration samples were on the first main branch,followed by control,low and medium concentrations.

The results indicate that the expression profiles of the high concentration MSC exposed cells are quite distinct.For TSC,the controls branched separately from all the treatment groups.The top 10 genes with the largest overall fold changes are listed in Table 2.All of the top 10 genes were significantly up-regulated with the exception of low density lipoprotein receptor,which was down-regulated in MSC exposed cells.Of the top 10 changing genes,five genes were common to both MSC and TSC.The GO terms associated with these commongenes included multicellular organismal development,vasculogenesis,regulation of transcription,and regulation of inflammatory response.Ingenuity Pathway Analysis was used to define the pathways that were significantly altered following exposure to MSC or TSC.Fig.3 shows the overlap in all the significant pathways between the two condensate types.The top five most significantly altered pathways for cells treated with MSC or TSC are listed in Table 3.NRF2-Mediated Oxidative Stress Response was the most significant pathway for cells exposed to TSC at all concentrations and time points,with the exception of lowest concentration at time 6 + 4 h where LXR/RXR Activation was the most significant.For cells exposed to MSC,the most significantly altered pathways were Biosynthesis of Steroids,as well as NRF2-Mediated Oxidative Stress Response,Aminoacyl-tRNA Biosynthesis and HMGB1 Signaling.Some of the top five pathways were common to both the MSC and TSC including those related to oxidative stress and xenobiotic metabolism.However,inflammation pathways were more predominant for the MSC,whereas cell cycling and cancer signaling pathways were more predominant for the TSC.To further elucidate differences between the two smoke condensates,the genes that were uniquely expressed following TSC exposure or uniquely expressed following MSC exposure at the highest concentrations for the two separate time points were compared in IPA.The findings confirm the importance of inflammation and steroid biosynthesis pathways in MSC exposed cells and highlight the significance of apoptotic pathways particularly at the 6 h time point.For cells exposed to TSC,Mphase cell cycle pathways appear to be of particular importance.

Gene Ontology in the Database for Visualization,Annotation and Integrated Discovery was used to apply functional annotation to all the significantly differentially expressed genes for each condensate.The full results are shown in Supplementary Tables 1 and 2.For cells exposed to MSC,cannabis drying racks significant perturbations were associated with steroid/cholesterol/lipid biosynthesis,NOD like receptor signaling,tRNA aminoacylation,transcription regulation,unfolded protein response and DNA binding.Like MSC,cells exposed to TSC had significant perturbations in transcription regulation,unfolded protein response and DNA binding.In addition,perturbations in cell cycle,p53 signaling,oxidative stress,and cancer signaling were also noted in TSC exposed cells.Fig.5 shows the overlap of all the significantly affected on tologies between the two condensate types.Functional annotation clustering in DAVID was used to minimize redundancy in the GO terms.This analysis revealed 19 clusters with enrichment scores greater than 2 for MSC and 19 clusters for TSC.The top clusters for MSC relevant to toxicological processes include lipid/steroid biosynthesis,RNA processing,cellular response to unfolded protein,tRNA aminoacylation,and positive regulation of transcription.The top clusters for TSC relevant to toxicological processes include cellular response to unfolded protein,cell cycle,positive regulation of transcription,response to steroid hormone stimulus,and positive/negative regulation of apoptosis and cell death.To investigate early versus downstream effects,functional annotation was applied to significantly differentially expressed genes at the two separate time points.The results are shown in Supplementary Tables 5–8.For cells exposed to MSC at the 6 h time point,the analyses revealed 79 significant terms including those related to transcription activity,DNA binding,and steroid/cholesterol biosynthesis.Four KEGG pathways and 1 Biocarta pathway were also deemed significant at this time point.At the 6 + 4 h time point,76 significant terms were identified.These terms included unfolded protein response,and tRNA aminoacylation,as well as steroid/cholesterol biosynthesis which was found at the 6 h time point.Three KEGG pathways were significant at this time point including Steroid Biosynthesis,Terpenoid Backbone Biosynthesis,and Aminoacyl-tRNA Biosynthesis.Analyses of cells exposed to TSC at the 6 hr time point revealed 67 significant terms including those associated with oxidative stress,cell death,protein unfolding,transcription regulation,DNA binding and cell cycle.In addition,2 KEGG pathways were significant.At the 6 + 4 h time point,32 GO terms were identified as significant with oxidative stress being the only relevant toxicological endpoint.In addition,only one KEGG pathway was significant.

Overall for MSC,the DAVID analyses confirmed many of the significant pathways identified by IPA including steroid biosynthesis,tRNA aminoacylation,inflammation and apoptosis.In addition,the analyses highlighted transcription regulation,DNA binding and unfolded protein response as also significant.For TSC,the DAVID analyses confirmed the significance of IPA pathways related to oxidative stress and cell cycle.As with the MSC,the DAVID analyses also further highlighted the importance of transcription regulation,DNA binding and unfolded protein response,as well as cell death.Transcription regulation and DNA binding were significant terms common to both MSC and TSC at the 6 h time point,whereas no common terms existed for the two condensates at the 6 + 4 h time point.In our previous genotoxicity study we showed that MSC and TSC were both cytotoxic and genotoxic.However,quantitatively,MSC was more cytotoxic and mutagenic than TSC,and TSC appeared to induce chromosomal damage in a concentration-dependent manner whereas MSC did not.Our earlier chemical analyses of MSC and TSC noted that aside from the nicotine in tobacco and the cannabinoids in marijuana,the two smoke condensates contained mixtures of chemicals that were qualitatively similar though quantitatively different.The similarities in the chemical profiles and some of the toxicity findings suggested that the two smoke condensates might elicit somewhat comparable gene expression profiles.Hierarchal clustering of all the MSC and TSC exposed samples in the present study supported this notion and samples clustered first by concentration as opposed to smoke type.In addition,analysis of the top ten greatest gene expression changes relative to control revealed that half of the genes were common to both marijuana and tobacco.A number of previous studies have examined gene expression changes in pulmonary cells following exposure to tobacco smoke.Generally,these studies have shown that tobacco smoke stimulates xenobiotic metabolism,and that metabolized smoke constituents contribute to DNA damage.Following early insult,DNA damage leads to disruptions in the cell cycle such as arrest at the G2 checkpoint to allow time for response.Cellular response can include DNA repair,mutation induction through faulty repair or lack of repair,and programmed cell death of heavily damaged cells.

The influence of the particle size distribution of the bioaggregates used has also been studied previously

The association between smoking and marijuana is often considered as an interaction effect for pregnancy complications, as the majority of women who use marijuana also smoke cigarettes. In fact, amongst women who used marijuana in the SCOPE cohort, 74% also smoked cigarettes. With a high concurrence rate, the independent effect of marijuana on pregnancy outcomes has generally been unrecognised and just considered to be subsidiary, partly due to the low availability of data on marijuana use compared to cigarette smoking for statistical analysis. However, our data from the SCOPE cohort, with 316 participants who were marijuana users, demonstrate that the association of marijuana use with SPTB is consistent across cigarette smokers and non-smokers. The consistent effect of marijuana use is also apparent when analysing the effect of the estimated number of episodes of marijuana use during pregnancy on the length of gestation. While there was a slight decrease in the predicted length of gestation amongst smokers, the trend for smokers and non-smokers was similar. In contrast, the predicted length of gestation for women who continued to use marijuana at 20 weeks’ gestation was significantly decreased compared to those who ceased earlier in gestation, regardless of smoking status. This is consistent with similar studies which showed that marijuana use is associated with a decreased length of gestation. Furthermore, apart from a cigarette smoking-marijuana interaction, it is also well recognised that cigarette smoking and illicit drug use are associated with low socio-economic status,vertical grow system along with a complex inter-relationship with obesity, where smoking cessation may also lead to obesity.

As described in many studies, the prevalence of cigarette smoking and obesity is higher amongst those who are socio-economically disadvantaged, and the incidence of SPTB is higher amongst women with lower income and lower educational status, which may indicate associations with other lifestyle risk factors. Furthermore, if there was no maternal marijuana exposure, with an estimated population attributable risk of 0.003 for marijuana use, the incidence of SPTB would be expected to decrease by 3 cases per 1000 pregnant women. With an overall rate of SPTB of 4.2% in this study, this represents an estimated 6.2% reduction in the incidence of SPTB in the population, i.e. about 3 out of 50 SPTB cases would be attributed to marijuana use. If we consider the Australian centre only, where any marijuana usage occurred in 11.6% of women compared to 3.6–4.5% in the other centres, the estimated PAR was 0.009 for marijuana use with an expected reduction of SPTB of 9 cases per 1000 pregnant women, and a 11.68% reduction in the incidence of SPTB in this centre if women did not use marijuana. That is, in the Australian study centre, almost 12% of SPTB could be attributable to maternal marijuana use.A major strength of this study was its large international multicentre prospective cohort with excellent follow-up and complete data available for this analysis. Women were recruited from a clearly defined population of nulliparous women, with meticulous data monitoring protocols to reduce data entry or transcription errors and ensure the quality of data. While there are other studies that have examined the effect of marijuana use on adverse pregnancy outcomes, interaction tests were not performed. Hence, with complete quality data available from this study, interactions between marijuana use and cigarette smoking status may be examined while also adjusting for potential confounders. It needs to be noted that the number of SPTB cases amongst women who reported marijuana use at 20 weeks’ gestation is small even in this large cohort. The use of self-reported marijuana use and cigarette smoking status may be a potential limitation, as it may be subject to participant recall bias. Furthermore, this study was undertaken in a nulliparous cohort so it may be the case that our findings apply only to nulliparous women.

Although medication for maternal asthma, thyroid disease, and PCOS were recorded, we found no evidence of association with pregnancy outcomes analysed in this study, therefore these were not included in the analysis. Further research is required to confirm these findings, and future studies should include appropriate corrections for the various important confounders.Bio-aggregate composites are formed from a mineral binder and bio-aggregate particles such as hemp, sun flower or rape stalk. The wet mixture can be cast or projection formed around a structural frame as an insulating infill with such walls exhibiting lower embodied energy than traditional alternatives. In addition composites of hemp and lime have been shown to offer a beneficial compromise between thermal conductivity and thermal inertia, enabling the passive moderation of building climate. Despite these advantages the application and utilisation of bio-aggregate composites remains low in construction due in part to the high variability of a bio-sourced product and in part to the conservative nature of the industry. A better understanding of the material’s performance, leading to control and optimisation of physical properties, is a necessary step in addressing these issues. As composite materials, alterations to the ratio and nature of the constituents are logical avenues of material development. The ratio of binder to aggregate and its influence on thermal conductivity and mechanical strength of hemp-lime have been studied extensively with unanimous agreement that an increase in the binder quantity increases the compressive strength, flexural strength and thermal conductivity. This is attributed to an increasing binder content tending the behaviour of the composite to that of the binder and several models for thermal conductivity and compressive strength have been proposed based broadly on this assessment. Mechanical properties and thermal conductivity have been modelled simplistically as a function of density, considered an indicator of binder content, and more recently, through multi-phase models that specifically accounts for the ratio of constituents.

While such models are logical, it should be noted that they assume an isotropic relationship in a material that is known to have an anisotropic structure and behaviour.While in all studies reviewed, particle size distribution has been shown to impact on the physical properties of materials, although there has been limited consensus between studies as to the relationship. It has been observed by some that a finer grade of particles provides an increase in mechanical strength and a smaller increase in thermal conductivity, attributable to a closer packing of the particles. Contrastingly, others found that a coarser grade of particles yielded better mechanical properties, attributed to a greater overlap of particle. A possible reason for the disagreement of these conclusions may be the small fluctuations in properties reported compared to relatively large natural variation. Alternatively it may also be argued that previous studies tend to express bio-aggregate grades simply as finer or coarser based on average length; other potentially significant factors such as the spread of the distribution or aspect ratio of particles may thus have been overlooked. Within the body of previous work it is noticeable that the effect of changing these variables is often only reported in one orientation but the observed relationships are assumed to apply globally. It is now known that the internal structure of the bio-aggregate composite hemp-lime is orientated as a result of the production method chosen and the elongated form of the particles. It has also been identified from a number of sources that the mechanical behaviour and thermal conductivity of bio-aggregate composites are anisotropic that may be attributed to the structure and presumed to apply in all cases where the bio-aggregates are elongated. It is therefore necessary to consider any influence of constituent variables within this context meaning it cannot be assumed that constituent variables have an isotropic effect. To the author’s knowledge it has not previously been ascertained if changing the binder concentration or the particle size distribution has a global or directionally dependant influence on physical properties.

This paper considers the thermal conductivity,cannabis grow equipment compressive strength and flexural strength of hemp-lime specimens produced with three ratios of hemp to binder and three distinct grades of hemp aggregate; the particle distribution of the hemp aggregate fully characterised in each instance by means of two dimensional imaging. In order to ascertain if any effects are directionally dependent, thermal and mechanical tests were conducted in two directions: parallel to the direction of casting force and perpendicular to it. A recently developed method for assessment of the internal structure of bio-aggregate composites was also used in each case to provide an insight into the internal topology and to help inform any conclusions drawn about the mechanisms involved.Five mixtures of hemp-lime were considered in the study covering a range of three distinct grades of hemp aggregate and three hemp to binder ratios.Hemp lime was chosen due to it being the most prominently assessed bio-aggregate composite within the literature and indeed industry. In order to minimise the total amount of material used, single sets of rectangular prism specimens were produced for all mechanical tests as well as the internal structure assessment.In all cases two sets of specimens were cast, one for testing parallel to the casting compaction and one perpendicular. The specimens were produced by first combining water and the binder in a revolving pan mixer to produce a uniform slurry. Once uniform, the hemp aggregate was added and further mixing conducted until a homogenous mixture was observed. The total mixing time was under 5 min in each case. The binder used throughout the study was a commercially available preformulated binder for use with bio-aggregates produced by Tradical. The hemp aggregate used was grown and processed in France and supplied by the producer in four grades 7, 8, 12 and 14. The three grades used for this study were 7 , 14 and 1:1 by mass mixture of 8 and 12. The rationale of mixing two of the manufactures’ grades to produce the medium grade was to ensure a wider distribution of particle sizes in this grade compared to the fine and coarse grades. The combined mixture was weighed out into the moulds prepared with release oil in 50 mm layers with light tamping between each layer. The amount of material weighed out in each case was predetermined in order to produce a similar compaction state across the specimens. In this study this was set at 45% densification of loose-state density, determined for each mix by weighing a set volume of un-compacted material placed carefully by hand,. The specimens were stored after production in a conditioned room at 20 C and 70% relative humidity, uncovered in the moulds for 6 days and uncovered out of the moulds thereafter.The three grades of aggregate used in this study: fine, medium and coarse were assessed for particle size distribution by a method of two dimensional image analysis developed by Picandet. This was selected over a simple sieving method in order to provide data about both particle length and width.

The analysis was conducted on a 20 g sample of each grade removed from a 20 kg bag by a process of quartering. Scanning was conducted by arranging a small amount of particles with their largest surface face down on the surface of a flatbed scanner by hand in order to segregate them. This was then scanned against a blue background at a resolution of 1200 dpi and the process repeated until the full 20 g was imaged. All image processing and measurements were conducted using the program ImageJ and the method used follows that described by Picandet and reported here in brief. In each case a colour threshold was applied to the image to produce a binary image of the hemp. The binary images were then enhanced using three iterations of an opening algorithm to remove noise and dust. Assessment of each image was conducted using the particle analysis tool that identifies the primary and secondary axis of each discrete binary object. This is done though equalising the particle’s second moments of area to that of an ellipse whose axes are then used to provide a measure of length and width. To produce a distribution comparable to a sieving analysis, an estimated volume for each particle is calculated based on the area of the particles and an assumption that average thickness is proportional to particle width.

The most common route of marijuana administration is inhalation via smoking

Marijuana has also been reported as a risk factor for stroke. Over 80 cases have been reported in which patients had strokes, with a higher prevalence of ischemic strokes, that were associated with either a recent increase, in the days leading up to the event, or chronic history of heavy marijuana use. They believed that the marked swings in blood pressure or the reversible cerebral vasoconstriction that resulted from marijuana use were likely mechanisms of stroke but admitted that no firm conclusions could be drawn without further studies.In addition, Lawson reported a similar belief that drug induced vasospasm was a plausible explanation for TIAs, but also with the caveat that due to the confounding medications/illicit substances being used in his patient, no direct association could be determined. Also of interest is marijuana use’s effect on other cardiovascular vessels. When cohort studies were performed comparing marijuana users with resultant limb arteritis to patients suffering from thromboangiitis obliterans, marijuana associated arteritis occurred in younger, usually male patients with a unilateral, lower limb as the common presentation.Due to the unfiltered nature of the marijuana cigarette compared to commercially available tobacco cigarettes,grow table the amount of carcinogens and irritants, like tar, that enter the upper airway is increased with approximately a three-fold increase in tar inhalation and one third more tar deposition in the respiratory tract.

More specifically, the tar produced from cannabis smoke contains greater concentration of benzanthracenes and benzopyrenes than tobacco smoke. In addition, as compared to smoking tobacco, there is a two-thirds greater puff volume, one-third greater depth of inhalation and a four-fold longer breath-holding time, all of which are common practices to try to maximize THC absorption, which is around 50% of cigarette content. These practices result in five times the amount of carboxyhemoglobin levels as compared to the typical tobacco smoker despite the presence of similar quantities of carbon monoxide from the incomplete combustion of the organic compounds found within each product. In reporting his case, Schwartz theorized that high temperatures in which marijuana burns compared to tobacco may increase the irritancy of marijuana to the mucous membranes. While the higher temperature is a possibility, the evidence of marijuana’s irritancy is well documented. In a cohort study comprised of 40 healthy patients, Roth et al. showed that cannabis smokers had significantly increased visual bronchitis index scores resulting from large airway epithelial damage, edema, and erythema. On mucosal biopsy, goblet cell hyperplasia with subsequent increase in secretions, loss of ciliated epithelium and squamous metaplasia were also present in 97% of smokers. They concluded that marijuana use is associated with airway inflammation that is similar to that of a tobacco smoker. A cross-sectional study on over 6000 patients, from 1988 to 1994, found an increased incidence of chronic bronchitis symptoms such as wheezing and productive cough occurring in patients 10 years younger, on average, than tobacco smokers. Case-control trials performed found similar findings with regards to increases in wheezing, shortness of breath, cough and phlegm as well as the similarities with tobacco use. Bryson also concluded based on his review of the literature, that the pulmonary complications in the chronic marijuana smoker are equivalent to those seen in the chronic tobacco smoker, while Wu et al. estimated that 3e4 cannabis cigarettes daily equates to about 20 tobacco cigarettes in terms of bronchial tissue damage.

Cannabis use has also been linked to a higher risk in cancers, possibly due to the increased carcinogens entering the airway. Similar to tobacco use, marijuana use plays a significant role in the development of lung cancer. In a case control study performed in New Zealand, young adults had an 8% increase in lung cancer risk for each joint year of cannabis smoking after adjusting for the cofounders, such as age, sex, ethnicity and family history. Berthiller et al. pooled data from a multitude of institutions across multiple countries, comprising of over 1200 patients, and reported an increased risk of lung cancer for every marijuana use. In addition, a 40 year cohort study with about 48,000 patients reported an increased risk of lung cancer in young men who had smoked marijuana more than 50 times. This study was limited however by the nature of patient self-reporting. Head and neck cancers have also been theorized to be at a higher risk similar to that of tobacco smoking. However, a pooled analysis performed by Berthiller et al. found that infrequent marijuana smoking did not confer a greater risk after adjusting for cofounders. The authors did note that due to the low prevalence of frequent smoking within the study population, that a moderately increased risk could not be ruled out. In another population based casecontrol study, there was an increased incidence of head and neck cancers in patients with a 30 joint-year history, yet the association did not exist when accounting for tobacco smoking suggesting the risk is greater with tobacco than marijuana.Marijuana’s prevalence is evident amongst all patient populations. In a cross sectional study conducted by Mills et al., the rate of marijuana use via patient self-reporting was found to be 14% amongst surgical patients in 2003. This led the authors to conclude that questions about illicit drug use should be a routine part of the preanesthetic assessment, especially in patients that the anesthesiologist finds hard to settle, due to anxiety or other psychologic manifestations, because of the potential anesthetic complications that may occur.

In a series of case reports, Guarisco presented three patients who suffered from significant respiratory distress due to isolated uvulitis, a disease of low incidence typically associated with infection or traumatic irritation from instruments used in the airway. Investigating further, all three patients were found to have inhaled large quantities of cannabis within six to twelve hours of the onset of symptoms leading to the conclusion of a possible correlation with inhaled irritants such as cannabis. Due to known cases of isolated uvulitis and the possible link with marijuana, the authors suggest that toxicology urine and blood studies for THC should be performed in cases where marijuana use is suspected but not confirmed by history taking. Multiple other cases have also been reported with similar findings. In a case series by Sloan, three adolescents suffered acute uvular inflammation post the heavy use of marijuana, having smoking at least three marijuana cigarettes, despite negative throat cultures. In 1971, a cohort study was performed in which a large quantity of marijuana, over 100 grams, was smoked over several months. Of the 31 subjects, almost half suffered from recurrent rhinopharyngitis as well as developed acute uvular edema after the heavy marijuana inhalation which lasted approximately 12e24 hours. These findings stress the importance in the maintenance of the airway during anesthesia following acute marijuana use due to the potential airway obstruction that may occur. In fact, in presenting a case of uvular edema and airway obstruction with cannabis inhalation 4 hours prior to surgery, Pertwee recommended that elective operations should be avoided altogether if a patient was recently exposed to cannabis smoke. This recommendation seems reasonable when taking into consideration the life-threatening bronchospasm leading to asphyxia, brain damage or death resulting from tracheal intubation in patients with obstructive airways. One proposed course of action has been the therapeutic use of steroids. In Guarisco’s study, he theorized that steroids should help inhaled irritant uvulitis. As steroids increase endotracheal permeability, decrease mucosal edema and stabilize lysosomalmembranes, thus decreasing the inflammatory response, the theory has scientific basis. In a prospective, randomized,4×8 grow table with wheels double-blind study, Silvanus et al. found that the addition of methylprednisolone to salbutamol in patients with a partially reversible airway obstruction helped in the diminution of the reflex bronchoconstriction that can result from tracheal intubation.

This led to Hawkins et al.’s recommendation that at the first signs of airway obstruction, dexamethasone should be used as the drug of choice, 1 mg/kg every 6e12 hours over the course of one to two days. This recommendation gained credence in the dramatic relief that dexamethasone provided in the post-traumatic cases. However, Mallat et al. concluded that although marijuana-induced uvular edema is a serious postoperative complication that has a potential for simple treatment, in the case of an elective surgical procedure with an acute history of cannabis exposure, surgery should be can celled as prophylactic treatment may not be effiffifficient. The complications of the airway are not limited to intubation however. The inhalation of toxic chemicals as well as smoke can cause laryngospasm by chemoreceptor stimulation. In addition, the inhalation of hot gasses can trigger laryngospasm via thermoreceptor stimulation, especially in the case of lowered sensory afferent neuron threshold potentials such as in light anesthesia. In line with this, White presented a case in which a known cannabis smoker suffered severe laryngospasm following extubation. As found within the reviews, multiple observations have been made showing cross tolerance between marijuana and barbiturates, opioids, prostaglandins, chlorpromazine and alcohol. In addition, animal studies have shown additive effects amongst them all except for alcohol. These drug interactions have led to further exploration of its reactions to other medication groups. As a result of fat sequestration and subsequent slow elimination from the tissues, cannabinoids may be present to interact with multiple anesthetic agents. In Symons’s case report, the patient required multiple boluses of propofol and two additional doses of midazolam to achieve appropriate sedation. In a prospective, randomized, single-blind study of 60 patients, chronic marijuana users required significantly increased doses of propofol to facilitate successful insertion of the laryngeal mask and thus suggesting that the increased doses, in chronic marijuana users, may be a requirement for appropriate loss of consciousness as well as jaw relaxation and airway reflex depression. The authors theorized that the variations in the level of delta9-THC can explain variations in propofol responses.

In a review written in the American Association of Nurse Anesthetists Journal, Dickerson reported the synergistic effects of cannabis to include: potentiation of nondepolarizing muscle relaxants, potentiation of norepinephrine, the augmentation of any drug causing respiratory or cardiac depression, as well as a more profound response to inhaled anesthetics sensitization of the myocardium to catecholamines due to the increased level of epinephrine. On the subject of muscle relaxants, THC depletes acetylcholine stores and exerts an anticholinergic effect and thus creates a potentiation of the nondepolarizing muscle relaxants. Areview by Hall et al. explored THC’s interaction with drugs affecting heart rate and arterial pressure and found that due to cannabis’s own cardiovascular effects , it may interact with medications such as beta-blockers, anticholinergics and cholinesterase inhibitors. Due to these potential autonomic reactions, as well as theoretical psychiatric complications, such as withdrawal effects and their interference with anesthetic induction or postoperative recovery, there has been a stress made to inquiring about drug history or avoiding elective operations altogether. Dickerson, in his review, recommended that, due to all potential effects and interactions, not only should an extensive history of drug use be elicited at the time of the preoperative assessment, including the frequency of use and time of last use, but that anesthesia should be avoided in any patient with cannabis use within the past 72 hours.This gained further credibility in a randomized, double-blind trial, in which an apparent drug interaction was observed in the patient population who underwent general anesthesia within 72 hours of marijuana use leading to a sustained postoperative tachycardia, a finding potentially due to an interaction between cannabinol metabolites and atropine administration during anesthesia.One of the most researched and known risk factor for perior postoperative complications, increased hospitals costs and resource usage is smoking, specifically tobacco smoke. In fact, the rates of perioperative respiratory events, such as reintubation, hypoventilation, hypoxemia, laryngospasm, bronchospasm, and aspiration, have a total incidence of 5.5% in smokers compared to 3.1% in nonsmokers, making these events 70% more prevalent with smoking. In addition, in a randomized controlled trial out of Denmark, orthopedic surgery patients who smoked were compared to those who underwent cessation counseling and nicotine replacement therapy. In the study, they found an overall complication rate of 18% compared to the 52% found in the smoking group, including a cardiac event rate of 0% compared to 10%.

Responses collected during the most recent interview were used for these analyses

The 13-items included: social, mellow, creative,top of the world, increased sex drive, energetic, dizzy, nauseous, drowsy, lazy, unable to concentrate, out of control, and guilty. Participants were asked “in the period shortly after you used did it make you feel…”? Responses were scored as present or absent and the item scores summed to make the positive and negative scales.To examine the dimensionality of the 13 subjective experiences examined for each substance, we conducted Mokken Scale Analysis using the statistical software STATA. Mokken scaling analysis extends traditional factor analysis by systematically hierarchically ordering items that are highly correlated. Mokken analysis provides a nonparametric, iterative scale-building technique that identifies the smallest set of internally consistent scales from a given item pool. This model assumes the presence of one or more latent traits that can be measured by subject responses to a set of items. MSA is probabilistic and hierarchical, meaning that the items can be ordered by a degree of “difficulty”;individuals who agree with a more difficultitem will tend to agree with less difficult items. Scales from MSA are formed by taking pairs of items with the highest correlation and including other items until there is no further improvement. Loevinger’s H coefficients, which indicate the fit of an item to the scale, are computed for each item within a scale and for the scale as a whole. H coefficients ranging between 0.3 and 0.4 indicate a weak scale, 0.4–0.5 a medium scale, and 0.5–0.9 a strong scale. In MSA, an item can remain “unscaled” because it could not be added to one of the alternative scales without weakening the scale’s homogeneity. Based on our previous analyses , we used the scaling derived from the CADD sample. Positive and negative scales were standardized by age, sex, vertical outdoor farming and clinical status with two groups. Pairwise correlations between the resulting two scales were then determined for alcohol, tobacco, and marijuana.

Two consistent subjective experience scales were revealed using MSA. The item guilty did not fit into either scale for any substance. The item out of control was dropped due to extremely low endorsement for tobacco and because this item fluctuated between the positive scale and the negative scale. For all three drugs the positive scale included: relaxed, sociable, creative, euphoric, energetic, and increased sex drive. Items included in the negative scale for all three drugs were: lazy, drowsy, unable to concentrate, dizzy, and nauseous.Table 2 provides the H-coefficients for the positive and negative scales for each of the three drugs with the items shown in their hierarchical ordering. For the positive subjective experiences H-coefficients for alcohol,tobacco, and marijuana were 0.45, 0.52, and 0.43, respectively. For the negative scale, the H-coefficients were 0.42, 0.52, and 0.54, respectively. Means and standard deviations for each subjective experience scale across all three drugs are shown in Table 3. Mean scores differed as a function of age, sex, and clinical status. For all but marijuana, younger subjects had significantly lower mean scores on both positive and negative scales. Males scored significantly higher for the positive scales across all drugs than females. Males also had a higher mean score for the alcohol negative scale and a lower mean score for the marijuana negative scale. Mean scores on the positive experiences to tobacco and negative experiences to marijuana scales were higher in our community sample than in our clinical sample. Mean scores were lower in our community sample than in our clinical sample for positive experiences to marijuana and negative experiences to alcohol scales.In the current report, we examined subjective experiences to three commonly used drugs of abuse among young adults from the general community and an area treatment program. In these data, we obtained results that supported previous observations indicating positive and negative subjective experiences for a particular drug were predictive of problem use of that same drug. We then extended this relationship in two ways. First, we obtained results that supported the notion that positive and negative experiences to one drug are similar to those experienced for another drug and second, that subjective experiences to a drug are predictive of the risk for problem use of other drugs.

We interpret these findings to suggest that subjective experiences may be a useful indicator of a common liability towards use and problem use of multiple substances. Following on our previous work on marijuana and subjective experiences , we used Mokken scaling to simultaneously examine whether subjective experiences to three drugs are associated with drug use outcomes. From these analyses we observed that the subjective experience scales for each of the three drugs were comparable to those found in previous studies despite using a different methodology. We observed differences in item means and hierarchical ordering of the items by substance suggesting that subjects are reporting drug specific subjective experiences. This interpretation is consistent with findings from laboratory based studies which have shown that subjects can differentiate between a placebo and a drug or between different drugs based on subjective experiences. As different combinations of alcohol, tobacco, and marijuana use are commonly reported in epidemiological studies, we investigated the relationship between subjective experiences to different drugs in poly-substance users. We observed that subjective experiences to one drug were significantly correlated with experiences to another drug, though the strength of the relationship varied for different drug combinations. The strongest relationships were between alcohol and marijuana, replicating two previous studies , and between alcohol and tobacco. These particular drug combinations target similar neuronal receptor systems and are reported to enhance the overall drug experience when taken together. Further, as subjective experiences are thought to reflect the underlying physiology of a drug’s actions , these cross-substance relationships may provide a closer approximation of a common risk factor suitable for molecular genetic investigation. In this sample of community and clinical subjects, subjective experiences for one drug were associated with outcomes related to a different drug.

Though our results replicate findings that relate positive experiences with greater use of other drugs, we also identified that negative experiences were predictive of abuse and dependence status of a different drug. In particular, negative effects of alcohol and marijuana were associated with misuse of these same drugs as well as tobacco. Although this may appear counter-intuitive, a possible explanation could be that subjects who needed greater amounts of a drug in order to feel its effects drove the observed association. Findings from laboratory-based drug discrimination studies suggest that some subjects are unable to differentiate between drug and placebo at a standard training dose. Differences between the two conditions could, however, be reported as non-discriminators were exposed to greater doses of a drug. Interestingly, those who were able to discriminate between non-exposure and exposure to a drug reported stronger positive and negative subjective experiences, often simultaneously , at greater doses. This underscores the importance of dose in determining individuals’ drug sensitivity as assessed by subjective experiences. The relationship between drug dose, the resulting subjective experiences, and problem drug use has also been examined using self-ratings to the effects of alcohol [SRE; 28]. The SRE primarily assesses negative experiences to alcohol such as dizziness and passing out as related to the dosing levels needed to feel the sedative effects of alcohol. Among adolescent and adult samples of both sexes and family-history positive studies of alcoholics , low levels of response, as measured by the SRE have been implicated as a risk factor for alcohol use disorders. This notion that some drinkers need to ingest greater amounts of alcohol to feel its sedative effects and that this effect is related to greater drinking quantities has been recently supported and extended to include the observation that this relationship is also relevant to those reporting lower levels of stimulant effects during the first five drinks. Our finding that negative alcohol experiences were predictive of problem alcohol use is consistent with this research, despite using a different questionnaire, and extends it to include the potential prediction of other drug use problem behaviors.

Findings from the current study should be considered in light of a number of limitations. First, subjective experiences were collected from participants who ranged between 11 and 30 years of age. Though scaling of the different experiences was consistent between younger and older subjects, the older subjects have typically had a longer use history of alcohol, tobacco, and marijuana. Second, subjective experiences were only collected from those who reported using alcohol and marijuana six or more times and daily use of tobacco for a month. Thus, we were not able to include experiences from those who had used only a few times. Third, we were not able to measure differences in dosage, quality of a drug, depth of inhalation, peer use and drug use setting some of which impact self-reported subjective experiences. Fourth, we were not able to establish the reference point from which people were making their ratings. This is due to the unclear phrasing of the stem questions that asks about experiences “shortly after using.” We cannot know whether subjects were reporting their initial experiences, experiences in the minutes or hours immediately following recent drug intake or the conglomeration of their drug experience, making causal inferences regarding the observed associations not possible. Lastly, the lower endorsement rates for the experiences of tobacco may be due to the dichotomous fashion of responses that limit the sensitivity to detect the milder effects. Further, there more stringent requirements for collecting subjective experiences to tobacco may have made it more difficult to detect significant relationships with subjective experiences to alcohol, tobacco,rolling grow table and their more problematic use behaviors.Despite the high co-morbidity between marijuana and nicotine use, only few studies have directly addressed the mechanisms that lead to their concurrent use. A recent review by Agrawal describes multiple etiologies that influence their comorbidity. This includes route of administration , cross drug adaptation, response to treatments, environmental effects and genetic factors. Others have also alluded to the “gateway drug” hypothesis whereby the use of one drug may potentiate the effects of the other. For example, in a longitudinal study in 14–15 year olds, marijuana use increased the likelihood of initiating nicotine use up to 8 times and developing nicotine dependence up to 3 times suggesting marijuana’s role as a gateway drug. This was further supported by findings showing that women who used marijuana were at 4.4 odds of later developing nicotine use and dependence. The same group also reported in 43,093 adults that nicotine smoking increased the risk for marijuana use and dependence up to 3 times. This latter finding suggests a bi-directional potentiating effect and indicates that more complex factors may drive combined use.

Although the animal literature has characterized the neural mechanisms that may underlie these potentiating effects, it is also possible that personality factors contribute to this phenomenon. Combined marijuana and nicotine use has been associated with differential effects on clinical diagnoses, cognitive and psychosocial problems, and outcomes. For example, Bonn-Miller and colleagues examined associations between negative emotions that discriminate marijuana-only users from co-morbid marijuana and nicotine users. They found that, in general, nicotine-only using individuals had significantly greater negative emotionality than marijuana users, co-morbid marijuana and nicotine users, and non-using controls. Earlier work by Degenhardt showed that while nicotine and marijuana use were both individually associated with increased rates of negative emotion, this relationship appeared to be driven by neuroticism in marijuana users. Taken together, these studies argue for different patterns of co-morbidity in nicotine and marijuana using populations. To date, however, distinctions in trait markers, such as personality factors, have not yet been addressed in this ubiquitous group of co-morbid users. These differences suggest the need for fine-tuning the ability to discriminate risk-profiles between these groups as they also relate to clinical treatment outcomes. Factors that contribute to risk profiles include personality traits that have been examined as putative markers for treatment outcomes. For example, in a prospective four-year study in 112 adults with chronic alcoholism, Krampe et al. determined that the presence of any personality disorder was associated with a decrease in four-year abstinence probability. Similarly, using the NEO Personality Inventory-Revised Betkowska-Korpala found that following treatment, abstinent patients have higher levels of agreeableness and conscientiousness than patients who relapsed within a year following the therapy. This suggests that personality profiles have high predictive values for SUD outcomes and should be considered during treatment programs.

The profile of the changing genes was comparable between tobacco and marijuana exposed cells

Exposure to tobacco smoke can also trigger an inflammatory response and induce oxidative stress through increased levels of reactive oxygen species. Persistent induction of these processes following repeated exposure contributes to loss of normal growth control mechanisms, which is a key step in cancer development. Our study supports many of these findings, with exposure to TSC inducing the expression of genes involved in xenobiotic metabolism , oxidative stress , and DNA damage response as evidenced by changes in the expression of genes involved in cell cycle arrest, protein unfolding,transcription regulation, and inflammation. These same pathways were also significantly affected following MSC exposure, indicating that, as expected, MSC impacts many of the same molecular processes and functions as TSC. Although the effects of the condensates were largely similar, dose–response analysis indicates that the MSC is substantially more potent than TSC, with BMDs that in many instances are an order of magnitude lower than those for TSC. In addition, the results also highlighted some differences in steroid biosynthesis , apoptosis and inflammation, which were more significantly affected following MSC exposure, and cell cycle , which was more affected following TSC exposure.IPA canonical pathways related to the metabolism of xenobiotics were significantly affected in both TSC and MSC exposed cells at both time points. These pathways included Xenobiotic Metabolism Signaling, Metabolism of Xenobiotics by CYP450,microgreen flood table and AHR Signaling. For both TSC and MSC, the number of genes that were significantly affected increased with increasing concentration and the greatest number of genes changing occurred at the 6 + 4 h time point.

Many of the genes that were differentially expressed in TSC exposed cells are among those that have been typically observed to be induced by cigarette smoke [e.g., Nqo1 , Esd , Hmox1 , Cyp1a1 and Cyp1b1. Moreover, the concentration response patterns support the assertion of initial metabolic responses , followed by responses to toxic insult and secondary metabolism. Similar concentration response trends were noted in our previous toxicogenomics analysis of three different TSCs. Although very few studies have been conducted with marijuana smoke, Roth et al. demonstrated the induction of cytochrome P450 genes following exposure of Hepa-1 cells to marijuana tar extracts. Furthermore, the authors showed that tar from marijuana cigarettes tends to be more effective than tar from tobacco at inducing Cyp1a1 gene expression. Since the cannabinoids present in marijuana are capable of acting through the aryl hydrocarbon receptor to induce cytochrome P450 enzymes , and Cyp1a1 is known to bioactivate procarcinogens such as PAHs , questions have been raised about the role of cannabinoids in augmenting the carcinogenic risk posed by marijuana smoke. The question becomes increasingly complex as the cannabinoids THC, CBD and CBN have also been shown to competitively inhibit Cyp1a1, potentially decreasing the production of carcinogens and curtailing negative consequences. In the present study, however, substantial differences in the expression profiles of cytochrome P450 genes between the two smoke types were not observed. The expression of Cyp1a1 following exposure to MSC was comparable to that following TSC exposure, and the micro-array results were supported by RT-PCR. One of the differences in the xenobiotic metabolism responses for the two condensate types is that Hsp90 and Rras2 were only upregulated following MSC exposure. Despite these findings, Hsp90 has been previously observed to be induced following cigarette smoke exposure , and mutations in genes from the Ras family are known to be associated with cigarette-induced cancers.The IPA Canonical Pathway most significantly affected by exposure to TSC was the NRF2-Mediated Oxidative Stress Response Pathway. In this pathway, the transcription factor Nrf2 is phosphorylated following exposure to reactive oxygen, and translocates to the nucleus where it binds to antioxidant response elements. It then activates the expression of detoxification and antioxidant genes that protect the cell against oxidative damage. Of the 192 genes in this pathway, 6–18 genes were perturbed by TSC at the various time points in a concentration dependent manner. The largest expression changes and number of genes were associated with the 6 h time point.

Nrf2-regulated antioxidant genes have been shown to play an important role in protection against the toxic effects of tobacco smoke. Iizuka et al. showed that neutrophilic lung inflammation was significantly enhanced in Nrf2-knockout mice following cigarette smoke exposure. In addition, emphysema was observed 8 and 16 weeks following cigarette smoke exposure in the knockout mice, whereas no pathological abnormalities were observed in wild-type mice. Similarly, Gebel et al. confirmed the protective nature of Nrf2 against the development of emphysema in cigarette smoke exposed wild type mice versus Nrf2 knockout mice, and further investigated the relationships between Nrf2 and inflammation and cell cycle arrest. Comandini et al. conducted a meta-analysis of eight genomic studies on the mechanisms of smoke-induced lung damage in healthy smokers, COPD smokers and non-smokers. They found the Nrf2-mediated oxidative stress response Pathway to be the most significantly altered pathway in healthy smokers compared to non-smokers. In contrast, the Nrf2 pathway was not significantly differentially expressed in COPD smokers, indicating that Nrf2-regulated genes play a key role in protecting against the toxic effects of TSC. The authors suggest that the response of Nrf2- regulated genes may potentially be used as a biomarker for COPD susceptibility. In the present study, we found that the NRF2-Mediated Oxidative Stress Response Pathway is also an important component of the toxicological response to MSC. IPA analyses identified it as one of the top five pathways for both time points and all concentrations of MSC, except for the lowest concentration at the 6 + 4 h time point. A comparison of the Nrf2 pathway at the 6 h time point for the highest exposure concentrations of TSC and MSC shows many similarities. The Nrf2 gene itself was up-regulated along with several basic leucine zipper family transcription factors such as Jun, Atf4, and Maff. In addition, several antioxidant and stress response proteins such as Nqo1, Prdx1, Hmox1, Sod, Txnrd1, Herpud1, Dnajb1/9 were up-regulated. Other studies have also noted that these genes are up-regulated following cigarette smoke exposure.

However, a notable difference between the two condensates studied here is that Gclc and Gclm, the rate limiting enzymes in glutathione synthesis, were significantly upregulated by TSC , but were not statistically significantly affected in MSC exposed cells. Furthermore Gsta genes were up-regulated in TSC and Gstm genes were down-regulated in MSC exposed cells. These findings were further confirmed by the significant up-regulation of the Glutathione Metabolism Pathway in tobacco exposed cells a tall times and concentrations and the significant down-regulation of this pathway in marijuana exposed cells, particularly at the high concentration at the 6 + 4 h time point. These results suggest that exposure to MSC elicits more severe oxidative stress than exposure to TSC. The relative difference between the two condensates to mount an antioxidant defense may account for the greater cytotoxicity of MSC observed here and in our earlier genotoxicity study, where it appeared that the acute toxicity of MSC prevented the manifestation of micro-nucleus induction. The assertion regarding the relative severity of oxidative stress induced by MSC and TSC is supported by published results from other studies. In a previous study, Sarafian et al. examined reactive oxygen species production and reduced glutathione levels as indicators of oxidative damage following exposure to marijuana smoke. They showed that exposure of human endothelial cells to marijuana smoke resulted in an 80% increase in ROS over control levels, and these levels were as much as three times higher than those resulting from tobacco smoke. Moreover, intracellular glutathione levels following marijuana exposure were lower than for tobacco, and were reduced by 81% relative to controls. The authors argued that the products produced by the pyrolysis of the cannabinoids were likely responsible for the oxidative damage. The same authors also conducted preliminary studies with cultured lung alveolar macrophages from non-smokers and marijuana smokers, and found that marijuana smokers had lower levels of GSH than non-smokers, suggesting a decrease in GSH dependent oxidative defenses in habitual marijuana smokers.

The Biosynthesis of Steroids Pathway was among the most significantly affected IPA Canonical Pathways for MSC exposed cells. This held true both when all of the significantly altered MSC genes were taken into account, and when only the genes unique to MSC were considered. The Biosynthesis of Steroids Pathway is a lipid metabolism pathway that controls the synthesis of cholesterol, which is an essential component of cell membranes and a precursor in the production of bile acids, steroid hormones,seedling grow rack and vitamin D. This pathway was significantly down-regulated for all concentrations of the MSC at both time points, and the number of genes that were significantly affected increased with increasing concentration. The greatest number of genes was affected at the 6 + 4 h time point, and these included Dhcr7, Fdft1, Fdps, Hmgcr, Idi1, Mvd, Mvk, Nqo1, Pmvk, Sc5dl, and Sqle. The majority ofthese genes are involved in the mevalonate and squalene synthesis portions of the pathway. Although no studies have been conducted to specifically investigate the effect of marijuana smoke on lipid metabolism and steroid biosynthesis, early investigations using rodent cells have shown that cannabinoids can affect lipid metabolism, and the effects include an increase in lipolysis in adipose tissue ,the inhibition of corticosteroidogenesis , and the reduced testosterone and progesterone production. The cannabinoid CBD has also been shown to affect cholesterol metabolism in human fibroblasts and aortic medial cells through the inhibition of cholesteryl ester formation. In the present study, HMG-CoA reductase , which is the rate-limiting enzyme for cholesterol synthesis, was notably down-regulated for the medium and high concentrations of MSC at both time points. Previous in vitro investigations with THC have shown that this cannabinoid reduces Hmgcr by 29% , whereas CBD had no effect on Hmgcr levels. When comparing TSC and MSC exposed cells, the Biosynthesis of Steroids Pathway was also significant for TSC, particularly for the 6 + 4 h time point.

However, only one to three genes were perturbed, depending on the concentration. These genes included Fdps, Ggps1, Nqo1, and Hmgcr. The LXR/RXR pathway, which is involved in the regulation of lipid metabolism and cholesterol to bile acid catabolism, was also significantly down-regulated at the 6 + 4 h time point in both MSC and TSC exposed cells. Of note in this pathway is Ldlr, which is the greatest down-regulated gene in MSC exposed cells. This gene was down-regulated 10 fold following the highest MSC exposure concentration but only 1.6 fold following the highest TSC exposure.Exposure to MSC but not TSC appears to have affected apoptosis pathways. Genes in the TWEAK Signaling, TNFR1 and TNFR2 Signaling Pathways were significantly up-regulated following exposure to MSC particularly at the 6 h time point. The up-regulation of these particular genes suggests that MSC inhibits apoptosis and may promote a TNF receptor mediated survival pathway.In a previous study, Sarafian et al. investigated the effects of marijuana smoke and tobacco smoke on apoptosis and necrosis in A549 lung tumor cells. They found that both tobacco and marijuana whole smoke inhibited Fasmediated apoptosis but promoted necrotic cell death. In addition, particulate phase smoke from marijuana was a more potent inhibitor of Fas-induced caspase-3 activity than tobacco. In a later study, the authors also noted the decreased expression of Bax and caspase-8 in human small airway epithelial cells exposed to THC, which they suggest could have accounted for the previously observed suppression in Fas-mediated apoptosis. Although apoptotic pathways were not significantly perturbed following TSC exposure in our present study, Sarafian et al. and other investigators of tobacco smoke effects have found this to be a commonly disrupted pathway. It is suspected that the gene expression fold change cutoff of 2 used in the present study likely prevented a number of apoptotic genes from being included in the analyses. Cursory analyses with a cutoff of 1.5 shows apoptotic pathways as being significant for TSC exposure as well. It is important to note that the marijuana used for this study was obtained from a contracted supplier that provides marijuana for therapeutic use in Canada. It is grown under strictly controlled and documented conditions. Although this study has only examined smoke condensate from a single lot of marijuana, the quality control measures would be expected to minimise differences between marijuana harvests.

Terpenes are usually classified by the number of isoprene units in the molecule

With the increase in production,advanced and standardized processing technologies,including drying,extraction and purification,are required to ensure the quality and safety of these products for food applications,as well as the processing efficiency and sustainability of hemp.Some terpenes,on the other hand,are considered generally regarded-as-safe substances,which are permitted to be added and have been used in foods.However,the incorporation of hemp terpenes in foods and preservation of terpenes during processing is still challenging,requiring further research.In recent years,many studies have been conducted to identify the functionalities and pharmaceutical values of hemp CBD and terpenes,as well as extraction technologies of CBD.However,there is currently not a comprehensive review that discusses the potential of hemp CBD and terpenes as future functional food ingredients and evaluates the available and potential processing technologies for hemp.Therefore,this article reviews the legal regulations,challenges in incorporating hemp CBD and terpenes in foods and potential solutions,as well as current research status and future prospects in processing technologies of hemp biomass.Through this review,we expect to draw a clearer image for food manufacturers and researchers on the potential of applying hemp CBD and terpenes as future functional food ingredients and provide information for standardizing and improving the processing technologies of hemp for efficient production of high quality and food-safe products.Future research needs are also identified in this article.In the hemp plant,cannabinoids mainly reside in the flowers and leaves.More specifically,they are primarily stored in the glandular and non-glandular epidermal appendages called trichomes,which are transparent glandular ‘hairs’ on the surface of inflorescence and leaves.

The cannabinoids are chemically bounded with the cell walls,secretory vesicles and fibrillar material in the secretory cavity of the disc cell.In this section,the physical properties and chemistry of CBD,cannabis growing system health benefits,potentials and associated challenges as future functional food ingredients are discussed.Chemically,cannabinoids are a type of molecules that contain terpenoids and alicyclic units.Currently,more than 120 types of cannabinoids have been found in hemp plants.Fig.3 shows the biosynthetic pathway of cannabinoids in hemp plant.The basic reaction in the cannabinoids synthesis involves the alkylation of the phenolic moiety of olivetolic acid with the terpenoid component of geranyl pyrophosphate ,which produces cannabigerolic acid ,the common precursor of all major cannabinoids in the hemp.CBGA can then convert into other cannabinoids such as tetrahydrocannabinolic acid ,cannabichromenic acid and cannabidiolic acid ,etc.,through the enzymatic catalytic reactions by THCA-synthase,CBCA-synthase and CBDA-synthase.It is worthy of mentioning that only the acidic cannabinoids exist naturally in hemp plants.According to their molecular structures,cannabinoids are non-polar,and thus have low solubility in aqueous solution.The boiling points of cannabinoids ranged from 157 °C to 220 °C,which is not volatile.However,CBD is thermally unstable and very sensitive to photolytic reaction and oxidation.The acidic form cannabinoids are not considered to be pharmacologically active since they do not affect the endocannabinoid system of human body in the same way as the neutral forms.Therefore,a decarboxylation process is usually needed to convert the CBDA to CBD,which involves the removal of a carboxyl group from the acidic molecule and the release of a CO2 under high temperature.The reaction mechanisms of the decarboxylation process are illustrated in Fig.3B.Recently,research has proven the functionalities of CBD,which include pain relief,reduction of anxiety/distress,nausea and promotion of relaxation.

In addition,since CBD is not psychoactive,it does not result in addictive effect as caused by THC.At present,there is an increasing prevalence of lifestyle induced chronic diseases,and consumers are pursuing healthier diets,seeking more functional foods reinforced with functional ingredients.Currently,the global health and wellness market is at $1.5 trillion,and is projected to increase annually at 5%–10%.In 2019,the global functional food market was $250 million,and was projected to $440 billion by 2022.Therefore,there is a high potential in this rising trend to add hemp CBD in foods or beverages as future functional food ingredients.However,there are several challenges that are limiting the development of CBD-containing foods,which involves legal regulations,consumer awareness,and technological deficiencies.Legal regulations and policies are one of the most important factors in directing the developments of markets and products.Currently,regulations on the hemp CBD varies country by country,and CBD is in the ‘grey zone’,of which the legality is not clearly defined.In the United States,the 2018 Farm Bill removed industrial hemp from the definition of marijuana,which allowed more research to be done on hemp.However,it is still prohibited in federal level to add CBD to any foods,beverages or nutrient supplements.FDA has not waived it from the illegal ingredients list due to safety concerns of the non-approved CBD products and the fact that CBD was first studied as a drug.In fact,in 2018,FDA approved the first and by far the only medicine containing CBD for the treatment of seizures associated with two rare and severe forms of epilepsy,Lennox-Gastaut syndrome and Dravet syndrome.Even though it is still not approved in federal level in the US,some food products are already in the markets in some states as they deregulated the CBD,such as tea,coffee and chocolate,etc..In Canada,cannabis is nationally legalized,but phyto-cannabinoids such as CBD is in the Prescription Drug List and cannot be legally sold in self-care natural health products or cosmetics.

Canadian Health Food Association has recently released a report,which emphasized the potential positive economic impacts of permitting CBD in NHPs,foods and beverages for the economic recovery.In Europe Union ,CBD was catalogued into ‘novel foods’ in January 2019,and the EU has required extensive testing and authorization of CBD products from food safety authorities.In addition,different countries have different standards in legalizing the THC level in the products.China was projected to be largest producer and consumer of hemp CBD,given the long cultivating traditional and production area,however,recently a national level regulation forbids any use of CBD in foods or cosmetics.The strict regulations have a significant impact on the development of the hemp industry,and the major food manufacturers are conservative in entering the CBD market.In fact,due to these strict regulations and the influence of pandemic on the global logistics,the hemp market and product development process have been significantly impacted.The hemp biomass and CBD are oversupplied in the market,and the price of CBD has hit the rock bottom in the first half of year 2021.The enthusiasm of farmers in cultivating hemp is cooling down.However,we envision that this ‘downturn’ could be temporary.With more research works done and more scientific evidence published proving the health benefits and safety of CBD,the regulations shall be more relaxed and standardized,which will be a strong booster for both the CBD-food market and in return benefit more related research to be conducted.In most cultures,the words ‘hemp’ and ‘cannabis’ are associated with ‘drugs’ and ‘illegal’,and thus are repelled.The word ‘CBD’ is still unfamiliar to most people in the world,not to mention its health benefits.Therefore,to promote the use of CBD as functional food ingredients,educating the consumers about the health benefits,safety,and its distinction from ‘drug’ is as important as the relaxing of legal regulations.At the same time,it is critical to find the right market position and target consumer groups.Currently,regular CBD consumers are buying CBD to obtain a functionality or health benefit,and usually taking it as a dietary supplement/medicine,which only represent a niche market.It is important to identify the types of foods that are compatible with CBD.Incorporating CBD into staple foods and beverages may potentially expand the consumer base,which is currently challenging and require more extensive research.The consumer needs for the CBD reinforced foods are another important factor to be considered in the product developments.For example,an afternoon pick-me-up ‘CBD-containing coffee’ or a sports drink need to be fast-responding,meanwhile it should not cause any adverse side effect to the human health.

Additionally,the food products need to be shelf-stable and maintain the activity of CBD under normal storage conditions,particularly given the fact that CBD is not a very stable substance.Besides the regulation and consumers aspects,there are currently some technological challenges that need to be resolved to add hemp CBD in foods and beverages.The types of products that can be reinforced with CBD are dependent on the physical and chemical properties of CBD.As discussed above,CBD is a highly non-polar molecule,meaning it has low aqueous solubility.Therefore,it is difficult to incorporate it into most aqueous-based food and beverage systems.Besides,recent studies have shown that the bio-accessibility of CBD is relatively poor in animal and human bodies,which may be due to the low cell penetration rate.In addition,CBD has relatively poor stability,which is affected by various factors such as temperature,humidity,pH,oxygen,light,and the solvent types,etc..Its instability suggests that CBD is vulnerable to deteriorate when it is inappropriately added to food systems or exposed under stress conditions.The oral ingestion of cannabinoids usually results in long lasting and slow effects,hydroponic rack system which is not desirable for the fast-responding needs,and is identified as an area of improvement.Currently,studies on the solubility and stability in various food and beverage systems are not well reported.The studies on the bioaccessbility of CBD in human body are also scarce.More extensive research in these aspects is urgently needed to address these challenges.The outcomes will provide scientific evidence to support the feasibility of adding CBD into foods and further prove their health benefits.Although the most of CBD-containing foods are considered illegal at present,the future can still be bright and optimistic.The 2018 Farm Bill of the U.S.opened the gate of industrial hemp to industries and researchers.Following that,more and more capital investments are putting into the hemp industry and scientific research.According to statistics,the global market size of hemp was $5.73 billion,and was expected to grow to $27.72 billion by 2028.This allows more universities and research institutions to conduct necessary research,which in return will be beneficial for the development of CBD-containing foods.Although current regulations prohibit the use of CBD as food ingredients,we envision that some regulations will ease up in the near future.This will depend on more scientific studies to be conducted and evidence that proves the health benefits and determines any side effects of CBD to human beings.In fact,United Nations has recently removed cannabis from its most rigid drug control list,the ‘Schedule IV of the 1961 Single Convention on Narcotic Drugs’,which was a huge win for the hemp industry.More organized and standardized regulations all over the world will also be helpful for the development of CBD-containing food products.In technological aspects,some studies have been conducted to improve the solubility,stability and bio-accessbility of CBD in medicine or food systems.Encapsulation,emulsification and microfluidization are being used to incorporate various bio-active compounds into food and beverage systems in the industry and offer potential solutions to the development of CBD-containing foods.

Micro-encapsulation is one possibility to improve the solubility and reduce the oxidative susceptibility of sensitive bio-active compounds,where the hydrophobic molecule is encapsulated and dispersed in aqueous phase.Feng et al.applied sesame oil as a delivery system for CBD in medicines and revealed that adding of medium-chain triglyceride improved the solubility of CBD and superior bio-availability.Lange and Schilderink found that micro-encapsulated CBD had higher CBD bio-accessibility compared to CBD-isolate without micro-encapsulation.Mozaffari et al.discovered that the CBD bio-accessbility was improved with the incorporation into a food system made of olive oil and baby food,which might be attributed to the improved efficiency of micelle forming from hydrolyzed lipids.Nanotechnology has already been applied in drug delivery systems and can be another promising solution.Durán-Lobato et al.developed cannabinoid-loaded lipid nanoparticles through solvent-emulsion evaporation and improved the stability of the products.With more relaxed regulations and more scientific research being conducted,it is envisioned that the technological challenges in the development of CBD edibles may be overcome in the future.Terpenes are another type of bio-active compounds and secondary metabolites found in hemp,which are gaining increasing interest in recent years.There are currently more than 120 terpenes already identified from hemp.The most distinct characteristic of terpenes is the smell,which depicts the unique aromatic characteristics of hemp plant and is used by the plant to repel and defense against herbivores,attract pollinators,and inhibit the microbial growth.Depending on the variety of hemp,the typical terpene contents in hemp range from 0.125% to 0.278% weight in leaves and 1.283% to 2.141% in the inflorescence on a dry basis.Although hemp is abundant in terpenes,it is not the only source.In fact,terpenes are found in lots of fruits,vegetables and herbs.Chemically,terpenes are hydrocarbons consisting of small isoprene units linked to one another to form chains.The biosynthetic pathway of terpenes is shown in Fig.4.Interestingly,terpenes and cannabinoids share a common precursor,which is the GPP,a 10-carbon molecule.As a result,the contents of terpenes and cannabinoids in the hemp are usually positively correlated.Monoterpenes are composed of two isoprenes such as pinene,limonene,myrcene etc..Sesquiterpenes consist of 3 isoprene units,such as humulene,farnesol and caryophyllene.More complex terpene molecules include triterpenes that are made of 6 isoprene units,and polyterpenes.As shown in Fig.4A,the monoterpenes and sesquiterpenes are the major terpene species found in the hemp.

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