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In vivo solid-phase microextraction (SPME) is a minimally invasive, non-exhaustive sample-preparation technique that facilitates the direct isolation of low molecular weight compounds from biological matrices in living systems. This technique is especially useful for the analysis of phytocannabinoids (PCs) in plant material, both for forensic purposes and for monitoring the PC content in growing Cannabis spp. plants. In contrast to traditional extraction techniques, in vivo SPME enables continuous tracking of the changes in the level of PCs during plant growth without the need for plant material collection. In this study, in vivo SPME utilizing biocompatible C18 probes and liquid-chromatography coupled to quadrupole time-of flight mass spectrometry (LC-Q-TOF-MS) is proposed as a novel strategy for the extraction and analysis of the acidic forms of five PCs in growing medicinal cannabis plants. The SPME method was optimized by testing various parameters, including the extraction phase (coating), extraction and desorption times, and the extraction temperature. The proposed method was validated with satisfactory analytical performance regarding linearity (10–3000 ng/mL), limits of quantification, and precision (relative standard deviations below 5.5 %). The proposed method was then successfully applied for the isolation of five acidic forms of PCs, which are main components of growing medicinal cannabis plants. As a proof-of-concept, SPME probes were statically inserted into the inflorescences of two varieties of Cannabis spp. plants (i.e., CBD-dominant and Δ9-THC-dominant) cultivated under controlled conditions for 30 min extraction of tetrahydrocannabinolic acid (Δ9-THCA), cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), cannabiviarinic acid (CBVA), and tetrahydrocannabivarinic acid (THCVA). The results confirmed that the developed SPME-LC-Q-TOF-MS method is a precise and efficient tool that enables direct and rapid isolation and analysis of PCs under in vivo conditions. The proposed methodology is highly appealing option for monitoring the metabolic pathways and compositions of multiple PCs in medicinal cannabis at different stages of plant growth. [Display omitted] • An analytical method to determine phytocannabinoids in Cannabis spp. is presented. • In vivo SPME allows direct isolation of acidic forms of phytocannabinoids from growing plants. • Precise tool for analysis of the composition of phytocannabinoids in in vivo conditions. • SPME-LC-Q-TOF-MS protocol for resolution and analysis of acidic forms of phytocannabinoids. • Monitoring of multiple phytocannabinoids at different stages of medicinal cannabis plant growth. [ABSTRACT FROM AUTHOR]

Conventional cannabis drying is time-consuming and energy intensive. A quick and dependable drying of cannabis is essential to ensure high-quality products to meet increasing demands. This study explored a combined microwave and infrared (MI) drying on cannabis comparing with control environmental (CE) drying. MI was very efficient with a short drying time of 16–200 min, high moisture diffusivity of 7.95×10−09-8.70×10−08 m2/s, and low energy consumption of 390.49–1611.42 kJ. The Page and Modified Page drying models fitted well to describe and predict the MI drying characteristics of cannabis. Microstructural images identified shrinkage in glandular trichomes of cannabis, whereas colorimetric assessment resulted in alteration of color attributes due to MI drying. It also facilitated the conversion of acidic cannabinoids to their neutral forms by decreasing tetrahydrocannabinolic acid (THCA) in g/g of dry matter from 20.15% to 7.57% and increasing tetrahydrocannabinol (THC) from 6.31% to 16.65% that insignificantly (p ≥0.05) affected the total THC level. MI drying resulted in a total terpenes concentration (%g/g of dry matters) of 0.541–0.730, insignificantly lower than CE drying (0.768). Overall, the study highlights MI as a rapid and energy-efficient drying for obtaining high quality cannabis, particularly for medicinal applications. [Display omitted] • The effects of microwave-infrared drying on medicinal cannabis were investigated. • Microwave-infrared drying was quite faster and saved 95.54–98.92% energy. • Scanning electron microscopy shows shrinkage and damage of cannabis trichomes. • Tetrahydrocannabinol content increased from 6.31% to 16.65%. • Total terpenes of dried samples were statistically similar but lower than fresh. [ABSTRACT FROM AUTHOR]

Objective: To describe marijuana's clinical role for urologic symptoms.Methods: Studies related to marijuana, voiding dysfunction, lower urinary tract symptoms (LUTS), and pain through January 2019 from PubMed were evaluated for relevance and quality.Results: Forty-eight studies were reviewed. Cannabinoids have mixed efficacy for neurogenic LUTS and little evidence for non-neurogenic LUTS, chronic non-cancer-related and perioperative pain. For cancer-related pain, high-level studies demonstrate cannabinoids are well-tolerated with unclear benefit.Conclusion: Cannabinoids appear well-tolerated in the short-term, but their efficacy and long-term impact is unproven and unknown in urologic discomfort. Cannabinoids for urologic symptoms should be further explored with well-designed randomized controlled trials. [ABSTRACT FROM AUTHOR]

Analysis of cannabis has gained new importance worldwide, mainly for quality control within the legalized recreational and medical cannabis industry, but also for forensic differentiation between drug-type cannabis and legal products such as fiber hemp and CBD-rich/THC-poor cannabis. We herein present an HPLC-DAD method for quantitative analysis of major neutral and acidic cannabinoids in herbal cannabis and hashish: Δ9-tetrahydrocannabinol (THC), Δ9-tetrahydrocannabinolic acid A (THCA), cannabidiol (CBD), cannabidiolic acid (CBDA), and cannabinol (CBN). Plant material was dried, homogenized and extracted with a mixture of methanol/hexane. Chromatographic separation of the analytes was achieved on a core-shell C8 column using gradient elution with water/acetonitrile containing 0.1% formic acid. The analytical run time was 13 min and analytes were detected at 210 nm. The method is selective, sensitive, accurate, and precise, as confirmed through validation according to ICH and AOAC guidelines. Linearity in herbal cannabis ranged from 0.04 to 4.00% for the neutral cannabinoids, and from 0.40 to 20% for the acids. Linear ranges in hashish samples were 0.13-13.33% and 1.33-66.66%, respectively. The presented method was successfully applied to characterize 110 cannabis samples seized by the Swiss police, demonstrating its applicability for routine cannabis potency testing in the forensic setting. [ABSTRACT FROM AUTHOR]

Background: The agreement between self-reported cannabis abstinence with urine cannabinoid concentrations in a clinical trials setting is not well characterized. We assessed the agreement between various cannabinoid cutoffs and self-reported abstinence across three clinical trials, one including contingency management for abstinence.Methods: Three cannabis cessation clinical trials where participants reported use and provided weekly urine samples for cannabis and creatinine concentration measurements were included. Bootstrapped data were assessed for agreement between self-reported 7+ day abstinence and urine cannabinoid tests using generalized linear mixed effects models for clustered binary outcomes. One study implemented contingency management for cannabis abstinence. Four hundred and seventy-three participants with 3787 valid urine specimens were included. Urine was analyzed for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol and creatinine using immunoassay methods Biological cutoffs of 50, 100, and 200 ng/ml, as well as changes in CN normalized THCCOOH (25%/50% decrease), were assessed for agreement with self-reported abstinence during the three clinical trials.Results: Agreement between measured THCCOOH and self-reported abstinence increases with increasing cutoff concentrations, while the agreement with self-reported non-abstinence decreases with increasing cutoff concentrations. Combining THCCOOH cutoffs with recent changes in CN-THCCOOH provides a better agreement in those self-reporting abstinence. Participants in the studies that received CM for abstinence had a lower agreement between self-reported abstinence and returned to use than those in studies that did not have a contingency management component.Conclusion: Using combinations of biological measurements and self-reported abstinence, confirmation of study related abstinence may be verifiable earlier and with greater accuracy than relying on a single measurement. [ABSTRACT FROM AUTHOR]

Medicinal and recreational Cannabis sativa is a sector that has exploded in popularity both in academia and industry due to the relaxation in legislation concerning the controlled substance. This business is currently valued at $37 billion in annual sales. As cultivation of cannabis increases, waste from this sector will increase, providing a challenge, with legislative constraints of Δ9-tetrahydrocannabinol, and opportunity in sustainable management of this waste. Research into the waste management of cannabis production waste is vital as sustainability of waste management is a pressing issue and will provide opportunities for businesses to make use of said waste. This paper will use databases such as Scopus, Web of Science and Google scholar to identify literature to review related to cannabis waste and cannabis waste management systems. It has been discovered that the majority of plant biomass waste is generated during the cultivation period, with growing media being a large contributor to waste generated. Currently there are four methods for appropriate cannabis waste management, that are landfilling, composting, incineration and anaerobic digestion. Although there is this current information available further research is required to determine the most efficient method of disposal and pre-treatments, or novel approaches, to improving valorisation of this waste. • Waste streams from medicinal cannabis manufacturing are discussed. • Legislative cannabis challenges grant valorisation opportunities. • Cannabis management include incineration, composting and anaerobic digestion. • Hydrothermal processing cannabis waste has valorisation potential. • Limited literature in cannabis waste management requires development. [ABSTRACT FROM AUTHOR]

Traffic policies show growing concerns about driving under the influence of cannabis, since cannabinoids are one of the most frequently encountered psychoactive substances in the blood of drivers who are drug-impaired and/or involved in accidents, and in the context of a legalization of medical marijuana and of recreational use. The neurobiological mechanisms underlying the effects of cannabis on safe driving remain poorly understood. In order to better understand its acute and long-term effects on psychomotor functions involved in the short term ability and long-term fitness to drive, experimental research has been conducted based on laboratory, simulator or on-road studies, as well as on structural and functional brain imaging. Results presented in this review show a cannabis-induced impairment of actual driving performance by increasing lane weaving and mean distance headway to the preceding vehicle. Acute and long-term dose-dependent impairments of specific cognitive functions and psychomotor abilities were also noted, extending beyond a few weeks after the cessation of use. Some discrepancies found between these studies could be explained by factors such as history of cannabis use, routes of administration, dose ranges, or study designs (e.g. treatment blinding). Moreover, use of both alcohol and cannabis has been shown to lead to greater odds of making an error than use of either alcohol or cannabis alone. Although the correlation between blood or oral fluid concentrations and psychoactive effects of THC needs a better understanding, blood sampling has been shown to be the most effective way to evaluate the level of impairment of drivers under the influence of cannabis. The blood tests have also shown to be useful to highlight a chronic use of cannabis that suggests an addiction and therefore a long-term unfitness to drive. Besides blood, hair and repeated urine analyses are useful to confirm abstinence. [ABSTRACT FROM AUTHOR]

Cannabis sativa L. is used to treat a wide variety of medical conditions, in light of its beneficial pharmacological properties of its cannabinoids and terpenes. At present, the quantitative chemical analysis of these active compounds is achieved through the use of laborious, expensive, and time-consuming technologies, such as high-pressure liquid-chromatography- photodiode arrays, mass spectrometer detectors (HPLC-PDA or MS), or gas chromatography-mass spectroscopy (GC-MS). Hence, we aimed to develop a simple, accurate, fast, and cheap technique for the quantification of major cannabinoids and terpenes using Fourier transform near infra-red spectroscopy (FT-NIRS). FT-NIRS was coupled with multivariate classification and regression models, namely partial least square-discriminant analysis (PLS-DA) and partial least squares regression (PLS-R) models. The PLS-DA model yielded an absolute major class separation (high-THC, high-CBD, hybrid, and high-CBG) and perfect class prediction. Using only three latent variables (LVs), the cross-validation and prediction model errors indicated a low probability of over-fitting the data. In addition, the PLS-DA model enabled the classification of chemovars with genetic-chemical similarities. The classification of high-THCA chemovars was more sensitive and more specific than the classifications of the remaining chemovars. The prediction of cannabinoid and terpene concentrations by PLS-R yielded 11 robust models with high predictive capabilities (R 2 CV and R 2 pred > 0.8, RPD >2.5 and RPIQ >3, RMSECV/RMSEC ratio <1.2) and additional 15 models whose performance was acceptable for initial screening purposes (R 2 CV > 0.7 and R 2 pred < 0.8, RPD >2 and RPIQ <3, 1.2 < RMSECV/RMSEC ratio <2). Our results confirm that there is sufficient information in the FT-NIRS to develop cannabinoid and terpene prediction models and major-cultivar classification models. Dried and homogenously ground cannabis inflorescence samples were directly analyzed using NIR spectrometer and then extracted with ethanol for the determination of cannabinoids and terpenes using HPLC-PDA and GC-MS, respectively. Finally, NIR spectra and the chemical composition of the samples were used to build PLS-R and PLS-DA models. [Display omitted] • FT-NIR based PLS-R model enables accurate quantification of cannabinoid and terpene. • FT-NIR based PLS-DA model enables accurate classification of cannabis chemovars. • FT-NIR has been proven as a promising fast alternative to chromatographic analysis. [ABSTRACT FROM AUTHOR]

Unlabelled: Since 2013 in the Italian market has been introduced the Nabiximols, a drug containing two of the main active cannabinoids: Δ(9)-tetrahydrocannabinol (Δ(9)-THC) and cannabidiol (CBD). This drug has been approved in Italy in the treatment of Multiple Sclerosis (MS). It is an oral spray formulation and each puff of 100μl contains 2.7mg of Δ(9)-THC and 2.5mg of CBD. In the present study we analyzed urine and blood samples collected from a group of 20 patients treated with Nabiximols in order to evaluate: blood Δ(9)-THC concentrations in relation to the dose administered and the duration of treatment and the potentiality of this medication to be used for drug habit.Methods: The study was conducted on a sample group of patients affected by MS, of both sexes, age: 49-61 years, treated with Nabiximols for short (28 days) or long-term. The results of our study allow affirming that it is unlikely to use this medication for drug habit or to sale it in the black market because of the low blood concentrations available and of its high costs. These statements were confirmed by: (a) the low Δ(9)-THC concentrations in the pharmaceutical formulation; (b) the low blood concentrations produced by Nabiximols administration, more than 10 times smaller than the blood concentrations known to produce psychotropic effects; (c) the presence of CBD (Δ(9)-THC natural antagonist); (d) the route of administration (inhaled, not smoked). [ABSTRACT FROM AUTHOR]

Introduction Individuals report using cannabis for the promotion of sleep, and the effects of cannabis on sleep may vary by cannabis species. Little research has documented preferences for particular cannabis types or cannabinoid concentrations as a function of use for sleep disturbances. Methods 163 adults purchasing medical cannabis for a physical or mental health condition at a cannabis dispensary were recruited. They provided self-report of (a) whether cannabis use was intended to help with sleep problems (e.g. insomnia, nightmares), (b) sleep quality (PSQI), (c) cannabis use (including preferred type), and (d) symptoms of DSM-5 cannabis dependence. Results 81 participants reported using cannabis for the management of insomnia and 14 participants reported using cannabis to reduce nightmares. Individuals using cannabis to manage nightmares preferred sativa to indica strains (Fisher's exact test (2) = 6.83, p < 0.05), and sativa users were less likely to endorse DSM-5 cannabis dependence compared with those who preferred indica strains (χ 2 (2) = 4.09, p < 0.05). Individuals with current insomnia ( t (9) = 3.30, p < 0.01) and greater sleep latency ( F (3,6) = 46.7, p < 0.001) were more likely to report using strains of cannabis with significantly higher concentrations of CBD. Individuals who reported at least weekly use of hypnotic medications used cannabis with lower THC concentrations compared to those who used sleep medications less frequently than weekly ( t (17) = 2.40, p < 0.05). Conclusions Associations between sleep characteristics and the type of cannabis used were observed in this convenience sample of individuals using cannabis for the management of sleep disturbances. Controlled prospective studies are needed to better characterize the impact that specific components of cannabis have on sleep. [ABSTRACT FROM AUTHOR]

Cannabis is used to treat various medical conditions, and lines are commonly classified according to their total concentrations of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Based on their ratio of total THC to total CBD, cannabis cultivars are commonly classified into high-THC, high-CBD, and hybrid classes. While cultivars from the same class have similar compositions of major cannabinoids, their levels of other cannabinoids and their terpene compositions may differ substantially. Therefore, a more comprehensive and accurate classification of medicinal cannabis cultivars, based on a large number of cannabinoids and terpenes is needed. For this purpose, three different chemometric-based classification models were constructed using three sets of chemical profiles. We examined those models to determine which provides the most accurate "chemovar" classification. This was done by analyzing profiles of cannabinoids, terpenes, and the combination of these substances using the partial least square-discriminant analysis multivariate (PLS-DA) technique. The chemical profiles were selected from the three major classes of medicinal cannabis that are most commonly prescribed to patients in Israel: high-THC, high-cannabigerol (CBG), and hybrid. We studied the correlations between cannabinoids and terpenes to identify major bio-indicators representing the plant's terpene and cannabinoid content. All three PLS-DA models provided highly accurate classifications, utilizing six to nine latent variables with an overall accuracy ranging from 2 to 11% CV. The PLS-DA model applied to the combined cannabinoid-and-terpene profile did the best job of differentiating between the chemovars in terms of misclassification error, sensitivity, specificity, and accuracy. The combined cannabinoid-and-terpene PLS-DA profile had cross-validation and prediction misclassification errors of 4% and 0%, respectively. This is the first study to demonstrate the highly accurate classification of samples of medicinal cannabis based on their cannabinoid and terpene profiles, as compared to cannabinoid profiles alone. Furthermore, our correlation analysis indicated that 11 cannabinoids and terpenes might serve as bio-indicators for 32 different active compounds. These findings suggest that the use of multivariate statistics could assist in breeding studies and serve as a tool for minimizing the mislabeling of cannabis inflorescences. [Display omitted] • Classification of major cannabis classes was good for all data sets. • Terpene-cannabinoid–based PLS-DA provided the best chemovar classification. • Eleven potential bio-indicators predicted 32 cannabinoids and terpenes. [ABSTRACT FROM AUTHOR]

Cannabis cultivation for medical purposes in Brazil has been increased in the last years. While cannabis crops are prohibited, hundreds patients have been granted with judicial authorizations and there is little information about the cultivation conditions, yields and chemical profiles of the plants. Cannabis plants contain hundreds of compounds, with cannabinoids and terpenes the main drivers of their toxicological and pharmacological properties. Besides the cannabinoids, terpene contents are useful for the chemotaxonomic classification of different varieties, and their role in forensic analyses should be further delineated. The present study monitored cannabis crops of fifteen participants who were granted special licenses by the Brazilian Courts in Rio de Janeiro and São Paulo. The cultivation conditions were monitored and five cannabinoids (tetrahydrocannabinol acid-THCA, tetrahydrocannabinol-THC, cannabidiolic acid-CBDA, cannabidiol-CBD and cannabinol-CBN) and nineteen terpenes were quantified in cannabis flowers. The total grow cycle of thirty-five cannabis plants ranged from 10 to 24 weeks. The dry flower yields ranged 22-90 g per plant. Most cannabis specimens were CBD-rich varieties (CBD levels from 1.6% to 16.7%, and THC levels from 0.0% to 2.6%, n = 22) used to treat epileptic patients. The THC-rich varieties contained CBD levels ranging from 0.03% to 0.8%, and THC levels from 0.7% to 20.1%, n = 11. Fewer of the samples contained THC:CBD ratios of approximately 1:1 (CBD levels of 3.3-3.8% and THC levels of 2.2-3.7%, n = 2). The most abundant terpenes in the cannabis flowers were beta-caryophyllene, alpha-humulene, guaiol and alpha-bisabolol. CBD-rich varieties showed significant higher levels of beta-caryophyllene and alpha-humulene in comparison with THC-rich varieties. Overall, the study herein provides data concerning medical cannabis crops grown in a region of Brazil that not only guide individual medical cannabis cultivation methods but also aid forensic analyses. [ABSTRACT FROM AUTHOR]

Cannabis (Cannabis sativa L.) for medical purposes has been legalized again in many countries in recent years. Currently, only two major cannabinoids (Δ9-THC and CBD) are considered in the legislation and medication, which is not sufficient in case of dried plant material or resulting extract. Other substances (mainly terpenes/terpenoids), or their specific combinations, could influence the resulting therapeutic effect for specific oncology diagnosis and specific patients. Six different genotypes (Conspiracy Kush, Jilly Bean, Jack Cleaner 2, Jack Skellington, Nordle and Nurse Jackie) were cultivated indoor at the Czech University of Life Sciences Prague. Ethanol extracts taken from the inflorescences were assayed for their content of main cannabinoids and terpenes/terpenoids. The extracts were used for in vitro cytotoxicity studies on hepatocarcinoma human cell lines Hep-G2 and colorectal carcinoma human cell lines Caco-2 and Ht-29. Healthy lung fibroblast MRC-5 and healthy intestinal cells FHs 74 Int were used to compare selectivity of cytotoxicity. The average content of Δ9-THC in extracts was 59.1 ± 2.43%, and of CBD 1.84 ± 0.17%. The content of main cannabinoids in the Nurse Jackie genotype extract was significantly greater than that of the other genotypes. Overall, more than 60 different terpenes/terpenoids were identified in the extracts. The major terpenes/terpenoids detected in most genotypes were limonene, linalool, α-terpineol, β-caryophyllene, trans -α-bergamotene, α-humulene, β-caryophyllene oxide, guaiol, γ-eudesmol, β-eudesmol and α-bisabolol. Differences in the terpene composition of individual genotypes were caused by minor terpenoids, such as β-ocimene, isopulegol acetate, β-elemene, β-selinene and spathulenol. All extracts were highly cytotoxic to Ht-29 colorectal carcinoma cells and showed positive selectivity compared to healthy FHs 74 Int colon cells. The Jack Cleaner 2 extract was cytotoxic to all cell lines tested at the lowest concentrations (8.48 ± 2.4–16.14 ± 0,07 μg/mL), but was positively selective only for colorectal cancer cells, especially Ht-29 and to a lesser extent for Caco-2. Similarly, the Nordle extract showed positive selectivity for Ht-29 and Caco-2 only. Jilly Bean was unique in this study, in that its extract functioned on all cell lines at the highest concentrations (20.13 ± 3.05–49.88 ± 1.5 μg/mL), whilst also being highly positively selective in all carcinoma lines (Ht-29, Caco-2 and Hep-G2 hepatocarcinoma) compared to healthy cell lines (FHs 74 Int and MRC-5). The results suggest that Δ9-THC and CBD are responsible for the in vitro cytotoxicity of the extracts, but observed differences in selectivity reveal their synergies with other substances. According to chemical analysis, higher concentrations of myrcene, β-elemene, β-selinene and α-bisabolol oxide found in the Jilly Bean genotype may positively affect the selectivity of cytotoxic activity. It is therefore vital that similar studies are performed on other cell lines, in order to be able to recommend these cannabis genotypes for preclinical and clinical studies, which are still lacking. • Two major cannabinoids and more than 60 terpenes/terpenoids have been identified in extracts. • Composition of cannabis extracts modifies cytotoxicity on various human cell lines. • All tested extracts were selectively cytotoxic to colorectal cancer cells Ht-29. • One of the six extracts tested was selectively cytotoxic for all cancer lines tested. [ABSTRACT FROM AUTHOR]

Abstract: Cannabis products (marijuana, hashish, cannabis oil) are the most frequently abused illegal substances worldwide. Delta-9-tetrahydrocannabinol (THC) is the main psychoactive component of Cannabis sativa plant, whereas cannabidiol (CBD) and cannabinol (CBN) are other major but no psychoactive constituents. Many studies have already been carried out on these compounds and chemical research was encouraged due to the legal implications concerning the misuse of marijuana. The aim of this study was to determine THC, CBD and CBN in a significant number of cannabis samples of Albanian origin, where cannabis is the most frequently used drug of abuse, in order to evaluate and classify them according to their cannabinoid composition. A GC–MS method was used, in order to assay cannabinoid content of hemp samples harvested at different maturation degree levels during the summer months and grown in different areas of Albania. This method can also be used for the determination of plant phenotype, the evaluation of psychoactive potency and the control of material quality. The highest cannabinoid concentrations were found in the flowers of cannabis. The THC concentrations in different locations of Albania ranged from 1.07 to 12.13%. The influence of environmental conditions on cannabinoid content is discussed. The cannabinoid content of cannabis plants were used for their profiling, and it was used for their classification, according to their geographical origin. The determined concentrations justify the fact that Albania is an area where cannabis is extensively cultivated for illegal purposes. [Copyright &y& Elsevier]

Abstract: In the last 15years there has been a major shift in the laws governing medical use of cannabis in the United States. Corresponding with this change there has been escalating interest in the role that cannabis, commonly referred to as marijuana, and cannabinoids play in the care of patients with cancer. This review will examine cannabis’ and cannabinoids’ current and potential roles in cancer care. Specifically, we will examine five areas of cannabis medicine: (1) pharmacologic properties of cannabis; (2) its potential role in the development of human cancers, particularly smoking-related malignancies; (3) cannabinoids’ potential as anti-cancer therapies; (4) cannabis and cannabinoids in the palliation of common cancer-associated symptoms; (5) current legal status of cannabis for medical purposes in the United States. [Copyright &y& Elsevier]

• Plant architectural modulation increases cannabinoid standardization. • Standardization increases by elevation of concentrations at the lower part of the plant. • Decarboxylation of the cannabinoids in-planta is not affected by structural modulation. • The effect of architecture modulation on cannabinoid standardization is genotype specific. • The spatial uniformity of cannabinoids in the plant is cannabinoid and genotype specific. A major challenge in utilizing cannabis (Cannabis sativa L.) for modern medicine is the lack of standardization throughout the plant of cannabinoids, the unique therapeutic secondary metabolites in cannabis. The present study focused on the interplay between plant architecture modulation and standardization of the secondary metabolite profile in medical cannabis plants. Secondary metabolism is considerably affected by endogenous and exogenous factors, including positional-developmental aspects and microclimate. We hypothesized that manipulation of the plant architecture, which alter morphological and reproductive development, as well as micro-climate in the shoot will impact secondary metabolism and spatial standardization of the cannabinoids. Eight plant architecture-modulation treatments were evaluated for effects on in-planta concentrations and standardization of the cannabinoids, and on the morpho-physiological state of the plants. Two medical-cannabis genotypes of 'drug-type' medical cannabis were analyzed to evaluate genotypic sensitivity. The results reveal that plant architecture modulation can increase standardization of the cannabinoid profile in cannabis, thereby supporting the hypothesis. The architectural modulating treatments increased uniformity of cannabinoid concentrations in the plant by increasing concentrations at the lower parts of the plant. The cannabinoid profile was most affected by treatments that had the largest impact on plant structure such as the removal of primary and secondary branches. Decarboxylation of the cannabinoids in-planta was not affected by structural modulation. The spatial uniformity of cannabinoid concentrations throughout the cannabis plant is cannabinoid and genotype specific, and the effect of architecture modulation on cannabinoid standardization is genotype specific. [ABSTRACT FROM AUTHOR]

As the frequency of cannabis-based therapy increases, the ability to distinguish intake of cannabis-based medicines from recreational cannabis use becomes desirable. Minor cannabinoids have been suggested to indicate recreational cannabis use in biological matrices but are unreliable when presumably also present in directly plantderived medicines. Thus, for therapeutics such as medical cannabis, Sativex® and Dronabinol, a more thorough investigation of cannabinoid profiles is required to identify possible distinguishing markers. In this study, 16 phytocannabinoids were quantified in samples of seized and medical cannabis, Sativex® and Dronabinol from two different manufacturers, using a validated LC-MS/MS method. Analytes included delta-9- tetrahydrocannabinol, tetrahydocannabinolic acid A, cannabidiol, cannabidiolic acid, cannabigerol, cannabigerolic acid, cannabinol, cannabinolic acid, cannabichromene, cannabichromenic acid, cannabicyclol, cannabicyclolic acid, tetrahydrocannabivarin, tetrahydrocannabivarinic acid, cannabidivarin and cannabidivarinic acid. Resultant cannabinoid profiles were compared, and markers were suggested. Characteristics of Sativex® included a specific cannabidiol/tetrahydrocannabinol ratio and presence of cannabichromene, while acidic cannabinoids, cannabigerol and cannabinol occurred in only low amounts. As expected, the predominant ingredient in Dronabinol was tetrahydrocannabinol, but minor cannabinoids were quantified as well. Medical marihuana and seized cannabis were compared separately in a principal component analysis. Several medical marihuana varieties were found to significantly differ from seized cannabis, mostly regarding contents of tetrahydocannabinolic acid A and tetrahydrocannabivarinic acid and cannabidiolic and cannabidivarinic acid respectively. [ABSTRACT FROM AUTHOR]

• Sensitivity analyses reveal a wide optimum range for P under short photoperiod. • Functional physiology and ionome profiling reveal genotypic variability in P sensitivity. • The threshold for optimal performance at the vegetative growth phase is about 30 mg L−1 P. • Excess P inhibits in-planta translocation of P and Mg. Phosphorus (P) is an essential macronutrient required for many central metabolic processes, and is therefore a major factor governing plant development, structure and function. Cannabis is a short-day plant that its' development progression involves a vegetative growth phase under long photoperiod, followed by a reproductive phase under a short photoperiod. The reproductive inflorescence yield potential in cannabis is therefore largely dependent on the morphology and physiological condition of the plants at the vegetative phase. Due to legal restrictions, there is lack of science-based knowledge about cannabis plant science, including mineral nutrition. The present study therefore focused on P nutrition of plants at the vegetative growth phase under long photoperiod. The plants were cultivated in pots in a controlled environment and subjected to 5 levels of P (5, 15, 30, 60, 90 mg L−1). We investigated impact on the ionome, physiological and morphological traits, uptake of nutrients into the plant, translocation to the shoot, and distribution in the plant organs for 2 medicinal cannabis genotypes. Plant biomass production, photosynthesis rate, stomatal conductance, transpiration rate and intercellular CO 2 at the vegetative growth phase exceled under 30 mg L−1 P supply. Uptake and translocation of nutrients from root to the shoot was highly influenced by the P treatment. Under excess P supply, most of the plant P accumulated in the roots, and translocation to the shoot was inhibited. Uptake of Mg into the plants, and its' translocation to the shoot was inhibited by P deficiency in both cultivars, and was enhanced by increased P supply. Calcium uptake was increased by P application but translocation to the shoot was inhibited. Zinc retention in roots under P deficiency was found in both varieties. Our results suggest a wide optimum range for P in medicinal cannabis at the vegetative growth stage, with a minimum requirement of 15 mg L−1 P and a recommended application of 30 mg L−1. The functional physiology and ionome profiling revealed genotypic variability in P sensitivity. [ABSTRACT FROM AUTHOR]

Context: Prior Phase 2/3 studies found that cannabinoids might provide adjunctive analgesia in advanced cancer patients with uncontrolled pain.Objectives: To assess adjunctive nabiximols (Sativex®), an extract of Cannabis sativa containing two potentially therapeutic cannabinoids (Δ9-tetrahydrocannabinol [27 mg/mL] and cannabidiol [25 mg/mL]), in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy.Methods: Phase 3, double-blind, randomized, placebo-controlled trial in patients with advanced cancer and average pain Numerical Rating Scale scores ≥4 and ≤8 despite optimized opioid therapy. Patients randomized to nabiximols (n = 199) or placebo (n = 198) self-titrated study medications over a two-week period, followed by a three-week treatment period at the titrated dose.Results: Median percent improvements in average pain Numerical Rating Scale score from baseline to end of treatment in the nabiximols and placebo groups were 10.7% vs. 4.5% (P = 0.0854) in the intention-to-treat population (primary variable) and 15.5% vs. 6.3% (P = 0.0378) in the per-protocol population. Nabiximols was statistically superior to placebo on two of three quality-of-life instruments at Week 3 and on all three at Week 5. In exploratory post hoc analyses, U.S. patients, but not patients from the rest of the world, experienced significant benefits from nabiximols on multiple secondary endpoints. Possible contributing factors to differences in nabiximols efficacy include: 1) the U.S. participants received lower doses of opioids at baseline than the rest of the world and 2) the subgroups had different distribution of cancer pain types, which may have been related to differences in pathophysiology of pain. The safety profile of nabiximols was consistent with earlier studies.Conclusions: Although not superior to placebo on the primary efficacy endpoint, nabiximols had benefits on multiple secondary endpoints, particularly in the U.S.Patients: Nabiximols might have utility in patients with advanced cancer who receive a lower opioid dose, such as individuals with early intolerance to opioid therapy. [ABSTRACT FROM AUTHOR]