Search Results (83)

Although cannabis is used in a wide range of fields, including medicine and pharmacology, its use is prohibited in Japan because it contains Δ⁹-tetrahydrocannabinol (Δ⁹-THC), a compound that exhibits narcotic effects. While cannabis is primarily detected via color-based screening methods at crime scenes, the reaction products and mechanisms associated with these screening methods have not been fully elucidated. To address this issue, the colored products were isolated via the diazo-coupling reactions of the major cannabinoids (cannabidiol, cannabinol, and Δ⁹-THC) in cannabis with the Fast Blue RR diazonium salt, and their structures were determined using NMR spectroscopy. As expected, azo compound 2 was formed from cannabidiol, whereas cannabinol and Δ⁹-THC produced quinoneimines 3 and 4, respectively. This study is expected to lead to the future development of more sensitive color-based reagents that produce fewer false positives. Full article

The therapeutic potential of cannabinoids and other ligands of cannabinoid receptors attracts considerable attention due to their diverse pharmacological effects and utility in various medical applications. However, challenges such as low solubility, limited bioavailability, and potential side effects hinder their broad clinical use. Nanoformulation techniques offer a promising approach to address these issues and optimize the therapeutic effectiveness of cannabinoids and other cannabinoid receptor ligands. This comprehensive review explores the advancements in nanoformulation strategies to enhance the therapeutic efficacy and safety of synthetic cannabinoids and related compounds, such as CB13, rimonabant, and HU-211, which have been studied in a range of preclinical models addressing conditions such as neuropathic pain, depression, and cancer. The review discusses various nanocarriers employed in this field, including lipid-based, polymeric, and hybrid nanoparticles, micelles, emulsions, and other nanoengineered carriers. In addition to formulation approaches, this review provides an in-depth analysis of chemical structures and their effect on compound activity, especially in the context of the affinity for the cannabinoid type 1 receptor in the brain, which is chiefly responsible for the psychoactive effects. The provided summary of research concerning either chemical modifications of existing cannabinoids or the creation of new compounds that interact with cannabinoid receptors, followed by the development of nanoformulations for these agents, allows for the identification of new research directions and future perspectives for Cannabis-based medicine. In conclusion, the combination of nanotechnology and cannabinoid pharmacology holds promise for delivering more effective and safer therapeutic solutions for a broad spectrum of medical conditions, making this an exciting area of research with profound implications for the healthcare and pharmaceutical industries. Full article

The current study focuses on a preliminary evaluation of the use of solid residues produced from the distillation of selected medicinal and aromatic plants (MAP) as fertilizers for alkaline soils. Specifically, the residues of hemp (Cannabis sativa L.), helichrysum (Helichrysum Italicum (Roth) G. Don), lavender (Lavandula angustifolia Mill.), oregano (Origanum vulgare L.), rosemary (Rosmarinus officinalis L.) and sage (Salvia officinalis L.) were added in an alkaline and calcareous soil at the rates of 0 (control), 1, 2, 4 and 8%, in three replications (treatments), and the treated soils were analyzed. The results showed that upon application of the residues, soil electrical conductivity (EC), organic C, total N and the C/N ratio significantly increased, especially at the 4 and 8% rates. The same was found for soil available P, K, B, Cu and Mn. The effects of the residues on soil pH, cation exchange capacity (CEC) and available Zn and Fe were rather inconclusive, whereas soil available N significantly decreased, which was somewhat unexpected. From the different application rates tested, it seems that all residues could improve soil fertility (except N?) when they were applied to soil at rates of 2% and above, without exceeding the 8% rate. The reasons for the latter statement are soil EC and available Mn: the doubling of EC upon application of the residues and the excessive increase in soil available Mn in treatments with 8% residues raise concerns of soil salinization and Mn phytotoxicity risks, respectively. This work provides the first step towards the potential agronomic use of solid residues from MAP distillation in alkaline soils. However, for the establishment of such a perspective, further research is needed in respect to the effect of residues on plant growth and soil properties, by means of at least pot experiments. Based on the results of the current study, the undesirable effect of residues on soil available N should be investigated in depth, since N is the most important essential element for plant growth, and possible risks of micronutrient phytotoxicities should also be studied. In addition, application rates between 2 and 4% should be studied extensively in order to recommend optimum application rates of residues to producers. Full article

Purpose: Suicide is a leading cause of death among children and adolescents worldwide. This study examined the prevalence and characteristics of suicides among children and adolescents (aged ≤ 19 years) over a 13-year period in the broader area of Athens, Greece. Key aspects analyzed included victim demographics, circumstances surrounding the incidents, and methods employed. Methods: A retrospective analysis was conducted on autopsy cases performed at the Department of Forensic Medicine and Toxicology, National and Kapodistrian University of Athens, from 1 January 2011, to 31 December 2023. Results: Out of 5819 autopsies conducted between 2011 and 2023, 371 were classified as suicides. Among these, 12 cases (representing 3.2% of suicides) involved children and adolescents aged ≤ 19 years and met the study’s inclusion criteria for detailed forensic analysis. The average age of the victims was 17.7 ± 2.1 years (range: 14–19), with males representing 58.3% of cases. Hanging was the most common method of suicide (9 cases, 75.0%), followed by firearm use, falls from height, and hydrogen sulfide inhalation (one case each). Death occurred in the home in 10 cases (83.3%), with 6 specifically taking place in the bedroom. Scars indicative of prior self-harming behavior were present in two cases (16.7%), while suicide notes were found in three cases (25.0%). Toxicological analysis revealed alcohol and cannabis use in one case, cannabis alone in one case, and alcohol alone in two cases. Four victims (33.3%) had a documented psychiatric diagnosis, with two of them under antidepressant treatment at the time of death. Conclusions: This study highlights the forensic value of autopsy-based investigations in unveiling hidden patterns of adolescent suicidality and informs targeted prevention strategies. Integrating medico-legal findings into public health responses may enhance early identification and intervention in vulnerable youth populations. Full article

Hemp (Cannabis sativa L.) seeds have been essential for human nutrition for millennia. The products and by-products of hemp seeds are gaining popularity nowadays as food, feed and medicine for their high nutritional and nutraceutical properties. In parallel, concerns about phytate, an antinutritional compound limiting nutrient bioavailability in hemp seeds and seed meal are rising. Hemp seeds contain an array of nutrients, but their bioavailability is mostly unknown. Here, we report nutrient and phytate concentrations and phytate contents in source seeds and multiplied seeds of seven industrial hemp varieties. We estimated the bioavailability of specific nutrients based on calculated molar ratios of phytate to minerals. Seed multiplication was carried out in a phytotron using a compost-based growth medium. Five macronutrients (P, K, Mg, S, Ca), four micronutrients (Fe, Mn, Zn, Cu) and Cr were measured in seeds using ICP-OES. Seed phytate was determined using a UV-visible spectrophotometer rapid colourimetric assay. The results revealed significant differences between seven industrial hemp varieties for most macro- and micronutrient concentrations (not Fe), phytate concentration and content and phytate-to-mineral molar ratios in both source and multiplied seeds. Multiplied hemp seeds had higher K, Mn and Zn and, lower Cr and phytate concentrations and lower phytate content than source seeds. Considering nutrient bioavailability, Ca and Fe are non-bioavailable, and Zn is bioavailable in hemp seeds. Ferimon has increased Zn bioavailability in source and multiplied seeds, indicating the variety’s potential for seed production in Western Australia. Full article

Obsessive–compulsive disorder (OCD) has an estimated prevalence between 1 and 2.3%. Existing treatments may not be suitable or effective for all people with OCD, and there is increasing interest in whether these individuals may benefit from the use of cannabis-based medical products (CBMPs). We document the characteristics of 257 people reporting a diagnosis of OCD within Project T21, a study of medical cannabis patients, and examined whether the use of prescribed cannabinoids improves quality of life. Individuals with OCD were prescribed an average of 2.2 CBMPs, with most products classified as THC-dominant flowers (73.7%). Three months after initiating treatment, there were substantial improvements in quality of life (Cohen’s d = 0.48; 95% CI = 0.29–0.65), general health (Cohen’s d = 0.43; 95% CI = 0.26–0.61), mood/depression (Cohen’s d = 0.85; 95% CI = 0.65–1.04), and sleep (Cohen’s d = 0.61; 95% CI = 0.43–0.79). There was a corresponding reduction in anxiety symptoms among the subsample who completed the GAD-7 (Cohen’s d = 1.14; 95% CI = 0.84–1.44). Eight individuals (5.7%) reported a total of 14 adverse effects, with the majority of these (57%) being described as mild. Given emerging evidence that those with OCD can benefit from CBMPs, coupled with the increased availability of these unlicensed products internationally, there is a need for more research, including clinical trials, to identify those who may benefit most from the use of these medicines. Full article

Neuropathic pain is a chronic disorder that arises from damaged or malfunctioning nerves. Hypersensitivity to stimuli, also known as hyperalgesia, can cause a person to experience pain from non-painful stimuli, termed allodynia. Cannabis-based medicines (CBMs) may provide new treatment options to manage neuropathic pain. A review of the relevant studies was conducted to evaluate the effectiveness of CBMs in treating neuropathic pain. Scientific literature was systematically searched from January 2003 to December 2024 using the Web of Science Core Collection, PubMed, and MEDLINE. A total of 22 randomized controlled trials (RCTs) were identified that considered the use of 1′,1′-dimethylheptyl-Δ⁸-tetrahydrocannabinol-11-oic acid (CT-3), Δ⁹-tetrahydrocannabinol (Δ⁹-THC), cannabidiol (CBD), combinations of Δ⁹-THC with CBD, and cannabidivarin for treatment of neuropathic pain. Significant reductions in pain were reported in 15 studies focused on the treatment of multiple sclerosis, spinal cord injuries, diabetic neuropathy, postherpetic neuralgia, HIV-associated sensory neuropathy, peripheral neuropathic pain, complex regional pain syndrome, chronic radicular neuropathic pain, and peripheral neuropathy of the lower extremities. These positive outcomes often adopted personalized and adjusted dosing strategies. By contrast, seven RCTs observed no significant pain relief compared to placebo, although some had minor improvements in secondary outcomes, such as mood and sleep. Collectively, CBM treatments may improve pain scores, but study limitations such as small sample sizes and study durations, high placebo response rates, and trial unblinding because of the psychoactive effects of cannabinoids all hinder data interpretation and the extrapolation to chronic pain conditions. Hence, future RCTs will need to have larger numbers and be more extended studies that explore optimal dosing and delivery methods and identify patient subgroups that are most likely to benefit. While CBMs show potential, their current use balances modest benefits against possible adverse effects and variable outcomes. Full article

Cannabis sativa L. is divided into three main groups: drug-type, intermediate-type, and fiber-type. The presence of tetrahydrocannabinol (THC) exceeding 0.2–0.3% in drug-type and intermediate Cannabis that utilized for recreational and medicinal purposes renders them illegal due to potential mental health implications. Fiber-type contains high cannabidiol (CBD) and low THC, making it suitable for household use such as textiles and animal feed. Accurate classification is essential to prevent misuse of the plant. High-performance thin-layer chromatography (HPTLC) and ultra-performance liquid chromatography (UPLC), used respectively for the qualitative and quantitative analyses of THC and CBD particularly in female inflorescences, categorized 85 samples of 46 cultivars used in this study into three distinct chemotypes. While chemotype analysis of a very specific organ of the plants accurately identifies Cannabis groups, it requires time-consuming plant development to maturity. Genotype analysis targeting tetrahydrocannabinolic acid synthase (THCAS) and cannabidiolic acid synthase (CBDAS) genes offers a faster alternative for classifying Cannabis types, allowing for sample determination from any part at any developmental stage of the plant. DNA sequencing allowed a phylogenetic analysis based on these genes, classifying all 85 samples of 46 cultivars into the same three groups identified by chemotype analysis. This study is the first to successfully examine the relationship between chemotype and genotype in 85 samples of 46 cultivars. Rapid identification of Cannabis types through genotype analysis lays the groundwork for future development of detection kits. Full article

Cannabis sativa L. is cultivated for therapeutic and recreational use. Delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD) are primarily responsible for its psychoactive and medicinal effects. As the global cannabis industry continues to expand, constant review and optimization of horticultural practices are needed to ensure a reliable harvest and improved crop quality. There is currently uncertainty about the optimal harvest time of C. sativa, i.e., when cannabinoid concentrations are at their highest during inflorescence maturation. At present, growers observe the color transition of stigmas from white to amber as an indicator of harvest time. This research investigates the relationship between stigma color and cannabinoid concentration using liquid chromatography–mass spectrometry (LCMS) and digital image analysis. Additionally, early screening prediction models have also been developed for six cannabinoids using near-infrared (NIR) spectroscopy and LCMS to assist in early cannabinoid determination. Among the genotypes grown, 22 of 25 showed cannabinoid concentration peaks between the third (mostly amber) and fourth (fully amber) stages; however, some genotypes peaked within the first (no amber) and second (some amber) stages. We have determined that the current ‘rule of thumb’ of harvesting when a cannabis plant is mostly amber is still a useful approximation in most cases; however, studies on individual genotypes should be performed to determine their individual optimal harvest time based on the desired cannabinoid profile or total cannabinoid concentration. Full article

Background/Objectives: Recent evidence supporting the medicinal use of cannabis has brought significant regulatory changes regarding its legal status, cultivation, and use. Several countries have adopted regulatory strategies enabling access to cannabis-based medicinal products; however, the regulation and availability of high-quality cannabis products differs globally. This work aimed to explore the regulatory pathways available for cannabis-based medicinal products, particularly those regulated as medicines, and establish the current landscape of those approved. Methods: The public repositories of the European Medicines Agency, U.S. Food and Drug Administration, and Therapeutic Goods Administration were searched. A consumer website, Amazon, was searched to provide illustrative examples of cannabis products readily available to consumers. Finally, clinical trial data were collected to evaluate trends in medicinal cannabis research. Results: Only Epidyolex™ has been approved by these three agencies. Whilst topical cannabinoid consumer products are popular, no topical cannabis-based medicines have been approved by regulators, despite being the focus of several clinical trials. There are few regulator-approved cannabis-based medicines available and, evidence supporting the therapeutic use of consumer products is very limited. A complex regulatory and legislative scenario hinders research on and development of cannabis-based medicines, leaving a market gap filled with unregulated products that are potentially misleading regarding their therapeutic claims. Full article

Introduction: Multiple Sclerosis (MS) is associated with a wide range of debilitating symptoms, and conventional therapies often fail to adequately address the disease’s multifaceted challenges. Cannabidiol (CBD) 13.0% + Delta9-tetrahydrocannabinol (THC) 9.0% (CBD13/THC9), a vaporized cannabis-based medicinal product, presents a novel therapeutic option for managing MS symptoms. Methods: This single-center longitudinal study followed 69 MS patients over a six-month period. Participants were assessed at treatment initiation and at three- and six-month intervals. Key measures included muscle spasticity, urine bladder dysfunction, and the evaluation of disability progression rate. The evaluation included the Modified Ashworth Scale (MAS), the Post Void Residual (PVR) volume, and the Expanded Disability Status Scale (EDSS). Results: Significant improvement was observed across all outcome assessments. The EDSS score was decreased over time (p = 0.009), indicating a slight reduction in disability progression rate, while MAS scores showed substantial improvement in muscle spasticity (p < 0.001). Urine bladder function improved significantly, with PVR volume showing notable improvement between baseline and the six-month assessment (p < 0.001). Correlation analyses revealed that a gradual increase in vaporized CBD13/THC9 dose was correlated with slightly lower EDSS scores, while the adverse effects were negatively associated with the frequency of cannabinoid use. Finally, patients who were smokers used CBD13/THC9 more frequently. Conclusions: The vaporized CBD13/THC9 formulation demonstrated notable efficacy in slightly improving disability progression rate via reduction in muscle spasticity and urine bladder dysfunction in MS patients. This highlights its addon therapeutic value during rehabilitation in MS patients with debilitating disability symptoms. Full article

Cannabis sativa is used for multiple purposes, notably for its medicinal properties. It produces various secondary metabolites, including cannabinoids, terpenes, and flavonoids, which have therapeutic value and typically produce high amounts in female plants. The growth of the global cannabis market has led to intensive breeding efforts to develop elite cultivars with enhanced secondary metabolite profiles. As a dioecious and anemophilous plant, it produces staminate and pistillate inflorescences on separate plants and relies on wind for pollination, rendering traditional propagation methods challenging owing to high genetic recombination in progeny. Consequently, asexual propagation (micropropagation) is commonly employed to maintain female clones entirely. Micropropagation/direct organogenesis is a tissue culture technique that produces numerous disease-free clone plants in vitro more rapidly than traditional rooted cuttings. Factors such as sterilization, hormonal balance, explant type, nutrient additives, carbon source, pH, and environment influence the success of cultivar-specific micropropagation. In this review, we discussed how these factors affect cannabis micropropagation based on recent findings, emphasizing the importance of optimizing cultivar-specific protocols for long-term germplasm conservation and efficient breeding based on a mechanistic background. Full article

Background: Cannabidiol (CBD) is a cannabinoid present in the hemp plant (Cannabis sativa L.). Non-medicinal CBD oils with typically 5–40% CBD are advertised for various alleged positive health effects. While such foodstuffs containing cannabinoids are covered by the Novel Food Regulation in the European Union (EU), none of these products have yet been authorized. Nevertheless, they continue to be available on the European market. Methods: The Permanent Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG) reviewed the currently available data on adverse and potential beneficial effects of CBD in the dose range relevant for foods. Results: Increased liver enzyme activities were observed in healthy volunteers following administration of 4.3 mg CBD/kg bw/day and higher for 3–4 weeks. As lower doses were not tested, a no observed adverse effect level (NOAEL) could not be derived, and the dose of 4.3 mg/kg bw/day was identified as the lowest observed adverse effect level (LOAEL). Based on the CBD content and dose recommendations of CBD products on the market, the SKLM considered several exposure scenarios and concluded that the LOAEL for liver toxicity may be easily reached, e.g., via consumption of 30 drops of an oil containing 20% CBD, or even exceeded. A critical evaluation of the available data on potential beneficial health effects of CBD in the dose range at or below the LOAEL of 4.3 mg/kg bw/day revealed no scientific evidence that would substantiate health claims, e.g., in relation to physical performance, the cardiovascular, immune, and nervous system, anxiety, relaxation, stress, sleep, pain, or menstrual health. Conclusions: The SKLM concluded that consumption of CBD-containing foods/food supplements may not provide substantiated health benefits and may even pose a health risk to consumers. Full article

Neuroinflammation is a key factor in the progression of neurodegenerative diseases, driven by the dysregulation of molecular pathways and activation of the brain’s immune system, resulting in the release of pro-inflammatory and oxidative molecules. This chronic inflammation is exacerbated by peripheral leukocyte infiltration into the central nervous system. Medicinal plants, with their historical use in traditional medicine, have emerged as promising candidates to mitigate neuroinflammation and offer a sustainable alternative for addressing neurodegenerative conditions in a green healthcare framework. This review evaluates the effects of medicinal plants on neuroinflammation, emphasizing their mechanisms of action, effective dosages, and clinical implications, based on a systematic search of databases such as PubMed, SCOPUS, and Web of Science. The key findings highlight that plants like Cleistocalyx nervosum var. paniala, Curcuma longa, Cannabis sativa, and Dioscorea nipponica reduce pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), inhibit enzymes (COX-2 and iNOS), and activate antioxidant pathways, particularly Nrf2. NF-κB emerged as the primary pro-inflammatory pathway inhibited across studies. While the anti-inflammatory potential of these plants is significant, the variability in dosages and phytochemical compositions limits clinical translation. Here, we highlight that medicinal plants are effective modulators of neuroinflammation, underscoring their therapeutic potential. Future research should focus on animal models, standardized protocols, and safety assessments, integrating advanced methodologies, such as genetic studies and nanotechnology, to enhance their applicability in neurodegenerative disease management. Full article

Introduction: The official implementation of pharmaceutical-grade cannabis raw materials for medicinal use has permitted doctors to prescribe and pharmacists to prepare cannabis-based formulations. The objective of the pharmaceutical development and manufacturing process optimization work was to propose a suppository formulation containing doses of 25 mg and 50 mg of tetra-hydrocannabinol (∆-9-THC) as an alternative to existing inhalable or orally administered formulations. The formulation could be used for rectal or vaginal administration, thereby providing dosage control in the treatment of endometriosis and other conditions involving pain. In this study, two substrates from suppositories with standardized Cannabis extractum normatum (CEX) were used: cocoa butter and Witepsol^® H15. Materials and Methods: The long-term stability of CEX was investigated over a period of up to 24 months. The concentrations of ∆-9-THC, cannabidiol (CBD), and cannabinol (CBN) were determined using an HPLC method. Furthermore, the water content of the extract, the ethanol residue, and the microbiological purity were determined. The pharmaceutical properties of CEX-incorporated suppositories, namely content uniformity, hardness, softening time, total deformation time, disintegration time, and the release profile of ∆-9-THC, CBD, and CBN, were evaluated in order to develop optimal preparation procedures for pharmacists. Results and Discussion: Following a 24-month stability study on CEX, no significant alterations in component content were observed beyond the specified requirements. The disintegration time, total deformation time, and hardness of the suppositories based on Witepsol^® H15 with CEX were found to be longer and higher, respectively, than those of suppositories formulated with cocoa butter. In vitro studies demonstrated that suppositories prepared with Witepsol^® H15 exhibited superior release of ∆-9-THC compared to those prepared with cocoa butter. Conclusions: We suggest that pharmacists making prescription drugs in a pharmacy setting in the form of medical marijuana suppositories will receive a better release profile of the drug by choosing Witepsol® H15 as a substrate. Full article