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Chemical profiling of Cannabis varieties cultivated for medical purposes in southeastern Brazil
Abstract
Cannabis cultivation for medical purposes in Brazil has been increased in the last years. While cannabis crops are prohibited, hundreds patients have been granted with judicial authorizations and there is little information about the cultivation conditions, yields and chemical profiles of the plants. Cannabis plants contain hundreds of compounds, with cannabinoids and terpenes the main drivers of their toxicological and pharmacological properties. Besides the cannabinoids, terpene contents are useful for the chemotaxonomic classification of different varieties, and their role in forensic analyses should be further delineated. The present study monitored cannabis crops of fifteen participants who were granted special licenses by the Brazilian Courts in Rio de Janeiro and São Paulo. The cultivation conditions were monitored and five cannabinoids (tetrahydrocannabinol acid-THCA, tetrahydrocannabinol-THC, cannabidiolic acid-CBDA, cannabidiol-CBD and cannabinol-CBN) and nineteen terpenes were quantified in cannabis flowers. The total grow cycle of thirty-five cannabis plants ranged from10 to 24 weeks. The dry flower yields ranged 22 to 90 g per plant. Most cannabis specimens were CBD-rich varieties (CBD levels from 1.6 to 16.7%, and THC levels from 0.0 to 2.6%, n=22) used to treat epileptic patients. The THC-rich varieties contained CBD levels ranging from 0.03 to 0.8%, and THC levels from 0.7 to 20.1%, n=11. Fewer of the samples contained THC:CBD ratios of approximately 1:1 (CBD levels of 3.3 to 3.8% and THC levels of 2.2 to 3.7%, n=2). The most abundant terpenes in the cannabis flowers were beta-caryophyllene, alpha-humulene, guaiol and alpha-bisabolol. CBD-rich varieties showed significant higher levels of beta-caryophyllene and alpha-humulene in comparison with THC-rich varieties.
Overall, the study herein provides data concerning medical cannabis crops grown in a region of Brazil that not only guide individual medical cannabis cultivation methods but also aid forensic analyses.
... The two main cannabinoids responsible for the pharmacological properties of Cannabis and its extracts are tetrahydrocannabinol (THC) and cannabidiol (CBD) [15]. Both exhibit paradoxical effects on the central nervous system, acting synergistically in pharmaceutical formulations: the former is a psychoactive compound with euphoric, antiemetic, and analgesic properties; while the latter is a depressant and antipsychotic with anticonvulsant, anxiolytic, anti-inflammatory, and antioxidant properties [16]. ...
... Subsequently, in 2019, the agency established a new category, 'Cannabis products', permitting the manufacture and importation of oils and products containing cannabidiol. More recently, the Superior Court of Justice authorized the cultivation of Cannabis with low THC content (0.3%) for medicinal purposes [15]. ...
... The developed method enables the efficient processing of more than 50 samples, showcasing practicality and reproducibility. Table 4. Results for CBD, THC, and CBN concentrations for four veterinary CHEs (1-4) and fourteen human CHEs (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Data are reported as mean ± standard deviation (n = 3). ...
The Cannabis market is experiencing steady global growth. Cannabis herbal extracts (CHE) are interesting and sought-after products for many clinical conditions. The medical potential of these formulations is mainly attributed to neutral cannabinoids, such as cannabidiol (CBD), tetrahydrocannabinol (THC), and cannabinol (CBN), and their non-standardized content poses a significant fragility in these pharmaceutical inputs. High-resolution mass spectrometry portrays a powerful alternative to their accurate monitoring; however, further analytical steps need to be critically optimized to keep up with instrumental performance. In this study, Full Factorial and Box–Behnken designs were employed to achieve a multivariate optimization of CBD, THC, and CBN extraction from human and veterinary commercial CHE using a minimum methanol/hexane 9:1 volume and short operational times. A predictive model was also constructed using the Response Surface Methodology and its accuracy was validated. Agitation and sonication times were identified as the most significant operational extraction parameters, followed by the extraction mixture volume. The final setup of the optimized method represented a significantly faster and cheaper protocol than those in the literature. The selected neutral cannabinoids quantification was conducted using ultra high-performance liquid chromatography coupled to high-resolution tandem mass spectrometry (UHPLC-HRMS/MS) with a precision of <15%, accuracy of 69–98%, sensitivity of 23–39 ng kg⁻¹, and linearity regarding pharmaceutical requirements. State-of-the-art levels of analytical sensitivity and specificity were achieved in the target quantification due to high-resolution mass spectrometry. The developed method demonstrated reliability and feasibility for routine analytical applications. As a proof-of-concept, it enabled the efficient processing of 16 samples of commercial CHE within a three-hour timeframe, showcasing its practicality and reproducibility, and highlighting its potential for broader adoption in similar scenarios for both human and veterinary medicines.
... The compounds can be distinguished using a variety of chromatographic techniques, including High-Performance Liquid Chromatography (HPLC), Thin-Layer Chromatography (TLC), and Gas Chromatography (GC) combined with mass spectrometry [67]. Carvalho et al. [81] conducted the first study to illustrate the chemical composition and potency of medicinal Cannabis cultivated in Brazil. The majority of the Cannabis samples contained high CBD (CBD total = 3.7%), with a maximum Δ 9 -THC content of 2.6%. ...
... Similarly, other reports have investigated various South African Cannabis strains or landraces and their cannabinoid profiles [85]. It was found that Mpondo Gold has a high Δ 9 -THC concentration (about 20%) and an earthy and woody Cannabis aroma [85,86], whereas the Cannabis strain called Durban Poison is known for its sweet, fruity flavour, high Δ 9 -THC level ranging from 15% and 25%, low CBD level (0.1-0.3%), and CBG (0.6-1.4%) and THCV (0.2-1.8%) [81]. The ...
... The compounds can be distinguished using a variety of chromatographic techniques, including High-Performance Liquid Chromatography (HPLC), Thin-Layer Chromatography (TLC), and Gas Chromatography (GC) combined with mass spectrometry [67]. Carvalho et al. [81] conducted the first study to illustrate the chemical composition and potency of medicinal Cannabis cultivated in Brazil. The majority of the Cannabis samples contained high CBD (CBD total = 3.7%), with a maximum ∆ 9 -THC content of 2.6%. ...
Cannabis sativa L. is a monotypic genus belonging to the family Cannabaceae. It is one of the oldest species cultivated by humans, believed to have originated in Central Asia. In pivotal judgements in 2016 and 2018, the South African Constitutional Court legalised the use of Cannabis within the country for medicinal and recreational purposes, respectively. These decrees opened opportunities for in-depth research where previously there had been varying sentiments for research to be conducted on the plant. This review seeks to examine the history, genetic diversity, and chemical profile of Cannabis. The cultivation of Cannabis by indigenous people of southern Africa dates back to the eighteenth century. Indigenous rural communities have been supporting their livelihoods through Cannabis farming even before its legalisation. However, there are limited studies on the plant’s diversity, both morphologically and genetically, and its chemical composition. Also, there is a lack of proper documentation of Cannabis varieties in southern Africa. Currently, the National Centre for Biotechnology Information (NCBI) has 15 genome assemblies of Cannabis obtained from hemp and drug cultivars; however, none of these are representatives of African samples. More studies are needed to explore the species’ knowledge gaps on genetic diversity and chemical profiles to develop the Cannabis sector in southern Africa.
... Though importation of Cannabis products has been regulated in 2013 and national production and trade have been regulated since 2019 in Brazil, several patients have claimed for the cultivation and formulation of extracts at home. In this scenario, hundreds of judicial authorizations for Cannabis cultivation and artisanal extract preparation have been granted in Brazil (Carvalho et al. 2022). ...
... Most were cultivated by clonal propagation and other specimens by seeds. Clonal propagation was done at the participant's home, with cultivation conditions, total grow cycle, harvest criteria, yields, and chemical profiles studied and previously published by our group (Carvalho et al. 2022). Cannabis varieties were chosen by the participants. ...
... The majority of the terpene levels were quantified before and after the decarboxylation process at 110 °C/5 h in nine specimens (seven Harle Tsu and two Tolomelli varieties) via a gas chromatographic-mass spectrometry (GC-MS) method partially validated and previously published by our group (Carvalho et al. 2022). Briefly, samples were prepared by mixing the crushed plant material (100 mg) with 4 ml hexane 96% HPLC grade supplied by Sharlau Chemicals® (Barcelona, Spain), in an ultrasound bath for 60 min, and centrifugation at 2007 g for 10 min. ...
The popularity of Cannabis extracts in the treatment of hard-to-manage clinical conditions and the lack of access to pharmaceutical grade Cannabis products have impacted the increase of clandestine and artisanal product consumption in Brazil. Currently, hundreds of judicial authorizations for Cannabis cultivation and artisanal extract preparation have been granted in Brazil. To evaluate the artisanal preparation techniques and improve Cannabis extract quality, preparations by patients were monitored between 2017 and 2022, and a preparation method by supercritical fluid extraction was developed. Between 2017 and 2018, the most common technique used by participants was the decoction of flowers in heated oil that provided extracts with low cannabinoid levels and the predominance of acid cannabinoids as well as high microbiological contamination. Between 2019 and 2022, decarboxylation by heating and extraction by maceration in ethanol were tested to decrease the microbiological contamination and increased the neutral cannabinoid levels in the extracts. Cannabidiol levels measured in 2021 (26.0 ± 31.1 mg/g) and 2022 (42.9 ± 15.5 mg/g) in the extracts prepared at home with pharmaceutical support were similar to industrial products and higher in cannabinoids than the products supplied by non-governmental organizations. Cannabis extracts prepared by supercritical fluid extraction at 50 °C at a pressure of 15 MPa and 800 g CO2 for 15–24 min from 9–24 g decarboxylated Cannabis flower provided cannabidiol recoveries > 80%. Soxhlet extraction, used as a comparison method, showed excellent recoveries and is a low-cost alternative technology that is feasible to implement in community pharmacies.
... Cannabis plants contain many phytocannabinoids, which are being researched for their therapeutic properties. Two primary ones are the D9tetrahydrocannabinol (THC) and cannabinol (CBN), while the others, such as cannabidiol (CBD), cannabidiol-carboxylic acid, cannabigerol (CBG), cannabichromene (CBC), are undergoing extensive investigation (Carvalho et al., 2022). ...
... Cannabis strains with high levels of CBD are classified as hemp (fiber and seed productions) or fiber types, whereas those with high levels of THC are classified as marijuana or narcotic types. Cannabis plants are considered intermediate when their THC/CBD ratio is approximately 1 (Carvalho et al., 2022). In this study, THC-, CBD-, and intermediate-type cultivars are examined to determine the effect of microbial bioinoculants on biomass production and associated microbial communities. ...
The root microbiome of medical cannabis plants has been largely unexplored due to past legal restrictions in many countries. Microbes that live on and within the tissue of Cannabis sativa L. similar to other plants, provide advantages such as stimulating plant growth, helping it absorb minerals, providing protection against pathogen attacks, and influencing the production of secondary metabolites. To gain insight into the microbial communities of C. sativa cultivars with different tetrahydrocannabinol (THC) and cannabidiol (CBD) profiles, a greenhouse trial was carried out with and without inoculants added to the growth substrate. Illumina MiSeq metabarcoding was used to analyze the root and rhizosphere microbiomes of the five cultivars. Plant biomass production showed higher levels in three of five cultivars inoculated with the arbuscular mycorrhizal fungus Rhizophagus irregularis and microbial suspension. The blossom dry weight of the cultivar THE was greater when inoculated with R. irregularis and microbial suspension than with no inoculation. Increasing plant biomass and blossom dry weight are two important parameters for producing cannabis for medical applications. In mature Cannabis, 12 phytocannabinoid compounds varied among cultivars and were affected by inoculants. Significant differences (p ≤ 0.01) in concentrations of cannabidivarinic acid (CBDVA), cannabidivarin (CBDV), cannabigerol (CBG), cannabidiol (CBD), and cannabigerolic acid (CBGA) were observed in all Cannabis cultivars when amended with F, K1, and K2 inoculants. We found microbes that were shared among cultivars. For example, Terrimicrobium sp., Actinoplanes sp., and Trichoderma reesei were shared by the cultivars ECC-EUS-THE, CCL-ECC, and EUS-THE, respectively. Actinoplanes sp. is a known species that produces phosphatase enzymes, while Trichoderma reesei is a fungal train that produces cellulase and contributes to organic matter mineralization. However, the role of Terrimicrobium sp. as an anaerobic bacterium remains unknown. This study demonstrated that the use of inoculants had an impact on the production of phytocannabinoids in five Cannabis cultivars. These inoculants could have useful applications for optimizing cannabis cultivation practices and increasing the production of phytocannabinoids.
... Analysis of phytocannabinoid concentrations revealed a preponderance of THC-dominant cannabis, with only a small minority of samples having a CBD-dominant or a THC: CBD equivalent chemotype. These three main cannabis chemotypes, with THC-dominant cannabis being the most prevalent, is typical of commercial and medicinal markets worldwide [57][58][59] . Minor phytocannabinoids, such as CBG, CBN and CBC, were present in low to negligible concentrations. ...
The Australian Capital Territory (ACT), a region that includes Australia’s capital, Canberra, decriminalised small-scale cannabis cultivation and possession in January 2020. Here, we examined cannabis use and cultivation behaviours, experiences and attitudes of current and past small-scale ACT cannabis cultivators. ACT residents (n = 311) who currently cultivate or have previously cultivated cannabis completed a cross-sectional online survey (‘CAN-ACT’) and provided home-grown cannabis for phytocannabinoid analysis (optional). Reasons for cultivation included a preference for home-grown cannabis to self-supply, enjoyment of the process and avoiding criminal networks. Cannabis intake was a median of 1 gram on a typical day used and the number of plants grown per year was a median of 4. Various cultivation challenges were identified, most commonly mould, nutrient deficiency and spider mites. Cannabis samples (n = 71) generally exhibited moderate THC content (mean 8.99 ± SEM 0.51% [w/w]) and low CBD content (< 0.1%). Few samples exceeded contaminant guidelines for heavy metals or pesticides. Respondents identified various grey areas in current legislation that might lead to inadvertent criminal activity, and many (52%) remained anxious about arrest. In general, recent legislative changes appear to support community needs. Options for further legislative refinement are discussed.
... A reasonable outcome is the stimulus to innovation in agriculture and biotechnology. Such advancements would not only benefit the pharmaceutical industry, but also have implications for other sectors, including food, cosmetics, and wellness products 7,8 . ...
Trema micranthum (Cannabaceae) has emerged as a promising new source of cannabinoids, including cannabidiol (CBD). Given the substantial medicinal demand for cannabinoids and the regulatory challenges associated with Cannabis sativa due to the presence of Δ⁹-tetrahydrocannabinol (THC), this study sought to explore the presence of CBD, THC, and their precursors, Δ⁹-tetrahydrocannabinolic acid A (THCA A) and cannabidiolic acid (CBDA), in various parts of Trema micranthum using UHPLC-HRMS/MS (Orbitrap). Extracts from fruits, leaves, inflorescences, and stems were obtained using a methanol/hexane (9:1, v/v) solvent mixture. UHPLC coupled with an Orbitrap mass spectrometer was employed for cannabinoid identification and quantification, with standard mixtures prepared in methanol. The extracts yielded significant quantities, such as 6.6%/g from leaves and 3%/g from fruits. Cannabinoids were detected in fruits, leaves, and inflorescences, with acidic forms (CBDA and THCA A) present in higher concentrations than their neutral counterparts. Notably, leaves contained 4.43 × 10⁻³ µg/g of CBD and 1.05 × 10⁻³ µg/g of THC. These findings, facilitated by high-resolution analytical methods, underscore the potential of Trema micranthum as an alternative source for cannabinoids, guiding future research in this area.
... A reasonable outcome is the stimulus to innovation in agriculture and biotechnology. Such advancements would not only bene t the pharmaceutical industry, but also have implications for other sectors, including food, cosmetics, and wellness products 7,8 . ...
Trema micranthum (Cannabaceae) has emerged as a promising new source of cannabinoids, including cannabidiol (CBD). Given the substantial medicinal demand for cannabinoids and the regulatory challenges associated with Cannabis sativa due to the presence of Δ ⁹ -tetrahydrocannabinol (THC), this study sought to explore the presence of CBD, THC, and their precursors, Δ ⁹ -tetrahydrocannabinolic acid A (THCA A) and cannabidiolic acid (CBDA), in various parts of Trema micranthum using UHPLC-HRMS/MS (Orbitrap). Extracts from fruits, leaves, inflorescences, and stems were obtained using a methanol/hexane (9:1, v/v) solvent mixture. UHPLC coupled with an Orbitrap mass spectrometer was employed for cannabinoid identification and quantification, with standard mixtures prepared in methanol. The extracts yielded significant quantities, such as 6.6%/g from leaves and 3%/g from fruits. Cannabinoids were detected in fruits, leaves, and inflorescences, with acidic forms (CBDA and THCA A) present in higher concentrations than their neutral counterparts. Notably, leaves contained 4.43 x 10⁻³ µg/g of CBD and 1.05 x 10⁻³ µg/g of THC. These findings, facilitated by high-resolution analytical methods, underscore the potential of Trema micranthum as an alternative source for cannabinoids, guiding future research in this area.
... 41 Such models have already been successfully applied to define groups of metabolic diversity in C. sativa cultivated in diverse locations, including Canada, 42 USA, 43 Iran, 44 and Brazil. 45 For instance, chemotaxonomic models have revealed only three clusters of metabolic diversity on 396 medicinal C. sativa samples available to patients in the US (state of Nevada). 42 A possible explanation for this loss of chemical diversity is the breeding programs favoring the production of Δ 9 -THC, which have been prevalent in the US, 46,47 the UK, 48 and Europe 49 over the last decades. ...
Introduction
Cannabis sativa is a highly versatile plant with a long history of cultivation and domestication. It produces multiple compounds that exert distinct and valuable therapeutic effects by modulating diverse biological systems, including the endocannabinoid system (ECS). Access to standardized, metabolically diverse, and reproducible C. sativa chemotypes and chemovars is essential for physicians to optimize individualized patient treatment and for industries to conduct drug‐discovery campaigns.
Objective
This study aimed to characterize and assess the phytochemical diversity of C. sativa chemotypes in diverse ecological regions of Colombia, South America.
Methodology
Ten cannabinoids and 23 terpenes were measured using liquid and gas chromatography, in addition to other phenotypic traits, in 156 C. sativa plants that were grown in diverse ecological regions in Colombia, a hotspot for global biodiversity.
Results
Our results reveal significant phytochemical diversity in Colombian‐grown C. sativa plants, with four distinct chemotypes based on cannabinoid profile. The significant amount of usually uncommon terpenes suggests that Colombia's environments may have unique capabilities that allow the plant to express these compounds. Colombia's diverse climates offer enormous cultivation potential, making it a key player in both domestic and international medicinal and recreational C. sativa trade.
Conclusion
These findings underscore Colombia's capacity to pioneer global C. sativa production diversification, particularly in South America with new emerging markets.
... The seeds of C. sativa contain a high amount of omega-3 fatty acids (Pattnaik et al., 2022). C. sativa has also medicinal benefits (Horne et al., 2020) having potential secondary metabolites including delta-9tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN) and, terpene compounds (Roman and Houston, 2020;Carvalho et al., 2022). C. sativa is a native plant of Central and South Asian countries evident for the last 5000 years like Pakistan, India, Russia, China, and Iran. ...
Cannabis sativa possess substantial amount of omega-3 fatty acids and several medicinal benefits with potential secondary metabolites. This study employed rbcL, matK, and trnH-psbA barcode markers and RAPD marker to explore genetic diversity in C. sativa populations in Punjab, Pakistan. In population genetic study using DNA barcode markers, cladogram showed investigated samples were genetically similar; however, demonstrated significant genetic diversity with the available DNA sequences of this plant from other regions and countries. The nucleotide sequence variation (% divergence) indicated high intraspecific variation in plants of different geographical zones. However, the RAPD marker analysis displayed genetic diversity among collected Cannabis sativa samples. The principal component analysis reinforced these findings by providing a spatial representation of genetic distances among the samples that revealed a considerable genetic diversity among the collected material and significant intraspecific variation was observed, indicating diverse genetic profiles across geographical regions. This research highlights the potential of molecular markers in germplasm selection for breeding programs.
Cannabis‐infused foods are currently on the rise in markets all around the world. Meanwhile, there are concerns over the health implications for consumers. Studies have explored the therapeutic potential and nutritional and economic benefits of cannabis usage. Yet, the phytonutrients, processing methods, and health implications of cannabis‐infused foods have not been well explored. This review evaluates existing evidence on the nutritional, processing, safety, and phytonutrient composition of cannabis‐infused food products and their medicinal and functional prospects. Cannabis seeds contain the highest amount of dietary nutrients, while flowers contain the highest amount of bioactive constituents. Oils, butter, seeds, flowers, and leaf extracts are the plant forms currently incorporated into food products such as beverages, baked products, cooking ingredients, functional foods, nutraceuticals, and nootropics. Cannabis‐infused foods have been found to offer therapeutic benefits for pain management, brain function, gut health, and certain cancers. Findings also show significant constraints associated with cannabis‐infused foods regarding dosage guidelines, limited research, efficacy, and long‐term health effects on consumers. This is further worsened by the lack of policies that regulate the industry. To realize the full potential of cannabis use in the food and health industries and in research, regulatory guidelines are needed to control dosages and improve its efficient use in these industries. This will go a long way to ensure the safety of cannabis users and enhance responsible production, marketing, and distribution.
O Transtorno do Espectro do Autismo (TEA) é caracterizado por déficits persistentes na comunicação, interação social e padrões de comportamento restritos e repetitivos. Pesquisas apontam um crescimento alarmante no número de crianças com TEA nas últimas décadas. As estimativas da prevalência do autismo vêm aumentado dramaticamente, chegando à prevalência de 1 para cada 59 em 2018. Alguns estudos vêm demonstrando que substâncias derivadas da Cannabis sativa estão apresentando melhora na qualidade de vida de crianças com TEA, sem causar efeitos colaterais graves, tornando-se uma alternativa terapêutica eficaz e segura para o tratamento dessa desordem neurológica, entretanto ainda muito cara e inacessível a muitos brasileiros. Nesse contexto, o cultivo doméstico da planta Cannabis sativa, autorizado por Lei através de salvo conduto, é uma realidade encontrada por muitas famílias em busca de autonomia e baixo custo para a aquisição de óleos ricos em fitocanabinoides para o tratamento de doenças graves e, muitas vezes, intratáveis com a terapia farmacológica atual. O objetivo desse estudo foi avaliar a eficácia clínica do óleo artesanal de Cannabis na proporção 2:1 de Ácido canabidiólico (CBDA): Ácido tetrahidrocanabinólico (THCA) em uma criança com TEA grave. Este artigo trata-se de um relato de caso de uma criança de 12 anos de idade, portadora de Transtorno do Espectro Autista (TEA) nível 3 de suporte, considerada grave, segundo a 5ª versão do Manual Diagnóstico e Estatístico de Transtornos Mentais (DSM-5). Essa criança utilizou o óleo de Cannabis na proporção 2:1 CBDA:THCA, produzido de forma artesanal por sua mãe com autorização judicial. Essa mãe participou do projeto Mães e Mulheres Jardineiras (MMJ), desenvolvido pela Sociedade Brasileira de Estudos da Cannabis (SBEC) com mulheres que possuem autorização judicial para cultivar e produzir o óleo artesanal de Cannabis para o tratamento de seus filhos. O projeto MMJ foi desenvolvido pela SBEC e proporciona suporte técnico para produção artesanal do óleo de Cannabis de qualidade e suporte jurídico para obtenção de autorização judicial para cultivo e produção do óleo, proporcionando a diversas mães a realização do sonho de ter a sua autonomia para produção de um óleo de qualidade a preço baixo para o tratamento de seus filhos. Antes de iniciar o óleo artesanal de Cannabis rico em CBDA produzido pela mãe, a criança apresentava crises de auto e heteroagressão, agitação psicomotora, gritos e choros, e tinha feito uso de todos os medicamentos disponíveis, mas sem melhora efetiva. Após tratamento com o óleo artesanal de Cannabis produzido pela mãe, com a ajuda do projeto MMJ desenvolvido pela SBEC, a criança diminuiu as crises de agressividade, de agitação psicomotora, de choros e gritos, conseguindo interagir com a família, além de retirar de forma gradativa todos os medicamentos alopáticos que usava. Pode-se concluir que o óleo artesanal de Cannabis, obtido pelo cultivo doméstico, apresenta eficácia clínica, baixo custo e segurança, pois melhorou significativamente os sintomas de agressividade, agitação psicomotora e interação social sem apresentar efeito colateral, melhorando a qualidade de vida da criança com TEA grave e de toda sua família. Palavras-chave: Autismo, Cannabis sativa, cultivo doméstico.
The medicinal properties of the Cannabis genus are evident and many studies indicate its usefulness to treat many diseases. However, the production of Cannabis-based products has been hampered by its criminalization. Currently its cultivation is not allowed in Brazil, except in specific situations. It increases the price of Cannabis-based products, as it requires the importation of inputs, making it difficult for most of the population to access such medicines. In this context, this review presents an overview of Brazilian legislation on medical Cannabis and the current market for Cannabis products in Brazil. The main goal is to encourage the cultivation of medical Cannabis and the distribution of its products by the Brazilian Unified Health System. In addition, it presents recommendations to implement cultivation based on a bibliographic survey carried out in scientific databases and clinical evidence of the effectiveness of Cannabis in treating patients suffering from several diseases and conditions, although more complete studies are needed to confirm both risk-benefit relationship and dose to be administered. After searching for legislation and bills on government websites, it became evident that there was a need for changes in Brazilian legislation to enable cultivation in Brazil. However, there are several proposals for legislation in progress, and Brazil can significantly benefit from this therapeutic option.
The 4- Aminophenol (4-AP) colorimetric test is a fast, easy-to-use, and cost-effective presumptive assay of cannabis plant material producing different chromophores with THC-rich cannabis (blue color) and with CBD-rich cannabis (pink color). The main drawback of the 4-AP test is a brief observation window where the color rapidly changes to black, limiting the utility of the test. We now report for the first time, the identification of the product chromophores between 4-AP and CBD/THC as well as propose an explanation and a solution for the color degradation of the chromophores. The identification of the chromophores is provided by spectroscopic (UV–Vis), chromatography, and mass spectrometry (TLC and LC-QToF-MS). Oxidation of excess 4-AP (Reagent A) in the presence of NaOH (Reagent B) produces the black color observed for the previously reported 4-AP tests and reported in the literature. The adjustment of reactants concentrations and volumes of 4-AP:THC/CBD to a 1:1 ratio significantly reduces the black oxidation by-product and increases the observation window up to 2 h instead of the previously reported 5–10 min. For the first time, mass spectrometry and chromatography confirmed that the reaction of THC and CBD with 4-AP produced chromophores with m/z (M + H) = 420, consistent with proposed indophenol structures. The TLC method developed confirmed the separation between CBD and THC chromophores. The specificity of the test is also reported, showing false positive results for the presence of THC (blue color) for samples of thyme and oregano. LDA and SIMCA models showed that the optimized 4-AP procedure performs better than the previously reported 4-AP color test.
Myrcene (β-myrcene) is an abundant monoterpene which occurs as a major constituent in many plant species, including hops and cannabis. It is a popular flavouring and aroma agent (food additive) used in the manufacture of food and beverages. This review aims to report on the occurrence, biological and toxicological profile of β-myrcene. The main reported biological properties of β-myrcene—anxiolytic, antioxidant, anti-ageing, anti-inflammatory, analgesic properties—are discussed, with the mechanisms of activity. Here we also discuss recent data regarding the safety of β-myrcene. Overall, β-myrcene has shown promising health benefits in many animal studies. However, studies conducted in humans is lacking. In the future, there is potential for the formulation and production of non-alcoholic beers, functional foods and drinks, and cannabis extracts (low in THC) rich in β-myrcene.
Access to medical and recreational cannabis has been regulated in several countries. Cannabinoids are secondary metabolites used as chemical markers of Cannabis genus plants. Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most abundant cannabinoids and their proportion is used to differentiate hemp (THC/CBD<1) from marijuana (THC/CBD>1) varieties. Brazilian sanitary regulations permit prescription, importation and sale of cannabis-derived products by pharmaceuticals distributors and drugstores, even though their crops are still prohibited, and the current scenario is characterized by marijuana trafficking, legal trade of medical cannabis products, and cultivation and production of cannabis-derived products by patients and non-governmental organizations (NGOs), with or without judicial authorizations. Medical cannabis regulation is in progress and there is an urgent need to implement analytical methods for monitoring the chemical profile of cannabis crops. Thus, the goal of the present study was to propose a methodology based on presumptive and confirmatory methods to differentiate the two principal chemovars of Cannabis genus plants, i.e., CBD-rich (hemp) and THC-rich (marijuana). A color test and a validated high-performance liquid chromatography (HPLC) method were applied to six cannabis samples cultivated by patients with judicial authorization. The methodology proved to be useful for forensic purposes and for quality control of medical cannabis. Plants cultivated by patients showed three profiles, classified as THC-rich, CBD-rich and approximately 1:1 THC/CBD ratio.
Current treatments for stroke, which account for 6.5 million global deaths annually, remain insufficient for treatment of disability and mortality. One targetable hallmark of stroke is the inflammatory response following infarct, which leads to significant damage post-infarct. Cannabinoids and their endogenous targets within the CNS have emerged as potential treatments for neuroinflammatory indications. We and others have previously shown that synthetic agonists of the cannabinoid CB2 receptor reduce infarct size and microglial activation in rodent models of stroke. The non-cannabinoid receptor mediated effects of the phytocannabinoid cannabidiol (CBD) have also shown effectiveness in these models. The present aim was to determine the single and combined effects of the cannabis-derived sesquiterpene and putative CB2 receptor agonist β-caryophyllene (BCP) and CBD on permanent ischemia without reperfusion using a mouse model of photothrombosis. Because BCP and CBD likely work through different sites of action but share common mechanisms of action, we sought to determine whether combinations of BCP and CBD were more potent than either compound alone. Therefore we determined the effect of BCP (3–30 mg/kg IP) and CBD (3–30 mg/kg IP), given alone or in combination (30:3, 30:10, and 30:30 BCP:CBD), on infarct size, microglial activation, and motor performance.
Terpenes are the primary constituents of essential oils and are responsible for the aroma characteristics of cannabis. Together with the cannabinoids, terpenes illustrate synergic and/or entourage effect and their interactions have only been speculated in for the last few decades. Hundreds of terpenes are identified that allude to cannabis sensory attributes, contributing largely to the consumer’s experiences and market price. They also enhance many therapeutic benefits, especially as aromatherapy. To shed light on the importance of terpenes in the cannabis industry, the purpose of this review is to morphologically describe sources of cannabis terpenes and to explain the biosynthesis and diversity of terpene profiles in different cannabis chemovars.
Objective
The cultivation and production of industrial hemp [Cannabis sativa containing <0.3% tetrahydrocannabinol (THC)] has increased. Information regarding the nutrient composition and cannabinoid concentration of different plant parts are deficient.
Materials and Methods
Single lots of industrial hemp plants and by-products of cannabinoid production were obtained from a licensed research station located in south-central Kansas. Samples obtained were (1) whole industrial hemp plants (no roots), (2) stalks remaining after seed harvesting, (3) unprocessed female flowers intended for cannabinoid extraction, (4) whole seed heads for seed production, (5) leaves obtained from the drying process, (6) chaff obtained after seed harvesting and cleaning, and (7) processed female flowers after cannabinoid extraction. Plant materials were submitted for nutrient concentration and digestibility analysis, and for cannabinoid concentration determination, to a commercial nutrition laboratory.
Results and Discussion
Dry matter of the plant material ranged from 65 to 96.6%. Crude protein ranged from 5.3 to 24.5%. Calcium concentration was from 1.0 to 5.7% DM. The plants tested had high fiber concentrations, with NDF ranging from 28 to 80% and ADF ranging from 18 to 65% DM. Total digestible nutrients was 19.8 to 61.5. Six of the 10 cannabinoids tested were detected in all samples. Cannabidiolic acid, cannabidiol, and Δ9-tetrahydrocannabinolic acid A were detected in all samples at the highest concentrations.
Implications and Applications
These findings will assist livestock producers in using industrial hemp in animal feeds through consideration of both the nutritional and cannabinoid concentrations in the ration.
Cannabis (Cannabis sativa) resin is the foundation of a multi-billion dollar medicinal and recreational plant bioproducts industry. Major components of the cannabis resin are the cannabinoids and terpenes. Variations of cannabis terpene profiles contribute much to the different flavor and fragrance phenotypes that affect consumer preferences. A major problem in the cannabis industry is the lack of proper metabolic characterization of many of the existing cultivars, combined with sometimes incorrect cultivar labeling. We characterized foliar terpene profiles of plants grown from 32 seed sources and found large variation both within and between sets of plants labeled as the same cultivar. We selected five plants representing different cultivars with contrasting terpene profiles for clonal propagation, floral metabolite profiling and trichome-specific transcriptome sequencing. Sequence analysis of these five cultivars and the reference genome of the Purple Kush (PK) cultivar revealed a total of 33 different cannabis terpene synthase (CsTPS) genes as well as variations of the CsTPS gene family and differential expression of terpenoid and cannabinoid pathway genes between cultivars. Our annotation of the PK reference genome identified 19 complete CsTPS gene models, and tandem arrays of isoprenoid and cannabinoid biosynthetic genes. An updated phylogeny of the CsTPS gene family showed three cannabis-specific clades, including a clade of sesquiterpene synthases within the TPS-b subfamily that typically contains mostly monoterpene synthases. The CsTPSs described and functionally characterized here include 13 that had not been previously characterized and collectively explain a diverse range of cannabis terpenes.
Importance
Cannabis use is consistently linked to poorer mental health outcomes, and there is evidence that use of higher-potency cannabis increases these risks. To date, no studies have described the association between cannabis potency and concurrent mental health in a general population sample or addressed confounding using longitudinal data.
Objective
To explore the association between cannabis potency and substance use and mental health outcomes, accounting for preceding mental health and frequency of cannabis use.
Design, Setting, and Participants
This cohort study used data from the Avon Longitudinal Study of Parents and Children, a UK birth cohort of participants born between April 1, 1991, and December 31, 1992. Present data on outcomes and exposures were collected between June 2015 and October 2017 from 1087 participants at 24 years of age who reported recent cannabis use.
Exposures
Self-reported type of cannabis most commonly used in the past year, coded to a binary exposure of use of high-potency cannabis or lower-potency cannabis.
Main Outcomes and Measures
Outcomes were reported frequency of cannabis use, reported cannabis use problems, recent use of other illicit drugs, tobacco dependence, alcohol use disorder, depression, generalized anxiety disorder, and psychotic-like experiences. The study used secondary data; consequently, the hypotheses were formulated after data collection.
Results
Past-year cannabis use was reported by 1087 participants (580 women; mean [SD] age at onset of cannabis use, 16.7 [3.0] years). Of these, 141 participants (13.0%) reported the use of high-potency cannabis. Use of high-potency cannabis was associated with increased frequency of cannabis use (adjusted odds ratio [AOR], 4.38; 95% CI, 2.89-6.63), cannabis problems (AOR, 4.08; 95% CI, 1.41-11.81), and increased likelihood of anxiety disorder (AOR, 1.92; 95% CI, 1.11-3.32). Adjustment for frequency of cannabis use attenuated the association with psychotic experiences (AOR 1.29; 95% CI, 0.67-2.50), tobacco dependence (AOR, 1.42; 95% CI, 0.89-2.27), and other illicit drug use (AOR, 1.29; 95% CI, 0.77-2.17). There was no evidence of association between the use of high-potency cannabis and alcohol use disorder or depression.
Conclusions and Relevance
To our knowledge, this study provides the first general population evidence suggesting that the use of high-potency cannabis is associated with mental health and addiction. Limiting the availability of high-potency cannabis may be associated with a reduction in the number of individuals who develop cannabis use disorders, the prevention of cannabis use from escalating to a regular behavior, and a reduction in the risk of mental health disorders.
Cannabis research has historically focused on the most prevalent cannabinoids. However, extracts with a broad spectrum of secondary metabolites may have increased efficacy and decreased adverse effects compared to cannabinoids in isolation. Cannabis’s complexity contributes to the length and breadth of its historical usage, including the individual application of the leaves, stem barks, and roots, for which modern research has not fully developed its therapeutic potential. This study is the first attempt to profile secondary metabolites groups in individual plant parts comprehensively. We profiled 14 cannabinoids, 47 terpenoids (29 monoterpenoids, 15 sesquiterpenoids, and 3 triterpenoids), 3 sterols, and 7 flavonoids in cannabis flowers, leaves, stem barks, and roots in three chemovars available. Cannabis inflorescence was characterized by cannabinoids (15.77–20.37%), terpenoids (1.28–2.14%), and flavonoids (0.07–0.14%); the leaf by cannabinoids (1.10–2.10%), terpenoids (0.13–0.28%), and flavonoids (0.34–0.44%); stem barks by sterols (0.07–0.08%) and triterpenoids (0.05–0.15%); roots by sterols (0.06–0.09%) and triterpenoids (0.13–0.24%). This comprehensive profile of bioactive compounds can form a baseline of reference values useful for research and clinical studies to understand the “entourage effect” of cannabis as a whole, and also to rediscover therapeutic potential for each part of cannabis from their traditional use by applying modern scientific methodologies.
There has been an increased use of medical Cannabis in the United States of America as more states legalize its use. Complete chemical analyses of this material can vary considerably between producers and is often not fully provided to consumers. As phytochemists in a state with legal medical Cannabis we sought to characterize the accumulation of phytochemicals in material grown by licensed commercial producers. We report the development of a simple extraction and analysis method, amenable to use by commercial laboratories for the detection and quantification of both cannabinoids and terpenoids. Through analysis of developing flowers on plants, we can identify sources of variability of floral metabolites due to flower maturity and position on the plant. The terpenoid composition varied by accession and was used to cluster cannabis strains into specific types. Inclusion of terpenoids with cannabinoids in the analysis of medical cannabis should be encouraged, as both of these classes of compounds could play a role in the beneficial medical effects of different cannabis strains.
Medical cannabis has been legally available for patients in a number of countries. Licensed producers produce a variety of cannabis strains with different concentrations of phytocannabinoids. Phytocannabinoids in medical cannabis are decarboxylated when subjected to heating for consumption by the patients or when extracted for preparing cannabis derivative products. There is little understanding of the true chemical composition of cannabis extracts, changes occurring during heating of the extracts, and their relevance to pharmacological effects. We investigated the extract from a popular commercial strain of medical cannabis, prior to and after decarboxylation, to understand the chemical profiles. A total of up to 62 compounds could be identified simultaneously in the extract derived from commercial cannabis, including up to 23 phytocannabinoids. Upon heating, several chemical changes take place, including the loss of carboxylic group from the acidic phytocannabinoids. This investigation attempts to reveal the chemical complexity of commercial medical cannabis extracts and the differences in the chemical composition of the native extract and the one subjected to heat. Comprehensive chemical analyses of medical cannabis extracts are needed for standardization, consistency, and, more importantly, an informed employment of this substance for therapeutic purposes.
In the United States, federal and state laws regarding the medical use of cannabis and cannabinoids are in conflict and have led to confusion among patients, caregivers, and healthcare providers. Currently, cannabis is legal for medical purposes in 50% of the states, and another seventeen states allow products that are high in cannabidiol (CBD) and low in THC (tetrahydrocannabinol) for medical use. Many of these artisanal products are sold in dispensaries or over the internet. However, none of these products has been approved by the Food and Drug Administration (FDA). Understanding how federal laws apply to clinical research and practice can be challenging, and the complexity of these laws has resulted in particular confusion regarding the legal status of CBD. This paper provides an up-to-date overview (as of August 2016) of the legal aspects of cannabis and cannabidiol, including cultivation, manufacture, distribution, and use for medical purposes.
Animal studies and preliminary clinical trials have shown that cannabidiol (CBD)-enriched extracts may have beneficial effects for children with treatment-resistant epilepsy. However, these compounds are not yet registered as medicines by regulatory agencies. We describe the cases of two children with treatment-resistant epilepsy (Case A with left frontal dysplasia and Case B with Dravet Syndrome) with initial symptom improvement after the introduction of CBD extracts followed by seizure worsening after a short time. The children presented typical signs of intoxication by Δ9-THC (inappropriate laughter, ataxia, reduced attention, and eye redness) after using a CBD-enriched extract. The extract was replaced by the same dose of purified CBD with no Δ9-THC in both cases, which led to improvement in intoxication signs and seizure remission. These cases support pre-clinical and preliminary clinical evidence suggesting that CBD may be effective for some patients with epilepsy. Moreover, the cases highlight the need for randomized clinical trials using high-quality and reliable substances to ascertain the safety and efficacy of cannabinoids as medicines.
Cannabis sativa L. is cultivated in most regions of the world. In 2013, the Brazilian Federal Police (BFP) reported 220. tons of marijuana seized and about 800,000 cannabis plants eradicated. Efforts to eradicate cannabis production may have contributed to the development of a new form of international drug trafficking in Brazil: the sending of cannabis seeds in small amounts to urban centers by logistics postal. This new and increasing panorama of cannabis trafficking in Brazil, encouraged the chemical study of cannabis seeds cultivated in greenhouses by gas-chromatography coupled with mass spectrometry (GC-MS) associated with exploratory and discriminant analysis. Fifty cannabis seeds of different varieties and brands, seized by the BFP were cultivated under predefined conditions for a period of 4.5. weeks, 5.5. weeks, 7.5. weeks, 10. weeks and 12. weeks. Aerial parts were analyzed and cannabigerol, cannabinol, cannabidiol, cannabichromene δ9-tetrahydrocannabinol (THC) and other terpenoids were detected. The chromatographic chemical profiles of the samples were significantly different, probably due to different variety, light exposition and age. THC content increased with the age of the plant, however, for other cannabinoids, this correlation was not observed. The chromatograms were plotted in a matrix with 50 rows (samples) and 3886 columns (abundance in a retention time) and submitted to PCA, HCA and PLS-DA after pretreatment (normalization, first derivative and autoscale). The PCA and HCA showed age separation between samples however it was not possible to verify the separation by varieties and brands. The PLS-DA classification provides a satisfactory prediction of plant age.
Despite its cultivation as a source of food, fibre and medicine, and its global status as the most used illicit drug, the genus Cannabis has an inconclusive taxonomic organization and evolutionary history. Drug types of Cannabis (marijuana), which contain high amounts of the psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC), are used for medical purposes and as a recreational drug. Hemp types are grown for the production of seed and fibre, and contain low amounts of THC. Two species or gene pools (C. sativa and C. indica) are widely used in describing the pedigree or appearance of cultivated Cannabis plants. Using 14,031 single-nucleotide polymorphisms (SNPs) genotyped in 81 marijuana and 43 hemp samples, we show that marijuana and hemp are significantly differentiated at a genome-wide level, demonstrating that the distinction between these populations is not limited to genes underlying THC production. We find a moderate correlation between the genetic structure of marijuana strains and their reported C. sativa and C. indica ancestry and show that marijuana strain names often do not reflect a meaningful genetic identity. We also provide evidence that hemp is genetically more similar to C. indica type marijuana than to C. sativa strains.
Tetrahydrocannabinol (THC) has been the primary focus of cannabis research since 1964, when Raphael Mechoulam isolated and synthesized it. More recently, the synergistic contributions of cannabidiol to cannabis pharmacology and analgesia have been scientifically demonstrated. Other phytocannabinoids, including tetrahydrocannabivarin, cannabigerol and cannabichromene, exert additional effects of therapeutic interest. Innovative conventional plant breeding has yielded cannabis chemotypes expressing high titres of each component for future study. This review will explore another echelon of phytotherapeutic agents, the cannabis terpenoids: limonene, myrcene, α-pinene, linalool, β-caryophyllene, caryophyllene oxide, nerolidol and phytol. Terpenoids share a precursor with phytocannabinoids, and are all flavour and fragrance components common to human diets that have been designated Generally Recognized as Safe by the US Food and Drug Administration and other regulatory agencies. Terpenoids are quite potent, and affect animal and even human behaviour when inhaled from ambient air at serum levels in the single digits ng·mL -1. They display unique therapeutic effects that may contribute meaningfully to the entourage effects of cannabis-based medicinal extracts. Particular focus will be placed on phytocannabinoid-terpenoid interactions that could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal and bacterial infections (including methicillin-resistant Staphylococcus aureus). Scientific evidence is presented for non-cannabinoid plant components as putative antidotes to intoxicating effects of THC that could increase its therapeutic index. Methods for investigating entourage effects in future experiments will be proposed. Phytocannabinoid-terpenoid synergy, if proven, increases the likelihood that an extensive pipeline of new therapeutic products is possible from this venerable plant.
Cannabis is the most commonly used illicit drug in the world. The use of cannabis continues to evolve, as it is available in a growing variety of forms and changing potencies. At the time of this writing, eleven states and the District of Columbia have legalized recreational cannabis use for adults. Studies of pediatric cannabis exposure after legalization have demonstrated an increase in related emergency department visits. Here we review some of the ways that pediatric cannabis exposure may present to the emergency care clinician, including accidental exposure, intentional exposure, drug facilitated sexual assault, commercial sexual exploitation of children, and caregiver use and impairment. We also review the ways in which substance abuse and child maltreatment intersect and illustrate how these examples of pediatric cannabis exposure should prompt consideration of child maltreatment.
This paper presents data about potency of herbal and resin cannabis products seized during 2010–2019 in north-east Italy. More than 12,000 cannabis samples were analyzed and concentrations of THC, CBD and CBN were collected. The results of our study provided clear evidence for an increase in the potency of cannabis products across the study period, which is consistent with other studies. Globally, the median THC concentrations increased from about 6%–11%, but differences were found between herbal and resin materials. THC potency in resin materials increased more consistently across the study period with a dramatic raise during 2018–2019, with median THC contents around 17%.
CBD concentrations were found to decrease constantly over the study period, especially in herbal materials, which had a mean CBD concentration of 0.3%. In particular, about 75% of the analyzed herbal samples had a CBD concentration which was less than 3% of the corresponding THC concentration. In contrast, more than 50% of the analyzed resin materials had a CBD concentration which was about 30% of the corresponding THC concentration. This is consistent with the increase in prevalence of high-potency seedless female herbal products observed in the same period and indicates that herbal and resin materials were produced from different varieties of cannabis plants. However, resin materials derived from high THC/low CBD cannabis plants were recently found. Different routes (e.g. northern Europe) or different modalities of distribution were assumed for these products.
CBN concentrations were also considered and found to be very low and consistent across the study period indicating reliability of THC values used in statistical analysis.
In conclusion, this study provided an accurate picture of cannabis products seized over a decade over a definite geographical area which can be extremely helpful for comparative purposes and for national and international statistical analyses on cannabis products.
The Marihuana Polygon production of Cannabis sativa L. supplies the northeastern region of Brazil and represents 30% of the nation’s market. The international trend of indoor cultivation is also occurring in Brazil, and the Brazilian Federal Police (BFP) has been increasing its apprehension of cannabis seeds sent by mail. The present work aims to assess the utility of the multi-element composition of different cannabis plant parts and soil samples where the plants were cultivated to determine their geographic origin. Statistical tools were applied to classification of marijuana samples from distinct geographic regions within northeastern Brazil, including indoor cultivated samples. The multi-element quantification was determined using inductively-coupled plasma – optical emission spectrometry (ICP-OES), and the data were compared by the Kruskal-Wallis H test, and subsequently, multiple discriminant analysis (MDA). The results of the multi-element concentration of cannabis plant samples were also subjected to a principal component analysis (PCA) and an orthogonal partial least squares discriminant analysis (OPLS-DA). The cannabis plant samples from the Marihuana Polygon could be clearly separated from those cultivated indoors, and the distance between them was detectable. The MDA revealed that phosphorus, calcium, magnesium, selenium, and arsenic concentrations were used as variables for this separation. Our results demonstrate that multi-element composition analysis can be used to indicate the origin or cultivation location of cannabis plants. Routine laboratory analyses consisting of multi-element composition combined with statistical analyses provide a reliable tool by which C. sativa movement, cultivation, and interdiction efforts in Brazil may be assessed.
Background and Objectives
The incorporation of drugs in the hair of young children differs from that of adults and the metabolism of cannabis cannot be the same. Our primary objective was to analyze the distribution of the different cannabinoids in children’s hair samples. The secondary objective was to correlate the intensity of toxic environmental exposure to cannabinoid metabolite levels.
Methods
This was a prospective, single-center, observational pilot study of a pediatric cohort. Included subjects were all children less than 6 years of age admitted to a tertiary pediatric emergency unit for proven cannabis intoxication during the reference period. A hair strand was sampled within 12 hours of emergency admission.
Results
Forty-one pediatric patients were consecutively enrolled. Hair analysis showed that 34 children were positive for Δ9-THC (range 0.06-284.4 ng/mg); 41% of them were also positive for THC-COOH (range 0.26-2.76 pg/mg). Depending on the Δ9-THC concentration (>1 ng/mg), 39% of the children could be considered exposed to an intensely toxic environment. The rate of THC-COOH detection steadily increased from 2015 to 2018 (18%, 40%, 50%, 58% for each consecutive year). Children intensely exposed weighed less on admission (p = 0.02), had more comatose presentations (p = 0.02), and more previous social issues (75% versus 12%, OR 22.0, p = 0.0002).
Conclusion
Hair testing in this context indirectly shows the intensity of children’s toxic environmental exposure by the cannabinoid metabolite threshold. This was very helpful during the collegial examination of the toddlers’ environment and led to a full investigation and to appropriate decisions concerning social measures.
Purpose:
Activation of CB1 receptors, produces anticonvulsant effect accompanied by memory disturbance both in animal seizure tests and in patients with epilepsy. Few reports considered the role of CB2 receptor on seizure susceptibility and cognitive functions. The aim of the present study was to explore the effect of a selective CB2 receptor agonist β-caryophyllene (BCP) in models of seizures and cognition in mice.
Methods:
Dose-dependent effects of BCP was studied in maximal electroshock seizure (MES) test, subcutaneous pentylenetetrazole (scPTZ) test and Morris water maze test. Phenytoin and diazepam were used as reference drugs in seizure tests. The effect of sub-chronic treatment with BCP for 7 days (50 and 100 mg kg-1) was assessed on status epilepticus (SE) induced by kainic acid (KA) model and oxidative stress through measurement of malondialdehyde (MDA) level in the hippocampus. The acute neurotoxicity was determined by a rotarod test.
Results:
The BCP exerted a protection in the MES test at the lowest dose of 30 mg kg-1at the 4-h interval tested comparable to that of the referent drug phenytoin. The CB2 agonist was ineffective in the scPTZ test. The BCP displayed no neurotoxicity in the rotarod test. The BCP decreased the seizure scores in the KA-induced SE, which effect correlated with a diminished lipid peroxidation. The CB2 agonist exerted a dose-dependent decrease of latency to cross the target area during the three days of testing in the Morris water maze test.
Conclusion:
Our results suggest that the CB2 receptor agonists might be clinically useful as an adjunct treatment against seizure spread and status epilepticus and concomitant oxidative stress, neurotoxicity and cognitive impairments.
The present work was aimed at the development and validation of a new, efficient and reliable technique for the analysis of the main non-psychoactive cannabinoids in fibre-type Cannabis sativa L. (hemp) inflorescences belonging to different varieties. This study was designed to identify samples with a high content of bioactive compounds, with a view to underscoring the importance of quality control in derived products as well. Different extraction methods, including maceration (DM), ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE) and supercritical-fluid extraction (SFE) were applied and compared in order to obtain a high yield of the target analytes from hemp. Dynamic maceration for 45 min with ethanol (EtOH) at room temperature proved to be the most suitable technique for the extraction of cannabinoids in hemp samples.
Cannabis contains a unique class of compounds known as the cannabinoids. Pharmacologically, the principal psychoactive constituent is Δ⁹–tetrahydrocannabinol (THC). The amount of THC in conjunction with selected additional cannabinoid compounds (cannabidiol/CBD, cannabinol/CBN), determines the strength or potency of the cannabis product. Recently, reports have speculated over the change in the quality of cannabis products, from nearly a decade, specifically concerning the increase in cannabinoid content. This article exploits the analytical data of cannabis samples analysed in the five French forensic police laboratories over 25 years. The increase potency of both herbal and resin cannabis in France is proved through the monitoring of THC content.
Increasing evidence suggests that plant-derived extracts and their isolated components are useful for treatment of seizures and, hence, constitute a valuable source of new antiepileptic drugs with improved efficacy and better adverse effect profile. β-Caryophyllene is a natural bicyclic sesquiterpene that occurs in a wide range of plant species and displays a number of biological actions, including neuroprotective activity. In the present study, we tested the hypothesis that β-caryophyllene displays anticonvulsant effects. In addition, we investigated the effect of β-caryophyllene on behavioral parameters and on seizure-induced oxidative stress. Adult C57BL/6 mice received increasing doses of β-caryophyllene (0, 10, 30, or 100 mg/kg). After 60 min, we measured the latencies to myoclonic and generalized seizures induced by pentylenetetrazole (PTZ, 60 mg/kg). We found that β-caryophyllene increased the latency to myoclonic jerks induced by PTZ. This result was confirmed by electroencephalographic analysis. In a separate set of experiments, we found that mice treated with an anticonvulsant dose of β-caryophyllene (100 mg/kg) displayed an improved recognition index in the object recognition test. This effect was not accompanied by behavioral changes in the open-field, rotarod, or forced swim tests. Administration of an anticonvulsant dose of β-caryophyllene (100 mg/kg) did not prevent PTZ-induced oxidative stress (i.e., increase in the levels of thiobarbituric acid-reactive substances or the decrease in nonprotein thiols content). Altogether, the present data suggest that β-caryophyllene displays anticonvulsant activity against seizures induced by PTZ in mice. Since no adverse effects were observed in the same dose range of the anticonvulsant effect, β-caryophyllene should be further evaluated in future development of new anticonvulsant drugs.
Background:
Marijuana is the most widely used illicit drug in the United States and all over the world. Reports indicate that the potency of cannabis preparation has been increasing. This report examines the concentration of cannabinoids in illicit cannabis products seized by the U.S. Drug Enforcement Administration over the last 2 decades, with particular emphasis on Δ(9)-tetrahydrocannabinol and cannabidiol.
Methods:
Samples in this report were received over time from materials confiscated by the Drug Enforcement Administration and processed for analysis using a validated gas chromatography with flame ionization detector method.
Results:
Between January 1, 1995, and December 31, 2014, 38,681 samples of cannabis preparations were received and analyzed. The data showed that although the number of marijuana samples seized over the last 4 years has declined, the number of sinsemilla samples has increased. Overall, the potency of illicit cannabis plant material has consistently increased over time since 1995 from ~4% in 1995 to ~12% in 2014. The cannabidiol content has decreased on average from ~.28% in 2001 to <.15% in 2014, resulting in a change in the ratio of Δ(9)-tetrahydrocannabinol to cannabidiol from 14 times in 1995 to ~80 times in 2014.
Conclusions:
There is a shift in the production of illicit cannabis plant material from regular marijuana to sinsemilla. This increase in potency poses higher risk of cannabis use, particularly among adolescents.
In recent years, increased 'cannabis potency', or Δ(9)-tetrahydrocannabinol (THC) content in cannabis products, has been reported in many countries. A survey of Japanese illicit cannabis was conducted from April 2010 to March 2011. In Japan, all cannabis evidence is transferred to the Minister of Health, Labour and Welfare after criminal trials. The evidence was observed at Narcotics Control Department offices in major 11 cities. The total number of cannabis samples observed was 9072, of which 6376 were marijuana. The marijuana seizures were further classified, and it was found that in terms of the number of samples, 65.2% of them were seedless buds, and by weight 73.0% of them were seedless buds. Seedless buds were supposed to be 'sinsemilla', a potent class of marijuana. THC, cannabinol (CBN) and cannabidiol (CBD) in marijuana seizures exceeding 1g were quantified. The number of samples analyzed was 1115. Many of them were shown to contain CBN, an oxidative product from THC. This was a sign of long-term storage of the cannabis and of the degradation of THC. Relatively fresh cannabis, defined by a CBN/THC ratio of less than or equal to 0.1, was chosen for analysis. Fresh seedless buds (335 samples) contained an average of 11.2% and a maximum of 22.6% THC. These values are comparable to those of 'high potency cannabis' as defined in previous studies. Thus, this study shows that highly potent cannabis products are distributed in Japan as in other countries.
Cannabis cultivation in order to produce drugs is forbidden in Switzerland. Thus, law enforcement authorities regularly ask forensic laboratories to determinate cannabis plant's chemotype from seized material in order to ascertain that the plantation is legal or not. As required by the EU official analysis protocol the THC rate of cannabis is measured from the flowers at maturity. When laboratories are confronted to seedlings, they have to lead the plant to maturity, meaning a time consuming and costly procedure. This study investigated the discrimination of fibre type from drug type Cannabis seedlings by analysing the compounds found in their leaves and using chemometrics tools. 11 legal varieties allowed by the Swiss Federal Office for Agriculture and 13 illegal ones were greenhouse grown and analysed using a gas chromatograph interfaced with a mass spectrometer. Compounds that show high discrimination capabilities in the seedlings have been identified and a support vector machines (SVMs) analysis was used to classify the cannabis samples. The overall set of samples shows a classification rate above 99% with false positive rates less than 2%. This model allows then discrimination between fibre and drug type Cannabis at an early stage of growth. Therefore it is not necessary to wait plants' maturity to quantify their amount of THC in order to determine their chemotype. This procedure could be used for the control of legal (fibre type) and illegal (drug type) Cannabis production.
Implications of the 2018 Canadian Cannabis Act: should regulation differ for medicinal and non-medicinal cannabis use?
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