Search Results (239)

Cannabis sativa is a multi-use crop with applications in food, fiber, construction, and medicinal industries. Cannabis plants with low Δ9-tetrahydrocannabinol (THC) concentrations (industrial hemp) have recently been legalized for industrial cultivation by multiple nations across the globe. This crop has been traditionally ignored and lags behind established crops like wheat, corn, and cotton in breeding and the development of novel traits. We employed chemical mutagenesis to develop novel traits in industrial hemp (Cannabis sativa L.). We used ethyl methanesulfonate (EMS) as the chemical mutagen and determined the lethal dose (LD50) to be 2% (v/v) for 5 h for the heat-tolerant (HT) (diploid, 2n) accession and 2% (v/v) for 8 h for the 4x (tetraploid, 2n = 4x = 40) accession. The variations in seed germination percentages among mutagen treatments were found to be highly significant (p < 0.05). The parental generation (M0) seeds were treated with the LD50 dosage of the mutagen to produce mutant M1 populations. The first mutant generation (M1) and second mutant generation (M2) plants displayed a wide array of phenotypes such as dwarf plants, twin seedlings, leaf variegation, fasciation, purple anthocyanins, hard/leathery leaf texture, trifoliate leaves, bushy stature, and unusual leaf shape, which is a testament to the effectiveness and accuracy of the LD50 dosage calibration results. Full article

Hexahydrocannabinol (HHC) is a semi-synthetic cannabinoid that has recently emerged in the European market, raising concerns regarding its detection in forensic toxicology. Reliable analytical approaches are required for the determination of HHC metabolites together with conventional cannabis biomarkers in biological samples. This study aimed to develop and validate a sample preparation method based on air-assisted liquid–liquid microextraction (AALLME) coupled to liquid chromatography–tandem mass spectrometry (LC–MS/MS) for the determination of 11-nor-9-carboxy-Δ⁹-tetrahydrocannabinol (THC-COOH) and HHC metabolites in urine. Urine samples underwent alkaline hydrolysis followed by AALLME using a cyclohexane/ethyl acetate mixture (9:1) prior to LC–MS/MS analysis. Experimental conditions affecting extraction performance were optimized. Method validation was performed according to international guidelines. The method achieved a limit of detection of 2.5 ng/mL and a lower limit of quantification of 5 ng/mL. Precision and accuracy fulfilled the established acceptance criteria across all concentration levels. The applicability of the method was evaluated using eleven authentic THC-COOH-positive routine casework urine samples. THC-COOH was successfully quantified, whereas no HHC metabolites were detected because no urine samples from confirmed HHC users were available. The proposed workflow provides a reduced-solvent sample preparation approach compared with conventional procedures and demonstrated adequate analytical performance for the simultaneous determination of THC-COOH and HHC metabolites in urine. Full article

Medical cannabis use is steadily increasing worldwide, including among pregnant and breastfeeding women. This Perspective provides an overview of current evidence regarding cannabis exposure during pregnancy and lactation and its implications for clinical decision-making. The available literature indicates relatively consistent evidence linking prenatal Δ⁹-tetrahydrocannabinol (THC) exposure with adverse perinatal outcomes, including reduced birth weight, increased risk of preterm delivery, and potential neurodevelopmental effects, although the findings remain heterogeneous and often confounded. In contrast, evidence regarding cannabis exposure during breastfeeding is sparse, and long-term infant outcomes associated with postnatal exposure through breast milk remain insufficiently characterized. Data on isolated cannabidiol (CBD) exposure during pregnancy and lactation are particularly limited, and most available evidence derives from preclinical studies or pharmacokinetic modeling rather than clinical outcome studies. Current recommendations from major health organizations uniformly advise avoiding cannabis and cannabinoid use during pregnancy and breastfeeding. This Perspective highlights the need to interpret the evidence according to cannabinoid type, exposure period, route and pattern of use, and the distinction between recreational exposure and regulated medical use. Such distinctions are particularly important because evidence is relatively stronger for prenatal THC exposure, whereas data on CBD and lactational exposure remain limited and are derived largely from indirect clinical, pharmacokinetic, and preclinical sources. Within this evidence landscape, individualized clinical interpretation may be needed when exposure has already occurred, cessation is not immediately feasible, or maternal treatment decisions remain complex, while remaining anchored in current avoidance recommendations. Full article

Cannabis sativa contains more than 120 phytocannabinoids, with Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) being the best characterized. This review synthesizes preclinical and clinical evidence on hemp-derived extracts, cannabinoids, and active compounds. THC primarily acts as a partial agonist at cannabinoid receptor type 1 (CB1) and type 2 (CB2), producing psychoactive, appetite-stimulating, antiemetic, and analgesic effects. CBD is non-intoxicating and has a multimodal profile involving CB1 negative allosteric modulation, CB2 inverse agonism or antagonism, inhibition of anandamide inactivation, and activity at 5-HT1A receptors, transient receptor potential channels, GPR55, and peroxisome proliferator-activated receptor gamma. Preclinical models of Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, epilepsy, and pain support anti-inflammatory, antioxidant, anti-excitotoxic, and glial-modulating mechanisms, but clinical translation remains uneven. The strongest evidence supports FDA-approved cannabidiol for Lennox–Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex, and THC-based agents for refractory chemotherapy-induced nausea and vomiting and AIDS-related anorexia. Moderate-certainty evidence supports nabiximols for multiple sclerosis spasticity and small benefits in selected chronic neuropathic pain populations. Evidence remains insufficient or negative for acute pain, insomnia, most psychiatric disorders, and many promoted indications. Key risks include cannabis use disorder, cognitive and psychiatric effects, cardiovascular events, sedation, high-dose CBD hepatotoxicity, and drug interactions. Rigorous, long-term, product-standardized trials are needed. Full article

Background: Osteoporosis, a debilitating bone disease characterized by low bone mineral density, poses a large burden on the population. Current pharmacological treatment options are limited, with antiresorptive drugs being the current first-line option. Recent research has shown that the endocannabinoid system, modulated by endocannabinoids and phytocannabinoids, may influence bone remodeling. As the prevalence of cannabis use and research into its medicinal potential continues to increase, its therapeutic potential has emerged. Objective: To investigate the role of Δ9-tetrahydrocannabinol (THC) inhalation in treating osteoporosis in a rodent model. Methods: Adult female Sprague–Dawley rats underwent ovariectomy (OVX) to induce osteoporosis. Four weeks post-OVX, rats received either THC or Air treatment via inhalation for 8 weeks. A control group of age-matched rats received sham surgery. Rats were then euthanized at 38 weeks old, and hindlimb samples were collected for caliper, microCT, and biomechanical analyses. Results: OVX Air-treated rats showed significantly decreased trabecular bone volume, trabecular bone volume fraction, trabecular separation, trabecular tissue mineral density, trabecular number, and connective density compared to sham surgery controls. Compared with Air controls, OVX rats treated with THC showed increased endosteal volume (20%; p < 0.05). THC-treated rats also showed decreased trabecular bone mineral density (2%; p < 0.005) and trabecular thickness (14%; p < 0.05). Conclusions: Chronic inhaled THC worsened key aspects of trabecular bone microarchitecture. Results do not support use of THC vapor as a therapeutic agent for osteoporosis and suggest THC may adversely affect bone quality in estrogen-deficient states. Further research is needed to evaluate dose-dependent effects and to distinguish the skeletal impacts of different cannabinoid components. Full article

Background: Poor appetite, a major contributor to malnutrition, is highly prevalent among older adults and associated with adverse clinical outcomes. Nevertheless, there are currently no widely accepted or consistently effective pharmacological treatments targeting appetite that are routinely recommended alongside nutritional interventions. Medical cannabis has been proposed as a potential appetite stimulant in older adults with poor appetite through modulation of appetite-regulating hormones such as glucagon-like peptide-1 (GLP-1) and total ghrelin, but the evidence remains limited. Aims: To investigate the effects of Sativex^® versus placebo on postprandial GLP-1 and total ghrelin concentrations following a single dose (8.1 mg Δ9-tetrahydrocannabinol (THC) and 7.5 mg cannabidiol (CBD)), and on subjective appetite following two separated doses, in older adults with poor appetite, and to investigate the associations between plasma concentrations of THC and its metabolites on these outcomes. Methods: This protocolized secondary analysis included 17 participants (≥65 years) with poor appetite from a double-blind, randomized, placebo-controlled crossover trial. Participants received Sativex^® or placebo on two separate study days. GLP-1 and total ghrelin were measured following one dose of Sativex^®/placebo and a standardized breakfast, and subjective appetite was assessed repeatedly using visual analog scales throughout the administration of two separate doses of Sativex^®/placebo, the consumption of a standardized breakfast, and an ad libitum lunch meal. Effects/associations were analyzed using linear mixed-effects models. Results: Compared with placebo, Sativex^® produced an estimated 2.38 pmol/L (95% confidence intervals (CI): −0.71 to 5.46; Bonferroni-corrected p = 0.274) reduction in mean GLP-1 and time-dependent changes in mean total ghrelin (Bonferroni-corrected p = 0.054). Compared with placebo, Sativex^® produced minimal changes in separate subjective appetite sensations (all Bonferroni-corrected p = 1.00) and a slightly lower combined appetite score (−5.2 mm; 95% CI: −24.4 to 4.0; Bonferroni-corrected p = 1.00). Increased plasma concentrations of THC and metabolites were associated with reduced estimates of mean GLP-1 concentrations and subjective appetite, as well as increased mean total ghrelin concentrations. However, no statistically significant differences were detected for any analyses, and estimates had wide CIs, warranting cautious interpretation. Conclusions: In conclusion, no statistically significant differences were detected between Sativex^® and placebo in postprandial GLP-1, total ghrelin, or subjective appetite over time in older adults with poor appetite. Similarly, no statistically significant associations were observed between plasma concentrations of THC and its metabolites and GLP-1, total ghrelin, or subjective appetite. Trial registration: ClinicalTrials.gov ID: NCT05503147; EudraCT nr.: 2021-002318-15. Full article

Medicinal cannabis has gained increasing attention from both the scientific community and clinical practice, due to the therapeutic potential of its major phytocannabinoids, particularly cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), for pain management. This review compiled and analyzed the available evidence regarding the antinociceptive effects of nanoencapsulated cannabinoids compared to free compounds. The published works have explored some pharmaceutical formulations and administration routes on different acute, chronic and neuropathic pain experimental models. The findings indicated that cannabinoids exhibited promising analgesic effects, while nanoencapsulation could enhance its stability and bioavailability. Despite these advances, the number of reports investigating nanostructured cannabinoid-based systems remains limited, with a predominance of preclinical research. A recurrent lack of structural information and quality control data for such works was also noted. Furthermore, there were not identified any research regarding the nanoencapsulation of full-spectrum cannabis oils or whole cannabis extracts, highlighting a significant gap in the current literature. Overall, nanoencapsulation emerges as a versatile strategy to overcome the intrinsic limitations of cannabinoids and expand its clinical applicability for pain treatment. Nevertheless, further efforts are required to determine standardized methodologies, facilitating the translation of preclinical findings into clinical practice, in order to provide stable, safe, effective and more accessible cannabinoid-based therapies. Full article

Semi-synthetic cannabinoids (SSCs) are chemically modified derivatives of naturally occurring phytocannabinoids that have rapidly emerged in commercial cannabis and hemp-derived products, including vape cartridges, edibles, infused oils, and concentrated extracts. Increasing availability of compounds such as hexahydrocannabinol (HHC), HHC analogues, and Δ⁸-tetrahydrocannabinol (Δ⁸-THC) has created significant challenges for forensic toxicology, analytical detection, public health surveillance, and regulatory control. This structured narrative review evaluated current evidence on the forensic, toxicological, pharmacological, and analytical implications of SSCs. The literature published between January 2019 and May 2026 was identified through searches of PubMed, Scopus, and Web of Science using predefined search terms related to SSCs, forensic toxicology, analytical detection, intoxication, metabolism, and public health. Recent evidence demonstrates that HHC-related compounds currently dominate the SSC market and scientific literature. Available studies indicate that SSCs undergo extensive Phase I and Phase II metabolism, producing hydroxylated, oxidized, and glucuronidated metabolites that frequently predominate over parent compounds in biological matrices. This metabolic complexity complicates forensic interpretation, particularly in postmortem investigations and impairment assessments where toxicological reference ranges remain poorly established. Emerging intoxication reports describe prolonged sedation, neuropsychiatric manifestations, cognitive impairment, and severe poisoning associated with HHC analogues, although much of the current evidence remains limited to case reports and small observational studies. From an analytical perspective, conventional toxicology screening methods may fail to detect SSC exposure, necessitating advanced analytical approaches such as liquid chromatography–tandem mass spectrometry (LC–MS/MS), high-resolution mass spectrometry (HRMS), and chiral chromatographic techniques for metabolite identification and epimer differentiation. However, limited reference standards, evolving structural diversity, and regulatory variability across jurisdictions continue to hinder standardized detection and interpretation. Overall, SSCs represent a rapidly evolving class of psychoactive compounds requiring coordinated advancements in forensic toxicology, analytical surveillance, pharmacological characterization, and public health monitoring to improve detection reliability, risk assessment, and regulatory response. Full article

Background: Adolescence is a sensitive period for brain maturation during which exposure to Δ⁹-tetrahydrocannabinol (THC) can induce long-lasting neurobehavioral alterations. Yet, preclinical and clinical studies report inconsistent long-term outcomes of adolescent THC exposure, ranging from clear impairments to apparently normalizing effects. We hypothesize that these discrepancies reflect stable individual differences in stress-coping abilities. Methods: To test this, selectively bred Dominant (Dom; stress-resilient, risk-prone) and Submissive (Sub; stress-vulnerable, depressive-like) Sabra mice received THC or vehicle during adolescence and were assessed in adulthood. Results: Anxiety-like and exploratory behavior, measured in the hole-board test, were differentially affected by THC as a function of stress vulnerability: in Sub mice, THC increased exploration and reduced anxiety-like behavior, whereas in Dom mice THC produced the opposite pattern. Recognition memory, evaluated by the novel object recognition test, showed modest, line-dependent alterations. Sensitivity to N-methyl-D-aspartate (NMDA) receptor hypofunction, a widely used index of vulnerability to schizophrenia-like symptoms, was examined using MK-801-induced locomotion. Adolescent THC potentiated MK-801-evoked hyperlocomotion in Dom mice but attenuated it in Sub mice. Conclusions: In the context of increasing medical and recreational cannabis exposure, these in vivo findings suggest that stress-vulnerability-related traits may be an important variable to consider in future preclinical and translational studies of adolescent THC exposure. 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

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