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For decades, Cannabis sativa had been illegal to sell or consume around the world, including in the United States. However, in light of the recent 2018 Farm Bill and the legalization of hemp across the US, various cannabis preparations have flooded the market, making it essential to be able to quantitate the levels of the different acidic and neutral cannabinoids in C. sativa and to have a complete cannabinoid profile of the different chemovars of the cannabis plant. A GC-FID method was developed and validated for the analysis of 20 acidic and neutral cannabinoids as trimethylsilyl (TMS) derivatives. The analyzed cannabinoids include cannabidivarinic acid (CBDVA), cannabidiolic acid (CBDA), cannabinolic acid (CBNA), cannabielsoic acid (CBEA), cannabicyclolic acid (CBLA), cannabichromenic acid (CBCA), trans-Δ9-tetrahydrocannabivarinic acid (Δ9-THCVA), trans-Δ9-tetrahydrocannabinolic acid A (Δ9-THCAA), cannabigerolic acid (CBGA), cannabidiol (CBD), cannabicyclol (CBL), cannabidivarin (CBDV), trans-Δ9-tetrahydrocannabivarin (THCV), cannabichromene (CBC), trans-Δ8-tetrahydrocannabinol (Δ8-THC), trans-Δ9-tetrahydrocannabinol (Δ9-THC), cannabigerol (CBG), cannabinol (CBN), cannabicitran (CBT), and cannabielsoin (CBE). The method limit of detection (LOD) was as low as 0.1 µg/mL, while the limit of quantitation ranged from 0.25 µg/mL to 0.5 µg/mL. The precision (%RSD) was

Primaquine (PQ), a prototype 8-aminoquinoline (8-AQ) drug used to treat malaria, is rapidly metabolized into different inactive and active metabolites. Due to the hemolytic toxicity, the uses of PQ have been confined. To understand its overall metabolism and its relation to drug efficacy and toxicity, profiling of urine for the parent drug and its metabolites is important. The current study presents a convenient and rapid method for simultaneously quantifying primaquine (PQ) and its metabolites in human urine. A simple liquid-liquid extraction followed by chromatographic separation and quantification through ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed and validated to quantify PQ and its eleven metabolites in the urine of healthy human volunteers who received a single oral dose of PQ. The developed method separated fourteen analytes, including internal standards, within nine minutes of run time. The linearity of all analytes was suitable in the range of 1-500 ng/mL. The extraction recovery for all concentrations of analytes from urine was ranged from 90.1 to 112.9 %. The relative standard deviation for intra- and inter-day precision were 9.8 and 10.7 %, respectively. Along with PQ, its different metabolites were detected in urine. Primaquine-5,6-orthoquinone, the N-carbamoylglucuronide conjugate of PQ and carboxyprimaquine were the major metabolites found in urine. Significant enantiomeric differences in the urinary excretion profiles for PQ and metabolites were observed. This analytical method can be implemented in the pharmacokinetic analysis of PQ to explain its toxicity and clinical decision making.

This review examines the concentration of seven major cannabinoids, including Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), in illicit herbal cannabis products seized by the Drug Enforcement Administration (DEA) over the last 10 years in the United States. Cannabis samples received from DEA regional laboratories were analyzed by a validated gas chromatography with flame ionization detection method, and the results are given in the report. A total of 14,234 samples of herbal cannabis have been analyzed over the last 10 years (between January 1, 2009, and December 31, 2019). The number of samples received over the last 5 to 6 years has decreased dramatically owing to the legalization of marijuana for either medical or recreational purposes in many U.S. states. The results showed that the mean Δ9-THC concentration has increased over the last 10 years, from 9.75% in 2009 to 14.88% in 2018 and 13.88% in 2019. The mean Δ9-THC:CBD ratio rose substantially from 24.81 in 2009 to 103.48 in 2017. A decrease in THC:CBD ratio was recorded in the last 2 years, 54.39 in 2018 and 24.58 in 2019, indicating the trend in the production of more high-CBD-containing products. Our results showed an overall increase in potency of illicit cannabis, from approximately 10% in 2009 to approximately 14% in 2019. These results are in agreement with other potency monitoring programs in several European countries. There appears to be a recent trend of the inclusion of higher CBD levels containing chemovars in illicit cannabis.

[Extract] "The iCannToolkit is a first important step to systematically gather evidence regarding the health effects of contemporary medical and non-medical cannabis use—over time, among licit and illicit settings, cultures and age groups—in order to inform policy development and to raise awareness concerning cannabis use-related risks and benefits."

Fifty four domestically produced cannabis samples obtained from different USA states were quantitatively assayed by GC–FID to detect 22 active components: 15 terpenoids and 7 cannabinoids. The profiles of the selected compounds were used as inputs for samples grouping to their geographical origins and for building a geographical prediction model using Linear Discriminant Analysis. The proposed sample extraction and chromatographic separation was satisfactory to select 22 active ingredients with a wide analytical range between 5.0 and 1,000 µg/mL. Analysis of GC-profiles by Principle Component Analysis retained three significant variables for grouping job (Δ9-THC, CBN, and CBC) and the modest discrimination of samples based on their geographical origin was reported. PCA was able to separate many samples of Oregon and Vermont while a mixed classification was observed for the rest of samples. By using LDA as a supervised classification method, excellent separation of cannabis samples was attained leading to a classification of new samples not being included in the model. Using two principal components and LDA with GC–FID profiles correctly predict the geographical of 100% Washington cannabis, 86% of both Oregon and Vermont samples, and finally, 71% of Ohio samples.

Cannabidiol, a non-intoxicating phytocannabinoid, has potential therapeutic effects over a broad range of disorders. Recently, there has been increased interest in CBD, as several studies showed promising anticonvulsant efficacy with few side effects. In 2018, a CBD-based oral solution, Epidiolex®, was approved by the FDA to treat two severe forms of pediatric epilepsy, Dravet syndrome, and Lennox-Gastaut syndrome. Although only these two syndromes are recognized indications for CBD, it has been consumed in an unregulated fashion for a variety of indications including chronic pain, muscle stiffness, inflammation, anxiety, smoking cessation, and even cancer. While CBD legislation in the USA is confusing due to the differences in state and federal laws, CBD has proliferated in the US market in several forms such as CBD oil or capsules, hemp oil/extract, and also as an ingredient in several dietary supplements, syrups, teas, and creams. With the ever-increasing use of CBD and its widespread availability to the general public, it is important to examine and report on possible drug-drug interactions between CBD and other therapeutic agents as well as addictive substances such as alcohol and tobacco. A detailed literature search for CBD's possible interactions was conducted using online databases. As expected, CBD has been reported to interact with anti-epileptic drugs, antidepressants, opioid analgesics, and THC, but surprisingly, it interacts with several other common medications, e.g. acetaminophen, and substances including alcohol. This review provides a comprehensive list of interacting drugs. The possible mechanisms for these drug-drug interactions are presented in table format. Given the growing popularity of CBD as a medication and the dearth of available information on CBD drug-drug interactions, it is critical to be aware of current drug-drug interactions and it will be important to investigate the impact of CBD upon concomitant medication use in future randomized, controlled trials.

Eleven new quinoxaline derivatives were designed and synthesized as modified VEGFR-2 inhibitors of our previous work. The synthesized compounds were tested against three human cancer cell lines (HepG-2, MCF-7 and HCT-116). Compounds 11g, 11e and 11c were the most potent members against the tested cells. Compound 11g (IC50 = 4.50, 2.40, and 5.90 μM) was the most potent member compared to doxorubicin (IC50 = 8.29, 9.65, and 7.68 μM) and sorafenib (IC50 = 7.33, 9.41, and 7.23 μM) against HepG-2 and HCT-116, and MCF-7 cell lines, respectively. Compound 11e showed better anti-proliferative activities than doxorubicin and sorafenib with IC50 values of 5.34, 4.19, and 6.06 μM, against HepG-2 and HCT-116 and MCF-7 cell lines, respectively. In addition, the most active anti-proliferative derivatives 11c, 11e, 11f, and 11g were selected to evaluate their inhibitory activities against VEGFR-2. The tested compounds displayed good inhibitory activity with IC50 values ranging from 0.75 to 1.36 μM. Among them, compound 11g was the most active member with an IC50 value of 0.75 μM, compared to the reference drug; sorafenib (IC50 = 1.29 μM). Moreover, docking studies revealed that the synthesized compounds have good binding patterns against the prospective molecular target; VEGFR-2. In addition, in silico, ADMET and toxicity studies showed a high level of drug likeness for the synthesized compounds.

The use of Δ9-tetrahydrocannabinol (THC) and Δ9-tetrahydrocannabinol-valine-hemisuccinate (THC-VHS; NB1111) has recently been investigated in the management of intraocular pressure (IOP). The current study was undertaken to develop an optimized THC-VHS-loaded nanoemulsion formulation (NE; THC-VHS-NE) that could improve the drug load and duration of activity. THC-VHS-NE formulation was prepared by homogenization followed by ultrasonication. Sesame oil, Tween®80, and Poloxamer®188 were used as the oil, surfactant, and cosurfactant, respectively. Stability of the optimized THC-VHS-NE formulation was observed at 4 °C. The IOP lowering effect of the lead formulations, commercial timolol, and latanoprost ophthalmic solutions, as well as an emulsion in Tocrisolve™ (THC-VHS-TOC), was studied in New Zealand White rabbits following topical administration. The effect of surfactant concentration and sterilization process on IOP-lowering activity was also studied. THC-VHS-NE formulations (0.5, 1.0, and 2.0% w/v) showed dose dependent duration of action. The 1.0%w/v THC-VHS-NE formulation was selected for further evaluation because of its desirable physical and chemical characteristics. THC-VHS-NE formulation prepared with 2% w/v Tween®80 exhibited a higher drop in IOP than the 0.75 and 4.0% w/v of Tween®80 containing formulations. The IOP-lowering duration was, however, similar for the formulations with 0.75 and 2.0% Tween®80, while that with 4.0% Tween®80 was shorter. THC-VHS-NE formulation produced a greater drop in IOP (p

In this research, cannabis varieties represent 23 USA States were assayed by GC-FID to generate their complex chemical profiles informative for plants clustering. Results showed that 45 cannabinoids and terpenoids were quantified in all plant samples, where 8 cannabinoids and 18 terpenoids were identified. Among organics, Δ9-THC, CBN (cannabinoids) and Fenchol (terpenoid) not only showed the highest levels overall contents, but also were the most important compounds for cannabis clustering. Among States, Washington, Oregon, California and Hawaii have the highest cannabis content. GC-FID data were subjected to PCA and HCA to find (1) the variations among cannabis chemical profiles as a result of growing environment, (2) to reveal the compounds that were responsible for grouping cultivars between clusters and (3) finally, to facilitate the future profile prediction and States clustering of unknown cannabis based on the chemical profile. The 23 cannabis USA States were grouped into three clusters based on only Δ9-THC, CBN, C1 and Fenchol content. Cannabis classification based on GC-profile will meet the practical needs of cannabis applications in clinical research, industrial production, patients' self-production, and contribute to the standardization of commercially-available cannabis cultivars in USA.

Premise How genetic variation within a species affects phytochemical composition is a fundamental question in botany. The ratio of two specialized metabolites in Cannabis sativa, tetrahydrocannabinol (THC) and cannabidiol (CBD), can be grouped into three main classes (THC-type, CBD-type, and intermediate type). We tested a genetic model associating these three groups with functional and nonfunctional alleles of the cannabidiolic acid synthase gene (CBDAS). Methods We characterized cannabinoid content and assayed CBDAS genotypes of >300 feral C. sativa plants in Minnesota, United States. We performed a test cross to assess CBDAS inheritance. Twenty clinical cultivars obtained blindly from the National Institute on Drug Abuse and 12 Canadian-certified grain cultivars were also examined. Results Frequencies of CBD-type, intermediate-type, and THC-type feral plants were 0.88, 0.11, and 0.01, respectively. Although total cannabinoid content varied substantially, the three groupings were perfectly correlated with CBDAS genotypes. Genotype frequencies observed in the test cross were consistent with codominant Mendelian inheritance of the THC:CBD ratio. Despite significant mean differences in total cannabinoid content, CBDAS genotypes blindly predicted the THC:CBD ratio among clinical cultivars, and the same was true for industrial grain cultivars when plants exhibited >0.5% total cannabinoid content. Conclusions Our results extend the generality of the inheritance model for THC:CBD to diverse C. sativa accessions and demonstrate that CBDAS genotyping can predict the ratio in a variety of practical applications. Cannabinoid profiles and associated CBDAS segregation patterns suggest that feral C. sativa populations are potentially valuable experimental systems and sources of germplasm.

Background The lack of an agreed international minimum approach to measuring cannabis use hinders the integration of multidisciplinary evidence on the psychosocial, neurocognitive, clinical and public health consequences of cannabis use. Methods A group of 25 international expert cannabis researchers convened to discuss a multidisciplinary framework for minimum standards to measure cannabis use globally in diverse settings. Results The expert-based consensus agreed upon a three-layered hierarchical framework. Each layer - universal measures, detailed self-report and biological measures - reflected different research priorities and minimum standards, costs and ease of implementation. Additional work is needed to develop valid and precise assessments. Conclusions Consistent use of the proposed framework across research, public health, clinical practice and medical settings would facilitate harmonisation of international evidence on cannabis consumption, related harms and approaches to their mitigation.

Hemp products are readily available and are aggressively marketed for their health and medicinal benefits. Most consumers of these products are interested because of cannabidiol (CBD), which has taken the natural products industry by storm. The CBD and Δ9-tetrahydrocannabinol (Δ9-THC) concentrations in these products are often absent, and even where labeled, the accuracy of the label amounts is often questionable. In order to gain a better understanding of the CBD content, fifty hemp products were analyzed by gas chromatography coupled with mass spectrometry (GC-MS) for CBD, Δ9-THC, tetrahydrocannabinolic acid (Δ9-THCAA), and cannabidiolic acid (CBDA). Δ9-THCAA and CBDA are the natural precursors of Δ9-THC and CBD in the plant material. Decarboxylation to Δ9-THC and CBD is essential to get the total benefit of the neutral cannabinoids. Therefore, analysis for the neutral and acid cannabinoids is important to get a complete picture of the chemical profile of the products. The GC-MS method used for the analysis of these products was developed and validated. A 10-m × 0.18-mm DB-1 (0.4 μ film) column was used for the analysis. The majority of the hemp products were oils, one of the products was hemp butter, one was a concentrated hemp powder capsule, and another was a hemp extract capsule. Most of the products contained less than 0.1% CBD and less than 0.01% Δ9-THC. Three products contained 0.1–1% CBD, and 2 products contained 0.1–0.9% Δ9-THC. All of the samples appeared to be decarboxylated since the CBDA and Δ9-THCAA results were less than 0.001%. The developed method is simple, sensitive, and reproducible for the detection of Δ9-THC, Δ9-THCAA, CBD, and CBDA in CBD oil/hemp products.

Lotus corniculatus L. (Fabaceae) is widely grown in Egypt. It has a great history of folkloric medicinal uses. All fractions of aerial parts of L. corniculatus L. showed significant antioxidant and...

Different USA-origin cannabis samples were analyzed by GC-FID to quantify all possible cannabinoids and terpenoids prior to their clustering. Chromatographic analysis confirmed the presence of seve...

The current study aimed to determine the effect of inclusion of a mucoadhesive agent on the intensity and duration of intraocular pressure (IOP) lowering activity of Δ

Primaquine (PQ) is a racemic drug used in treatment of malaria for six decades. Recent studies suggest that the two enantiomers of PQ are differentially metabolized in animals, and this results in different pharmacological and toxicological profiles. The current study characterizes the pharmacokinetic (PK) properties, metabolism and tolerability of the individual enantiomers of PQ in healthy human volunteers with normal glucose-6-phosphate dehydrogenase (G6PD) activity. Two cohorts (at two dose levels), each with 18 subjects, participated in three study arms in a crossover fashion: a single dose of the (-)-R enantiomer (RPQ), a single dose of the (+)-S enantiomer (SPQ), and a single dose of racemic PQ (RSPQ). PQ and its key metabolites carboxyprimaquine (cPQ) and PQ-N-carbamoyl glucuronide (PQ-N-CG) were analyzed. Clear differences were observed in PK and metabolism of the two enantiomers. Relative PQ exposure was higher with SPQ as compared to RPQ. PQ maximum plasma concentration (C

Cryopreservation is the only method allowing the safe and cost-effective long-term conservation of important germplasm. Recent use of the cryo-plate system has proven beneficial in further simplifying the cryopreservation protocols.Developing an efficient protocol for the cryopreservation of axillary buds of Cannabis sativa elite cultivars (MX and V1-20) by the V-cryoplate droplet-vitrification technique.Stem segments (~5 cm in length) with mature axillary buds collected from indoor-grown plants were surface sterilized and then either precultured on MS basal medium with 0.1 M sucrose (1The survival and regrowth rates of cryopreserved axillary buds of cultivar MX following this two-step preculture were 45% and 42% respectively, while those of cultivar V1-20 were 47% and 44% respectively. A direct preculture of axillary buds (2The resulting plants after cryopreservation appeared normal without any callus formation or morphogenetic variation. On maturity, mother plants and re-grown cryopreserved plants were comparable in terms of Δ

Purpose: Cannabidiol (CBD), active component of plant Cannabis sativa, has anti-inflammatory properties that could potentially help treat diabetic retinopathy-induced pain and inflammation...

Cannabis sativa L. (marijuana or hemp) is recognized worldwide for its psychoactive properties as well as for fiber production. This study focused on the evaluation of 3 droplet vitrification protocols for long-term conservation of shoot tips in liquid nitrogen (LN). Shoot tips (∼0.5 mm) were excised from 3- to 4-week-old in vitro-grown shoots of 3 cultivars (MX, VI-20, and B-5: high tetrahydrocannabinol [THC], high cannabidiol [CBD], and intermediate THC∼CBD, respectively) and pretreated on 5% dimethyl sulfoxide agar plates for 48 h. The shoot tips were then vitrified in LN using 3 separate cryoprotectant (plant vitrification solutions [PVS] #2, #3, and #4) droplets on an aluminum cryoplate. There was no significant difference between the regrowth of cryopreserved shoot tips exposed to PVS2 for 15 and 20 min, but regrowth of all 3 cultivars significantly declined after 20 min of exposure. Exposure duration of 15 min was adapted for subsequent experiments. Regrowth of cryopreserved MX was significantly higher with PVS2 (63%) than with PVS3 and PVS4 (≤5%). Regrowth of cryopreserved VI-20 was highest with PVS2 (57%) and significantly higher than with PVS3 and PVS4 (≤25%). The regrowth of cryopreserved shoot tips of B-5 was significantly different between all 3 protocols with PVS2 > PVS4 > PVS3. Both PVS2 and PVS4 produced regrowth above 55%, while regrowth with PVS3 was significantly lower (31%). These results indicate that 15–20 min of exposure to PVS2 are most suitable for cryopreservation of these varieties. This is the first report on protocol development for the cryopreservation of organized tissues of C. sativa L. for germplasm conservation.

Through the potency monitoring program at the University of Mississippi supported by National Institute on Drug Abuse (NIDA), a total of 18108 samples of cannabis preparations have been analyzed over the last decade, using a validated GC/FID method. The samples are classified as sinsemilla, marijuana, ditchweed, hashish, and hash oil (now referred to as cannabis concentrate). The number of samples received over the last 5 years has decreased dramatically due to the legalization of marijuana either for medical or for recreational purposes in many US states. The results showed that the mean Δ9-THC concentration has increased dramatically over the last 10 years, from 8.9% in 2008 to 17.1% in 2017. The mean Δ9-THC:CBD ratio also rose substantially from 23 in 2008 to 104 in 2017. There was also marked increase in the proportion of hash oil samples (concentrates) seized (0.5-4.7%) and their mean Δ9-THC concentration (6.7-55.7%) from 2008 to 2017. Other potency monitoring programs are also present in several European countries such as The Netherlands, United Kingdom, France, and Italy. These programs have also documented increases in Δ9-THC concentrations and Δ9-THC:CBD ratios in cannabis. These trends in the last decade suggest that cannabis is becoming an increasingly harmful product in the USA and Europe.

The chemical study of Cannabis sativa roots led to the isolation and identification of 10 compounds. Their chemical structures were unambiguously established on the basis of 1D and 2D NMR spectroscopy and mass spectrometry as friedelan-3-one (1), epifriedelanol (2), β-sitosterol (3), ergost-5-en-3-ol (4), methyl hexadecanoate (5), pentadecanoic acid (6), 10E-hexadecenoic acid (7), 4-hydroxy-3-methoxybenzaldehyde (8), β-sitosterol-β-D-glucoside (9) and p-coumaroyltyramine (10). Compounds 5–9 were reported for the first time from C. sativa roots. All the isolated compounds were tested for their antimicrobial activity. Compound 4 showed modest activity against Cryptococcus neoformans with an IC50 value of 13.7 μg/mL, while compound 10 displayed potent activity against Escherichia coli with an IC50 value of 0.8 μg/mL. A high-performance liquid chromatography method was developed and validated for the detection and quantification of p-coumaroyltyramine (10) in the extracts of different varieties of C. sativa roots.

Purpose: To isolate new antimicrobial agents from the leaves of Markhamia platycalyx (Baker) Sprague and assess their phytochemical characteristics and antimicrobial activity. Methods: Different chromatographic and spectroscopic techniques (NMR and ESI-MS) were applied for the identification of antimicrobial compounds. Agar-well diffusion technique was used for determination of antimicrobial activity. Anti-HCV effects were investigated using VITROS Anti-HCV assay. Results: Eighteen compounds were isolated for the first time from this genus. These were phytol, noctacosanoic acid (OCTA), tormentic acid and β-sitosterol-3-O-(6'-O-heptadecanoyl)-β-Dglucopyranoside. The other compounds were β-sitosterol, ursolic acid (URSA), oleanolic acids, pomolic acid (POMA), 2-epi-tormentic and β-sitosterol-3-O-β-D-glucopyranoside. However, stigmasterol and acteoside, which were seen in previous studies, were also present. Total ethanol extract (TEE) was the most effective against Escherichia coli, with the lowest minimum inhibitory concentration (MIC) of 1.0 μg/mL. Acteoside, URSA and 2-epi-tormentic acid showed the highest antibacterial effect on Pseudomonas aeruginosa while 2-epi-tormentic acid and acteoside produced the least MIC on Candida glabrata. These effects were superior to those produced by standard antibiotics. However, 2-epitormentic acid and β-sitosterol-3-O-β-D-glucopyranoside had no anti-HCV effects. Conclusion: Due to the good antimicrobial properties of Markhamia platycalyx, it is a potential source of new antimicrobial drugs.