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Scientific evidence exists about the association between neurological diseases (i.e., Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, depression, and memory loss) and oxidative damage. The increasing worldwide incidence of such diseases is attracting the attention of researchers to find palliative medications to reduce the symptoms and promote quality of life, in particular, in developing countries, e.g., South America and Africa. Among potential alternatives, extracts of Cannabis Sativa L. are suitable for people who have neurological disorders, spasticity, and pain, nausea, resulting from diseases such as cancer and arthritis. In this review, we discuss the latest developments in the use of Cannabis, its subtypes and constituents, extraction methods, and relevant pharmacological effects. Biomedical applications, marketed products, and prospects for the worldwide use of Cannabis Sativa L. extracts are also discussed, providing the bibliometric maps of scientific literature published in representative countries from South America (i.e., Brazil) and Africa (i.e., South Africa). A lack of evidence on the effectiveness and safety of Cannabis, besides the concerns about addiction and other adverse events, has led many countries to act with caution before changing Cannabis-related regulations. Recent findings are expected to increase the social acceptance of Cannabis, while new technologies seem to boost the global cannabis market because the benefits of (-)-trans-delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) use have been proven in several studies in addition to the potential to general new employment.

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INTRODUCTION: Cannabis sativa L. is a well-recognized medicinal plant. Cannabis regulations in Argentina are insufficient to solve the problem of patient access to full-spectrum cannabis-based products. So, the market of artisanal products with unknown quality and dosage of cannabinoids is increasing, and so is the local demand and need for analyzing these products. However, much of the latest validated methodologies for cannabinoid quantification include expensive instrumentation that is not always available in laboratories of health institutions in Argentina. METHODS: The aim of this work was to develop and validate a simple and rapid HPLC-UV method for the identification and quantification of principal cannabinoids in cannabis resins, inflorescences, and medicinal oils using standard HPLC equipment. The cannabinoids selected for validation were cannabidiol acid (CBDA), cannabigerol (CBG), cannabidiol (CBD), cannabinol (CBN), delta-9-tetrahydrocannabinol (Δ9-THC), cannabichromene (CBC), and tetrahydrocannabinol acid (THCA). A method for the simultaneous identification and quantification of these 7 main cannabinoids was developed and then validated. Some data parameters were comparable to other reports with more sophisticated analytical instruments for the analysis of cannabis. The assessed limits of detection and the limits of quantitation ranged from 0.9 to 3.66 µg/mL and 2.78 to 11.09 µg/mL, respectively. The concentration-response relationship of the method indicated a linear relationship between the concentration and peak area with R2 values of > 0.99 for all 7 cannabinoids. RESULTS: The relative standard deviation (RSD%) varied from 2.34 to 4.82 for intraday repeatability and from 1.16 to 3.15 for interday repeatability. The percentage of recovery values was between 94 to 115% (resins) and 80 to 103% (inflorescence extract). The cannabis industry is growing rapidly, and there is a need for reliable testing methods to ensure the safety and efficacy of cannabis products. In addition, current methods for cannabinoid analysis are often time-consuming and expensive, while the HPLC-UV method herein reported is a simple, rapid, accurate, and cost-effective alternative for the analysis of cannabinoids in cannabis resins, inflorescences, and medicinal oils. CONCLUSION: This method will be proposed to be included in the Cannabis sativa L. monograph of the Argentine Pharmacopoeia.

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In recent years, the therapeutic use of cannabis products, especially cannabis oils, has increased significantly, due to the pharmacological potential of their cannabinoids, for the treatment of conditions, such as pain management, cancer, and epilepsy. In Argentina, patients with medical prescriptions can access to cannabis oil, through self-cultivation, a third-person (grower or importer), or a civil organization authorized for that purpose. However, these products remain largely unregulated in Argentina, and information available regarding labeling accuracy, especially cannabidiol (CBD)/ Δ9-tetrahydrocannabinol (Δ9-THC) concentrations are inconsistent or nonexistent, nor long-term product stability, and lot to lot variability. Understanding these properties is fundamental if these products are to be used in patients with a determinate pathology. Therefore, we analyzed commercially available cannabis oils (n: 500) in Argentina for qualitative and quantitative cannabinoids content. In order to provide a detailed overview of their cannabinoids profiles, and determine Δ9-THC, CBD, and cannabinol (CBN) concentrations, samples were diluted and analyzed by gas chromatography- mass spectrometry (GC/MS). Most of the samples tested positive for cannabinoids (n: 469) with Δ9-THC and CBD as the predominant cannabinoids. Among products tested, only 29.8% (n: 149) gave specific CBD label claims, and testing indicated a CBD tested positive of 70.5% (n: 105). For products (n: 17) with a THC-free label claim, testing indicated 76.5% (n: 13) of Δ9-THC positive, and cannabinoids were not detected in four products. Δ9-THC concentrations ranged from 0.1 to 143.0 mg/mL, CBD concentrations from 0.1 to 125.3 mg/mL, and CBN concentrations from 0.04 to 60.10 mg/mL; CBN/ Δ9-THC ratios ranged from 0.0012 to 2.31, and CBD/ Δ9-THC ratios from 0.0008 to 178.87. Furthermore, the (Δ9-THC + CBN)/CBD ratio of most samples was greater than one. In summary, our results indicate that cannabis oil products show wide variability in cannabinoids content, purity, and labeling.

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Sexual reversal methods are commonly used in plant breeding programs, allowing male flowers from female plants or vice versa. This work evaluated sexual reversal methods in female Cannabis plants and their effect on gas exchange activity. Plants treated with 1, methyl-cyclopropene (1-MCP), and aminoetoxyvinylglycine (AVG) showed differences in net photosynthesis (A) and stomatal conductance (gs) between the periods before and after sexual reversal treatments. Quantum yield (Qy), electron transport rate (ETR), and non-photochemical quenching (NPQ) did not show a relationship to the treatments, an increase in Qy and ETR, and a reduction in NPQ were observed after applying treatments. 1-MCP, AVG, and STS (silver thiosulfate) were effective in sexual reversal, while photoperiod changes did not induce the formation of male flowers. Induction of sexual reversion in Cannabis plants did not generate variations in energy dissipation mechanisms through photosystems.

Los métodos de reversión sexual se utilizan comúnmente en los programas de fitomejoramiento, permitiendo la formación de flores masculinas a partir de plantas femeninas y viceversa. Este trabajo tuvo como objetivo evaluar métodos de reversión sexual en plantas femeninas de Cannabis y su efecto sobre el intercambio de gases. Plantas tratadas con 1-metil-ciclopropano (1-MCP) y aminoetoxivinilglicina (AVG) mostraron diferencias en fotosíntesis neta (A) y conductancia estomática (gs) entre los periodos antes y después de los tratamientos de reversión sexual. El rendimiento cuántico (Qy), la tasa de transporte de electrones (ETR) y la disipación no fotoquímica (NPQ) no mostraron relación con los tratamientos, se observó un incremento en Qy y ETR y una reducción en NPQ después de la aplicación de los tratamientos. 1-MCP, AVG y STS (tiosulfato de plata) fueron efectivos en la reversión sexual, mientras que los cambios en el fotoperiodo no indujeron la formación de flores masculinas. La inducción de la reversión sexual en plantas de Cannabis no generó variaciones en los mecanismos que disipan la energía a través de los fotosistemas.

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Absolute content of terpenes in inflorescences of two strains of Cannabis sativa L., CAT 1 and CAT 3, has been determined. Twenty terpenes commonly present in these samples were quantified by solid phase microextraction combined with gas chromatography and flame ionization detection (SPME/GC-FID). High amounts of ß-myrcene, α-pinene, ß-pinene, limonene, (E)-ß-ocimene, ß-caryophyllene, α-humulene, (E)-nerolidol, and linalool, were found in both strains. Lower concentrations (< 20 µg·g-1) of other terpenes were also determined. Only (E)-ß-ocimene was detected at 50 µg·g-1 in CAT 3 whereas it was below the LOD in CAT 1. Concentrations of other compounds for which standards were not available, were estimated based on a response factor obtained from the calibration curves of compounds with similar chemical structures. Fingerprints of both CAT strains were obtained and the identities of most volatile compounds were assigned using gas chromatography coupled to mass spectrometer detector (GC-MS). Additionally, an assessment of variability of terpenes was achieved by analyzing ten plants of each strain grown under controlled conditions and harvested at the same time. This variability was about 20%, considering terpenes at concentration above 20 µg·g-1.

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A utilização medicinal da Cannabis sativa L., usualmente chamada de maconha, é conhecida desde tempos remotos devido a suas elevadas propriedades terapêuticas. As discussões acerca de seu uso medicinal no Brasil são urgentes, notadamente porque já há comprovação científica dos benefícios relacionados ao tratamento de diversas enfermidades. Este artigo teve como foco demonstrar que os argumentos apresentados para criminalizar a C. sativa, além de concorrerem para uma conjuntura racista e criminalizadora de classes sociais baixas, violam os princípios bioéticos da beneficência, autonomia e justiça, ao impedir que o sujeito tenha acesso a prescrições médicas adequadas e menos onerosas, a fim de proporcionar o alívio de suas dores físicas e psíquicas. Para tanto, utilizou-se da metodologia qualitativa, por meio da qual se realizou revisão bibliográfica de artigos científicos publicados em português, entre os anos de 2015 e 2020, nas bases de dados Google Scholar e Scientific Electronic Library Online, juntamente com pesquisa de resoluções da Agência Nacional de Vigilância Sanitária e do Conselho Federal de Medicina. De posse desses dados, constatou-se a necessidade de democratização no acesso à C. sativa medicinal, sendo imprescindível o fornecimento gratuito de canabidiol pelo Sistema Único de Saúde, bem como uma normatização que permita o cultivo da C. sativa para fins medicinais para a produção de medicamentos no país.

The medicinal use of Cannabis sativa L., usually called marijuana, has been known since ancient times, due to its enhanced therapeutic properties. Discussions about its medicinal use in Brazil are urgent, especially because there is already scientific proof of the benefits that it can produce in treatment of various diseases. Therefore, it is essential that there is support from the State so that access to C. sativa for medicinal purposes is universal, considering the right to health treatments as a fundamental right, provided for in the Constitution. However, the use and possession for own consumption are still criminalized. Thus, the article seeks to demonstrate that the justifications presented to criminalize this plant, in addition to contributing to a racist marginalization of low social classes, violate Bioethical precepts, by preventing patients from accessing medical prescriptions that are adequate and less costly, to provide relief from their physical and mental pain. For that, we used a qualitative methodology. A bibliographic review of scientific articles published in Portuguese, between the years 2015 and 2020, was carried out in the Google Scholar and Scientific Electronic Library Online databases. Resolutions of the Brazilian Health Regulatory Agency, as well as of the Federal Council of Medicine were also considered. With these data, this article concludes that the need for democratization in access to medicinal C. sativa is imperative, by supplying patients with CBD compounds through the Brazilian National Public Health System, and by enacting legislation that allows for the cultivation of C. sativa for medicinal purposes and for medicine production in Brazil.

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The aim of this study was to use instrumental neutron activation analysis and multivariate analysis to determine the provenance of Jamaican Cannabis sativa L. Sixty-three samples were collected from various areas in Jamaica, with no other data but their known or self-reported growing regions. The samples were analysed for Al, As, Br, Ca, Cd, Co, Cs, Fe, K, La, Mg, Mn, Na, Rb, Sb, Sc, Sm, Sr, V, and Zn. The resulting elemental data were statistically evaluated using agglomerative hierarchical cluster analysis and principal component analysis. Cluster analysis was able to group the samples into their known or reported growing regions with a high degree of accuracy. Principal component analysis was also able to elucidate some of the underlying geochemical factors that could explain the clustering. These included the underlying bauxitic geochemistry and the influence of fertilizer inputs. Of the analysed elements, Al, As, Cd, Co, Fe, K, La, Mg, Mn, Sc, Sm, V, and Zn appear to be most significant in identifying the growing regions of the cannabis samples. Results indicate the promise of this methodology with an increased dataset and potentially further refinement of the identifying elements.

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The present research aims to give an added value to the chain production of Cannabis sativa L plant, taking advantage of the non-psychoactive residual biomass (stems and leaves). Total phenolic content (TPC) and total antioxidant capacity (TAC) were analysed. A factorial design 23 was carried out using extraction time (T), Particle size (PS), and solid-solvent ratio (SS) as factors. The extractions were made with ethanol at 96% as solvent. The maximum concentration of TPC found was 1264.61 mg GA/g DW at 6:250 g/mL, 8 h, and 109.28 µm for SS, T and PS, respectively. Similarly, the maximum TAC obtained was 0.467 mM Trolox equivalent, at 8 h, 6:250 g/mL and 109.28 µm for T, SS and PS, respectively. Additionally, the presence of oil was found in some samples of cannabis extracts for which FITR was performed, obtaining the presence of C-OH bonds associated with alcohols, phenols and possible cannabinoids.

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The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems. In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development. The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development. The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases. This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as "C. sativa L." or "medical cannabis"), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.

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Oral and dental diseases are a major global burden, the most common non-communicable diseases (NCDs), and may even affect an individual's general quality of life and health. The most prevalent dental and oral health conditions are tooth decay (otherwise referred to as dental caries/cavities), oral cancers, gingivitis, periodontitis, periodontal (gum) disease, Noma, oro-dental trauma, oral manifestations of HIV, sensitive teeth, cracked teeth, broken teeth, and congenital anomalies such as cleft lip and palate. Herbs have been utilized for hundreds of years in traditional Chinese, African and Indian medicine and even in some Western countries, for the treatment of oral and dental conditions including but not limited to dental caries, gingivitis and toothaches, dental pulpitis, halitosis (bad breath), mucositis, sore throat, oral wound infections, and periodontal abscesses. Herbs have also been used as plaque removers (chew sticks), antimicrobials, analgesics, anti-inflammatory agents, and antiseptics. Cannabis sativa L. in particular has been utilized in traditional Asian medicine for tooth-pain management, prevention of dental caries and reduction in gum inflammation. The distribution of cannabinoid (CB) receptors in the mouth suggest that the endocannabinoid system may be a target for the treatment of oral and dental diseases. Most recently, interest has been geared toward the use of Cannabidiol (CBD), one of several secondary metabolites produced by C. sativa L. CBD is a known anti-inflammatory, analgesic, anxiolytic, anti-microbial and anti-cancer agent, and as a result, may have therapeutic potential against conditions such burning mouth syndrome, dental anxiety, gingivitis, and possible oral cancer. Other major secondary metabolites of C. sativa L. such as terpenes and flavonoids also share anti-inflammatory, analgesic, anxiolytic and anti-microbial properties and may also have dental and oral applications. This review will investigate the potential of secondary metabolites of C. sativa L. in the treatment of dental and oral diseases.

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Introduction: Cannabinoids such as ▵-9-THC and CBD can downregulate the immune response by modulating the endocannabinoid system. This modulation is relevant for the treatment of prevalent autoimmune diseases (ADs), such as multiple sclerosis (MS), systemic lupus erythematosus (SLE), diabetes mellitus type 1 (DMT1), and rheumatoid arthritis (RA). These conditions require new therapeutic options with fewer side effects for the control of the autoimmune response. Objective: to conduct a literature review of preclinical scientific evidence that supports further clinical investigations for the use of cannabinoids (natural or synthetic) as potential immunomodulators of the immune response in ADs. Methodology: A systematic search was carried out in different databases using different MeSH terms, such as Cannabis sativa L., cannabinoids, immunomodulation, and ADs. Initially, 677 journal articles were found. After filtering by publication date (from 2000 to 2020 for SLE, DMT1, and RA; and 2010 to 2020 for MS) and removing the duplicate items, 200 articles were selected and analyzed by title and summary associated with the use of cannabinoids as immunomodulatory treatment for those diseases. Results: Evidence of the immunomodulatory effect of cannabinoids in the diseases previously mentioned, but SLE that did not meet the search criteria, was summarized from 24 journal articles. CBD was found to be one of the main modulators of the immune response. This molecule decreased the number of Th1 and Th17 proinflammatory cells and the production of the proinflammatory cytokines, interleukin (IL)-1, IL-12, IL-17, interferon (IFN)-γ, and tumor necrosis factor alpha, in mouse models of MS and DMT1. Additionally, new synthetic cannabinoid-like molecules, with agonist or antagonist activity on CB1, CB2, TRPV1, PPAR-α, and PPAR-γ receptors, have shown anti-inflammatory properties in MS, DMT1, and RA. Conclusion: Data from experimental animal models of AD showed that natural and synthetic cannabinoids downregulate inflammatory responses mediated by immune cells responsible for AD chronicity and progression. Although synthetic cannabinoid-like molecules were evaluated in just two clinical trials, they corroborated the potential use of cannabinoids to treat some ADs. Notwithstanding, new cannabinoid-based approaches are required to provide alternative treatments to patients affected by the large group of ADs.

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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.

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Resumo A Cannabis sativa L. vem sendo utilizada, antes mesmo da Era Cristã, para tratar inúmeras enfermidades, mas, no início do século 20, seu uso passou a ser proibido em vários países, inclusive com escopo medicinal, por ser considerada droga ilícita. Entretanto, a necessidade de obter alternativas aos tratamentos convencionais aumentou o interesse pelo uso terapêutico dessa droga vegetal, razão por que diversos estudos passaram a ser realizados, constatando que o Canabidiol (CBD), um dos principais compostos da planta, possui grande potencial terapêutico. No Brasil, a comercialização do CBD permanece proibida, mas, a partir de 2015, o uso compassivo e importação da substância foram autorizados pelo Conselho Federal de Medicina (CFM) e pela Agência Nacional de Vigilância Sanitária (Anvisa), porém, a demanda por CBD continua sendo judicializada. Justamente neste aspecto residiu o objetivo da pesquisa interdisciplinar, que foi analisar o exterior constitutivo do problema do acesso ao referido fármaco para tratamento de doenças. Para tanto, foi realizada pesquisa documental e exploratória, utilizando a abordagem qualitativa, além da revisão bibliográfica. O estudo de caso foi realizado com os processos judiciais do Tribunal de Justiça de Pernambuco (TJ/PE) sobre o assunto, localizados a partir da inserção agrupada das palavras-chave "fornecimento" e "Canabidiol" no campo "jurisprudência" do sítio virtual desse Tribunal. Como resultado, constatou-se que os sujeitos que ingressam com ação judicial atendem aos requisitos exigidos pelos órgãos reguladores, o que permite concluir que a negativa administrativa de fornecimento do medicamento pelo estado de Pernambuco caracteriza violação ao direito à saúde deles.

Abstract Cannabis sativa L. has been used since before the Christian Era to treat numerous diseases, but in the early 20th century, its use has been banned in several countries, including for medicinal purposes, for being considered illicit drug. However, the need to obtain alternatives to conventional treatments increased the interest for the therapeutic use of this plant, reason why several studies have been carried out, which verified that Cannabidiol (CBD), one of the main compounds of the plant, has great therapeutic potential. In Brazil, its internal commercialization is prohibited, but since 2015 the compassionate use and importation of the substance has been authorized by the Federal Council of Medicine (CFM) and by the National Health Surveillance Agency (Anvisa); however, the demand for CBD continues to be judicialized. The objective of this interdisciplinary research was precisely in this aspect, which was to analyze the constitutive exterior of the problem of access to the referred drug. For that, a documentary and exploratory research was performed, using the qualitative approach, in addition to the bibliographic review. The case study was carried out with the Judicial Processes of the Court of Justice of Pernambuco (TJ/PE) on the subject, located from the grouped insertion of the keywords "supply" and "Cannabidiol" in the field "jurisprudence" of the virtual site of this Court. As a result, it was found that individuals who file a lawsuit meet the requirements of regulatory agencies, which allows to conclude that the administrative refusal to provide the drug by the state of Pernambuco characterizes violation of their right to health.

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It is known that Cannabis in Brazil could either originate from Paraguay or be cultivated in Brazil. While consumer markets in the North and Northeast regions are maintained by national production, the rest of the country is supplied with Cannabis from Paraguay. However, the Brazilian Federal Police (BFP) has exponentially increased the seizure number of Cannabis seeds sent by mail. For this reason, the aim of the study was to assess the 13-loci short tandem repeat (STR) multiplex system proposed by Houston et al. (2015) to evaluate the power of such markers in individualization and origin differentiation of Cannabis sativa samples seized in Brazil by the BFP. To do so, 72 Cannabis samples seized in Brazil by BFP were analyzed. The principal coordinate analysis (PCoA) and probability identity (PI) analysis were computed. Additionally, the Cannabis samples' genotypes were subjected to comparison by Kruskal-Wallis H, followed by a multiple discriminant analysis (MDA). All samples analyzed revealed a distinct genetic profile. PCoA clearly discriminated the seizure sets based on their geographic origin. A combination of seven loci was enough to differentiate samples' genotypes, and the PI for a random sample is approximately one in 50 billion. The Cannabis samples were 100% correct as classified by Kruskal-Wallis H, followed by an MDA. The results of this study demonstrate that the 13-loci STR multiplex system successfully achieved the aim of sample individualization and origin differentiation and suggest that it could be a useful tool to help BFP intelligence in tracing back-trade routes.

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