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.

Indications for the use of cannabinoids / Indicação do uso de canabinoides

ABSTRACT BACKGROUND AND OBJECTIVES: The increasingly widespread use of cannabinoids in the management of acute and chronic pain generates an urgent need to study how cannabinoids act on CB1 and CB2 receptors and what their effects are on the organism. It is important to understand the difference in action between natural cannabinoids (cannabidiol, delta 9-tetrahydrocannabinol, cannabigerol, cannabinoil, terpenes) and synthetic ones, so that the appropriate choice is made in each case, and depending on the pathophysiology of pain, one or the other active is more indicated. CONTENTS: Studies collected in the Pubmed, Cochrane Library and Web of Science databases were analyzed. These studies focus were on natural cannabinoids (cannabidiol, delta 9-tetrahydrocannabinol, cannabigerol, cannabinoil, terpenes) and synthetic cannabinoids in the use for the treatment of chronic pain, their action on the endocannabinoid system through the activation of the CB1 and CB2 receptor and their effect after activating this receptor, aiming to compile which cannabinoid is more indicated in the treatment of pain pathology. CONCLUSION: The subject still requires much study and new articles are being published daily. The analysis of the studies must be carried out with criteria to evaluate their seriousness. The endocannabinoid system is closely linked to the treatment of chronic pain and some cannabinoids such as: cannabidiol, delta 9-tetrahydrocannabinol, cannabigerol, cannabinoil, as well as some terpenes are already considered important in the treatment of chronic pain inferring sparing effect of opioids, anticonvulsants, antidepressants among others.

RESUMO JUSTIFICATIVA E OBJETIVOS: O uso cada vez mais disseminado dos canabinoides no controle da dor aguda e crônica gera uma necessidade urgente do estudo de como os canabinoides agem nos receptores CB1 e CB2 e quais seus efeitos no organismo. É importante entender a diferença de ação entre os canabinoides naturais (canabidiol, delta 9-tetrahidrocanabinol, canabigerol, canabinol, terpenos) e os sintéticos, para que a escolha adequada seja realizada em cada caso, sendo que dependendo da fisiopatologia da dor é mais indicado um ou outro ativo. CONTEÚDO: Foram analisados estudos coletados na Pubmed, Cochrane Library e Web of Science. Os estudos se concentram em canabinoides naturais (canabidiol, delta 9-tetrahidrocanabinol, canabigerol, canabinoil, terpenos) e canabinoides sintéticos no uso para o tratamento da dor crônica, sua ação no sistema endocanabinoide através da ativação do receptor CB1 e CB2 e seu efeito após ativar esse receptor, visando compilar qual canabinoide é mais indicado no tratamento da patologia álgica. CONCLUSÃO: O assunto ainda requer muito estudo e diariamente novos artigos vem sendo publicados. A análise dos estudos deve ser realizada com critério para avaliar sua seriedade. O sistema endocanabinoide está intimamente ligado ao tratamento da dor crônica e alguns canabinoides como: canabidiol, delta 9-tetrahidrocanabinol, canabigerol, canabinoil, assim como alguns terpenos já são considerados importantes no tratamento da dor crônica inferindo efeito poupador de opioides, anticonvulsivantes, antidepressivos entre outros.

Cannabis: 12,000 years of experiences and prejudices / Cannabis: 12.000 anos de experiências e preconceitos

ABSTRACT BACKGROUND AND OBJECTIVES: Cannabis Sativa has been part of human evolution and has been used by different populations for different purposes. By reviewing the history and main advances in cannabinoid medicine, the aim of this study was to identify the major discoveries in recent years, which have prompted the publication of articles. CONTENTS: The following topics were searched: "history of cannabis", "history of hashish", "history of marijuana" and "main advances in endocannabinoid medicine"; in SCIELO, Pubmed, Google Scholar, Brazilian Digital Library of Theses and Dissertations (BDTD), Latin American and Caribbean Literature in Health Sciences (LILACS) and Medline (Capes platform) databases. CONCLUSION: There has been an increase in the number of publications following major discoveries about the endocannabinoid system, including receptors and endocannabinoids, but prejudice and the difficulty of accessing this therapeutic tool prevent further development.

RESUMO JUSTIFICATIVA E OBJETIVOS: A Cannabis Sativa acompanha a evolução humana e foi utilizada por diversas populações para diversos propósitos. Ao revisar a história e os principais avanços na medicina canabinoide, o objetivo deste estudo foi identificar as maiores descobertas nos últimos anos, que fomentaram a publicação de artigos. CONTEÚDO: Os seguintes tópicos foram foram pesquisados: "história da cannabis", "história do haxixe", "história da maconha" e "principais avanços na medicina endocanabinoide"; nos bancos de dados SCIELO, Pubmed, Google Scholar, Biblioteca Digital Brasileira de teses e dissertações (BDTD), Literatura Latino-Americana e do Caribe em Ciências da saúde (LILACS) e Medline (plataforma Capes). CONCLUSÃO: Foi demonstrado o aumento no número de publicações após as grandes descobertas a respeito do sistema endocanabinoide, incluindo os receptores e os endocanabinoides, porém o preconceito e a dificuldade de acesso a essa ferramenta terapêutica impede um maior desenvolvimento.

Cannabis recreativo: Perfil de los cannabinoides presentes en muestras de marihuana suministradas por población consumidora / Recreational cannabis: Profile of cannabinoids present in marijuana samples supplied by the consuming population

RESUMEN El cannabis o marihuana es una de las sustancias psicoactivas más consumida en todo el mundo, por lo que conocer la composición y el tipo de cannabis que se comercializa en los entornos urbanos es un insumo necesario para el diseño de políticas en salud pública sustentadas en la evidencia científica. Este estudio caracterizó los principales fitocannabinoides de muestras de marihuana (cigarrillos o cogollos) obtenidas en áreas urbanas y rurales de la ciudad Medellín, en octubre de 2021. Se realizó un muestreo no probabilístico a conveniencia en el que se recolectaron 87 muestras de marihuana donadas por consumidores en diferentes puntos de recolección en toda la ciudad, aplicando las técnicas de cromatografía de gases masas e ionización de llama para la caracterización de los fitocanabinoides. Se encontró el tetrahidrocannabinol como el constituyente principal de la marihuana circulante en Medellín, donde el 67,8% de las muestras presentaba un rango toxicológico alto o superior para THC; lo anterior en un contexto donde el mercado desregulado limita la posibilidad que tienen los consumidores en la práctica de calibrar o decidir la concentración de cannabinoides en sus dosis.

ABSTRACT As cannabis/marijuana is one of the most consumed psychoactive substances in the world, knowing the composition and type of cannabis sold in urban environments is a necessary input for the design of public health policies based on scientific evidence. This study characterized the main phytocannabinoids of marijuana samples (cigarettes or buds) obtained in urban and rural areas of the city of Medellín in October 2021. Non-probabilistic convenience sampling was carried out in which 87 marijuana samples donated by consumers were collected at different collection points throughout the city, and gas chromatography-mass spectrometry and flame ionization techniques were employed for the characterization of phytocannabinoids. Tetrahydrocannabinol (THC) was found to be the main constituent of circulating marijuana in Medellín, where 67.8% of the samples had a high or higher toxicological range for THC; the foregoing in a context where the deregulated market in practice limits the possibility that consumers have to calibrate or decide the concentration of cannabinoids in their doses.

Cannabinoid CB1 receptors are expressed in a sub-set of dopamine neurons and underlie cannabinoid modulation of DA release and DA-related behavior in mice / 中国药理学与毒理学杂志

OBJECTIVE Cannabinoids modulate do-pamine(DA)transmission and DA-related behavior,which has been thought to be mediated initially by acti-vation of cannabinoid CB1 receptors(CB1Rs)on GABA neurons.However,the cellular and receptor mechanisms underlying cannabinoids' psychoactive effects are not fully understood.The present study is to explore the pos-sible expression character of CB1Rs and elucidated the underlying mechanism of them.METHODS We took advantage of RNAscope in situ hybridization(ISH)assays and triple-staining assays to detect the CB1R-expressing neurons.We established an optical intracranial self-stimulation(OICSS)behavioral model by using opto-genetics to study dopaminergic reinforcement function.Natural and synthetic cannabinoids were used to study the function of CB1Rs.Conditional genetic depletion of CB1Rs and behavioral assay were performed to study the modulatory role of CB1Rs in DA-related behaviors.RESULTS We found that CB1Rs are also expressed in a subset of DA neurons and functionally underlie cannabi-noid action in male and female mice.ISH assays demon-strated CB1 mRNA in tyrosine hydroxylase(TH)-posi-tive DA neurons in the ventral tegmental area(VTA)and glutamate decarboxylase 1(GAD1)-positive GABA neu-rons.The CB1R expressing DA neurons were located mainly in the middle portion of the VTA with the number of CB1-TH colocalization progressively decreasing from the medial to the lateral VTA.Triple-staining assays indi-cated CB1R mRNA colocalization with both TH and vesicular glutamate transporter 2(VgluT2,a glutamate neuronal marker)in the medial VTA close to the midline of the brain.Optogenetic activation of this population of DA neurons was rewarding as assessed by OICSS.D9-tetrahydrocannabinol(D9-THC)or ACEA(a selective CB1R agonist)dose-dependently inhibited optical intra-cranial self-stimulation in DAT-Cre control mice,but not in conditional knockout mice with the CB1R gene absent in DA neurons.In addition,deletion of CB1Rs from DA neurons attenuated D9-THC-induced reduction in DA release in the NAc,locomotion,and anxiety.CONCLU-SION Our results indicated that CB1Rs are expressed in a subset of DA neurons that corelease DA and gluta-mate,and functionally underlie cannabinoid modulation of DA release and DA-related behavior.

Cannabis. Usos y aplicaciones en la práctica odontológica diaria: revisión de la literatura / Cannabis. Uses and applications in daily dental practice: a review of the literature

La evidencia científica presente en la literatura indica que el cannabis puede ser utilizado con fines terapéuticos para tratar distintas afecciones odontológicas. Dado el acceso sencillo a la cavidad bucal, las distintas formulaciones de cannabis pueden aplicarse de forma tópica. La aplicación local de dosis bajas de cannabis ha demostrado alta efectividad para tratar distintas afecciones bucales, constituyendo un tratamiento seguro con baja probabilidad de generar repercusiones sistémicas indeseadas. En la actualidad, está siendo incorporado a materiales convencionales de uso e higiene odontológica con la finalidad de aprovechar sus efectos terapéuticos. El cannabis tiene múltiples usos en odontología: como componen-te de enjuagues bucales y soluciones para la desinfección de conductos radiculares, en tratamientos de trastornos de ansiedad bucal, como complemento en terapias oncológicas, como analgésico para atenuar el dolor inflamatorio y el neuropático, como miorrelajante y condroprotector para tratar trastornos de articulación témporomandibular (ATM) y bruxismo, como osteomodulador para el tratamiento de patologías que comprometen la integridad ósea, como la enfermedad periodontal y la osteoporosis, y para la cicatrización ósea asociada a fracturas, extracciones dentarias e implantes, y como inmunomodulador con potencial terapéutico para tratar patologías autoinmunes como las enfermedades reumáticas. El trata-miento local con cannabis es efectivo, bien tolerado por el paciente y con pocos efectos adversos. Por lo tanto, se puede concluir que el cannabis aporta un enorme abanico de posibilidades terapéuticas para tratar distintas afecciones odontológicas, aunque aún se requiere mayor cantidad de estudios científicos que avalen su utilización en cada situación fisiopatológica particular (AU)

The scientific evidence present in the literature indicates that cannabis can be used for therapeutic purposes to treat different dental conditions. Given the easy access to the oral cavity, the different cannabis formulations can be applied topically. The local application of low doses of cannabis has shown high effectiveness in treating different oral conditions, constituting a safe treatment with a low probability of generating unwanted systemic repercussions. It is currently being incorporated into conventional materials for dental use and hygiene in order to take advantage of its therapeutic effects. Cannabis has multiple uses in dentistry: as a component of mouthwashes and solutions for disinfecting root canals, in the treatment of oral anxiety disorders, as a complement in oncological therapies, as an analgesic to reduce inflammatory and neuropathic pain, as a muscle relaxant and chondroprotective to treat temporomandibular joint disorders and bruxism, as an osteomodulator for the treatment of pathologies that compromise bone integrity, such as periodontal disease and osteoporosis, and or bone healing associated with fractures, dental extractions and implants, and as immunomodulator with therapeutic potential to treat autoimmune pathologies such as rheumatic diseases. Local treatment with cannabis is effective, well tolerated by the patient and with few adverse effects. Local treatment with cannabis is effective, well tolerated by the patient and with few adverse effects. Therefore, it can be concluded that cannabis provides an enormous range of therapeutic possibilities to treat different dental conditions, although more scientific studies are still required to support its use in each particular pathophysiological situation (AU)

Efficacy of cannabinoids in fibromyalgia: a literature review / Eficacia de los cannabinoides en la fibromialgia: revisión de la literatura

Abstract Fibromyalgia is a chronic disease of unclear etiology, involving a neural oversensitization and impaired pain modulation, in addition to a clinical deficiency of the endocannabinoid system. Fibromyalgia is associated with a number of somatic and psychological disorders and hence multiple pharmacological approaches have been used, including opioids, antidepressants, antiepileptics, and more recently medical cannabis. This narrative review comprises a review of the current literature on the efficacy of cannabinoids in fibromyalgia. The studies describe a possible influence of cannabis on pain control in patients with fibromyalgia, with positive effects on quality of life and sleep. The use of cannabis seems to be beneficial in patients with fibromyalgia; however, more robust studies are still needed to establish is actual efficacy in pain management, quality of life and improvement of associated symptoms.

Resumen La fibromialgia es una enfermedad crónica, cuya etiología no es clara, en la que se involucra una sobresensibilización neural y disminución de la modulación del dolor, así como una deficiencia clínica del sistema endocannabinoide. Está asociada a una variedad de trastornos somáticos y psicológicos, por lo cual se han utilizado múltiples abordajes farmacológicos, entre ellos opioides, antidepresivos, antiepilépticos y, recientemente, cannabis medicinal. En esta revisión narrativa se hace una reseña de la literatura actual relacionada con la eficacia de los cannabinoides en la fibromialgia. Los estudios describen una posible influencia del cannabis sobre el control del dolor en pacientes con fibromialgia, con efectos positivos sobre la calidad de vida y el sueño. El uso del cannabis parece tener beneficios en los pacientes con fibromialgia; sin embargo, aún se requieren estudios más robustos para establecer su verdadera eficacia en el manejo del dolor, calidad de vida y mejoría de los síntomas asociados.

New targeted compounds-biosynthesis of phytocannabinoids / 生物工程学报

Phytocannabinoids are bioactive terpenoids that are exclusive to Cannabis sativa L. The main pharmacologically active phytocannabinoids are Δ9-tetrahydrocannabinol and cannabidiol, both target endogenous cannabinoid receptors. Δ9-tetrahydrocannabinol and cannabidiol have extensive therapeutic potential due to their participation in many physiological and pathological processes in human body by activating the endocannabinoid system. At present, Δ9-tetrahydrocannabinol, cannabidiol and their analogues or combination preparations are used to treat epilepsy, vomiting in patients with cancer chemotherapy, spasticity in multiple sclerosis and relieve neuropathic pain and pain in patients with advanced cancer. With the further exploration of the application value of Δ9-tetrahydrocannabinol and cannabidiol as well as the increasing demand for standardization of pharmaceutical preparations, it is imminent to achieve large-scale production of Δ9-tetrahydrocannabinol and cannabidiol in the pharmaceutical industry. In this article, pharmacological research progress of phytocannabinoids in recent years, biosynthetic pathways of phytocannabinoids and the mechanism of key enzymes as well as various product development strategies of cannabinoids in pharmaceutical industry are reviewed. By exploring the potential of synthetic biology as an alternative strategy for the source of phytocannabinoids, it will provide a theoretical basis for the research and development of microbial engineering for cannabinoids synthesis, and promote the large-scale production of medicinal cannabinoids.

Chemical Characteristics, Therapeutic Uses, and Legal Aspects of the Cannabinoids of Cannabis sativa: A Review

Abstract Marijuana (Cannabis sativa) is an important annual medicinal plant that belongs to the Cannabaceae family. It contains 421 substances of 18 chemical types-the most significant compound is δ-9-tetrahydrocannabinol, which causes several effects, both in the Central Nervous System and in several peripheral locations in the organism. The objectives of this scientific review are to mention the anatomical distribution, chemical characteristics and biosynthesis of cannabinoids, as well as its actions mechanisms. The endogenous cannabinoid system, the therapeutic properties of C. sativa and its action on the nociceptive control are described. Finally, the modulators of the cannabinoid system in clinical use are indicated, together with marijuana legalization benefits.

Application and Development of Non-psychoactive Medicinal Cannabis / 中国实验方剂学杂志

Non-psychoactive medicinal cannabis is the cannabis that contain less than 0.3% of tetrahydrocannabinol (THC) and high content of cannabidiol (CBD) (more than 2.0% is reasonable), and mainly used for medicinal purpose. Cannabis have a long medical history, in this review, we retrospected the medicinal history of cannabis in China and the world. We summarized the cannabinoid especially CBD application of medicine in epilepsy, mental disease, tumor, analgesic and inflammatory, also the widely application in food, healthy products, cosmetics and other fields. Based on the problems like shortage of high CBD cultivars, weakness of fundamental research existed in non-psychoactive medicinal cannabis industry. We should fully utilize the genetic information of medicinal cannabis, establish the comprehensive identification system of non-psychoactive medicinal cannabis varieties, accelerate the breeding process of non-psychoactive medicinal cannabis cultivars, to ensure the safety and effectiveness of non-psychoactive medicinal cannabis. Strengthen the basic research on CBD and other cannabinoids to promote the application of non-psychoactive medicinal cannabis products and sustainable development of medical cannabis industry.

Determinación y comparación cualitativa de cannabinoides presentes en productos naturales comerciales del departamento del Cauca, Colombia / Determination and qualitative comparison of cannabinoids present in commercial natural products of the Cauca Department-Colombia

RESUMEN Actualmente, hay un creciente interés por el estudio de Cannabis sativa y sus componentes ya que se le atribuye propiedades terapéuticas en el tratamiento de enfermedades. En Colombia y específicamente en el departamento del Cauca se comercializan productos de cannabis tanto para fines no medicinales como terapéuticos. En consecuencia, es necesario el análisis de estos productos de manera que se pueda conocer la composición de los mismos y el posible efecto que pueda tener sobre la salud. El análisis de los componentes de estos productos se llevó a cabo empleando la cromatografía líquida de alta resolución (CLAR) y espectrometría de masas (EM), de tal manera que permitieron la identificación de las principales especies cannabinoides; Δ9-tetra hidrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG). La separación de los analitos se llevó a cabo mediante la implementación de una columna analítica C18 de fase reversa, elución isocrática 1 mL/ min, presión del sistema 800 PSI, una mezcla de acetonitrilo ACN y buffer fosfato (KHPO4) en relación 65/35 como fase móvil, volumen de inyección de 10 µL, un tiempo de análisis de 15 min, y detección a 220 nm.

SUMMARY Cannabis sativa has now experienced an increasing interest in the study of its components since it is attributed therapeutic properties in the treatment of diseases. In Colombia and specifically in the Cauca Department, Cannabis products are marketed both for non-medicinal and therapeutic purposes. Consequently, it is necessary to analyze these products in such a way that the composition of the products and their possible effect on health can be known. The analysis ofthe components of these products was carried out using high performance liquid chromatog-raphy (HPLC) and mass spectrometry (MS), in such a way that they allowed the identification of the main cannabinoid species; Δ9-tetra hydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG). The separation of the analytes was carried out by means of the implementation of a reverse phase C18 analytical column, isocratic elution 1 mL/min, system pressure 800 PSI, a mixture of acetonitrile ACN and phosphate buffer (KHPO4) in relation 65/35 as mobile phase, injection volume of10 µL, analysis time of15 min, and detection at 220 nm.

Therapeutic applications based on cannabinoids action / Aplicaciones terapéuticas por acción de los cannabinoides

The interest on cannabinoids became evident between the 1940 and 1950 decades. Although the active substance of the plant was not known, a series of compounds with cannabinomimetic activity were synthesized, which were investigated in animals and clinically. The most widely tested was Δ6α, 10α-THC hexyl. Δ6α, 10α-THC dimethylheptyl (DMHP) antiepileptic effects were studied in several children, with positive results being obtained in some cases. DMHP differs from sinhexyl in that its side chain is DMHP instead of n-hexyl. The first cannabinoid isolated from Cannabis sativa was cannabinol, although its structure was correctly characterized several years later. Cannabidiol was isolated some years later and was subsequently characterized by Mechoulam and Shvo. In 2013, the National Academy of Medicine and the Faculty of Medicine of the National Autonomous University of Mexico, through the Seminar of Studies on Entirety, decided to carry out a systematic review on a subject that is both complex and controversial: the relationship between marijuana and health. In recent years, studies have been conducted with cannabis in several diseases: controlled clinical trials on spasticity in multiple sclerosis and spinal cord injury, chronic, essentially neuropathic, pain, movement disorders (Gilles de Latourette, dystonia, levodopa dyskinesia), asthma and glaucoma, as well as non-controlled clinical trials on Alzheimer’s disease, neuroprotection, intractable hiccups, epilepsy, alcohol and opioid dependence and inflammatory processes.

The dimerization of -tetrahydrocannabinolic acid A (THCA-A)

The renewed interest in dimeric salicylates as broad-spectrum anti-inflammatory and anti-diabetic agents provided a rationale to investigate the dimerization of the substituted salicylate -tetrahydrocannabinolic acid (THCA-A, ) as a strategy to solve its instability to decarboxylation and to generate analogues and/or pro-drugs of this native pre-cannabinoid. Activation of the carboxylic group with the DCC-HOBt-DMAP protocol afforded a high yield of the OBt ester , that was next converted into the highly crystalline di-depsidic dimer upon treatment with DMAP. The mono-depsidic dimer was also formed when the reaction was carried out with partially decarboxylated THCA-A samples. The structure of the depsidic dimers was established by spectroscopic methods and by aminolysis of into the pre-cannabinoid amide . Both dimers showed excellent shelf stability and did not generate significant amounts of -THC upon heating. However, only the didepsidic dimer activated PPAR-, the major target of pre-cannabinoids, but strong binding to serum proteins abolished this activity, also shielding it from the action of esterases.

Action of ketamine and endocannabinoid system in rapid anti-depression therapy / 上海交通大学学报（医学版）

Major depression disorder (MDD) is a common but serious affective disorder in modern society. Suicide idea and suicide behaviour induced by MDD during its later stage put a heavy burden on society and family. Anti-depression drugs lack efficiency in treating a portion of MDD patients. This is referred to as treatment resistant depression (TRD). A study reported the rapid onset and long lasting anti-depression effect of ketamine, which also come into effect in TRD patients. △9-Tetrahydrocannabinol is the active substance of marijuana, which also exerts rapid anti-depression effect via targeting at brain cannabinoid receptors. The two central nerve system stimulants belonging to the tightly controlled psychoactive substances have obvious adverse effects. This article summarizes the action of ketamine and endocannabinoid system in rapid anti-depression therapy in recent researches.

Action of ketamine and endocannabinoid system in rapid anti-depression therapy / 上海交通大学学报（医学版）

Major depression disorder (MDD) is a common but serious affective disorder in modern society. Suicide idea and suicide behaviour induced by MDD during its later stage put a heavy burden on society and family. Anti-depression drugs lack efficiency in treating a portion of MDD patients. This is referred to as treatment resistant depression (TRD). A study reported the rapid onset and long lasting anti-depression effect of ketamine, which also come into effect in TRD patients. Δ9-Tetrahydrocannabinol is the active substance of marijuana, which also exerts rapid anti-depression effect via targeting at brain cannabinoid receptors. The two central nerve system stimulants belonging to the tightly controlled psychoactive substances have obvious adverse effects. This article summarizes the action of ketamine and endocannabinoid system in rapid anti-depression therapy in recent researches.

Development and validation of reverse phase high performance liquid chromatography method for the determination of delta-9-tetrahydrocannabinol and cannabidiol in oromucosal spray from cannabis extract

ABSTRACT A simple, fast, precise, accurate and responsive high performance liquid chromatography method was developed and validated carefully for determining an amount of delta-9-tetrahydrocannabinol and cannabidiol. A reverse phase Zorbax C-18 column 4.6 mm × 100 mm, 3.5 µm was eluted by using a mixture (85:15) of methanol and water as the mobile phase in an isocratic system with a flow rate of 1.0 ml/min and the injection volume was 10 µl, at a wavelength of 220 nm. The method was developed and validated through linearity, accuracy, precision and detection and quantitation limits studies. A good linear relationship (R2) of delta-9-tetrahydrocannabinol and cannabidiol were 0.9998 and 0.9995, respectively. The obtained % recoveries were found to be 98.3% and 96.5%. The relative standard deviations values of peak areas were found to range from 0.20% to 2.55% and 0.30% to 3.28% for delta-9-tetrahydrocannabinol and cannabidiol, respectively. Delta-9-tetrahydrocannabinol and cannabidiol presented limits of detection of 0.12, 0.23 µg/ml and limits of quantitation of 0.40, 0.76 µg/ml. The developed method could be employed for quantitative analysis of cannabis extract and oromucosal spray formulation.

Determination of Three Kinds of Cannabinoids in Cannabis UsingUltra-high Performance Liquid Chromatography-Tandem MassSpectrometry and Analysis of Phenotype of Cannabis / 分析化学

An analytical method of ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC/PDA-QDa) for the qualitative and quantitative analysis of Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD), and cannabinol (CBN) in confiscated cannabis was developed.The seized cannabis was extracted in methanol by sonication.The binary mobile phase consisted of methanol (containing 0.1% formic acid) and water.After centrifugation, the supernatant was separated on Waters UPLC BEH C18 column (50 mm×2.1 mm, 1.7 μm) with isocratic elution at a flow rate of 0.2 mL/min.The three cannabinoids were analyzed by photodiode array (PDA) detector at 220 nm and confirmed by mass spectrometer QDa.The correlation coefficient of standard curve for the three cannabinoids in linearity range was not less than 0.999, as well as the recoveries were 82%-102% with the relative standard deviations (RSD) of 0.36%-4.12% at three spiked levels.The method is specific, easy, quick and suitable for confirmation of the cannabinoids in seized cannabis.Cannabis plants in different areas were classified by their chemical phenotype as drug-type or fiber-type plants, taking into account the phenotypic index Δ9-THC, (Δ9-THC+CBN)/CBD, or the Δ9-THC/CBD and the (Δ9-THC+CBN)/CBD ratios.The analysis of the original composition of plant material is necessary for the detection and the quality control of cannabis plants.

Validación de un método para cuantificar ácido-11-nor-9-carboxi-delta 9-tetrahidrocannabinol en orina por cromatografía gaseosa-espectrometría de masas previa extracción en fase sólida / Validation of a method for quantify 11-nor-9-carboxy-delta 9-tetrahydrocannabinol in human urine using solid phase extraction and gas chromatography-mass spectrometry

El cannabis es una de las drogas ilegales más usadas a nivel mundial. Su consumo se relaciona con diferentes hechos en el ámbito forense, laboral, deportivo y clínico. Para su detección se utilizan métodos con diferentes fundamentos y alcances (inmunológicos, cromatográficos). En este trabajo se describe un método preciso, reproducible y validado, para la cuantificación del principal metabolito urinario del Δ9-tetrahidrocannabinol, el ácido-11-nor-9-carboxi- Δ 9-tetrahidrocannabinol (THC-COOH), por cromatografía gaseosa-espectrometría de masas (GC-MS). Se efectuó una extracción en fase sólida (SPE) a partir de la orina, previa hidrólisis alcalina. Se utilizó el análogo deuterado (THC-COOH D3) como estándar interno. El análisis por GC-MS se realizó en modo SIM. La curva de calibración fue lineal en el rango de trabajo (10-100 ng/ml, r > 0,999) y el límite de cuantificación fue de 10 ng/ml. La recuperación absoluta estuvo comprendida entre el 91,0 y 99,0 %. La precisión intra e inter ensayo fue de 1,06 a 1,26 y 3,59 a 9,80 %, respectivamente. El método fue aplicado a muestras reales, positivas por test inmunológico, resultando ser muy útil y fiable en el análisis de rutina de THC-COOH en orina humana con fines toxicológicos.

Cannabis is one of the most widely used illegal drug in the world. Its consumption is related to different forensic, work, sports and clinical events. In order to determinate the presence of cannabis, different methods with distinct fundamentals and scopes (immunoassay and chromatography) are applied. This report described an accurate, reproducible, and validated gas chromatography-mass spectrometry (GC-MS) method for the quantitation of 11-nor-9-carboxy- Δ9-tetrahydrocannabinol (THCCOOH), the major metabolite of Δ9-tetrahydrocannabinol in urine. A solid phase extraction (SPE), previous alkaline hydrolysis, was performed on the urine sample. Its deuterated analog (THC-COOH D3) was used as internal standard. The GC-MS analysis made by selected ion monitoring (SIM). Calibration curve was linear over the specified range (10 -100 ng/ml; r > 0.999) and limit of quantitation was 10 ng/ml. Absolute recoveries ranged from 91.0 to 99.0. Intra-assay and inter assay precision ranged from 1.06 to 1.26 and 3.59 to 9.80 %, respectively. The method has been applied to real samples, positive to immunological screening test, resulting to be very useful and reliable in routine analysis of THC-COOH in human urine for toxicological purposes.

Simultaneous Determination of Three Kinds of Effective Constituents in Cannabis Plants by Reversed-phase HPLC / 法医学杂志

OBJECTIVES@#To establish a high performance liquid chromatographic （HPLC） method for simultaneous determination of three effective constituents, including tetrahydrocannabinol （THC）, cannabidiol （CBD） and cannabinol （CBN） in Cannabis plants.@*METHODS@#A C₁₈ column was used in this study, and acetonitrile-phosphate buffer （0.015 mol/L KH₂PO₄） was used as mobile phase at a flow rate of 1.0 mL/min. At a detection wavelength of 220 mm, UV absorption spectra were collected at the wavelength range of 190-400 nm, and the spectra and retention time were counted as qualitative evidence.@*RESULTS@#THC, CBD and CBN could be well separated by this method. Three components had good linear relationship in the range of 0.4-40 μg/mL （R²≥0.999 3）. The recoveries were over 87%. The limits of detection were 1.8 ng, 2.0 ng and 1.3 ng, respectively. The relative standard deviation （RSD） were less than 5% for both inter-day and intra-day precisions.@*CONCLUSIONS@#Reversed-phase HPLC method is simple, rapid and accurate, and it is suitable for the qualitative and quantitative detection of THC, CBD and CBN in Cannabis plants.

Los pro y contra de la legalización de la marihuana / Pros and cons of legalizing marijuana

Ya son varios los países que han aceptado la marihuana como una droga "blanda", diferente a otras más peligrosas. Incluso se le ha atribuido diversas propiedades terapéuticas. Otros sin embargo piensan que su uso debería prohibirse, dadas las interferencias mentales y las alteraciones del comportamiento que produce, ya sea por su consumo esporádico, como también por los daños permanentes a que lleva su consumo crónico. Con el objeto de aclarar estas divergentes apreciaciones, se revisa la literatura científica existente. De ello se deduce el grave riesgo de su consumo crónico, especialmente para el adolescente por el significativo incremento de cuadros psicóticos y esquizofrénicos, los cuales pueden llegar a ser permanentes, mientras que su consumo durante el embarazo daña el desarrollo cerebral del feto en forma similar a lo que hace el alcohol en el síndrome fetal alcohólico. Investigaciones científicas también señalan que al fumar sus hojas, se va produciendo un daño bronquial, aún más grave que con el tabaco, incluyendo el cáncer pulmonar. En conclusión, el concepto de que la marihuana es una droga "blanda", libre de riesgos para la salud, constituye un grave error, dado la concluyente investigación científica disponible que señala lo contrario.

There are already several countries that have accepted marijuana as a soft drug, separating it from more dangerous ones. Yarious therapeutic properties have even been attributed to its use. Others, however, think that its use should be prohibited due to the mental interference and behavioral changes produced either by its occasional use as well as the permanent mental damage linked to chronic marijuana use. In order to clarify this divergence of opinions, the scientific literature is reviewed. It is concluded that there is a serious risk, especially for teenagers, associated to chronic marijuana use due to the presence of more frequent psychotic and schizophrenic episodes, which can be permanent, while consumption during pregnancy results in brain damage to the fetus, similar to fetal alcohol syndrome. Scientific research also indicated that smoking marijuana produces an even more severe bronchial damage than tobacco, with risk of lung cancer. In conclusion, the notion that marijuana is a risk-free soft drug is a serious mistake, based on the available conclusive scientific research that shows the opposite.