Search Results (262)

Cannabinoids, including the psychoactive D9-tetrahydrocannabinol (THC) and the non-psychoactive cannabidiol (CBD), interact with receptors within the endocannabinoid system. The major receptors within this system are CNR1 (cannabinoid receptor 1) and CNR2 (cannabinoid receptor 2), which are both seven-transmembrane G-protein-coupled receptors. In this report, we used the Catalogue of Somatic Mutations in Cancers (COSMIC) to map and analyze mutations arising in CNR1 and CNR2. The goal was to determine if any trends or signatures could be identified. We identified several mutations in both CNR1 and CNR2. In silico 3D structure of proteins reveals that these mutations cluster on the intracellular regions of CNR1 and CNR2, and certain residues may be able to destabilize the interaction with the G-alpha protein due to their close proximity. mRNA expression showed that CNR1 and CNR2 are within normal expression levels in most cancer types except kidney, where there is a tendency towards over-expression. Neither CNR1 nor CNR2 is a driver gene, and our analysis shows that mutations in cancer cells are deactivating (e.g., loss of function). Full article

Background/Objectives: Dermatomyositis is an autoimmune disease with heterogeneous symptoms and many potential drivers. Nonpsychoactive cannabinoids have shown promise in treating some subtypes of DM; however, the reasons behind this were unclear. In this project, we tested the effects of CB2R activation on PBMCs from amyopathic and classic DM patients to determine its anti-inflammatory effects on pathways biologically relevant to DM. Methods: We determined the % CB2R positivity and intracellular cytokines in PBMCs from amyopathic DM and classic DM patients. CB2R positivity was determined by analyzing patient PBMCs via flow cytometry. PBMCs were stimulated by dsRNA for RIG1, dsDNA for cGAS, LPS for TLR4, and LPS/ATP for NLRP3, with and without CB2R pretreatment, and IFNβ, IFNγ, p65 NFkB, and pSTING levels were used as markers of pathway activation. The CB2R agonist JWH133 was used to pretreat PBMCs before stimulation. Results: Amyopathic DM PBMCS were found to be 101.3% more positive for CB2R compared to classic DM PBMCS (p < 0.05). In amyopathic DM PBMCs stimulated by LPS/ATP to target the NLRP3 inflammasome, CB2R activation resulted in a significant reduction in IFNβ MFI for MoDCs (p < 0.05) and Macs (p < 0.05), with a similar trend observed in cDCs relative to classic DM PBMCS. On the other hand, no difference in IFNβ response to CB2R activation was observed across all cell types investigated between classic and amyopathic DM PBMCs stimulated with LPS only to target TLR4. Conclusions: Amyopathic DM PBMCs were significantly more positive for CB2R and had better anti-inflammatory responses to CB2R activation for many inflammatory pathways implicated in DM. Full article

COVID-19 has spurred much interest in complementary and alternative agents for therapeutic purposes having antiviral and immunomodulatory effects. In these, natural products and bioactive compounds from plants have been at the center of attention due to their easy access, relatively low risk and long history of use in traditional medicine. This paper reviews in detail and critically assesses the scientific data that presently proposes the use of certain cannabinoids, cannabimimetic compounds and Artemisia species in the treatment and prevention of COVID-19. It gives an account of medicinal approaches to cannabinoids like cannabidiol (CBD), Δ9-tetrahydrocannabinol (THC) alongside other minor cannabinoids and synthetic and naturally-occurring cannabimimetics. The paper reports the potential of Artemisia annua and other species as treatments, especially focusing on their antiviral, anti-regulatory, anti-inflammatory and immunomodulating properties. It highlights the molecular interactions with SARS-CoV-2 targets as well as cytokine regulation and modulation of oxidative stress pathways, with special emphasis on these areas. The paper raises multiple issues like preclinical and clinical studies, safety aspects, regulatory hurdles and drawbacks related to the use of these natural compounds. After analyzing all the available data, the article entertains the idea of a cannabinoid–Artemisia combination as a supportive or adjunct therapy in COVID-19 treatment. It also points out that the clinical trials are insufficient concerning the establishment of effectiveness, determination of the appropriate dosage and assurance of the long-term safety of the treatment. Full article

Cannabis sativa L. is a predominantly dioecious species, but sex expression is highly plastic and can be modified by genetic, hormonal, developmental, and environmental factors. This plasticity has major implications for commercial production because hermaphroditic expression in female plants can cause unintended pollination, seed formation, reduced floral quality, and losses in cannabinoid yield. This review summarizes current understanding of sex determination and sex-expression instability in C. sativa, with emphasis on hermaphroditism and its agronomic significance. We examine the genomic architecture of sex determination, the roles of ethylene and gibberellin signaling, and the effects of exogenous chemical treatments used to alter sexual phenotype. Particular attention is given to silver-based ethylene inhibitors, especially silver thiosulfate, which remain the most effective tools for induced masculinization and feminized seed production. We also assess the role of environmental stressors in sex instability and review current approaches for early detection, including visual inspection, Raman spectroscopy, and sex-linked molecular markers. Overall, the available evidence supports a multilayered and context-dependent model in which genotype, treatment regime, developmental stage, and environmental conditions interact to shape sexual phenotype. Improved understanding of these processes will be essential for reducing hermaphroditic risk, improving breeding strategies, and supporting stable, high-value cannabis production. Full article

Cannabis sativa L. is a medicinal plant cultivated globally due to its remarkable historical and scientific relevance. Through the consumption of its flowers, also referred to as inflorescences, which contain a high content of cannabinoids, terpenes and polyphenols, the therapeutic properties of C. sativa can be harnessed. This study therefore aimed to determine the chemical profile, antioxidant and anti-inflammatory activities of the essential oils (EOs) obtained from the fresh and dried flowers of two C. sativa cultivars, Lifter and Cherrywine, grown in Komga, South Africa, to assess which cultivar has greater biological potential. The chemical profiles of the hydro-distilled EOs were analyzed by gas chromatography–mass spectrometry (GC-MS), while the in vitro antioxidant and anti-inflammatory activity of the EOs was analyzed using the DPPH and EAD methods, respectively. The identified constituents from the EOs were molecularly docked against NOX2 and NIK (NF-κB-inducing kinase) protein, which are implicated in oxidative stress. The afforded EOs were yellow (pale and bright yellow) in color with a sweet to mildly sweet aroma description. A total of 51 constituents were identified in both fresh and dry oils from the Lifter cultivar, while the Cherrywine cultivar contained a total of 44 constituents. Eighteen compounds, were found to be the main chemical constituents consistent in the flower EOs of both cultivars, notably, caryophyllene (10.71–19.96%), levo-β-pinene (1.37–13.21%), humulene (5.88–9.77%), caryophyllene oxide (4.32–7.49%), D-limonene (1.40–5.48%), α-pinene (2.22–5.22%), nerolidol (0.63–4.97%), cis-β-ocimene (0.22–4.37%), linalool (1.12–4.28%), selina-3,7(11)-diene (0.15–4.23%), humulene-1,2-epoxide (1.23–3.32%), guaiol (0.17–2.60%), (+)-β-selinene (1.20–2.51%), trans-α-bergamotene (0.68–2.37%), β-ocimene (0.90–2.27%), fenchol exo- (0.15–1.27), terpineol (0.14–1.38%) and α-terpineol (0.19–0.75%). The fresh Lifter flower oil (LFO) showed 50% inhibition at 100 μg/mL, with an IC₅₀ of 69.50 ± 4.05 µg/mL against DPPH, suggesting moderate to low radical scavenging activity. The maximum percentage inhibition response of DLFO, CFO and DCFO remained below 50% at all concentrations. The antioxidant activity of fresh LFO may be attributed to its overall chemical composition. The flower oils showed in vitro inhibition of protein denaturation; however, the high standard deviation relative to the mean IC₅₀ values limited the ability to rank the samples’ potencies. Further in silico studies on the putative constituents in the Lifter and Cherrywine cultivars revealed β-bisabolene and α-curcumene as potential molecular targets, with binding energy scores of −7.7 and −7.9 kcal/mol, respectively. Thus, the study findings highlight the promising biological importance of C. sativa inflorescences in the management of oxidative stress-related conditions. Further studies may investigate the influence of environmental growing conditions on their chemical composition, total ROS analysis, pharmacokinetic properties, and in vivo efficacy against oxidative damage to DNA, proteins and lipids. Evaluating the toxicity of the flower EOs is also recommended. Full article

Cannabis is the most widely consumed illicit substance worldwide, and the rise of synthetic and semi-synthetic cannabinoids poses growing public health concerns due to their high potency and unpredictable effects. This study presents a new analytical methodology for the simultaneous determination of natural and semi-synthetic cannabinoids (cannabidiol (CDB), Δ⁸-tetrahydrocannabinol (∆⁸-THC), Δ⁹-tetrahydrocannabinol (∆⁹-THC), and hexahydrocannabinol (HHC)) in saliva using gas chromatography coupled with mass spectrometry (GC-MS) in combination with bar adsorptive microextraction (BAμE) as a green sample preparation. The optimized method showed satisfactory recoveries (57.3–80.6%), low detection and quantification limits (1.25 and 4.13 ng/mL, respectively), excellent linearity (r² ≥ 0.9963), and robust precision and accuracy. Application to authentic saliva samples demonstrated cannabinoid levels consistent with literature values. Overall, the proposed methodology offers a cost-effective, miniaturized, and environmentally sustainable platform for routine oral fluid cannabinoid analysis, highlighting its potential for forensic, clinical, and toxicological applications. Full article

Purpose: Cannabidiol (CBD) is a primary bioactive, non-intoxicating cannabinoid found in the cannabis plant. Studies have shown that CBD causes anticancer activity by inhibiting the expression of growth factors and inducing apoptosis, leading to cell cycle arrest. In this study, we aimed to determine how CBD influences the expression of genes that affect cancer pathways in doxorubicin-sensitive (MCF-7) and doxorubicin-resistant (MCF-7/Adr) breast cancer cells. Materials and Methods: IC₅₀ concentrations of CBD in MCF-7 and MCF-7/Adr cell lines were determined by the MTT cell cytotoxicity assay. RNA isolation and subsequent cDNA synthesis were performed for qPCR experiments with the determined IC₅₀ values. The effects of CBD on the cell cycle and apoptosis were studied using flow cytometry. IC₅₀ values of CBD were determined in MCF-7 and MCF-7/Adr breast cancer cell lines at eight different concentrations and at three different incubation periods (24 h, 48 h, and 72 h) with different doses. RT-qPCR was used to investigate the molecular mechanisms underlying the expression of genes involved in cancer pathway analysis. Results: Treatment with CBD at concentrations of 17.57 μM (MCF-7) and 11.41 μM (MCF-7/Adr) for 48 h decreased colony formation, induced apoptosis, and inhibited cell invasion in both cell lines. In addition, we observed significant alterations of angiogenesis, apoptosis, cell cycle, cellular senescence, DNA damage and repair, epithelial-to-mesenchymal transition, hypoxia, metabolism, telomeres, and telomerase in both cell lines. Conclusions: Our research indicates that CBD could be an effective natural bioactive compound for breast cancer treatment, inhibiting tumor cell proliferation and inducing apoptosis. Full article

Biostimulants represent a sustainable strategy to enhance the therapeutic potential of medicinal plants, which often exhibit low and variable levels of bioactive compounds. Cannabis sativa, a medicinally important species, produces diverse cannabinoids, such as THC, CBD, CBG, and CBC, whose profiles depend on plant chemotype and determine pharmacological activity. We developed a novel plant-based biostimulant, Tricostimulant™, to optimize cannabinoid production in Cannabis sativa. Field trials demonstrated increased biomass and selective enhancement of cannabinoid content. In high-CBD chemotypes, Tricostimulant™ was associated with higher CBD and CBG without relevant changes in THC levels, whereas in high-THC chemotypes, higher THC values were observed without evident variation in CBD. The most pronounced differences were observed when the biostimulant was applied during the vegetative stage, highlighting the importance of application timing. These results indicate the potential of Tricostimulant™ to modulate cannabinoid profiles, contributing to improved optimization and standardization of cannabis-based therapeutics. Further research is required to confirm these findings and elucidate the underlying mechanisms of biostimulant action. Full article

Cannabis use is generally restricted worldwide because it contains the narcotic compound Δ⁹-tetrahydrocannabinol (Δ⁹-THC). Although cannabis is detected at crime scenes using color-based primary screening methods, the details of the reaction mechanism have not yet been elucidated. In this study, we isolated the products generated during the color reaction between the diazonium salt prepared from para-nitroaniline and nine cannabinoids and determined their structures. Azo compounds 6, 11, 16, and 17 were produced from cannabidiol, cannabigerol, cannabichromene, and cannabidiolic acid, respectively, while quinoneimines 7–10 and 12–15, which contained positional isomers, were produced from cannabinol, Δ⁹-THC, and hexahydrocannabinol. The reaction barely proceeded with Δ⁹-THC acetate and HHC acetate. Full article

Addiction poses a major global public health challenge. It is characterized by high prevalence, chronic relapse and limited efficacy of available pharmacotherapies across different substance use disorders. Increasing evidence demonstrates that incretin-based therapies directly modulate metabolic signaling pathways that intercross with central reward and motivational circuits, including hypothalamic-mesolimbic networks and dopaminergic neurotransmission. As a result, agents such as glucagon-like peptide 1 receptor agonists, originally developed for the treatment of type 2 diabetes and obesity, are now being actively investigated for their role in addiction treatment. This narrative review summarizes the current knowledge on the role of incretin-based therapies in the neurobiology of addiction. Evidence from preclinical models and human studies supports the potential therapeutic effect of glucagon-like peptide 1 receptor agonists in the treatment of alcohol use disorder, nicotine dependence, and the administration of other psychoactive substances, including psychostimulants, opioids, and cannabinoids. Preclinical studies consistently demonstrate that glucagon-like peptide 1 receptor agonists reduce substance intake, attenuate reward-related behaviors, and suppress relapse-like responding. So far, human evidence remains limited and is largely derived from observational studies. Preliminary research suggests potential reductions in substance use severity and overdose risk among individuals treated with incretin-based agents. While these findings highlight incretin signaling as a promising therapeutic option in addiction, the current evidence is insufficient to support their routine clinical use in the treatment of substance dependence. Therefore, further research is required to clarify underlying mechanisms and establish clinical efficacy. In particular, well-designed randomized controlled trials are needed to determine safety, tolerance and effectiveness of incretin-based therapies across different substance use disorders. Full article

Background: n-3 PUFA derived from marine sources, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exhibit potential for breast cancer prevention. In contrast, higher dietary intakes of n-6 PUFA, such as linoleic acid (LA), have been implicated in promoting mammary tumourigenesis. However, there is a need for further exploration into how n-3 PUFA influence breast cancer development in comparison to different amounts and sources of LA. Objective: The purpose of this study was to compare the effects of n-3 PUFA-enriched diets versus n-6 PUFA diets differing in LA content, including corn oil (50% LA) and safflower oil (70% LA), on mammary tumour development in a HER2+ breast cancer model. Methods: Using the HER2+ breast cancer MMTV-neu(ndl)YD5 transgenic mouse model, this study determined the effects of: (1) 10% w/w corn oil (CO, n-6 PUFA, n = 14), (2) 10% w/w safflower oil (SO, n-6 PUFA, n = 14), (3) 3% w/w menhaden oil + 7% w/w CO (3% FO 7% CO, n-3 PUFA, n = 12), and (4) 3% w/w menhaden oil + 7% w/w SO (3% FO 7% SO, n-3 PUFA, n = 14) on puberty onset, tumour incidence, tumour volume, and tumour number in utero until 20 weeks of age. Results: Mice fed the n-3 PUFA-enriched diets showed a lower trajectory of tumour development compared to the n-6 PUFA diets, although the differences for palpated tumour volume and number over time reached significance only between the 10% CO and 3% FO 7% CO groups. This suggests that high LA content in CO may represent a threshold for promoting tumour growth whereby further LA content marginally influences additional tumour development. Exposure to the CO n-6 PUFA diet further resulted in earlier onset of puberty compared to the n-3 PUFA-enriched diet containing CO. To investigate the underlying mechanisms, a qPCR analysis of mammary glands and tumour tissue revealed that the n-3 PUFA diets downregulated the expression of pro-tumourigenic immune markers, including CD206 and F4/80 in the mammary glands and the cannabinoid receptor CB2 in tumours, compared to the n-6 PUFA diets. Conclusions: These findings indicate that the presence of dietary n-3 PUFA plays a key role in modulating mammary tumour development, which may be further influenced by the underlying n-6 PUFA background. The associated changes in immune markers suggest that n-3 PUFA exert anticancer effects in part by shifting the tumour immune microenvironment toward an anti-tumour phenotype and modulating cannabinoid receptor signalling. Collectively, this work informs future human studies investigating the role of dietary fat composition in breast cancer risk. Full article

Obesity is a chronic metabolic disorder characterized by excessive accumulation of body fat and is a major risk factor for various diseases, including type 2 diabetes, hypertension, and cardiovascular diseases. This study investigated the anti-obesity effects of cannabigerol-dominant C. sativa inflorescence extracts (CEs) obtained using various ethanol concentrations. The extracts were analyzed by UPLC to determine their major components. Additionally, anti-obesity mechanisms of the extracts were further determined through RT-qPCR and Western blot analysis to evaluate gene and protein expression levels. A total of seven cannabinoids, including cannabigerol as a major constituent, were identified within CE. Differentiation of 3T3-L1 cells was dose-dependently inhibited by CE at all ethanol concentrations. Furthermore, the gene and protein expression levels of key adipogenic and lipogenic markers, such as PPARγ, C/EBPα, SREBP-1c, and FAS, were significantly downregulated by CE treatment. In contrast, the expression of factors involved in lipolysis and white adipose tissue browning, such as HSL, ATGL, UCP1, and PGC-1α, was markedly increased by CE treatment. These effects were enhanced in an ethanol concentration-dependent manner. In conclusion, these results demonstrate that cannabigerol-dominant C. sativa effectively mitigates obesity by suppressing adipogenesis and lipogenesis while concurrently stimulating lipolysis and white adipose tissue browning. Full article

Synthetic cathinones, frequently used in chemsex, are difficult to identify in postmortem blood due to their short half-life and in vitro degradation. This unusual case of chemsex involving 3-CMC highlights the importance of freezing a blood aliquot and testing for metabolites. A 62-year-old man was found dead with chemsex paraphernalia beside him. Peripheral blood with sodium fluoride (PB), cardiac blood (CB) and urine were collected at autopsy. A PB sample was frozen at −20 °C for cathinone testing. In PB at +4 °C, alcohols were measured by HS-GC/FID, drugs and narcotics by LC-HRMS, GHB by GC-MS and cannabinoids by LC-MS/MS. Analysis of PB at +4 °C revealed a toxic concentration of GHB (330 µg/mL). Determination of cathinones in frozen PB revealed the presence of 3-CMC (17 ng/mL), dihydro-3-CMC and N-desmethyldihydro-3-CMC, while no cathinones or metabolites were identified in samples stored at +4 °C. Only metabolites were detected in urine. This case confirms the need to systematically screen for cathinones in suspected chemsex cases and, due to their instability, to screen for different metabolites and to freeze a blood sample after autopsy. Full article

Projects integrating Science, Technology, Engineering, and Mathematics (STEM) are essential to interdisciplinary research. This study presents a STEM (Science, Technology, Engineering, and Mathematics) methodology with the primary objective of designing, constructing, and validating a functional cannabinoid extraction device. To inform the device’s drying parameters, the dehydration kinetics of female hemp buds or flowering buds (FHB) were first analyzed using infrared drying at 100 °C for different durations. The plants were cultivated and harvested in accordance with good agricultural practices using Dinamed CBD Autoflowering seeds. The FHB were harvested and prepared by manually separating them from the stems and leaves. Six 5 g samples were prepared, each with a slab geometry of varying surface area and thickness. Two of these samples were ground: one into a fine powder and the other into a coarse powder. Mathematical fits were obtained for each resulting curve using either an exponential decay model or the logarithmic equation $y\left(t\right)=A\left(e^{-kt}\right)+y_0$ calculate the equilibrium moisture (m_E). The Moisture Rate (MR) was calculated, and by modelling with the logarithmic equation, the constant k and the effective diffusivity (Deff) were determined with the analytical solution of Fick’s second law. The Deff values (ranging from 10⁻⁷ to 10⁻⁵) were higher than previously reported. The coarsely ground powder sample yielded the highest k and Deff values and was selected for oil extraction. The device was then designed using Quality Function Deployment (QFD), specifically the House of Quality (HoQ) matrix, to systematically translate user requirements into technical specifications. A 200 g sample of coarsely ground, dehydrated FHB was prepared for ethanol extraction. Chemical results obtained by Liquid Chromatography coupled with Photodiode Array Detection (LC-PDA) revealed the presence of THC, CBN, CBC, and CBG. The extraction device design was validated using previous results showing the presence of CBD and CBDA. The constructed device successfully extracted cannabinoids, including Δ9-THC, CBG, CBC, and CBN, from coarsely ground FHB, validating the integrated STEM approach. This work demonstrates a practical framework for developing accessible agro-technical devices through interdisciplinary collaboration. Full article

Background/objectives: Cannabidiol (CBD) is a non-psychoactive constituent of Cannabis sativa, which has potential skeletal benefits through modulation of bone cell function and inflammatory signalling. However, evidence of its effects and mechanisms in bone health remains fragmented. This scoping review summarised the current findings on the impact of CBD on bone outcomes and its mechanisms of action. Methods: A systematic search of PubMed, Scopus, and Web of Science was conducted in October 2025 for original studies published in English, with the primary objective of examining the effects of CBD on bone health, regardless of study design. After applying inclusion and exclusion criteria, 24 primary studies were included. Data on model design, CBD formulation, treatment parameters, bone-related outcomes, and proposed mechanisms were extracted and analysed descriptively. Results: Among the studies included, eleven demonstrated beneficial effects of CBD on bone formation, mineralisation, callus quality, or strength; eleven showed mixed outcomes; and two demonstrated no apparent benefit. Previous studies have shown that CBD suppresses bone resorption by reducing osteoclast differentiation and activity while promoting osteoblast proliferation and matrix deposition. Mechanistically, CBD’s effects involve activation of cannabinoid receptor 2, modulation of the receptor activator of nuclear factor-κB ligand/osteoprotegerin pathway, and regulation of osteoblastogenic and osteoclastogenic signalling through bone morphogenetic protein, Wnt, mitogen-activated protein kinase, nuclear factor-κB, and peroxisome proliferator-activated receptor signalling. The anti-inflammatory and antioxidant actions of CBD further contribute to a favourable bone microenvironment. Conclusions: Preclinical evidence suggests that CBD has a bone-protective role through multifaceted pathways that enhance osteoblast function and suppress osteoclast activity. Nevertheless, robust human trials are necessary to confirm its efficacy, determine its optimal dosing, and clarify its long-term safety. Full article