Search Results (280)

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

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

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

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

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

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

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

In the search for new therapeutic strategies for the treatment of skin cancer, cannabinoids have become the focus of scientific interest. The present study investigated the effects of the phytocannabinoids Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD) on the viability, apoptosis, and mitochondrial function of human melanoma (A375) and cutaneous squamous cell carcinoma (SCC) cells (A431). Both cannabinoids caused a time- and concentration-dependent loss of viability and an upregulation of caspase-3/7 activity, associated with the induction of initiator caspases-8 and -9, PARP cleavage, and an increase in the autophagy marker LC3A/B-II. Inspired by the latest work on the dual role of heme oxygenase-1 (HO-1) in cell fate, the expression of this enzyme was examined and found to be upregulated at the mRNA and protein level by THC and CBD. Inhibition of HO-1 activity by tin protoporphyrin IX (SnPPIX) reduced the loss of viability caused by both cannabinoids, suggesting a cytotoxic rather than cytoprotective mediator role for this enzyme here. At the mitochondrial level, THC and CBD caused a reduction in membrane potential, a release of cytochrome c into the cytosol, and electron microscopically detectable mitochondrial damages. A more detailed functional analysis revealed an inhibition of mitochondrial oxygen consumption rate, accompanied by a decrease in various subunits of mitochondrial oxidative phosphorylation complexes. In conclusion, our data demonstrate a strong cytotoxic effect of THC and CBD on melanoma and cutaneous SCC cells involving mitochondrial apoptosis and mitochondrial dysfunction. Full article

Cannabidiol (CBD) is one of the most studied compounds of Cannabis sativa and has attracted significant interest due to its therapeutic and beneficial properties, which have been confirmed in numerous preclinical and clinical studies over the last few years. A great advantage of CBD over the other widely known Cannabis sativa ingredient, Δ-9-tetrahydrocannabinol (THC), is that CBD does not exert intoxicating and psychoactive effects, making it an attractive candidate for therapeutic applications in neurological disorders. CBD has been shown to exert antioxidant, analgesic, anti-inflammatory, and neuroprotective effects, with therapeutic potential for various neurological conditions. To date, the only drug that consists solely of highly purified CBD is Epidiolex, which is used in the management of severe forms of epilepsy such as Dravet syndrome and Lennox–Gastaut syndrome. Another legal medication containing CBD (albeit with the addition of THC) is Sativex, used to alleviate spasticity in multiple sclerosis. Besides epilepsy, preclinical data suggest that CBD alone may be potentially beneficial in treating chronic pain, multiple sclerosis, Alzheimer’s and Parkinson’s diseases, or stroke. The safety profile of CBD is generally considered favorable, as the most commonly reported adverse effects are mild (e.g., somnolence, diarrhea). However, much attention should be paid as CBD-driven drug–drug interactions have been reported. This review article aims to assess the outcomes of preclinical and clinical research on CBD’s effects in various neurological conditions while also addressing potential risks and concerns related to its use. Full article

Cannabis sativa, a species within the Cannabaceae family, produces a diverse range of phytochemicals, notably cannabinoids and terpenoids, with significant physiological and pharmacological relevance. Among its phytochemicals, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most studied for their psychoactive and medicinal properties. However, emerging evidence indicates that chronic or excessive exposure to these phytocannabinoids may adversely affect male fertility. This review synthesizes current knowledge on the influence of C. sativa and its constituents on the male reproductive system, with emphasis on spermatogenesis, sperm function, hormonal regulation, and the role of the endocannabinoid system (ECS). Experimental and clinical studies demonstrate that cannabinoids interact with CB1 and CB2 receptors expressed in the testes, epididymis, and spermatozoa, thereby modulating testosterone synthesis, sperm motility, morphology, and capacitation. THC, in particular, disrupts the hypothalamic–pituitary–gonadal (HPG) axis, leading to reduced luteinizing hormone and testosterone levels, impaired mitochondrial activity, and abnormal sperm morphology. Although CBD exhibits anti-inflammatory and antioxidant properties, its long-term impact on reproductive function remains uncertain. The review further highlights the complex interplay between exogenous cannabinoids and the endogenous ECS in maintaining reproductive homeostasis. Understanding these molecular mechanisms is critical for balancing the therapeutic potential of Cannabis-derived products with their reproductive risks. This knowledge could inform safe medicinal applications and contribute to the development of targeted cannabinoid-based therapies for male infertility. Full article

The use of cannabis during pregnancy is increasing, in line with its growing societal acceptance and legalization. Cannabis use mainly concerns its active components Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD). While cannabis has therapeutic effects on pain, nausea, and vomiting, its impact on fetal development remains a significant public health concern. Given the existence of a local endocannabinoid system (ECS) in the placenta, with proven effects on placental development and blood flow, it is likely that THC and CBD exert effects via interference with the placental ECS. This review summarizes how cannabis use affects the placental ECS and describes the consequences of such use on placental function and fetal development. It starts with discussing the placental ECS, the effects of THC and CBD on placental function, and the pharmacokinetics of cannabinoids during pregnancy. It then describes the effects of both paternal and maternal cannabis use and provides epidemiological data linking placental insufficiency, impaired fetal growth, and preeclampsia to cannabis use. It also raises awareness for the possibility that cannabis use, by altering DNA methylation, might result in transgenerational effects. It is concluded that current evidence supports abstaining from cannabis use during preconception, pregnancy, and lactation to optimize maternal, fetal, and intergenerational health outcomes. Full article

Synthetic cannabinoids (SCs) represent one of the rapidly growing groups of new psychoactive substances (NPS) on the illicit drug market. SCs mimic the effects of Δ⁹-tetrahydrocannabinol, but they have a greater affinity to the receptors, resulting in more potent psychoactive effects than traditional substances. The toxicity and high abuse potential of SCs could pose serious health risks to their users. The challenges posed by the SCs require innovative monitoring strategies like the analysis of untreated wastewater, known as wastewater-based epidemiology (WBE). In this review article, we summarized the available literature on the detection and quantification of SCs in raw wastewater samples published between 2013 and 2025. We paid special attention to challenges related to different experimental stages of WBE analysis that hinder the accurate measurement of SCs and their metabolites. The reviewed studies show that wastewater analysis reflected the dynamic evolution of the illicit SCs market. As studies on the analysis of SCs in wastewater remain scarce, large monitoring campaigns and research performed in more locations are needed. Modern analytical hyphenated systems such as LC-MS are essential for the sensitive and accurate quantification of SC biomarkers in wastewater and their sound identification. Future studies should address further stability tests, investigation of SC metabolism, and careful selection of the effective SC extraction method from the complex environmental matrix. Full article