Search Results (596)

The present study aimed to establish a robustness modeling framework for the determination of cannabidiol (CBD) and Δ⁹-tetrahydrocannabinol (THC) in cannabis extract using a multivariate approach. A two-level full factorial design was implemented to examine four critical analytical factors, including methanol concentration (80–85% v/v), flow rate (0.8–1.2 mL/min), column temperature (23–27 °C), and detection wavelength (208–212 nm). Seven analytical responses for each compound were assessed, including peak area, retention time, resolution, asymmetry factor, number of theoretical plates, capacity factor, and peak area difference relative to the reference method. Statistical analysis demonstrated that both main effects and interaction effects significantly influenced the measured responses. Design space construction was performed based on predefined acceptance criteria to ensure method robustness: resolution > 1.5, asymmetry < 1.5, number of theoretical plates > 2000, capacity factor > 2, and peak area difference within −5% to 5%. Predictive performance of the developed models was verified by comparing predicted and experimental results. Good agreement was observed under most conditions, whereas deviation was noted for THC quantification at a detection wavelength of 212 nm. Furthermore, CBD and THC contents determined under three selected operating conditions within the established design space were statistically comparable to those obtained using the reference method, except for the condition employing 212 nm detection. The Analytical GREEnness Metric Approach (AGREE) assessment indicated moderate greenness performance of the analytical procedure. Overall, the multivariate two-level full factorial design proved to be an effective tool for robustness modeling of the HPLC method for simultaneous quantification of CBD and THC. Full article

Background: Cannabinoids are studied as anticancer agents, but their effects vary across tumors, compounds, and experimental settings, underscoring the need to define consistent patterns. Our objective was to map cannabinoid efficacy across cancer preclinical models and identify tumor settings with the greatest translational promise. Methods: The protocol was registered on PROSPERO (CRD42025543744); PubMed, Embase, and CENTRAL were searched on 4 April 2024 for in vitro and in vivo studies assessing cannabinoid antitumor effects alone or with chemotherapy versus vehicle or chemotherapy only. Random-effects models yielded pooled mean differences (MD) with 95% confidence intervals (CI). MDs of viable cells were calculated for in vitro assays and tumor volume (mm³) for in vivo studies. Reports of various compounds, cannabidiol (CBD), tetrahydrocannabinol (THC) or synthetic cannabinoids, were pooled. Results: We included 189 studies in the final analysis. In vitro, cannabinoids reduced cell viability modestly overall, with significant effects in glioblastoma (MD −18.77 [CI: −27.15; −10.39]) and a nonsignificant trend in breast cancer (MD −6.75 [CI: −13.90; 0.40]). For in vivo, monotherapy showed the most consistent efficacy in glioblastoma, significantly reducing tumor volume by MD −980.58 mm³; [CI: −1270.2; −690.88]. Addition to temozolomide produced a favorable but nonsignificant decrease of MD −220.65 mm³; [CI: −579.34; 138.03, vs. temozolomide]. In breast cancer, cannabinoids achieved smaller yet significant tumor reductions (MD −402.64 mm³); [CI: −671.84; −133.45]. Synthetic agents had the largest effect (MD −1295.19 mm³); [CI: −1664.33; −928.05] -CBD plus doxorubicin vs. doxorubicin). Lung cancer (MD −562.17 mm³); [CI: −693.99; −430.35] and prostate cancer (MD −1136.59 mm³); [95% CI: −1320.97; −952.21] also had a significant response, whereas colon, pancreatic, and hepatocellular carcinoma models showed inconsistent or null responses. Conclusions: Cannabinoids show promise as adjuncts in oncotherapy, particularly in glioblastoma and breast cancer, to enhance chemotherapy efficacy. These findings should be interpreted with caution given the high inter-study heterogeneity typical of preclinical research and should be considered hypothesis-generating, warranting further validation in standardized and clinically relevant models. Full article

Recreational (“party”) drug use is prevalent in social environments and is increasingly relevant in ophthalmic care. While the neurological and cardiovascular consequences of these subokstances are well documented, their ocular and visual effects may not be fully recognized or consistently reported in clinical practice. This invited narrative review summarizes clinical observations and translational mechanisms underlying ophthalmic manifestations associated with commonly used recreational substances, including sympathomimetic stimulants (cocaine, amphetamines), empathogens (3,4-methylenedioxymethamphetamine (MDMA), inhalants (alkyl nitrites, “poppers”), and cannabinoids (cannabis/Δ9-tetrahydrocannabinol (THC)). Particular focus is placed on vascular dysregulation, altered ocular perfusion pressure, venous outflow impairment, oxidative stress, and neuro-ophthalmic dysfunction. Characteristic presentations, diagnostic pitfalls, and management considerations are discussed. Improved awareness of drug-related ocular effects may facilitate earlier recognition of such conditions and help reduce the risk of visual complications. Other recreational substances, including hallucinogens and emerging psychoactive compounds, may also have ocular effects, although current evidence remains limited. Full article

Three-dimensional (3D) printing has emerged as a versatile platform in pharmaceutical sciences, enabling fabrication of personalized dosage forms with controlled drug release and tailored properties using printable hydrogel bioinks. This study aimed to develop mucoadhesive hydrogel buccal films for cannabinoid delivery using extrusion-based 3D bioprinting. The films incorporated cannabidiol (CBD) and tetrahydrocannabinol (THC) as cyclodextrin inclusion complexes with HPMC or Carbopol as mucoadhesive hydrogel-forming polymers, while terpenes were evaluated as permeation enhancers. Terpenes including 1,8-cineole, d-limonene, α-pinene, and L-menthol were investigated individually and in combinations to assess their ability to enhance buccal cannabinoid permeation. Hydrogel bioinks were prepared and characterized for viscosity, pH, and drug content prior to printing under optimized conditions. The printed films were evaluated for mechanical properties, swelling behaviour, mucoadhesion, in vitro drug release, and ex vivo buccal mucosal penetration. Ex vivo penetration studies demonstrated that combinations of natural terpenes significantly improved CBD penetration compared with individual terpenes and the synthetic enhancer Azone. HPMC-based hydrogel films exhibited superior mechanical strength, cohesive gel matrices, and sustained non-Fickian cannabinoid release, while enhancing transmucosal penetration compared with unformulated drugs. Carbopol-based films showed higher mucoadhesion but weaker mechanical properties and faster erosion-driven release. These findings demonstrate the potential of 3D-printed mucoadhesive hydrogel films as gel-based systems for transmucosal cannabinoid delivery. 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

The phytochemical variability in Cannabis sativa L. chemovars represents an underexplored factor in environmentally sustainable nanomaterial production. In this study, three distinct chemovars, (i) High-Δ⁹-Tetrahydrocannabinol (THC) (89% THC), (ii) Balanced (60% Cannabidiol (CBD)), and (iii) High-CBD (89% CBD), were comparatively evaluated to determine their suitability for the green synthesis of silver nanoparticles (AgNPs). Ethanolic inflorescence extracts were used to recover bioactive secondary metabolites; among them, the High-CBD extract exhibited the highest total phenolic (3.34 mg gallic acid equivalent/g) and flavonoid (29.49 mg quercetine equivalent/g) contents, together with superior antioxidant capacity (53.16% 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH) inhibition), indicating enhanced redox potential for nanoparticle formation. The terpene profile of High-CBD showed a dominance of myrcene (21.4%), contributing to the stabilization of the system. Using the High-CBD extract, predominantly spherical nanoparticles of 5 ± 0.9 nm were synthesized and confirmed by UV–vis, EDS, and TEM. The biogenic AgNPs demonstrated significant dose-dependent antibacterial activity, with minimum bactericidal concentration (MBC) of 1.0 mg/mL against Staphylococcus aureus and 4.5 mg/mL against Escherichia coli. These findings highlight the critical role of chemovar-dependent phytochemical composition and support a phytochemistry-guided approach for developing silver nanoparticles with potential biomedical applications. Full article

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer accounting for the majority of cases and exhibiting persistent challenges related to therapy resistance and metastatic progression. Increasing evidence indicates that dysregulated G protein-coupled receptor signaling and ion channel activity function cooperatively as master regulators of tumor cell proliferation, migration, survival, and therapeutic response. Cannabinoids, including phytocannabinoids such as delta-9-tetrahydrocannabinol and cannabidiol, as well as endogenous endocannabinoids, are uniquely positioned to modulate both G protein-coupled receptors and ion channels, thereby influencing key oncogenic signaling networks. This review synthesizes current knowledge on the role of major ion channel families, including transient receptor potential channels, potassium channels, and sodium channels, and principal G protein-coupled receptor pathways involved in lung cancer progression. We further discuss how cannabinoids reprogram these interconnected signaling systems through canonical cannabinoid receptors, non-classical targets such as G protein-coupled receptor 55 and adenosine receptors, and direct modulation of ion channel activity. Special attention is given to G protein-coupled receptor–ion channel coupling within membrane microdomains and to the capacity of cannabinoids to act as biased ligands, redirecting downstream pathways, such as the phosphoinositide 3-kinase–protein kinase B–mechanistic target of rapamycin and epidermal growth factor receptor signaling, toward apoptosis and reduced metastatic potential. Emerging strategies, including cannabinoid-based combination therapies, selective receptor biasing, and targeted delivery systems, are also highlighted. Altogether, cannabinoid-driven rewiring of G protein-coupled receptor and ion channel signaling represents a promising mechanistic framework for developing innovative therapeutic approaches against lung cancer. Full article

The chemotaxonomic classification of Cannabis sativa L. has historically relied on the Δ⁹-tetrahydrocannabinol (THC) to cannabidiol (CBD) ratio, yielding canonical chemotypes I, II, and III. However, this binary framework overlooks the chemical diversity contributed by the minor cannabinoids. High-performance liquid chromatography (HPLC) following the AOAC Official Method 2018.10 was employed to quantify nine cannabinoids (THCA, THC, CBDA, CBD, CBGA, CBG, CBC, CBDV, and CBN) across 36 commercially and medicinally relevant cannabis varieties. Quantitative profiling revealed substantial phytochemical heterogeneity, with total THC ranging from 0.41% to 15.64% and total CBD ranging from 0.09% to 12.32% (w/w). Unsupervised principal component analysis (PCA) demonstrated that the first two principal components explained 62.7% of the total variance. PC1 (37.6%) captured the THCA–CBDA polarity axis, while PC2 (25.1%) was dominated by minor cannabinoids (CBC; loading 0.417), CBGA (0.314), and CBG (0.258). Supervised partial least squares discriminant analysis (PLS-DA) using only the nine cannabinoid variables achieved 94.2% cross-validated accuracy and 100% test-set accuracy in predicting the chemotype class, with CBC identified as the third most discriminatory variable (variable importance in projection, VIP = 1.34). Hierarchical clustering resolved three principal clades and further subdivided THC-dominant accessions into CBC-enriched (Sour Diesel, Cinderella Jack) and CBGA-enriched (Mother Gorilla, Auto Lemon Kix) subclusters. A multivariate “metabolic coordinate” system based on PC1/PC2 scores is proposed as a quantitative and reproducible alternative to the traditional Type I/II/III and sativa/indica nomenclatures. This study introduces an empirically grounded framework for variety authentication, quality control, and enhanced precision breeding in the rapidly growing medicinal cannabis sector, for both human and veterinary applications. Full article

Chronic osteoarthritis (COA) is a progressive and degenerative condition that causes joint inflammation and pain, often requiring long-term pharmacological management. Conventional treatments may lead to adverse effects, tolerance, and limited analgesic efficacy. This randomized, double-blind clinical trial evaluated the analgesic potential of a full-spectrum Cannabis sativa oil extract administered orally twice daily over six weeks in dogs with COA. Subjects were assigned to three groups: Cannabis, Placebo, and Control. Pain was assessed using the Canine Brief Pain Inventory (CBPI) and the Canine Osteoarthritis Staging Tool (COAST), which ranges from 0 to 4. The Cannabis extract (46.4 mg/mL) total cannabinoids: Cannabidiol (CBD), Cannabidiolic acid (CBDA), Delta-9-Tetrahydrocannabinol (Δ⁹-THC), and Tetrahydrocannabinolic acid (THCA), were administered using a cautious dose escalation protocol. Treatment began at ~0.1 mg/kg every 12 h, increasing by one drop (1.16 mg) every 72 h. This gradual titration continued until reaching the maximum tolerated dose (2 mg/kg every 12 h), which was maintained for the final two weeks. The protocol was designed to minimize adverse effects and allow close monitoring, especially in geriatric or clinically fragile dogs. By day 28, when the DMT was reached, the Cannabis group showed a 39.6% reduction in CBPI scores, compared to 24.7% in the Placebo group and a 1.6% increase in the Control group. COAST scores improved from level 4 to level 3 in 55.5% of dogs in the Cannabis group, with no changes observed in the other groups. We hypothesize that the co-administration of carprofen, meloxicam, or pregabalin with a full-spectrum Cannabis sativa extract—rich in acidic cannabinoids and terpenes—enhances pain relief and mobility in dogs with COA more effectively than conventional therapies alone. This study aimed to assess the efficacy of an oily full-spectrum Cannabis sativa extract as an adjunctive treatment to NSAIDs in twenty-seven dogs diagnosed with COA, and to compare pain intensity across three treatments groups. Full article

Medicinal hemp (Cannabis sativa L.) has gained global attention due to its high-value phytocannabinoids, particularly cannabidiol (CBD) and tetrahydrocannabinol (THC), which exhibit significant therapeutic potential. Protected cultivation offers a climate-resilient and sustainable strategy to optimize hemp production by controlling environmental factors, ensuring year-round supply, and improving quality attributes. This paper outlines the key principles and technologies for protected hemp cultivation, including light spectrum management, temperature and humidity control, CO₂ enrichment, nutrient and water management, pest and disease suppression, and post-harvest handling techniques. Advanced greenhouse and indoor production systems enable precise regulation of microclimate, reduce crop losses, and enhance cannabinoid and terpene profiles compared to open-field production. The integration of smart technologies and autonomous control systems can further enhance operational efficiency and consistency. The paper concludes that protected cultivation systems represent an effective approach to overcome climatic uncertainties and meeting the increasing demand for medicinal hemp production on sustainable grounds. Full article

Cannabis is the most-used psychoactive drug in Aotearoa—New Zealand (NZ); recreational use remains illegal, while medicinal use was legalized in 2020. Cannabis use is associated with increased risk of injury; however, there is little known on the causes and circumstances of cannabis-related fatal injuries. This retrospective population study utilized coronial case files to describe the contribution and circumstances of cannabis-related fatal injuries in NZ. Between 2012 and 2016, cannabis was reported in 273 of 3599 unintentional/assault injury deaths (1.32 deaths per 100,000 person-years, 95% CI 1.17, 1.49). High-risk groups included males aged 15–44 years, Indigenous Māori, and those in deprived areas, for whom higher rates of post mortem testing were conducted. Cannabis-related fatalities mainly resulted from road crashes and multi-drug poisonings with concomitant alcohol use common, especially in traffic crashes on public roads (49% of concomitant use). Cannabis use was mainly observed in the decedent (n = 256, 94%). One in five deaths involved a worker, either as a user or as a bystander to another’s use. Coronial files identified important opportunities for safety countermeasures targeting cannabis use among drivers and its concomitant use with alcohol. Improved coverage of post mortem testing could address data limitations, including biased testing patterns and missing medical use. Full article

Background: Prenatal cannabinoid exposure (PCE) causes neurodevelopmental impairments affecting learning and memory; however, the receptor-level interactions underlying these cognitive deficits remain poorly understood. This study investigated whether a moderate dose of prenatal Δ⁹-tetrahydrocannabinol (THC) exposure alters the biophysical properties of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, which are critical mediators of excitatory neurotransmission and synaptic plasticity. Methods: Pregnant Sprague-Dawley rats received a moderate dose (5 mg/kg) of THC or vehicle control via oral gavage throughout gestation and early postnatal development. Single-channel electrophysiological activity of the AMPA receptors (AMPARs) was recorded using patch-clamp techniques on synaptosomal AMPARs reconstituted into artificial lipid bilayers from adolescent offspring. Western blot analysis of GluA1- and GluA2-containing AMPAR subunits and the postsynaptic scaffold protein postsynaptic density 95 (PSD95) was conducted to assess protein levels. Results: Prenatal THC exposure decreased AMPAR open-channel probability, reduced mean open time, increased mean closed time, and altered burst channel activity significantly, without altering GluA1, GluA2, or PSD95 protein levels. Furthermore, the interactive channel-gating activity observed in control synaptosomes was absent in synaptosomes derived from THC-exposed offspring. Conclusions: Prenatal cannabinoid exposure induces early alterations in glutamatergic synaptic function primarily mediated by changes in AMPAR channel kinetics rather than receptor abundance. By identifying AMPAR single-channel dysfunction as a sensitive marker of PCE-induced synaptic disruption, this work provides a mechanistic framework linking prenatal THC exposure to long-term alterations in learning and memory. 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

Current treatments for breast cancer (BC) include surgery, radiation, chemotherapy, targeted therapy, hormonal therapy, and immunotherapy. However, adverse effects such as pain, nausea, cardiotoxicity, and neuropathy have prompted interest in complementary approaches. Cannabinoids (CBS), particularly cannabidiol and delta-9-tetrahydrocannabinol, are already used by cancer patients for symptom relief, and preclinical studies in cell culture and mouse models suggest additional therapeutic potential at the cellular level: combining CBS with chemotherapy may sensitize tumour cells to chemotherapeutic agents, inhibit tumour proliferation, and increase apoptosis. In murine models, such combinations may also mitigate chemotherapy-induced cardiotoxicity by enhancing antioxidant activity, modulating cannabinoid receptor signalling to reduce pro-inflammatory markers, and restoring mitochondrial function in myocytes. In addition, CBS may augment hormonal therapy in estrogen receptor-positive (ER+) BC cells, primarily via aromatase inhibition and modulation of ER and EGR3 signalling. Notably, evidence on combining CBS with targeted therapies in BC is lacking, while studies of CBS–immunotherapy combinations have been conducted in non-BC cancers; in BC, they are scarce and limited to in vitro models. This represents a key area for future research, particularly given the heterogeneity across non-BC cancers, where CBS–immunotherapy combinations have demonstrated mixed effects, both beneficial and detrimental (e.g., reduced response rates and overall survival), with the underlying mechanisms remaining unclear. Translation of these findings into clinical practice faces several challenges. Although over 120 CBS have been identified, only a few are well-characterized. CBS exhibit diverse mechanisms and effects, including potential adverse outcomes and interactions with conventional therapies (e.g., effects on chemotherapeutic drug metabolism). Variability among BC cells may also result in differing responses to the same therapeutic combinations. Future research should delineate the effects of individual CBS in combination strategies and prioritize well-controlled, standardized clinical studies to build on in vitro and animal data, while also exploring genetically informed personalized approaches. Ultimately, clinical guidelines specifying CBS type, formulation, and delivery are needed. Full article

Salicylic acid (SA) is a key signaling molecule regulating secondary metabolism and stress responses in plants, but its preharvest role as a low-cost elicitor in cannabis remains underexplored. This study evaluated the effects of preharvest foliar SA application at different concentrations and application intervals on pigments, antioxidants, and cannabinoids in Cannabis sativa L. leaves and inflorescences. In leaves, moderate SA (0.1 M) significantly enhanced total phenolic content, total flavonoid content, and antioxidant activity (%DPPH inhibition), while higher concentrations suppressed these responses, reflecting a regulated metabolic trade-off rather than irreversible tissue damage. A significant interaction between SA concentration and preharvest time was observed for chlorophyll a (p < 0.01), whereas chlorophyll b and total chlorophyll were not significantly influenced by the interaction. In inflorescences, short-term application of 0.1 M SA (1 h preharvest) maximized phenolics, flavonoids, antioxidant capacity, and pigment accumulation, whereas the untreated controls showed the lowest levels. Cannabinoids exhibited distinct responses: Δ⁹-tetrahydrocannabinol (Δ⁹-THC), total tetrahydrocannabinol (Total THC), and tetrahydrocannabinolic acid (THCA) peaked at 0.1 M SA applied 1 h preharvest, while cannabidiol (CBD) was less concentration-dependent, with maximum accumulation observed at 1.0 M SA applied 24 h preharvest. Preharvest SA elicitation strongly modulated cannabis secondary metabolism. Short-term application of moderate SA promoted total phenolic, total flavonoid, antioxidant, pigment, and THC-group cannabinoid accumulation, while CBD displayed broader tolerance to concentration and application timing. These findings highlighted the potential of SA as a preharvest elicitor to improve cannabis phytochemical quality. Full article