Search Results (53)

Cannabis sativa L. is a versatile plant with significant medicinal, industrial, and recreational applications. Its therapeutic potential is attributed to cannabinoids like THC and CBD, whose production is influenced by environmental factors, such as radiation, temperature, and humidity. Radiation, for instance, is essential for photosynthetic processes, acting as both a primary energy source and a regulator of plant growth and development. This review covers key factors affecting C. sativa cultivation, including photoperiod, light spectrum, cultivation methods, environmental controls, and plant growth regulators. It highlights how these elements influence flowering, biomass, and cannabinoid production across different growing systems, offering insights for optimizing both medicinal and industrial cannabis cultivation. Studies indicate that photoperiod sensitivity varies among cultivars, with some achieving optimal flowering and cannabinoid production under extended light periods rather than the traditional 12/12 h cycle. Light spectrum adjustments, especially red, far-red, and blue wavelengths, significantly impact photosynthesis, plant morphology, and secondary metabolite accumulation. Advances in LED technology allow precise spectral control, enhancing energy efficiency and cannabinoid profiles compared to conventional lighting. The photoperiod plays a vital role in the cultivation of C. sativa spp., directly impacting the plant’s developmental cycle, biomass production, and the concentration of cannabinoids and terpenes. The response to photoperiod varies among different cannabis cultivars, as demonstrated in studies comparing cultivars of diverse genetic origins. On the other hand, indoor or in vitro cultivation may serve as an excellent alternative for plant breeding programs in C. sativa, given the substantial inter-cultivar variability that hinders the fixation of desirable traits. Full article

This study describes the development and validation of a fully automated workflow for serum sample preparation, enabling the quantitative determination of cannabidiol (CBD) and its active metabolite, 7-hydroxy-CBD, via liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) analysis. Implemented on an automated platform, the workflow performs key steps such as solvent dispensing, mixing, centrifugation, filtration, and supernatant transfer, producing 96-well plates ready for analysis. Human serum samples were obtained from patients with epilepsy treated with CBD. All samples were processed using both manual and automated methods to evaluate method agreement. Quantification was performed by LC–MS/MS with CBD-d₃ as the internal standard (IS). Method validation was conducted in accordance with European Medicine Agency (EMA) guidelines, confirming that the automated protocol meets the recommended acceptance criteria for both intraday and interday precision and accuracy. Calibration curves demonstrated excellent linearity across the concentration ranges. Comparative analysis using Passing–Bablok regression and Bland–Altman plots demonstrated strong agreement between the methods. These findings support the clinical applicability of the automated method for the therapeutic drug monitoring (TDM) of CBD and 7-hydroxy-CBD, and its robust performance and scalability provide a solid foundation for the development of an expanded analytical panel covering a broader range of antiseizure medications (ASMs), enabling more standardized TDM protocols in clinical practice. Full article

As high-CBD cannabis (Cannabis sativa L.) gains legal and commercial relevance in the United States, studies evaluating how external inputs impact critical traits remain limited. This study investigates the effects of methyl jasmonate (MeJA), ammonium bicarbonate (AB), and the genetic source (mother plant identity) on the growth and secondary metabolite traits of indoor cannabis. Plants were treated with 1 mM MeJA and/or AB under controlled conditions, and key traits, such as plant height, chlorophyll content, biomass, trichome density, and cannabinoid concentration, were measured. The MeJA treatment led to a significant 32% increase in trichome density. However, it did not significantly alter CBD or THC concentrations. The AB treatment enhanced vegetative growth, increasing chlorophyll content and plant height while reducing CBD concentrations, but the biomass gains could compensate for the lower cannabinoid in the total production. An interaction between MeJA and AB altered the CBD content, suggesting that MeJA may mitigate AB’s negative effect on cannabinoid synthesis. The genetic source significantly influenced most of the measured traits, highlighting the role of the genotype in trait expression and the importance of clonal consistency. These findings highlight the complex dynamics of external inputs and genetic factors in cannabis production, emphasizing the need for further research to optimize cultivation strategies. Future studies should refine input combinations and doses to improve both yield and cannabinoid profiles. Full article

Cannabidiol (CBD), a phytocannabinoid commonly isolated from chemotype III Cannabis sativa plants, is known for its therapeutic potential. However, comprehensive information on its bioavailability is still lacking. The key objective of this study was to investigate the impact of specific formulations on CBD delivery to the site of action and, in particular, the brain of experimental animals. As brain tissue is an extremely complex matrix, a highly sensitive method employing liquid chromatography–tandem mass spectrometry (LC-MS/MS) had to be implemented. To make it applicable for multiple analytes, the method was validated for 17 other phytocannabinoids and selected metabolites. Using this method, a pharmacokinetic study was conducted on 200 brain samples collected from rats that had been administered various CBD formulations (carriers) via oral gavage. The peak concentration in brain occurred within 1–2 h; notably, the highest was reached with carriers containing triacylglycerols with the shortest fatty acid chains (caprylic/capric). In addition to the parent compound, 7-hydroxy-cannabidiol and 7-carboxy-cannabidiol were detected, confirming rapid post-administration metabolism. Overall, this research enhances understanding of CBD distribution in the brain and underscores the impact of specific formulations on its bioavailability, offering insights into optimizing CBD-based therapies to be both effective and ‘patient-friendly’. Full article

Water availability is a key factor affecting both morphological development and secondary metabolite production in Cannabis sativa L. This study evaluated the effects of water stress applied during the vegetative and flowering stages on plant performance, cannabinoid concentration, and terpene composition in two Chemotype III (cannabidiol-dominant) varieties. Plants were subjected to moderate and severe water stress, and responses were assessed through biomass measurements, GC-MS analyses, and multivariate statistics. Water stress significantly influenced biomass allocation, with increased dry biomass but reduced harvest index, particularly under flowering-stage stress. Cannabidiol (CBD) content declined with increasing stress, while tetrahydrocannabinol (THC) levels increased under vegetative stress, indicating a stress-induced shift in cannabinoid biosynthesis. Cannabinol (CBN) levels also increased, suggesting enhanced THC degradation. Terpene composition was predominantly genotype-driven. PCA-MANOVA showed significant effects of variety, stress level, and their interaction, yet only minor volatiles were modulated by stress, while the most abundant terpenes remained stable across treatments, preserving the varietal aroma profile. These results underline the importance of genetic background and irrigation timing in determining cannabis yield and quality. Optimized water management is essential to ensure phytochemical consistency and sustainable production, especially in high-value medicinal and aromatic applications. Full article

Bacteria of the genus Pseudomonas are the most studied microorganisms that biodegrade persistent perfluoroorganic pollutants, and the research of their application for the remediation of environmental sites using biotechnological approaches remains relevant. The aim of this study was to investigate the ability of a known destructor of perfluorooctane sulfonic acid from the genus Pseudomonas to accelerate and enhance the destruction of long-chain perfluorocarboxylic acids (PFCAs), specifically perfluorooctanoic acid and perfluorononanoic acid, in water and soil in association with the strain P. mosselii 5(3), which has previously confirmed genetic potential for the degrading of PFCAs. The complete genome (5.86 million base pairs) of the strain 2,4-D, probably belonging to a new species of Pseudomonas, was sequenced, assembled, and analyzed. The genomes of both strains contain genes involved in the defluorination of fluorinated compounds, including haloacetate dehalogenase H-1 (dehH1) and haloalkane dehalogenase (dhaA). The strain 2,4-D also has a multicomponent enzyme system consisting of a dioxygenase component, an electron carrier, and 2-halobenzoate 1,2-dioxygenase (CbdA) with a preference for fluorides. The strain 2,4-D was able to defluorinate PFCAs in an aqueous cultivation system within 7 days, using them as the sole source of carbon and energy and converting them to perfluorheptanoic acid. It assisted strain 5(3) to convert PFCAs to perfluoropentanoic acid, accelerating the process by 24 h. In a model experiment for the bioaugmentation of microorganisms in artificially contaminated soil, the degradation of PFCAs by the association of pseudomonads also occurred faster and deeper than by the individual strains, achieving a degree of biodestruction of 75% over 60 days, with the perfluoropentanoic acid as the main metabolite. These results are of great importance for the development of methods for the biological recultivation of fluorinated organic pollutants for environmental protection and for understanding the fundamental mechanisms of bacterial interactions with these compounds. Full article

Dimethyl fumarate (DMF) is an immunomodulatory treatment for multiple sclerosis (MS) that can cross the blood–brain barrier, presenting neuroprotective potential. Its mechanism of action is not fully understood, and there is a need to characterize whether DMF or its bioactive metabolite monomethyl fumarate (MMF) exerts neuroprotective properties. Moreover, the combination of adjuvant agents such as cannabidiol (CBD) could be relevant to enhance neuroprotection. The aim of this study was to compare the neuroprotective and immunomodulatory effects of DMF, MMF, and CBD in neurons and microglia in vitro. We found that DMF and CBD, but not MMF, activated the Nrf2 antioxidant pathway in neurons. Similarly, only DMF and CBD, but not MMF, prevented the LPS-induced activation of the inflammatory pathway NF-kB in microglia. Additionally, the three drugs inhibited the production of nitric oxide in microglia and protected neurons against apoptosis. Transcriptomically, DMF modulated a greater number of inflammatory and Nrf2-related genes compared to MMF and CBD in both neurons and microglia. Our results show that DMF and MMF, despite being structurally related, present differences in their mechanisms of action that could be relevant for the achievement of neuroprotection in MS patients. Additionally, CBD shows potential as a neuroprotective agent. Full article

Cannabis sativa L. contains numerous compounds with antioxidant and anti-inflammatory properties, including the flavonoids and the cannabinoids, particularly Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Cannabinoids have an effect on the endocannabinoid system (ECS), a cellular communication network, and are, hence, widely studied for medical applications. Epidiolex^®, a 99% pure oral CBD extract, has been approved by the FDA for the treatment of epilepsy. Nabiximols (Sativex) is an oromucosal spray containing equal volume of THC and CBD, and it is commonly used as an add-on treatment for unresponsive spasticity in multiple sclerosis (MS) patients. Several in vitro and in vivo studies have also shown that cannabinoids can be used to treat various types of cancer, such as melanoma and brain glioblastoma; the first positive clinical trials on the anticancer effect of a THC:CBD blend with temozolomide (TMZ) in the treatment of highly invasive brain cancer are very promising. The cannabinoids exert their anticancer properties in in vitro investigations by the induction of cell death, mainly by apoptosis and cytotoxic autophagy, and the inhibition of cell proliferation. In several studies, cannabinoids have been found to induce tumor regression and inhibit angiogenic mechanisms in vitro and in vivo, as well as in two low-numbered epidemiological studies. They also exhibit antiviral effects by inhibiting ACE2 transcription, blocking viral replication and fusion, and acting as anti-inflammatory agents; indeed, prior CBD consumption (a study of 93,565 persons in Chicago) has also been associated with a much lower incidence of SARS-CoV-2 infections. It is postulated that cannabis extracts can be used in the treatment of many other diseases such as systemic lupus erythematosus, type 1 diabetes, or various types of neurological disorders, e.g., Alzheimer’s disease. The aim of this review is to outline the current state of knowledge regarding currently used medicinal preparations derived from C. sativa L. in the treatment of selected cancer and viral diseases, and to present the latest research on the potential applications of its secondary metabolites. Full article

Background: The reintroduction of hemp production has resulted in increased consumption of cannabidiol (CBD) products, particularly CBD oil, yet their effects on intestinal health are not fully understood. Proper mitochondrial function and antioxidant defenses are vital for maintaining the intestinal epithelial barrier. AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator (PGC)1α are key mediators of mitochondrial metabolism. Methods & Results: Using Caco-2 cells, we found that CBD oil promoted AMPK phosphorylation, upregulated differentiation markers, and enhanced PGC1α/SIRT3 mitochondrial signaling. CBD oil reduced reactive oxygen species production and increased antioxidant enzymes. Moreover, CBD oil also increased levels of citrate, malate, and succinate—key metabolites of the tricarboxylic acid cycle—alongside upregulation of pyruvate dehydrogenase and isocitrate dehydrogenase 1. Similarly, pure CBD induced metabolic and antioxidant signaling. Conclusions: CBD enhances mitochondrial metabolic activity and antioxidant defense in Caco-2 cells, making it a promising candidate for treating intestinal dysfunction. Full article

The approaching legalisation and associated increasing demand for medicinal and recreational Cannabis sativa L. will lead to a growing relevance for lighting systems designed for Cannabis sativa L. The interplay between plant density, light spectrum, light distribution, yield, and secondary metabolite distribution within the plant has not yet been studied. To fill this knowledge gap, a CBD-dominant Cannabis sativa L. strain was grown in a greenhouse experiment with two plant densities (2.66 and 12 plants ⁻¹ m⁻²) under two different light spectra. The chosen light spectra were two LED fixtures, Solray385 (SOL) and AP67, with an R: FR ratio of 12.9 and 3.7, respectively. The results indicated that light-induced effects on individual plants can be transferred to the plant stock. A low R: FR ratio induced a 16% increase in dry flower yield in the last ten days of flowering, while a change in the light spectrum could increase the potential maximum plant density per square metre. The two spectra did not affect (CBD + CBDA) yield, as a lower flower yield compensated for a higher concentration. CBDA concentration was not significantly affected by plant density. In contrast, the higher density led to an increased total cannabidiol concentration (CBD + CBDA) and altered the distribution of terpenes. Here, the light distribution over the plant stock is particularly decisive, as a more homogenous illumination led to an increased terpene concentration of up to 41%. A Photon Conversion Efficacy (PCE) of 0.05 g mol⁻¹ under SOL and 0.06 g mol⁻¹ under AP67 was achieved. Plants in the centre under the highest light intensity of 1200 PAR showed up to 48% reduced efficacy. These results strongly suggest that light intensity needs to be fine-tuned to the cultivation system to prevent a reduction in efficacy, resulting in yield and quality losses. Full article

Cannabis sativa (C. sativa L.) has garnered significant attention worldwide due to its widespread use as a pharmaceutical agent. With the increasing clinical application of C. sativa and cannabinoid therapeutics, there is strong interest in the development of superior plant varieties and optimisation of growth conditions to enhance secondary metabolite yield. Our RNA sequencing analysis revealed differential expression of hormone-related transcripts in developing C. sativa trichomes, suggesting the involvement of hormone signalling pathways in cannabinoid production. Leveraging the potency of exogenous hormones on plants, this study sought to determine if the application of cytokinin (CK), gibberellic acid (GA) and jasmonic acid (JA) modified trichome morphology and the cannabinoid profile over an 8-week period following the induction of flowering. Exogenous hormone application led to alterations in trichome morphology, with each treatment significantly reducing trichome head width by the final week of assessment. Interestingly, GA application also resulted in a significant reduction in the concentration of Δ-9-tetrahydrocannabinol (THC), Δ-9-tetrahydrocannabinolic acid (THCA), cannabidiol (CBD) and cannabidiolic acid (CBDA) by week 8 post floral induction, however, JA and CK treatment did not consistently modulate the accumulation of these cannabinoids. The minor cannabinoids, cannabidivaranic acid (CBDVA), cannabicyclolic acid (CBLA), cannabicyclol (CBL), cannabichromene (CBC), cannabigerolic acid (CBGA) and cannabigerol (CBG), were also affected by hormone treatments, with varying degrees of accumulation observed. These findings underscore the intricate interplay between phytohormones and secondary metabolite biosynthesis in C. sativa. Our study highlights the potential of hormone modulation as a strategy to enhance cannabinoid yield and offers some insights into the regulatory mechanisms governing cannabinoid biosynthesis in C. sativa trichomes. Full article

Light is crucial for higher plants, driving photosynthesis and serving as a powerful sensory signal that profoundly modulates growth, development, physiological functions, hormone activation, and biochemical pathways. Various light parameters—quality, intensity, composition, and photoperiod—exert a tremendous influence on plant growth and development, particularly in industrial hemp (Cannabis sativa L.). C. sativa, a crop of historical significance and unparalleled versatility, holds immense value in the food, fiber, and medicinal industries. The cultivation of medicinal cannabis is burgeoning in controlled environments due to evolving healthcare regulations. Optimal light conditions significantly enhance both yield and harvest quality, notably increasing the density of apical inflorescences and the ratio of inflorescence to total aboveground biomass. C. sativa metabolites, especially phenolic and terpene compounds and Phytocannabinoids like CBD (cannabidiol), THC (tetrahydrocannabinol), and CBG (cannabigerol), possess immense medicinal value. Secondary metabolites in C. sativa predominantly accumulate in the trichomes of female flowers and surrounding sugar leaves, underscoring the critical need to boost inflorescence weight and metabolite concentrations while ensuring product consistency. Different light parameters distinctly impact C. sativa’s metabolic profile, providing a robust foundation for understanding the optimal conditions for synthesizing specific secondary metabolites. While the effects of light measurement on various crops are well-established, scientific evidence specifically relating to light quality effects on C. sativa morphology and secondary metabolite accumulation remains scarce. In this review, we critically summarized how different light properties can alter cannabis growth (vegetative and reproductive), physiology and metabolism. Furthermore, the mechanisms by which specific wavelengths influence growth, development, and secondary metabolite biosynthesis in C. sativa are not fully elucidated, which could be a prospective task for future researchers. Our review paves the way for a profound understanding of light’s influence on C. sativa growth and advancements in greenhouse settings to maximize metabolite production for commercial use. Full article

Cannabielsoin (CBE) is primarily recognized as an oxidation byproduct of cannabidiol (CBD) and a minor mammalian metabolite of CBD. The pharmacological interactions between CBE and cannabinoid receptors remain largely unexplored, particularly with respect to cannabinoid receptor type 1 (CB₁). The present study aimed to elucidate the interaction dynamics of CBE in relation to CB₁ by employing cyclic adenosine monophosphate (cAMP) and β-arrestin assays to assess its role as an agonist, antagonist, and positive allosteric modulator (PAM). To our knowledge, this is the first publication to investigate CBE’s receptor activity in vitro. Our findings reveal that S-CBE acts as an agonist to CB₁ with EC₅₀ = 1.23 µg/mL (3.7 µM) in the cAMP assay. No agonist activity was observed in the β-arrestin assay in concentrations up to 12 µM, suggesting a noteworthy affinity towards G-protein activation and the cAMP signaling pathway. Furthermore, in silico molecular docking simulations were conducted to provide a structural basis for the interaction between CBE and CB₁, offering insights into the molecular determinants of its receptor affinity and functional selectivity. Full article

To mitigate pyrethroid resistance in mosquito vectors of emerging and re-emerging human pathogens, there is an urgent need to discover insecticides with novel modes of action. Natural alternatives, such as extracts derived from plants, may serve as substitutes for traditional synthetic insecticides if they prove to be sustainable, cost-effective, and safe for non-target organisms. Hemp (Cannabis sativa) is a sustainable plant known to produce various secondary metabolites with insecticidal properties, including terpenoids and flavonoids. The goal of this study was to assess the larvicidal activity of hemp leaf extract on mosquito larvae from both pyrethroid-susceptible (PS) and pyrethroid-resistant (PR) strains of Aedes aegypti. Another goal was to identify which components of the extract were responsible for any observed larvicidal activity. We found that a methanol extract of hemp leaves induced similar concentration-dependent larvicidal activity against PS (LC₅₀: 4.4 ppm) and PR (LC₅₀: 4.3 ppm) strains within 48 h. Partitioning of the leaf extract between methanol and hexane fractions revealed that full larvicidal activity was restricted to the methanol fraction. Analysis of this fraction by gas chromatography–mass spectrometry and nuclear magnetic resonance showed it to be dominated by cannabidiol (CBD). Larvicidal assays using authentic CBD confirmed this compound was primarily responsible for the toxicity of the hemp leaf extract against both strains. We conclude that hemp leaf extracts and CBD have the potential to serve as viable sources for the development of novel mosquito larvicides. Full article

Cannabis sativa L. (hemp) is a herbaceous plant rich in cannabinoids with a long history of use in pain treatment. The most well-characterized cannabinoids, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC), garnered much attention in chemotherapy-induced peripheral neuropathy (CIPN) treatment. However, few studies have investigated the biological benefits and mechanism of hemp extract on CIPN. In the present study, hemp extract (JG) rich in cannabinoids was extracted by supercritical fluid carbon dioxide extraction (SFCE). The antinociceptive efficacy was evaluated using a paclitaxel-induced peripheral neuropathy (PIPN) rat model based on behavioral tests. Further omics-based approaches were applied to explore the potential mechanisms. The results showed that JG decreased mechanical allodynia, thermal hyperalgesia, and inflammatory cytokines in PIPN rats significantly. Transcriptome analysis identified seven key genes significantly regulated by JG in PIPN model rats, mainly related to the neuroactive ligand–receptor interaction pathway, PPAR signaling pathway, and cAMP signaling pathway. In metabolomic analysis, a total of 39 significantly altered metabolites were identified, mainly correlated with pentose and glucuronate interconversions and the glycerophospholipid metabolism pathway. Gut microbiota analysis suggested that increased community Lachnoclostridium and Lachnospiraceae_UCG-006 in PIPN rats can be reversed significantly by JG. In conclusion, hemp extract exhibited antinociceptive effects on PIPN. The analgesic mechanism was probably related to the regulation of inflammation, neuroactive ligand–receptor interaction pathway, sphingolipid metabolism, etc. This study provides novel insights into the functional interactions of Cannabis sativa L. extract on PIPN. Full article