Cannabidiol (CBD) is the main component of plant Cannabis (Cannabis sativa), which exhibits strong antioxidant and anti-inflammatory activities. With the legalization of CBD in the United States, it is an inevitable tendency for its global legalization in the future. Therefore, it has become an urgent task to conduct the toxicological evaluation of CBD before clinical application. In this study, the developmental toxicities of CBD on zebrafish embryos were systematically evaluated, and the mechanisms were revealed. The results showed that the phenotype of liver degeneration was observed in 96 hpf zebrafish embryos after 0.1-5 μmol/L CBD exposure, further RT-qPCR experiments indicated that the above result may attributed by the the alterations of FABP10A, GCLC, and GSR. Besides, 1 and 5 μmol/L CBD contributed to the developmental toxicities of heart and eye in zebrafish embryos, characterizing by the decrease in heart rate, the phenotype of pericardial edema, and the reduce of eye area. Compared to other organs, the liver of zebrafish displayed the most sensitive characteristic to CBD exposure, as 0.1 μmol/L CBD already led to the phenotype of liver degeneration. In summary, this paper provided theoretical supports for CBD toxicology research, and laid the foundation for its future clinical application.

Cannabis sativa, otherwise known as hemp, is discussed to highlight the various problems and prospects associated with its use as an herbal ingredient. The chemical composition of hemp, with classification based on cannabinoid contents, its biological activities, current global scenarios and legality issues, economic importance, and future prospects, are discussed.

This study delves into the transformative effects of supercritical carbon dioxide (scCO2) cannabis extracts and prebiotic substances (dextran, inulin, trehalose) on gut bacteria, coupled with a focus on neuroprotection. Extracts derived from the Białobrzeska variety of Cannabis sativa, utilising supercritical fluid extraction (SFE), resulted in notable cannabinoid concentrations (cannabidiol (CBD): 6.675 ± 0.166; tetrahydrocannabinol (THC): 0.180 ± 0.006; cannabigerol (CBG): 0.434 ± 0.014; cannabichromene (CBC): 0.490 ± 0.017; cannabinol (CBN): 1.696 ± 0.047 mg/gD). The assessment encompassed antioxidant activity via four in vitro assays and neuroprotective effects against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The extract boasting the highest cannabinoid content exhibited remarkable antioxidant potential and significant inhibitory activity against both enzymes. Further investigation into prebiotic deliveries revealed their proficiency in fostering the growth of beneficial gut bacteria while maintaining antioxidant and neuroprotective functionalities. This study sheds light on the active compounds present in the Białobrzeska variety, showcasing their therapeutic potential within prebiotic systems. Notably, the antioxidant, neuroprotective, and prebiotic properties observed underscore the promising therapeutic applications of these extracts. The results offer valuable insights for potential interventions in antioxidant, neuroprotective, and prebiotic domains. In addition, subsequent analyses of cannabinoid concentrations post-cultivation revealed nuanced changes, emphasising the need for further exploration into the dynamic interactions between cannabinoids and the gut microbiota.

OBJECTIVE: Cannabis sativa L. is renowned for its medicinal and recreational uses. With the increasing global legalization of C. sativa L.-based products for medicinal purposes, there is a growing need for well-characterized products. While the stability of cannabinoids such as tetrahydrocannabinol and cannabidiol is well understood, information on the chemical and enantiomeric stability of terpenes remains scarce. This is despite the fact that terpenes are also thought to have pharmacological activity and may contribute to the overall effect of C. sativa L.
METHODS: To address these challenges, four analytical methods based on chiral, polar, and apolar gas chromatographic separation combined with either MS or FID detection were developed and validated. These methods successfully separated and quantified a total of 29 terpenes, including 13 enantiomers and 5 diastereomers specific to C. sativa L. Furthermore, terpenes and authentic C. sativa L. flowers and extracts were subjected to UV and heat treatments to observe potential degradation reactions over time.
RESULTS: Each terpene generates a unique pattern of degradation products resulting in a diverse array of oxidation and cyclization products. P-cymene was identified as a major product of terpene aging. Notably, no enantiomeric conversion was detected, suggesting that the formation of (-)-α-pinene in cannabis extracts, for example, originates from other terpenes.
CONCLUSIONS: Terpenes have different degradation rates, even though they are structurally similar. In addition, cultivar- and growth-condition-specific enantiomeric ratios were observed in C. sativa L., confirming that enantiomer production is species-specific and has to be considered for therapeutical applications.

Lectin receptor-like kinase(LecRLK) is a class of phytokinase with lectin conserved domain, which plays an important role in plant resistance to biological and abiotic stresses, as well as plant growth and development. Cannabis sativa is an important multi-purpose plant, widely used in food, textile, medicine, and other fields. Genome-wide screening and expression analysis of the LecRLK family of C. sativa were performed in this paper, so as to provide scientific reference for functional analysis of the LecRLK family of C. sativa. Based on BLAST and HMM methods, 93 LecRLKs were identified in the whole genome of C. sativa, including 69 G types, 23 L types, and one C types. Subsequently, a series of bioinformatics analyses were performed on the LecRLK family members, and the physicochemical properties of the protein of the LecRLK family members were initially revealed. The prediction of cis-acting elements of promoters in family members showed that family members were regulated by hormones and stress response. The expression analysis showed that some family members were highly expressed in the roots, which may participate in the process of stress resistance. Several members were highly expressed in female flowers and may be involved in female flower development. This study provides a theoretical basis for further study of LecRLK gene function. Meanwhile, the expression analysis screens candidate LecRLK members who may participate in the resistance of C. sativa, which provides a theoretical basis for the subsequent selection of C. sativa varieties against resistance.

The essential oil (EO) obtained from hemp (Cannabis sativa L.) biomass is rich of bioactive constituents and its oral administration can be valuable. In this paper two different hemp EOs were orally administered to CD1 mice. One EO, obtained from the fresh plant material, resulted rich in monoterpenes (monoterpene rich oil, MRO) and the other, obtained from the dried biomass, contained mainly sesquiterpenes and CBD (sesquiterpene rich oil, SRO). The blood levels of the most abundant constituents were evaluated in the animals 30 and 90 min after oral administration of hemp EOs. Furthermore, compounds were also measured in brain, liver, kidney, spleen, and cecum content to evaluate their tissue distribution at the same times. Results showed the easy absorption and the ability of the major hemp EOs constituents to reach brain, liver, and kidney. Oral administration of MRO resulted in blood levels of monoterpenes in the range 45-115 ng/g at 30 min and significant tissue distribution with the detection of monoterpenes in brain, liver, and kidney. Oral administration of SRO resulted in blood levels, at 30 min, in the range 70-80 ng/g of sesquiterpenes and 139 ng/g of CBD. The compounds are still detectable in blood and brain 90 min after oral administration and significant concentrations of terpenoids are observed in liver and kidney. MRO and SRO can be considered as valuable sources of these bioactive compounds and further investigations are needed to evaluate the potential uses of hemp EO as constituent of innovative drug formulations.

This study investigated the molecular, phytochemical, and biological aspects of ten local Moroccan traditional landrace Cannabis seeds. Genetic polymorphisms were analyzed using DNA barcode determination, revealing two distinct molecular profiles: \"Cannabis, species sativa, subspecies indica\" and \"Cannabis, species sativa, subspecies sativa\". Furthermore, a new sequence was identified by sequencing of the THCA synthase coding gene. Chemical profiling via HPLC-ESI-FULL-MS and GC-MS-MS of AMSD1 maceration extracts revealed 13 non-volatile chemicals, including 3 inactive cannabinoids and 3 polyphenols, and 24 intriguing volatile compounds, including 7 previously unreported in Cannabis seed extracts. Moreover, the in vitro/in silico analysis provision of biological activities through their antioxidant power, antimicrobial effect, and cytotoxicity potency, as well as antiviral activity, were realized. These results contribute to a thorough comprehension of Moroccan Cannabis seeds, illuminating their molecular, phytochemical, and biological features. Furthermore, they highlight the seeds as a potential source of nutritious components with antioxidant properties, offering valuable insights for future research.

The research focused on analyzing the UGT gene family in Cannabis sativa, which plays a crucial role in the plant\'s metabolism and glycosylation of secondary metabolites. The study identified 125 UGTs using conserved plant secondary product glycosyltransferase (PSPG) motif amino acid sequences. These UGT genes were categorized into 17 groups (A-Q) through phylogenetic analysis, showing their distribution across 10 chromosomes in C. sativa. The expansion of the CsUGT gene family was attributed to tandem and duplication events, as suggested by gene duplication analysis. Furthermore, the study found various cis-acting regulatory elements related to phytohormones and stress responses in CsUGT promoter regions. Subcellular localization analysis revealed that CsUGT is present in the cytoplasm, chloroplast, and nucleus. The study revealed that CsUGT plays a significant role in various biological processes, cellular components, and molecular functions as highlighted by Gene Ontology analysis. Additionally, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that some CsUGTs are associated with the biosynthesis of secondary metabolites. This research provides valuable insights into the genomic organization, evolutionary history, and potential regulatory mechanisms of UGT genes in C. sativa. It lays the foundation for further exploration of their specific biological roles and potential applications in the plant\'s metabolism and stress responses. These findings contribute to a better understanding of the UGT gene family and its relevance to the metabolic pathways in C. sativa.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s13205-024-04025-3.

The separation of cannabinoids from hemp materials is nowadays one of the most promising industrial applications of liquid-liquid chromatography (LLC). Despite various experimental research efforts to purify cannabinoids, there are currently few works on process modeling. Thus, this study aimed to explore a straightforward approach to model the LLC separation of cannabinoids from two hemp extracts with different compositions. The feed materials were simplified to mixtures of preselected key components (i.e., cannabidiol, tetrahydrocannabinol, cannabigerol, and cannabinol). The elution profiles of cannabinoids were simulated using the equilibrium-cell model with an empirical nonlinear correlation. The model parameters were derived from the elution profiles of single-solute pulse injections. For the validation of the proposed approach, LLC separations with the two hemp extracts were performed in descending mode with the solvent system composed of hexane/methanol/water 10/8/2 (v/v/v). The injected sample concentrations were gradually increased from 5 to 100 mg/mL. The results showed that the approach could describe reasonably well the elution behavior of the cannabinoids, with deviations of only 1-2 min between simulated and experimental elution times. However, to improve the prediction accuracy, the model parameters can be refitted to the elution profiles of 3-4 systematically selected pulse injections with specific hemp extracts.

Anxiety disorders are highly prevalent psychiatric disorders, characterized by a chronic course and often accompanied by comorbid symptoms that impair functionality and decrease quality of life. Despite advances in basic and clinical research in our understanding of these disorders, currently available pharmacological options are associated with limited clinical benefits and side effects that frequently lead to treatment discontinuation. Importantly, a significant number of patients do not achieve remission and live with lifelong residual symptoms that limit daily functioning. Since the 1970s, basic and clinical research on cannabidiol (CBD), a non-psychotomimetic compound found in the Cannabis sativa plant, has indicated relevant anxiolytic effects, garnering attention for its therapeutic potential as an option in anxiety disorder treatment. This chapter aims to review the history of these studies on the anxiolytic effects of CBD within the current understanding of anxiety disorders. It highlights the most compelling current evidence supporting its anxiolytic effects and explores future perspectives for its clinical use in anxiety disorders.