Medicina cannabinoide en el territorio orofacial: estado actual y perspectivas a futuro / Cannabinoid medicine in the orofacial region: status and prospects

Introducción: El interés por emplear cannabis y cannabinoides como herramienta terapéutica ha tomado relevancia en la medicina en los últimos años. En sintonía con ello en odontología se ha incrementado el interés por su estudio. El objetivo de la presente revisión narrativa fue analizar y sintetizar la información disponible acerca de las posibilidades terapéuticas actuales del cannabis en odontología y sus perspectivas futuras. Materiales y métodos: Se realizó una búsqueda electrónica que abarcó artículos hasta diciembre del 2022, en las bases de datos MEDLINE, Scopus, Scielo y Google Académico. Se utilizaron las siguientes palabras claves principales: "dental", "dentistry", "cannabis", "cannabinoids", "benefits", "therapeutics", "treatment", "potential". En las búsquedas iniciales se encontraron un total de 834 registros. Se evaluó la elegibilidad de 45 artículos de texto completo. Se incluyeron 35 estudios para el análisis cualitativo de la presente revisión. Resultados: Los estudios muestran gran variedad de cannabinoides y derivados empleados, preparados comerciales, así como preparados experimentales. Se han llevado adelante estudios in vitro, in vivo y clínicos que evalúan la acción de los cannabinoides en el control del dolor orofacial, de la inflamación, como cicatrizante, en la regeneración del tejido óseo, como antimicrobiano y su capacidad anticancerígena. Conclusiones: Los cannabinoides han demostrado potencial en el tratamiento de diversas condiciones y/o alteraciones bucales. Aún la estandarización de los productos y protocolos de tratamiento es insuficiente por los que son necesarios más estudios que evalúen presentaciones, derivados, métodos de extracción, concentraciones y vías de administración.

Introduction: The interest in using cannabis and cannabinoids as a therapeutic tool has gained relevance in medicine in recent years. In line with this, interest in its study has increased in dentistry. The aim of the present narrative review was to analyze and synthesize the available information about the current therapeutic possibilities of cannabis in dentistry and its future perspectives. Materials and methods: an electronic search conducted that included articles until December 2022, in the MEDLINE, Scopus, Scielo and Google Scholar databases. The following main keywords used: "dental," "dentistry," "cannabis," "cannabinoids," "benefits," "therapeutics," "treatment," "potential." A total of 834 records founded in the first searches. Forty-five full-text articles assessed for eligibility. Thirty-five studies included for the qualitative analysis of the present review. Results: Studies show a great variability of cannabinoids and derivatives used, including commercial preparations, as well as experimental preparations. In vitro, in vivo, and clinical studies had conducted evaluating the action of cannabinoids in the control of orofacial pain, as anti-inflammatory and healing, in bone tissue regeneration, as antimicrobial and evaluating their anti-cancer ability. Conclusions: Cannabinoids have shown potential in the treatment of various oral conditions and/or disorders. Even the standardization of products and treatment protocols is insufficient, which is why more studies are necessary to evaluate presentations, derivatives, extraction methods, concentrations, and routes of administration for their best use.

Biomasa residual de industria del Cannabis, una alternativa para la obtención de productos de alto valor agregado

A medida que como sociedad vamos dando más importancia a lograr una economía circular, se hace importante encontrar fuentes renovables aptas para la producción de biocombustibles y bioquímicos. En los últimos años, diversas fuentes de biomasa lignocelulósica han sido estudiadas para estos propósitos. Dentro de estas fuentes de biomasa se encuentra el cáñamo (Cannabis sativa L.), siendo parte de una industria que ha crecido a pasos agigantados en las últimas décadas, en Colombia, desde su legalización. Específicamente, la industria del cannabis medicinal es responsable de generar una enorme cantidad de residuos en forma de los tallos de la planta, considerados un subproducto de bajo valor. En esta revisión se compila la información de diferentes estudios sobre el aprovechamiento de la fracción de polisacáridos de biomasa cáñamo, mediante transformaciones químicas y bioquímicas, para la obtención de productos de valor agregado. Se encontró que la mayoría de estudios están enfocados en la obtención de bioetanol o biogás; se encontraron también reportes de otras moléculas como ácido succínico, ácido láctico, furfural, polihidroxialcanoatos y bisaboleno. La viabilidad a nivel industrial de todos estos procesos permanece siendo una incógnita, pues los pasos de pretratamiento, hidrólisis y de conversión final utilizados suelen ser costosos. Es necesario que los estudios que realicen en el futuro se enfoquen en optimizar las condiciones de estos procesos y hacerlos verdes y así asegurar que puedan ser escalados.

As we as a society, give more importance to achieving a circular economy, it becomes important to find renewable sources suitable for the production of biofuels and biochemicals. In the last years, several different sources of lignocellulosic biomass have been studied for these purposes. One of these biomass sources is hemp (Cannabis sativa L), being part of an industry that has grown through giant steps in the last decades, in Colombia, since its legalization. Specifically, the industry of medicinal hemp is responsible for the generation of huge amounts of residues in the form of the plant stalks, considered a low value subproduct. This review compiles the information of several studies about the exploitation of the polysaccharide portion of hemp biomass through chemical and biochemical transformations, obtaining value-added products. It was found that most of these studies focus on the production of bioetanol or biogas; reports of other molecules such as succinic acid, furfural, polyhydroxyalkanoates and bisabolene were also found. Industrial viability of these processes remains a question, since pretreatment, hydrolysis and final conversion steps are usually expensive. It necessary that future studies focus on optimizing conditions of these processes as well as making them green, ensuring that they can be scaled.

Cannabis: Drug of Abuse and Therapeutic Agent, Two Sides of the Same Coin

ABSTRACT The consumption of Cannabis sativa plant, known as marijuana in the Western world, for different purposes (therapeutic, intoxicating, and spiritual) due to its psychoactive effects, can be traced back to ancient times. Cannabis is the most used illicit drug worldwide; however, its legal status is changing rapidly. Cannabis regulation will allow a better understanding of its effects as a misused drug, including new challenges, such as the availability of highly potent Cannabis extracts. Furthermore, scientific research is making significant efforts to take advantage of the potential therapeutic uses of Cannabis active compounds. The science of Cannabis derivatives started with the identification of the phytocannabinoids Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), allowing the formal study of the complex set of effects triggered by Cannabis consumption and the deciphering of its pharmacology. Δ9-THC is recognized as the compound responsible for the psychoactive and intoxicating effects of Cannabis. Its study led to the discovery of the endocannabinoid system, a neuromodulatory system widespread in the human body. CBD does not induce intoxication and for that reason, it is the focus of the search for cannabinoid potential clinical applications. This review examines the current state of knowledge about contrasting perspectives on the effects of Cannabis, Δ9-THC, and CBD: their abuse liability and potential therapeutic use; two sides of the same coin.

Utilização da cannabis sativa para tratamento de dor crônica em cães / Use of cannabis sativa for the treatment of chronic pain in dogs / Uso de cannabis sativa para el tratamiento del dolor crónico en perros

A Cannabis sativa é uma planta que apresenta vários benefícios terapêuticos para animais, como tratamento da dor neuropática, inflamatória e osteoartrose. A dor é bastante recorrente na rotina clínica, sendo importante seu manejo para que seja ofertada uma melhor qualidade e conforto de vida para o paciente. O estudo objetivou identificar, a partir de evidências científicas, as características da utilização medicinal do uso de Cannabis Sativa no tratamento da dor crônica no cão, utilizando um dos seus princípios ativos, canabidiol (CBD). Foi feito uma revisão bibliográfica onde foi realizada a busca de estudos experimentais e relatos de caso em bases de dados eletrônicos, sendo incluídas fontes contendo a utilização do CBD em animais, que abordaram controle da dor, assim como escore avaliativo da dor antes, durante e após o tratamento proposto. Após eleger e analisar 54 estudos percebe-se que na medicina veterinária o uso do canabidio é insuficiente, uma vez que o foco da maior parte dos estudos clínicos é voltado para medicina humana. Ainda assim, a utilização de CBD mostrou-se eficaz, confirmando uma nova alternativa para o controle da dor em animais.(AU)

Cannabis sativa is a plant that has several therapeutic benefits for animals, such as the treatment of neuropathic and inflammatory pain and osteoarthritis. Pain is quite recurrent in the clinical routine, and its management is important to offer a better quality and comfort of life for the patient. The study aimed to identify, based on scientific evidence, the characteristics of the medicinal use of Cannabis Sativa in the treatment of chronic pain in dogs, using one of its active principles, cannabidiol (CBD). A bibliographical review was carried out in which experimental studies and case reports were searched in electronic databases, including sources containing the use of CBD in animals, which addressed pain control, as well as pain assessment score before, during and after the proposed treatment. After choosing and analyzing 54 studies, it is clear that in veterinary medicine the use of CBD is few, and the focus of clinical studies is on human medicine. The use of CBD proved to be effective, thus confirming a new alternative for pain control in animals.(AU)

El cannabis sativa es una planta que tiene varios beneficios terapéuticos para los animales, como el tratamiento del dolor neuropático e inflamatorio y la osteoartritis. El dolor es bastante recurrente en la rutina clínica, y su manejo es importante para ofrecer una mejor calidad y comodidad de vida al paciente. El estudio tuvo como objetivo identificar, con base en la evidencia científica, las características del uso medicinal de Cannabis Sativa en el tratamiento del dolor crónico en perros, utilizando uno de sus principios activos, el cannabidiol (CBD). Se realizó una revisión bibliográfica en la que se buscaron estudios experimentales y reportes de casos en bases de datos electrónicas, incluyendo fuentes que contengan el uso de CBD en animales, que abordaran el control del dolor, así como la puntuación de evaluación del dolor antes, durante y después del tratamiento propuesto. Después de elegir y analizar 54 estudios, queda claro que en medicina veterinaria el uso de cannabidio es insuficiente, ya que el foco de la mayoría de los estudios clínicos está en la medicina humana. Aun así, el uso de CBD demostró ser efectivo, confirmando una nueva alternativa para el control del dolor en animales.(AU)

Cannabis versus neuromodulators in chronic pain / Cannabis versus neuromoduladores na dor crônica

ABSTRACT BACKGROUND AND OBJECTIVES: The change of paradigm in relation to the medical use of cannabis and its components in the treatment of pain is undeniable nowadays. Understanding the functioning of the endocannabinoid system and its interaction with drugs already available on the market is necessary for professionals who care for patients with chronic pain. The aim of this study was to show the mechanisms by which cannabinoids act, not only on CB1 and CB2 receptors, but also on various other receptors, modulating chronic pain, and encourage health professionals to recognize the need to expand the knowledge about its functioning and synergism with several medications so that the safe use of cannabis occurs in the treatment of multiple diseases, especially chronic pain. CONTENTS: The action of cannabinoids on the endocannabinoid system has the ability to neuro and immunomodulate pain transmission in a multifactorial and extremely complex way, acting simultaneously on multiple targets, in the peripheral, spinal and supraspinal nervous system. The analgesia mechanisms determined by cannabinoids include the inhibition of the release of neurotransmitters and neuropeptides in presynaptic nerve terminals, modulation of postsynaptic neuronal excitability, activation of the descending inhibitory pathway and reduction of neural inflammation. There is also the possibility that the interaction of cannabinoids with opioid and serotonergic receptors has an amplifying effect on the analgesic effect of drugs belonging to the opioid class. CONCLUSION: The endocannabinoid system plays a key role in pain control and its pathophysiology. It is expected that this system will continue to be studied for a better understanding of its signaling pathways and metabolism, and also that more clinical trials of greater size and duration will be carried out to understand to what extent this approach can be beneficial in the treatment of chronic pain.

RESUMO JUSTIFICATIVA E OBJETIVOS: A mudança de paradigma, em nível mundial, em relação ao uso medicinal de cannabis e seus respectivos componentes no tratamento da dor é indiscutível nos tempos atuais. Entender o funcionamento do sistema endocanabinoide e sua interação com fármacos já disponíveis no mercado se faz necessário aos profissionais que cuidam de pacientes com dor crônica. O objetivo deste estudo foi mostrar os mecanismos pelos quais os canabinoides atuam, não somente nos receptores CB1 e CB2, mas também em diversos outros receptores, agindo na modulação da dor crônica, bem como incentivar os profissionais da saúde a reconhecerem a necessidade de ampliar o conhecimento acerca desse funcionamento e sinergismo com diversos fármacos para que ocorra o uso seguro da cannabis no tratamento de múltiplas doenças, sobretudo dores crônicas. CONTEÚDO: A ação dos canabinoides no sistema endocanabinoide tem a capacidade de neuro e imunomodulação da transmissão da dor de forma multifatorial e extremamente complexa, atuando simultaneamente em múltiplos alvos, no sistema nervoso periférico, espinhal e supraespinhal. Os mecanismos de analgesia determinados pelos canabinoides incluem a inibição de liberação de neurotransmissores e neuropeptídeos nos terminais nervosos pré-sinápticos, a modulação da excitabilidade neuronal pós-sináptica, a ativação da via inibitória descendente e a redução da inflamação neural. Existe ainda a possibilidade de que a interação dos canabinoides com receptores opioides e serotoninérgicos tenha uma ação amplificadora do efeito analgésico de fármacos pertencentes à classe opioide. CONCLUSÃO: O sistema endocanabinoide desempenha um papel fundamental no controle da dor e na sua fisiopatologia. Espera-se que esse sistema continue a ser estudado para uma melhor compreensão das suas vias de sinalização e metabolismo. É preciso também que se realizem mais ensaios clínicos, de maior dimensão e duração, para compreender até que ponto essa abordagem poderá ser benéfica no tratamento da dor crônica.

The inhibitory effect of Cannabis Sativa L. and Morus nigra L. against lipid peroxidation in goat liver and brain homogenates / O efeito inibitório de Cannabis Sativa L. e Morus nigra L. contra a peroxidação lipídica em homogenatos de fígado e cérebro de cabra

Abstract The present study was aimed to evaluate the antioxidant potential and inhibitory effect ofCannabis sativa and Morus nigra against lipid peroxidation in goat brain and liver homogenates. The formation of free radicals, highly reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a normal metabolic process for cellular signaling and countering the antigens. However, they may cause serious damage if they produced at amplified tolls. In addition, metabolic disorders also serve as sources of these reactive species. Although the issue can be addressed through supplements and other phytochemicals. In this study, two plant species were evaluated for their biological potential by employing a spectrum of antioxidant assays. The antioxidant activity was performed by lipid peroxidation assay. The water extract prepared from leaves of Cannabis sativa and Morus nigra showed significant (P<0.05) inhibition as compared to control i.e., 522.6±0.06 and 659.97±0.03 µg/mL against iron-induced lipid peroxidation in goat brain homogenate while the inhibitions were 273.54±0.04 and 309.18±0.05 µg/mL against nitroprusside induced lipid peroxidation of the brain. The iron and nitroprusside induced lipid peroxidation was also significantly inhibited by leaf extracts of Cannabis sativa and Morus nigra in liver homogenates such as 230.63±0.52 and 326.91±0.01 µg/mL (iron-induced) while 300.47±0.07 and 300.47±0.07 µg/mL (nitroprusside induced), respectively. The extracts of Cannabis sativa extract showed promising activity (96.04±0.060%) against DPPH radicals while Morus nigra showed a moderate activity (34.11±0.120%). The results suggest that different accessions ofCannabis sativa and Morus nigra are a potential source of antioxidants and have a therapeutic effect against disease induced by oxidative stress and hence can be used for novel drug discovery and development.

Resumo O presente estudo teve como objetivo avaliar o potencial antioxidante e o efeito inibitório de Cannabis sativa e Morus nigra contra a peroxidação lipídica em homogenatos de cérebro e fígado de cabras. A formação de radicais livres, espécies altamente reativas de oxigênio (ROS) e espécies reativas de nitrogênio (RNS), é um processo metabólico normal para sinalização celular e combate aos antígenos. No entanto, eles podem causar sérios danos se forem produzidos em portagens ampliadas. Além disso, distúrbios metabólicos também servem como fontes dessas espécies reativas, embora o problema possa ser resolvido por meio de suplementos e outros fitoquímicos. Neste estudo, duas espécies de plantas foram avaliadas quanto ao seu potencial biológico, empregando um espectro de ensaios antioxidantes. A atividade antioxidante foi realizada por ensaio de peroxidação lipídica. O extrato de água preparado a partir de folhas de Cannabis sativa e Morus nigra mostrou inibição significativa (P < 0,05) em comparação com o controle, ou seja, 522,6 ± 0,06 e 659,97 ± 0,03 µg / mL contra peroxidação lipídica induzida por ferro em homogenato de cérebro de cabra, enquanto as inibições foram 273,54 ± 0,04 e 309,18 ± 0,05 µg / mL contra a peroxidação lipídica do cérebro induzida por nitroprussiato. A peroxidação lipídica induzida por ferro e nitroprussiato também foi significativamente inibida por extratos de folhas de Cannabis sativa e Morus nigra em homogenatos de fígado, como 230,63 ± 0,52 e 326,91 ± 0,01 µg / mL (induzida por ferro), enquanto 300,47 ± 0,07 e 300,47 ± 0,07 µg / mL (induzida por nitroprussiato), respectivamente. Os extratos do extrato de Cannabis sativa apresentaram atividade promissora (96,04 ± 0,060%) contra os radicais DPPH enquanto Morus nigra apresentou atividade moderada (34,11 ± 0,120%). Os resultados sugerem que diferentes acessos de Cannabis sativa e Morus nigra são uma fonte potencial de antioxidantes e têm efeito terapêutico contra doenças induzidas por estresse oxidativo e, portanto, podem ser usados ​​para a descoberta e desenvolvimento de novos medicamentos.

The inhibitory effect of Cannabis Sativa L. and Morus nigra L. against lipid peroxidation in goat liver and brain homogenates / O efeito inibitório de Cannabis Sativa L. e Morus nigra L. contra a peroxidação lipídica em homogenatos de fígado e cérebro de cabra

The present study was aimed to evaluate the antioxidant potential and inhibitory effect of Cannabis sativa and Morus nigra against lipid peroxidation in goat brain and liver homogenates. The formation of free radicals, highly reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a normal metabolic process for cellular signaling and countering the antigens. However, they may cause serious damage if they produced at amplified tolls. In addition, metabolic disorders also serve as sources of these reactive species. Although the issue can be addressed through supplements and other phytochemicals. In this study, two plant species were evaluated for their biological potential by employing a spectrum of antioxidant assays. The antioxidant activity was performed by lipid peroxidation assay. The water extract prepared from leaves of Cannabis sativa and Morus nigra showed significant (P<0.05) inhibition as compared to control i.e., 522.6±0.06 and 659.97±0.03 µg/mL against iron-induced lipid peroxidation in goat brain homogenate while the inhibitions were 273.54±0.04 and 309.18±0.05 µg/mL against nitroprusside induced lipid peroxidation of the brain. The iron and nitroprusside induced lipid peroxidation was also significantly inhibited by leaf extracts of Cannabis sativa and Morus nigra in liver homogenates such as 230.63±0.52 and 326.91±0.01 µg/mL (iron-induced) while 300.47±0.07 and 300.47±0.07 µg/mL (nitroprusside induced), respectively. The extracts of Cannabis sativa extract showed promising activity (96.04±0.060%) against DPPH radicals while Morus nigra showed a moderate activity (34.11±0.120%). The results suggest that different accessions of Cannabis sativa and Morus nigra are a potential source of antioxidants and have a therapeutic effect against disease induced by oxidative stress and hence can be used for novel drug discovery and development.

O presente estudo teve como objetivo avaliar o potencial antioxidante e o efeito inibitório de Cannabis sativa e Morus nigra contra a peroxidação lipídica em homogenatos de cérebro e fígado de cabras. A formação de radicais livres, espécies altamente reativas de oxigênio (ROS) e espécies reativas de nitrogênio (RNS), é um processo metabólico normal para sinalização celular e combate aos antígenos. No entanto, eles podem causar sérios danos se forem produzidos em portagens ampliadas. Além disso, distúrbios metabólicos também servem como fontes dessas espécies reativas, embora o problema possa ser resolvido por meio de suplementos e outros fitoquímicos. Neste estudo, duas espécies de plantas foram avaliadas quanto ao seu potencial biológico, empregando um espectro de ensaios antioxidantes. A atividade antioxidante foi realizada por ensaio de peroxidação lipídica. O extrato de água preparado a partir de folhas de Cannabis sativa e Morus nigra mostrou inibição significativa (P < 0,05) em comparação com o controle, ou seja, 522,6 ± 0,06 e 659,97 ± 0,03 µg / mL contra peroxidação lipídica induzida por ferro em homogenato de cérebro de cabra, enquanto as inibições foram 273,54 ± 0,04 e 309,18 ± 0,05 µg / mL contra a peroxidação lipídica do cérebro induzida por nitroprussiato. A peroxidação lipídica induzida por ferro e nitroprussiato também foi significativamente inibida por extratos de folhas de Cannabis sativa e Morus nigra em homogenatos de fígado, como 230,63 ± 0,52 e 326,91 ± 0,01 µg / mL (induzida por ferro), enquanto 300,47 ± 0,07 e 300,47 ± 0,07 µg / mL (induzida por nitroprussiato), respectivamente. Os extratos do extrato de Cannabis sativa apresentaram atividade promissora (96,04 ± 0,060%) contra os radicais DPPH enquanto Morus nigra apresentou atividade moderada (34,11 ± 0,120%). Os resultados sugerem que diferentes acessos de Cannabis sativa e Morus nigra são uma fonte potencial de antioxidantes e têm efeito terapêutico [...].

The inhibitory effect of Cannabis Sativa L. and Morus nigra L. against lipid peroxidation in goat liver and brain homogenates

Abstract The present study was aimed to evaluate the antioxidant potential and inhibitory effect ofCannabis sativa and Morus nigra against lipid peroxidation in goat brain and liver homogenates. The formation of free radicals, highly reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a normal metabolic process for cellular signaling and countering the antigens. However, they may cause serious damage if they produced at amplified tolls. In addition, metabolic disorders also serve as sources of these reactive species. Although the issue can be addressed through supplements and other phytochemicals. In this study, two plant species were evaluated for their biological potential by employing a spectrum of antioxidant assays. The antioxidant activity was performed by lipid peroxidation assay. The water extract prepared from leaves of Cannabis sativa and Morus nigra showed significant (P 0.05) inhibition as compared to control i.e., 522.6±0.06 and 659.97±0.03 µg/mL against iron-induced lipid peroxidation in goat brain homogenate while the inhibitions were 273.54±0.04 and 309.18±0.05 µg/mL against nitroprusside induced lipid peroxidation of the brain. The iron and nitroprusside induced lipid peroxidation was also significantly inhibited by leaf extracts of Cannabis sativa and Morus nigra in liver homogenates such as 230.63±0.52 and 326.91±0.01 µg/mL (iron-induced) while 300.47±0.07 and 300.47±0.07 µg/mL (nitroprusside induced), respectively. The extracts of Cannabis sativa extract showed promising activity (96.04±0.060%) against DPPH radicals while Morus nigra showed a moderate activity (34.11±0.120%). The results suggest that different accessions ofCannabis sativa and Morus nigra are a potential source of antioxidants and have a therapeutic effect against disease induced by oxidative stress and hence can be used for novel drug discovery and development.

Resumo O presente estudo teve como objetivo avaliar o potencial antioxidante e o efeito inibitório de Cannabis sativa e Morus nigra contra a peroxidação lipídica em homogenatos de cérebro e fígado de cabras. A formação de radicais livres, espécies altamente reativas de oxigênio (ROS) e espécies reativas de nitrogênio (RNS), é um processo metabólico normal para sinalização celular e combate aos antígenos. No entanto, eles podem causar sérios danos se forem produzidos em portagens ampliadas. Além disso, distúrbios metabólicos também servem como fontes dessas espécies reativas, embora o problema possa ser resolvido por meio de suplementos e outros fitoquímicos. Neste estudo, duas espécies de plantas foram avaliadas quanto ao seu potencial biológico, empregando um espectro de ensaios antioxidantes. A atividade antioxidante foi realizada por ensaio de peroxidação lipídica. O extrato de água preparado a partir de folhas de Cannabis sativa e Morus nigra mostrou inibição significativa (P 0,05) em comparação com o controle, ou seja, 522,6 ± 0,06 e 659,97 ± 0,03 µg / mL contra peroxidação lipídica induzida por ferro em homogenato de cérebro de cabra, enquanto as inibições foram 273,54 ± 0,04 e 309,18 ± 0,05 µg / mL contra a peroxidação lipídica do cérebro induzida por nitroprussiato. A peroxidação lipídica induzida por ferro e nitroprussiato também foi significativamente inibida por extratos de folhas de Cannabis sativa e Morus nigra em homogenatos de fígado, como 230,63 ± 0,52 e 326,91 ± 0,01 µg / mL (induzida por ferro), enquanto 300,47 ± 0,07 e 300,47 ± 0,07 µg / mL (induzida por nitroprussiato), respectivamente. Os extratos do extrato de Cannabis sativa apresentaram atividade promissora (96,04 ± 0,060%) contra os radicais DPPH enquanto Morus nigra apresentou atividade moderada (34,11 ± 0,120%). Os resultados sugerem que diferentes acessos de Cannabis sativa e Morus nigra são uma fonte potencial de antioxidantes e têm efeito terapêutico contra doenças induzidas por estresse oxidativo e, portanto, podem ser usados para a descoberta e desenvolvimento de novos medicamentos.

Effects of Cannabis sativa oil on the symptom improvement and intestinal flora in UC model rats / 中国药房

OBJECTIVE To study the improvement effects of Cannabis sativa oil on the symptoms in dextran sodium sulfate （DSS）-induced ulcerative colitis （UC） model rats， and to investigate its effects on intestinal flora of rats. METHODS Forty SD rats were randomly divided into control group， model group， C. sativa oil group （1 g/kg） and sulfasalazine group （positive control， 300 mg/kg）， with 10 rats in each group. The rats in control group and model group were given 0.5% polysorbate 80 by gavage， and the rats in C. sativa oil group and sulfasalazine group were given corresponding drug solution by gavage once a day for 10 days. From the 4th day， rats in model group， C. sativa oil group and sulfasalazine group were given 4% DSS solution for 7 consecutive days to establish UC model. The body weight， disease activity index （DAI） score， colon length， colon weight， weight per unit length of colon， the pathological changes of colon tissue， and the contents of tumour necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-10 in serum of rats were determined. The changes of intestinal flora in rats were detected by high- throughput sequencing. RESULTS Compared with control group， the body weight and the length of colon were decreased significantly in model group， while DAI score， the weight of colon， weight per unit length of colon， serum contents of TNF-α and IL-6 were increased significantly， and the content of IL-10 was decreased significantly （P＜0.05）； epithelial layer of colon tissue fell off， inflammatory cells infiltrated and invaded the submucosa， and intestinal glands were disordered. Compared with model group， above indexes of C. sativa oil group and sulfasalazine group were reversed significantly （P＜0.05）， and related symptoms were improved significantly. The result of flora sequencing showed that ACE index and Chao1 index of model group were decreased significantly， compared with control group （P＜0.05）； while Chao1 index of C. sativa oil group was increased significantly， compared with model group （P＜0.05）. Compared with control group， 41 genera of bacteria in the model group changed； compared with model group， C. sativa oil could return 3 of the 41 genera to normal state， including Dubosilla， Porphyrobacter and Allobaculum. CONCLUSIONS C. sativa oil can improve the symptoms of UC model rats by regulating the diversity of intestinal flora， increasing beneficial bacteria and decreasing pathogenic bacteria.

A new dihydrostilbene from aerial part of Cannabis sativa / 中国中药杂志

The present study investigated the chemical constituents in the aerial part of Cannabis sativa. The chemical constituents were isolated and purified by silica gel column chromatography and HPLC and identified according to their spectral data and physicochemical properties. Thirteen compounds were isolated from the acetic ether extract of C. sativa and identified as 3',5',4″,2-tetrahydroxy-4'-methoxy-3-methyl-3″-butenyl p-disubstituted benzene ethane(1), 16R-hydroxyoctadeca-9Z,12Z,14E-trienoic acid methyl ester(2),(1'R,2'R)-2'-(2-hydroxypropan-2-yl)-5'-methyl-4-pentyl-1',2',3',4'-tetrahydro-(1,1'-biphenyl)-2,6-diol(3), β-sitosteryl-3-O-β-D-glucopyranosyl-6'-O-palmitate(4), 9S,12S,13S-trihydroxy-10-octadecenoate methyl ester(5), benzyloxy-1-O-β-D-glucopyranoside(6), phenylethyl-O-β-D-glucopyranoside(7), 3Z-enol glucoside(8), α-cannabispiranol-4'-O-β-D-glucopyranose(9), 9S,12S,13S-trihydroxyoctadeca-10E,15Z-dienoic acid(10), uracil(11), o-hydroxybenzoic acid(12), and 2'-O-methyladenosine(13). Compound 1 is a new compound, compound 3 is a new natural product, and compounds 2, 4-8, 10, and 13 were isolated from Cannabis plant for the first time.

Neuroprotective potential of cannabidiol: Molecular mechanisms and clinical implications / 中西医结合学报

Cannabidiol (CBD), a nonpsychotropic phytocannabinoid that was once largely disregarded, is currently the subject of significant medicinal study. CBD is found in Cannabis sativa, and has a myriad of neuropharmacological impacts on the central nervous system, including the capacity to reduce neuroinflammation, protein misfolding and oxidative stress. On the other hand, it is well established that CBD generates its biological effects without exerting a large amount of intrinsic activity upon cannabinoid receptors. Because of this, CBD does not produce undesirable psychotropic effects that are typical of marijuana derivatives. Nonetheless, CBD displays the exceptional potential to become a supplementary medicine in various neurological diseases. Currently, many clinical trials are being conducted to investigate this possibility. This review focuses on the therapeutic effects of CBD in managing neurological disorders like Alzheimer's disease, Parkinson's disease and epilepsy. Overall, this review aims to build a stronger understanding of CBD and provide guidance for future fundamental scientific and clinical investigations, opening a new therapeutic window for neuroprotection. Please cite this article as: Tambe SM, Mali S, Amin PD, Oliveira M. Neuroprotective potential of Cannabidiol: Molecular mechanisms and clinical implications. J Integr Med. 2023; 21(3): 236-244.

Implicações bioéticas do uso terapêutico da Cannabis sativa L. no Brasil / Bioethical implications of the therapeutic use of Cannabis sativa L. in Brazil

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.

Medical cannabis and cannabidiol: A new harvest for Malawi

In February 2020 parliament passed the Cannabis Regulation Bill (2020) which regulates the cultivation and production of industrial hemp and medical cannabis. The country will only fully benefit from this development if the medical and scientific community can take the lead in enabling the country to exploit the plant's potential to help address some of our economic and public health challenges. This special communication provides some basic information on cannabis and discusses its history and medical uses. Cannabidiol (CBD) has emerged as one of the most important cannabis-derived phytochemicals and has formed the basis for the growth of the medical cannabis industry. The scientific data on the mechanisms of the effects of CBD on the human neuroendocrine-immune network is reviewed and the first effective cannabis-based FDA-approved treatment for epilepsy discussed. Some clinical research that is being done on the antipsychotic and neuroprotective properties of CBD is also reviewed. A case is made for the potential of CBD as a neuroprotective adjunctive therapy for the prevention of neuropsychological sequelae associated with complicated malaria. The safety profile of CBD is reviewed and finally, the potential importance of the re-medicalization of cannabis-based therapies for the broader field of phytomedicine is pointed out

Cultivation and breeding of industrial Cannabis sativa / 中国中药杂志

Cannabis sativa,with a long history of cultivation, is a traditional industrial crop widely used for food, textiles, and me-dicine. This study discussed industrial C. sativa and medicinal C. sativa. According to the characteristics of management policies of C. sativa in different periods, we divided the development stages of C. sativa into three stages and analyzed the changes in breeding and cultivation goals under the influence of policies. Meanwhile, a comprehensive analysis was carried out based on the breeding conditions of industrial C. sativa in China. Because of the vast territory of China, the differences in agricultural planting environment, economic development, and social development in the southern and northern areas result in different used parts of C. sativa. To be speci-fic, flowers and leaves are used in Yunnan, fiber in Heilongjiang, and seeds in Shanxi. The breeding of C. sativa varieties highlights fiber, seeds, or both of them. As the value of cannabidiol is explored, medicinal C. sativa has been approved in recent years. Based on the cultivation characteristics and value of industrial C. sativa, it is proposed that industrial C. sativa has a broad application prospect as an important industrial crop, and the existing products contain almost no tetrahydrocannabinol. The cultivation of C. sativa should be rationally guided to promote the development of the C. sativa industry. Moreover, it is recommended to actively apply advanced breeding techniques such as molecular breeding to overcome the problems of the uncertainty of the existing induced breeding and the excessively long hybrid breeding cycle, and develop high value-added applications such as medicinal products of C. sativa to enhance the exploitation of the economic value of C. sativa.

Efecto del consumo de marihuana sobre los parámetros espermáticos humanos: Aproximación in vivo / Effect of Marijuana Use on Human Semen Parameters: In Vivo Approach

La evidencia sugiere que la exposición a sustancias psicoactivas se relaciona con alteraciones en la espermatogénesis que afectan la calidad espermática. El objetivo de este trabajo fue determinar los parámetros espermáticos en consumidores habituales de cigarrillos de marihuana. Se analizaron muestras seminales de 42 consumidores activos de cigarrillos de marihuana y de 16 voluntarios no consumidores de marihuana. Mediante un análisis de semen, se determinaron los parámetros seminales convencionales (viabilidad, movilidad, morfología, y concentración de los espermatozoides) siguiendo los lineamientos establecidos por la Organización Mundial de la Salud (OMS). Adicionalmente, se evaluó la capacidad antioxidante del plasma seminal mediante la determinación del porcentaje de inhibición del radical estable 1,1-difenil-2-picril-hidracilo. Los valores de la mediana de los consumidores respecto al grupo control fueron: volumen ­ 2,98 mL versus 3,95 mL (p = 0,0221); concentración total ­ 189 millones/mL versus 291,1 millones/mL (p = 0,0636); movilidad progresiva ­ 50% versus 56,5% (p = 0,0052); viabilidad ­ 65,3% versus 73,1% (p = 0,0732); y morfología normal ­ 5% versus 7% (p = 0,0167), respectivamente. Los resultados obtenidos en este estudio indican que el consumo de cigarrillos de marihuana afecta negativamente la movilidad progresiva, la morfología normal y la concentración total de espermatozoides; además, la concentración total de espermatozoides está afectada por la frecuencia del consumo de cigarrillos de marihuana.

Evidence suggests that exposure to psychoactive substances is related to spermatogenesis alterations that affect sperm quality. The objective of the present work was to determine sperm parameters in regular users of marijuana cigarettes. Seminal samples from 42 active consumers of marijuana cigarettes and 16 volunteer non-marijuana users were analyzed. Through a semen analysis, we identify conventional seminal parameters (viability, motility, morphology, and sperm concentration) according to the guidelines established by the World Health Organization (WHO). The antioxidant effect of the seminal plasma was evaluated through the determination of the percentage of inhibition of the stable radical 1,1-diphenyl-2-picrylhydrazyl. The median values of consumers with respect to the control group were respectively: volume ­ 2.98 mL versus 3.95 mL (p = 0.0221); total concentration ­ 189 million/mL versus 291.1 million/mL (p = 0.0636); progressive motility ­ 50% versus 56.5% (p = 0.0052); viability ­ 65.3% versus 73.1% (p = 0.0732); and normal morphology ­ 5% versus 7% (p = 0.0167). The results obtained in the present study indicate that the consumption of marijuana cigarettes negatively affects progressive motility, normal morphology, and total sperm concentration. In addition, the total sperm concentration is affected by the frequency of consumption of marijuana cigarettes

Uso terapêutico da cannabis medicinal em pessoas com doença neurológica degenerativa / Therapeutic use of medicinal cannabis in people with degenerative neurological disease / Uso terapéutico de cannabis medicinal en personas con enfermedad neurológica degenerativa

Objetivo: apresentar o estado da arte das publicações expressas na literatura cientifica mundial sobre a temática, bem como identificar os benefícios terapêuticos da Cannabis medicinal no tratamento dos sintomas das doenças neurodegenerativas especificamente doenças de Parkinson, esclerose múltipla e Alzheimer. Método: trata-se de uma revisão integrativa da literatura, cuja busca de dados foi realizada nas bibliotecas virtuais. Web of Science, Scopus, Medline, Lilacs, Cochrane Library e Scielo no período de agosto a outubro de 2021. Resultados: foram encontrados 158 artigos. Vinte e tres artigos foram selecionados para serem lidos na íntegra e 8 atenderam aos critérios desta revisão. Conclusão: as evidências mostram que embora cada vez mais prescritos ou autorizados, a cannabis medicinal ou os Canabinóides para a doenças neurodegenerativas continuam a ser controversos para muitos médicos.

Objective: to present the state of the art of publications expressed in the world Scientific literature on the subject, as well as to identify the therapeutic benefits of medicinal cannabis in the treatment of neurodegenerative diseases, specifically, Parkinson's diseases, multiple sclerosis and Alzheimer's. Method: this is an integrative literature review, whose data search was performed in virtual librares. Web of Science, Scopus, Medline, Lilacs, Cochrane Library and Scielo from August to October 2021. Results:158 articles were found. Twenty-three articles were selected to be read in full and 8 met the criteria of this review. Conclusion: evidence shows that although increasingly prescribed or authorized, medical cannabis or Cannabinoids for chronic pain remain controversial for many physicians.

Objetivo: presentar el estado del arte de las publicaciones expresadas en la literatura científica mundial sobre el tema, así como identificar los beneficios terapéuticos del cannabis medicinal en el tratamiento de enfermedades neurodegenerativas, en concreto, las enfermedades de Parkinson, la esclerosis múltiple y el Alzheimer. Método: se trata de una revisión integradora de la literatura, cuya búsqueda de datos se realizó en bibliotecas virtuales. Web of Science, Scopus, Medline, Lilacs, Cochrane Library y Scielo de agosto a octubre de 2021. Resultados: se encontraron 158 artículos. Se seleccionaron veintitrés artículos para ser leídos en su totalidad y ocho cumplieron los criterios de esta revisión. Conclusión: la evidencia muestra que, aunque cada vez más se prescribe o autoriza, el cannabis medicinal o los cannabinoides para el dolor crónico siguen siendo controvertidos para muchos médicos.

Sistema endocannabinoide y cannabidiol en el manejo del dolor en perros: revisión narrativa

Introducción: la marihuana (Cannabis sativa L.) es una planta originaria de Asia cada vez más reconocida por su valor terapéutico en la medicina humana y veterinaria. Contiene una gran cantidad de componentes entre los que destacan los fitocannabinoides, de los cuales los más representativos son el delta-9-tetrahidrocannabinol (THC) y Cannabidiol (CBD) que se acoplan respectivamente a los receptores CB1 y CB2 en el sistema endocannabinoide que es un sistema neurotransmisor entre células que regula varios procesos en los vertebrados como memoria, dolor, inflamación, apetito y procesos inmunológicos entre otros. Objetivo: realizar una síntesis narrativa del sistema endocannabinoide y cannabidiol en el manejo del dolor en perros, a partir de la búsqueda de publicaciones en bases de datos electrónica PubMed, NCBI, SciELO, Science Direct, Dialnet, Google y Google Académico. Resultados: el CBD es el principal cannabinoide utilizado en la terapia del manejo del dolor en perros por sus propiedades analgésicas y carencia de efectos psicoactivos. Conclusión: se evidencia la necesidad de realizar más investigaciones con ensayos clínicos controlados sobre el uso terapéutico del cannabidiol, que tengan validez interna y externa, con poblaciones más significativas en la especie de interés.

SUMMARY Introduction: marijuana (CannabissativaL.) is a plant native to Asia that is increasingly recognized for its therapeutic value in human and veterinary medicine. It contains a large number of components among which the phytocannabinoids stand out, of which the most representative are delta-9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) that are coupled respectively to the CB1 and CB2 receptors in the endocannabinoid system, which is a neurotransmitter system between cells that regulates various processes in vertebrates such as memory, pain, inflammation, appetite and immune processes among others. Aim: to carry out a narrative synthesis of the endocannabinoid and cannabidiol system in the management of pain in dogs, from the search of publications in electronic databases PubMed, NCBI, SciELO, Science Direct, Dialnet, Google and Google Scholar. Results: CBD is the main cannabinoid used in pain management therapy in dogs due to its analgesic proper-ties and lack of psychoactive effects. Conclusion: there is evidence of the need for more research with controlled clinical trials on the therapeutic use of cannabidiol, which have internal and external validity, with more significant populations in the species of interest.

Introdução: a maconha (Cannabis sativa L.) é uma planta nativa da Ásia que é cada vez mais reconhecida por seu valor terapêutico na medicina humana e veterinária. Ele contém muitos componentes entre os quais se destacam os fitocanabinóides, dos quais os mais representativos são delta-9-tetrahidrocanabinol (THC) e Canabidiol (CBD) que estão acoplados respectivamente aos receptores CB1 e CB2 no sistema endocanabinóide, que é um sistema neurotransmissor entre as células que regula vários processos nos vertebrados, como memória, dor, inflamação, apetite e processos imunológicos, entre outros. Objetivo: realizar uma síntese narrativa do sistema endocanabinoide e canabidiol no manejo da dor em cães, a partir da busca de publicações nas bases de dados eletrônicas PubMed, NCBI, SciELO, Science Direct, Dialnet, Google e Google Scholar. Resultados: O CBD é o principal canabinoide utilizado na terapia de controle da dor em cães devido às suas propriedades analgésicas e ausência de efeitos psicoativos. Conclusão: há evidências da necessidade de mais pesquisas com ensaios clínicos controlados sobre o uso terapêutico do canabidiol, que tenham validade interna e externa, com populações mais significativas nas espécies de interesse.

Analysis on YABBY Transcription Factor Family of Original Plant Cannabis sativa of Traditional Chinese Medicine Cannabis Fructus / 中国实验方剂学杂志

Objective:To analyze the sequence characteristics，chromosomal location，gene structure，conserved motifs，phylogenetic evolution and differential gene expressions of the <italic>Cannabis sativa</italic> YABBY transcription factor family，in order to provide a molecular basis for in-depth study of <italic>YABBY</italic> gene function and theoretical support for the selection and breeding of superior hemp varieties. Method:The bio-informatics method was used to identify and analyze the <italic>CsYABBY </italic>gene family of the original hemp seed plant. PlantTFDB，ExPASy，MEME，CELLO，PLANTCARE and other online websites and TBtools，MEGA，DNAMAN and other software were used for prediction，visualization and analysis. Result:<italic>C. sativa</italic> contains 6 <italic>YABBY</italic> gene members distributed on 5 chromosomes，in which 5 members are localized in the nucleus and 1 in extracellular， they consist of 185-235 amino acids， and the isoelectric point is between 5.05 and 9.34， the molecular weight is between 20 582.45-26 282.7 Da. All of CsYABBY proteins contain two conserved domains， namely Zinc finger domain and YABBY domain. <italic>CsYABBY</italic> genes have multiple cis-acting elements，and their expressions differ in different tissues and cultivars. Conclusion:The expressions of CsYABBY may be affected by hormones and externally environmental factors. <italic>CsYABBY</italic> gene expressions are tissue-specific. In addition，YABBY transcription factor family may play an important role in regulating the development of <italic>C. sativa</italic> female flowers，and subfamilies YAB1 and YAB5 may be involved in the synthesis of cannabinoids.

Identification and expression analysis of the C2H2 gene family in Cannabis sativa L / 药学学报

C2H2 transcription factors play an important role in plant growth, development and the regulation of secondary metabolism. This article identifies members of the C2H2 gene family in Cannabis sativa L. at the genome level. Chromosomal location and linkage, evolutionary relationships, and identification of conserved motifs was determined from the C. sativa genome and transcriptome data using bioinformatics tools and on-line websites such as TBtools, MEGA software, NCBI, PlantTFDB, ExPASy, HMMSCAN, MEME, WoLFPSORT and PlantCARE. The results show that C. sativa contains 30 members of the C2H2 gene family (named CsC2H2-1-CsC2H2-30) distributed on 9 chromosomes. The encoded proteins range in length from 138 to 635 amino acids, and the theoretical isoelectric points range from 5.85 to 9.52. Molecular weights range from 15 909.48 to 68 445.53 Da. Transcriptome analysis showed that CsC2H2 was differentially expressed in the female flowers, bracts, leaves, and stems of the Diku variety and female flowers of nine different varieties of C. sativa. Quantitative real-time PCR verified that CsC2H2-1, CsC2H2-5, and CsC2H2-19 were significantly expressed in the female flowers and bracts of the Diku variety. This provides a theoretical basis for in-depth study of the function of the C2H2 gene family and the breeding of high-quality C. sativa varieties.

Identification of Cannabis Sativa L. Based on rbcL Sequence / 法医学杂志

Objective To assess the feasibility of the rbcL sequence of chloroplast DNA as a genetic marker to identify Cannabis sativa L. Methods The rbcL sequences in 62 Cannabis sativa L. samples, 10 Humulus lupulus samples and 10 Humulus scandens DNA samples were detected, and 96 rbcL sequences of the Cannabaceae family were downloaded from Genbank. Sequence alignment was performed by MEGA X software, the intraspecific and interspecific Kimura-2-Parameter （K2P） genetic distances were calculated, and the system clustering tree was constructed. Results The rbcL sequence length acquired by sequencing of Cannabis sativa L. and Humulus scandens were 617 bp and 649 bp, respectively, and two haplotypes of Cannabis sativa L. were observed in the samples. The BLAST similarity search results showed that the highest similarity between the sequences acquired by sequencing and Cannabis sativa L. rbcL sequences available from Genbank was 100%. The genetic distance analysis showed that the maximum intraspecific genetic distance （0.004 9） of Cannabis sativa L. was less than the minimum interspecific genetic distance （0.012 9）. The results of median-joining network and system clustering tree analysis showed that Cannabis sativa L. and other members of the Cannabaceae family were located in different branches. Conclusion The rbcL sequence could be used as a DNA barcode for identifying Cannabis sativa L., and combined with comparative analysis of the rbcL sequence and system cluster analysis could be a reliable and effective detection method for Cannabis sativa L. identification in forensic investigation.