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.

Latest advances in the diagnosis and treatment of interstitial cystitis/bladder pain syndrome / 现代泌尿外科杂志

Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by pain, oppressing sensation, or discomfort associated with the bladder, accompanied by lower urinary tract symptoms, lasting for more than 6 weeks (or 6 months). Since IC/BPS was first reported, its diagnosis and treatment have been a challenge to clinicians. This article will review its classification and phenotype, fundamental research, imaging, symptom score, cystoscopy, treatment and potential therapeutic targets.

Action mechanism of vinpocetine in improving learning and memory disorders in depressive rats after MECT / 西安交通大学学报(医学版)

【Objective】 To explore the action mechanism of vinpocetine in improving learning and memory disorders in depressive rats after modified electroconvulsive therapy (MECT). 【Methods】 The models of depressive rats were constructed by chronic unpredictable mild stress (CUMS) method. A total of 30 rats with depression were randomly divided into depression group, MECT group, and MECT+vinpocetine (10 mg/kg) group, with 10 in each group. A total of 10 untreated healthy rats were enrolled as control group. The learning and memory ability were tested by Morris water maze test and novel object recognition test. The depression state was evaluated by sugar preference test. The brain slices of the hippocampus were prepared for electrophysiological experiments. The density of dendritic spine was detected by Golgi staining. The expressions of endocannabinoids related genes [diacylglycerol lipase (DAGLα), monoacylglycerol lipase (MAGL), and endocannabinoid type-I receptor (CB1R)] were detected by qPCR and Western blotting. The lentivirus was injected to downregulate the expressions of CB1R and DAGLα in the hippocampus. After re-modeling and treatment, behavioral tests were performed. 【Results】 Compared with control group, sugar preference, spatial exploration time, relative discrimination index, long-term potentiation (LTP), density of dendritic spine, expressions of DAGLα and CB1R were decreased, while escape latency and MAGL were increased in depression group (P<0.05). Compared with depression group, sugar preference, escape latency, and MAGL were increased, while spatial exploration time, relative discrimination index, LTP, density of dendritic spine, expressions of DAGLα and CB1R were decreased in MECT group (P<0.05). Compared with depression group, sugar preference, spatial exploration time, relative discrimination index, LTP, density of dendritic spine, expressions of DAGLα and CB1R were increased, while escape latency and MAGL were decreased in MECT+vinpocetine group (P<0.05). Compared with MECT group, sugar preference, spatial exploration time, relative discrimination index, LTP, density of dendritic spine, expressions of DAGLα and CB1R were increased, while escape latency and MAGL were decreased in MECT+vinpocetine group (P<0.05). The down-regulation of DAGLα or CB1R by lentivirus could inhibit the improvement effect of vinpocetine on behavioral performance of depressive rats after MECT. 【Conclusion】 Vinpocetine can significantly improve learning and memory disorders in depressive rats after MECT, which may be related to regulating the expressions of endocannabinoid-related genes and enhancing synaptic plasticity.

Caracterización y seguimiento de una población de uruguayos usuarios de derivados de cannabis medicinal artesanal / Characterization and follow up of a population of Uruguayan cannabis derivatives users in artisanal medicine / Caracterização e monitoramento de uma população de usuários uruguaios de derivados artesanais de cannabis medicinal

Introducción: el conocimiento del cannabis medicinal data de hace más de 10.000 años y tiene sus orígenes en el continente asiático y en la medicina oriental. En el último tiempo ha surgido especial interés en su uso terapéutico, y Uruguay desde 2013 cuenta con una ley que regula la tenencia y uso de la planta de cannabis. Objetivo: caracterizar el uso de los derivados de cannabis medicinal (DCM) en una población de usuarios uruguayos. Metodología: se realizó un estudio observacional, prospectivo, en una población de usuarios de DCM, a través de encuestas telefónicas. Los datos obtenidos se analizaron utilizando Excel®, mediante estadística descriptiva. Resultados: se incluyeron 32 usuarios entre 29 y 78 años, la mayoría de sexo femenino. La forma farmacéutica más utilizada fue el aceite y la principal indicación fue para el tratamiento del dolor. Se observó una disminución en la intensidad del dolor postratamiento. El principal efecto adverso observado fue la sequedad de boca. Conclusiones: es el primer estudio nacional en caracterizar el uso de DCM artesanal. Se incluyeron 32 usuarios de DCM artesanal. La principal indicación de DCM fue para el tratamiento del dolor, siendo la artrosis su principal causa. Todos los usos fueron para indicaciones no aprobadas si se compara con sus equivalentes industrializados. Predominó el uso en mujeres adultas. Se destacó una gran expectativa frente al inicio del uso. Los eventos adversos observados estuvieron dentro de los esperados y de entidad leve.

Summary: Introduction: knowledge on medical cannabis is over 10,000 years old and stems from Asian and Eastern medicine. In recent years, special interest on its therapeutic use has arisen, and in 2013 Uruguay passed a law to regulate possession and use of cannabis plants. Objective: to characterize the use of medicinal cannabis derivatives in a population of Uruguayan users. Method: observational, prospective study in a population of medicinal cannabis derivatives users through telephone surveys. Data obtained were analysed with Excel®, by using descriptive statistics. Results: thirty two users were included in the study, between 29 and 78 years old, most of which were female. The most widely used pharmaceutical form was oil and the main indication was to treat pain. A decline in pain intensity after treatment was observed. The main adverse effect observed was dry mouth. Conclusions: this is the first national study to characterize the use of artisanal medicinal cannabis derivatives. Thirty two users of artisanal medicinal cannabis derivatives were included in the study. The main indication for artisanal medicinal cannabis derivatives was the treatment of pain, arthrosis being the main cause. All users followed non-approved indications if compared to industrialized equivalents. The use was more extended among women. Great expectation upon initiation of use was noticed. Adverse events observed were mild and the expected.

Introdução: o conhecimento da cannabis medicinal remonta a mais de 10.000 anos e tem suas origens no continente asiático e na medicina oriental. Nos últimos tempos, surgiu um interesse especial em seu uso terapêutico e, desde 2013, o Uruguai possui uma lei que regula a posse e o uso da planta de cannabis. Objetivo: caracterizar o uso de derivados de cannabis medicinal (DCM) em uma população de usuários uruguaios. Metodologia: Foi realizado um estudo observacional, prospectivo, em uma população de usuários de DCM, por meio de inquéritos telefônicos. Os dados obtidos foram analisados ​​no programa Excel®, por meio de estatística descritiva. Resultados: foram incluídos 32 usuários entre 29 e 78 anos, a maioria do sexo feminino. A forma farmacêutica mais utilizada foi o óleo e a principal indicação foi para o tratamento da dor. Observou-se diminuição da intensidade da dor pós-tratamento. O principal efeito adverso observado foi boca seca. Conclusões: este é o primeiro estudo nacional a caracterizar o uso de DCM artesanal. Foram incluídos 32 usuários artesanais de DCM. A principal indicação da CMD foi para o tratamento da dor, sendo a osteoartrite sua principal causa. Todos os usos foram para indicações não aprovadas quando comparados aos seus equivalentes industrializados. Predominou o uso em mulheres adultas. Houve uma grande expectativa desde o início do uso. Os eventos adversos observados estavam dentro do esperado e de entidade leve.

The CB1 cannabinoid receptor regulates autophagy in the tibialis anterior skeletal muscle in mice

The endocannabinoid system (ECS) regulates energy metabolism, has been implicated in the pathogenesis of metabolic diseases and exerts its actions mainly through the type 1 cannabinoid receptor (CB1). Likewise, autophagy is involved in several cellular processes. It is required for the normal development of muscle mass and metabolism, and its deregulation is associated with diseases. It is known that the CB1 regulates signaling pathways that control autophagy, however, it is currently unknown whether the ECS could regulate autophagy in the skeletal muscle of obese mice. This study aimed to investigate the role of the CB1 in regulating autophagy in skeletal muscle. We found concomitant deregulation in the ECS and autophagy markers in high-fat diet-induced obesity. In obese CB1-KO mice, the autophagy-associated protein LC3 II does not accumulate when mTOR and AMPK phosphorylation levels do not change. Acute inhibition of the CB1 with JD-5037 decreased LC3 II protein accumulation and autophagic flux. Our results suggest that the CB1 regulates autophagy in the tibialis anterior skeletal muscle in both lean and obese mice.

Practical aspects of the use of medicinal cannabis in chronic pain / Aspectos práticos do uso da cannabis medicinal em dor crônica

ABSTRACT BACKGROUND AND OBJECTIVES: Evidence has revealed an important role in the use of medical cannabis, and the interaction of the endocannabinoid system with other drugs for the treatment of chronic neuropathic and nociplastic pain. The objective of this review is to bring an update on published data on doses and care with the use of cannabinoids that demonstrate the interaction in the pathophysiology of chronic pain and its treatment. CONTENTS: A research-based review was carried out in the MEDLINE, PUBMED database using the keywords "cannabis and pain", "endocannabinoid"; "neuropathic pain"; "nociplastic pain"; "drug interactions". CONCLUSION: Drug interaction with cannabinoids requires further scientific knowledge and doses are individual, which makes it difficult to create a protocol for treatment.

RESUMO JUSTIFICATIVA E OBJETIVOS: As evidências têm revelado um papel importante sobre o uso da cannabis medicinal e da interação do sistema endocanabinoide com outros fármacos para o tratamento de dor crônica neuropática e nociplástica. O objetivo deste estudo foi prover atualização sobre os dados publicados quanto a doses e cuidados com o uso dos canabinoides que mostrem interação na fisiopatologia da dor crônica e seu tratamento. CONTEÚDO: Foi realizada uma revisão baseada em pesquisa na base de dados Medline, Pubmed com uso dos unitermos "cannabis e dor", "endocannabinoid", "neuropathic pain", "nociplastic pain" e "drug interactions". CONCLUSÃO: A interação farmacológica com os canabinoides requer aprofundamento do conhecimento científico e as doses são individuais, o que dificulta a criação de um protocolo para tratamento.

Retrograde inhibition of hyperactive central pathways in nociplastic pain / Inibição retrógrada das vias centrais hiperativas nas dores nociplásticas

ABSTRACT BACKGROUND AND OBJECTIVES: Nociplastic pain occurs due to a combination of hyperexcitability and decreased inhibitory activity in the central nervous system, responsible for a state of amplification of different stimuli, present in many chronic disorders. Among them: fibromyalgia, chronic migraine, irritable bowel syndrome, myofascial pain syndrome and complex regional pain syndrome. Often, several of these diseases are associated. Nociplastic pain therapy is a challenge in clinical practice, since most traditional treatments are not effective in controlling symptoms, often causing difficulty in adherence or even interruption of treatment due to undesirable adverse effects. The objective of this article was to demonstrate the importance of identifying the presence of nociplastic pain in the patient's condition, and also the pathophysiological mechanisms involved. Thus, due to retrograde neuromodulation, a unique feature of the endocannabinoid system until now, evaluate the use of pharmaceutical grade medicines based on the cannabis plant as an adjunct in the therapy of pain and other symptoms associated with this disorder. CONTENTS: This article was addressed the pathophysiology of nociplastic pain, the physiology to the endocannabinoid system, the cannabis plant with its components and its use as an adjuvant medication in the multimodal treatment of nociplastic pain (due to retrograde neuromodulation), based on published scientific articles between 1981 and 2022. CONCLUSION: Although the scientific evidence supporting the use of medical cannabis in nociplastic pain therapy is insufficient so far, it can and should be considered as a possible adjuvant medication in multimodal pain therapy, always on an individual basis, when recommended treatments fail or are not tolerated.

RESUMO JUSTIFICATIVA E OBJETIVOS: A dor nociplástica ocorre por uma combinação de hiperexcitabilidade e diminuição da atividade inibitória no sistema nervoso central, responsável por um estado de amplificação de estímulos diversos, presente em muitas doenças crônicas. Entre essas doenças estão: fibromialgia, migrânea crônica, síndrome do intestino irritável, síndrome dolorosa miofascial e síndrome de dor complexa regional. Frequentemente, várias dessas doenças se apresentam associadas. A terapia da dor nociplástica é um desafio na prática clínica, uma vez que a maioria dos tratamentos tradicionais não são eficazes no controle dos sintomas, causando muitas vezes dificuldade de adesão ou até mesmo interrupção do tratamento, devido aos efeitos adversos indesejáveis. O objetivo deste artigo foi demonstrar a importância da identificação da presença da dor nociplástica no quadro do paciente, e do conhecimento dos mecanismos fisiopatológicos envolvidos. Dessa forma, devido à neuromodulação retrógrada, característica exclusiva do sistema endocanabinoide até o momento, avaliar a utilização de fármacos de grau farmacêutico à base da planta cannabis como coadjuvante na terapia da dor e dos outros sintomas associados a essa doença. CONTEÚDO: Este artigo abordou a fisiopatologia da dor nociplástica, a fisiologia do sistema endocanabinoide, a planta cannabis com seus componentes e sua utilização como medicação coadjuvante no tratamento multimodal da dor nociplástica (decorrente da neuromodulação retrógrada), com base em artigos científicos publicados entre 1981 e 2022. CONCLUSÃO: Apesar das evidências científicas que apoiam o uso da cannabis medicinal na terapia da dor nociplástica serem insuficientes até o momento, ela pode e deve ser considerada como um possível fármaco coadjuvante na terapia multimodal da dor, sempre de forma individualizada, quando os tratamentos preconizados falharem ou não forem tolerados.

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

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.

The research progress of novel anxiolytics / 中国药理学通报

Anxiety disorder holds the highest prevalence among adults in China, whereas the research and development of its therapeutic drugs are relatively backward. At present, the commonly used anxiolytics in clinical practice are some benzodiazepines, non-benzodiazepines, and antidepressants, most of which have unpleasant side effects. By searching the literature in Pubmed, we here summarized the research progress of novel anxiolytics in recent years from the following aspects: endocannabinoid system, gut-microbe-brain axis, and GABA

Kahweol, a natural diterpene from coffee, induces peripheral antinociception by endocannabinoid system activation

Kahweol is a compound derived from coffee with reported antinociceptive effects. Based on the few reports that exist in the literature regarding the mechanisms involved in kahweol-induced peripheral antinociceptive action, this study proposed to investigate the contribution of the endocannabinoid system to the peripheral antinociception induced in rats by kahweol. Hyperalgesia was induced by intraplantar injection of prostaglandin E2(PGE2) and was measured with the paw pressure test. Kahweol and the drugs to test the cannabinoid system were administered locally into the right hind paw. The endocannabinoids were purified by open-bed chromatography on silica and measured by LC-MS. Kahweol (80 µg/paw) induced peripheral antinociception against PGE2-induced hyperalgesia. This effect was reversed by the intraplantar injection of the CB1 cannabinoid receptor antagonist AM251 (20, 40, and 80 μg/paw), but not by the CB2 cannabinoid receptor antagonist AM630 (100 μg/paw). Treatment with the endocannabinoid reuptake inhibitor VDM11 (2.5 μg/paw) intensified the peripheral antinociceptive effect induced by low-dose kahweol (40 μg/paw). The monoacylglycerol lipase (MAGL) inhibitor, JZL184 (4 μg/paw), and the dual MAGL/fatty acid amide hydrolase (FAAH) inhibitor, MAFP (0.5 μg/paw), potentiated the peripheral antinociceptive effect of low-dose kahweol. Furthermore, kahweol increased the levels of the endocannabinoid anandamide, but not of the other endocannabinoid 2-arachidonoylglycerol nor of anandamide-related N-acylethanolamines, in the plantar surface of the rat paw. Our results suggested that kahweol induced peripheral antinociception via anandamide release and activation of CB1 cannabinoid receptors and this compound could be used to develop new drugs for pain relief.

Endocannabinoid Signaling in Spermatozoa: A Mini-Review

Spermatozoa undergoes array of signaling and intracellular pathways and ultimately become competent enough to accomplish fertilization. Hormones, ion channels and signaling molecules in both male and female reproductive tract show bidirectional cross play. The recent discovery of endocannabinoids and their receptors in male and female reproductive system opened new vistas for their research in regulating sperm function. Interestingly, endocannabinoids regulate sperm motility, capacitation, hyperactivity and eventually acrosome reaction. However, their complex intracellular pathways are still to be understood in regulating spermatozoa function. The present review highlights the major breakthrough research in the area of endocannabinoids in male reproduction and in more specific in sperm cells, and their association with regulation of sperm fertilizing competence

Cannabis: from plant condemned by prejudice to one of the greatest therapeutic options of the century / Cannabis: de planta condenada pelo preconceito a uma das grandes opções terapêuticas do século

BACKGROUNG: Cannabis sativa has a fascinating history and has been used by mankind for millennia. Many societies such as Greek, Roman, Chinese, African, Indian and Arabic take advantage of the plant's qualities, which are consumed as food, medicine, fuel, fibers or tobacco. The first reference found related to the therapeutic use of the plant data from 2700 B.C. and is present in the pharmacopoeia of the Chinese Emperor Shen-Nung, where this plant was recommended in the treatment of malaria, rheumatic pain, in irregular and painful menstrual cycles. The book "De Matéria Médica", written by the doctor Pedânio Dioscórides considered thefounder of pharmacology, exposes Cannabis as one of the natural substances that can relieve inflammatory pain. In Brazil, African slaves brought a cannabis during the colonial period, around 1549. Then, its use spread quickly among black slaves and Indians, who started to cultivate it. Once the plant was popularized among French intellectuals and English doctors in the Indian imperial army, it started to be considered in our country as an excellent medicine for men, until it was suppressed by the police authorities in the 1930s. Only 60 years later important findings were highlighted around Cannabis with the System Endocannabinoid and its receptors, neurotransmitters such as anandamide and 2-AG, revolutionizing the understanding of molecular signaling that modulates pain and analgesia, inflammation, appetite, gastrointestinal motility and sleep cycles, immune cell activity and hormones among others.We are in front of a huge revolution in the therapeutic area, in which phytocabinoids represent one of the great therapeutic options of the century. We need a widespread disclosure that CBD is not marijuana and that its use for recreational purpose has nothing to do with the use of medical cannabis. Scientific research is seriously committed to the use of the substance in various pathologies. The role of information is absolute, being the main tool to clarify a society

A cannabis sativa tem uma história fascinante e é utilizada pela humanidade há milênios. Muitas sociedades como a grega, a romana, a chinesa, a africana, indiana e árabe aproveitaram as qualidades da planta, fosse ela consumida como alimento, medicina, combustível, fibras ou fumo. A primeira referência encontrada relativa à utilização terapêutica da planta data de 2700 a.C. e está presente na farmacopeia do Imperador chinês Shen-Nung, onde esta planta era recomendada no tratamento da malária, de dores reumáticas, nos ciclos menstruais irregulares e dolorosos. O livro "De Matéria Médica", escrito pelo médico Pedânio Dioscórides considerado o fundador da farmacologia, traz a Cannabis como uma das substâncias naturais que podem aliviar dores de origem inflamatória. No Brasil, a Cannabis foi trazida por escravos africanos no período colonial, por volta de 1549. Em seguida, o seu uso disseminou-se rapidamente entre os negros escravos e índios, que passaram a cultivá-la. Devido à popularização da planta dentre intelectuais franceses e médicos ingleses do exército imperial da Índia, ela passou a ser considerada em nosso meio como excelente medicamento para muitos males, até ser reprimida pelas autoridades policiais na década de 1930. Descobertas importantes foram destaque no campo da Cannabis somente 60 anos depois com o Sistema Endocanabinoide e seus receptores, neurotransmissores como a anandamida e o 2-AG, revolucionando o entendimento da sinalização molecular que modula dor e analgesia, inflamação, apetite, motilidade gastrointestinal e ciclos de sono, atividade de células imunes, hormônios e muito mais. Estamos diante de uma enorme revolução na área terapêutica em que os fitocanabinoides representam uma das grandes opções terapêuticas do século. Precisamos de uma divulgação ampla de que o CBD não é maconha e que o uso recreativo da maconha nada tem a ver com o uso da Cannabis medicinal, que as pesquisas científicas estão seriamente empenhadas em estabelecer a eficácia da substância em várias patologias. O papel da informação é absoluto e se constitui na principal ferramenta para esclarecer a sociedade.

Cannabis and the exocannabinoid and endocannabinoid systems. Their use and controversies

Cannabis (marijuana) is one of the most consumed psychoactive substances in the world. The term marijuana is of Mexican origin. The primary cannabinoids that have been studied to date include cannabidiol and delta-9-tetrahydrocannabinol, which is responsible for most cannabis physical and psychotropic effects. Recently, the endocannabinoid system was discovered, which is made up of receptors, ligands and enzymes that are widely expressed in the brain and its periphery, where they act to maintain balance in several homeostatic processes. Exogenous cannabinoids or naturally-occurring phytocannabinoids interact with the endocannabinoid system. Marijuana must be processed in a laboratory to extract tetrahydrocannabinol and leave cannabidiol, which is the product that can be marketed. Some studies suggest cannabidiol has great potential for therapeutic use as an agent with antiepileptic, analgesic, anxiolytic, antipsychotic, anti-inflammatory and neuroprotective properties; however, the findings on cannabinoids efficacy and cannabis-based medications tolerability-safety for some conditions are inconsistent. More scientific evidence is required in order to generate recommendations on the use of medicinal cannabis.

El Sistema de Endocannabinoides como regulador de la lipogénesis y su posible modulación por la Mangiferina

RESUMEN Actualmente es innegable la participación del sistema endocannabinoides (SEC) en la regulación metabólica; ya que su sobre estimulación ha sido relacionada con varias patologías entre las que se encuentran obesidad, diabetes mellitus, retinopatía e hígado graso no alcohólico. Éstas se relacionan mutuamente a través de alteraciones del metabolismo de los lípidos, como lo es una sobre estimulación de la síntesis de ácidos grasos, una disminución en la beta-oxidación, hiperglicemia causada por un aumento de la gluconeogénesis, así como en la glucólisis; procesos en los cuales se ha descrito al SEC como un participante crucial. Por otro lado, algunos compuestos fitoquímicos, tales como la mangiferina (MGF), han probado sus efectos farmacológicos en el metabolismo de lípidos a nivel hepático y en el control glicémico. Hasta el momento se desconoce el efecto de la mangiferina sobre los receptores de endocannabinoides, por lo que esta revisión aborda la regulación a nivel sistémico (órganos y tejidos) y central (sistema nervioso) de la lipogénesis por el SEC y la regulación negativa que tiene la mangiferina sobre éste. Finalmente se sugiere, con base en la información publicada hasta el momento, una relación entre el posible efecto que pueden tener la MGF sobre el SEC.

ABSTRACT Currently, the participation of the endocannabinoid system in metabolic regulation is undeniable; because its hyperactivation has been related to several pathologies such as obesity, diabetes mellitus, retinopathy and non-alcoholic fatty liver, and others. These pathologies are related through alterations in lipid metabolism, e.g. over stimulation of fatty acid synthesis, beta-oxidation decrease, hyperglycemia increase, all these changes are caused by increase in gluconeogenesis, as well as glycolysis, processes in which the SEC has been described as a main character. On the other hand, some phytochemicals such as mangiferin (MGF) have shown their pharmacological effects on lipid metabolism, as well as glycemic control. So far, the effect of mangiferin on cannabinoid receptors is unknown. In this review, we try to demonstrate how mangiferin and these receptors participate in the opposite manner in the adaptation of lipid metabolism in many organs like as liver, tissue adipose and SN (nervous system). In addition, we suggest, based on the published information to until now, a relationship between the MGF´s effect on the SEC.

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.

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.

Ingesta de comida rápida y su influencia en la producción de N-aciletanolaminas involucradas en el ciclo hambre-saciedad / Fast food intake and its influence on the production of N-acylethanolamines involved in the hunger-satiety cycle

Resumen En los últimos años, como resultado de una mayor oferta de «comida rápida¼ (CR), se ha inducido un incremento en la cantidad y el contenido calórico de los alimentos consumidos. El objetivo de este trabajo fue realizar una revisión de las investigaciones relativas al efecto de los ácidos grasos (AG) sobre el ciclo hambre-saciedad. En la CR predominan los AG saturados de cadena larga, los cuales tienden a incrementar el apetito. No obstante, las N-aciletanolaminas que se sintetizan minutos después de la ingesta de alimento pueden modular los niveles de apetito o de saciedad. Esto gracias a la capacidad de inducir la secreción de diferentes hormonas involucradas en la activación de las señales orexigénicas o anorexigénicas. Por el contrario, los AG insaturados pueden secretar hormonas anorexigénicas que inducen saciedad; tal es el caso de los omegas 3 y 9, por lo que sería recomendable incrementar su proporción en el proceso de elaboración de la CR. Por tanto, se concluye que el tipo de efecto que los AG tengan en el ciclo hambre-saciedad depende, por un lado, de la longitud de su cadena y, por otro, del número de insaturaciones que contengan.

Abstract In recent years, as a result of a greater offer of 'fast food' (FF), an increase has been induced in the quantity and caloric content of the foods consumed. The aim of this work was to carry out a review of the investigations related to the effect of fatty acids (FA) on the hunger-satiety cycle. Long-chain saturated FA predominate in FF, which tend to increase appetite. However, the N-acylethanolamines that are synthesized minutes after food intake can modulate appetite or satiety levels. This is due to the ability to induce different hormones secretion involved in orexigenic or anorexigenic signals activation. In contrast, unsaturated FA can secrete anorexigenic hormones that induce satiety, such as omegas 3 and 9, so it would be advisable to increase their proportion in the FF production process. Therefore, it is concluded that the type of effect that FA have on hunger-satiety cycle depends, on the one hand, on the length of their chain and, on the other hand, on the number of unsaturations contained in them.

Neurobiología de las adicciones / Neurobiology of addictions

Resumen La proporción de usuarios de una droga de abuso que desarrolla dependencia sólo representa una parte de ellos. Es decir, hay una proporción de usuarios que no presentan un trastorno por consumo de sustancias (TCS). Por ejemplo, en Mexico sólo el 15% de quienes consumen alcohol desarrollan un trastorno por consumo de alcohol (ТСА). Este 15% sugiere una vulnerabilidad en esta población, por lo que determinar los mecanismos que predisponen a estos sujetos a la adicción es indispensable para la prevención о para la rehabilitación del TCS. Se ha sugerido la participación de factores genéticos y medioambientales en el desarrollo de dicha vulnerabilidad al TCS. Por ejemplo, se ha demostrado que los sujetos que son psicópatas o sociópatas у que son agresivos, que presentan falta de atención y son impulsivos, entre otras características clínicas, presentan comorbilidad con el abuso y dependencia a sustancias. Por otro lado, se ha observado que existe una relación entre las experiencias adversas en los primeros años de vida y el consumo de sustancias de abuso. En estudios preclínicos, hemos demostrado que las ratas privadas de cuidado materno en los días posnatales 2 al 16 (DPN2-DPN16), al llegar a la edad adulta (DPN90) consumen más alcohol que las que han recibido cuidado materno todo el tiempo. Además, presentan una desregulación en la expresión de los receptores para canabinoides del tipo ו (CB1R) en algunas zonas del cerebro, por ejemplo, el núcleo accumbens y la corteza prefrontal. En breve, podríamos suponer que un sujeto es vulnerable a tener una adicción si nace psicópata o desarrolla una personalidad antisocial, o bien, si durante la infancia ha contendido con situaciones adversas, como son un pobre cuidado parental o el abuso verbal, fisco o sexual. Cabe señalar que estos no son los únicos factores que han sido asociados a este trastorno, pero para los fines de esta revisión, sólo discutiremos esta vulnerabilidad con base en los mecanismos epigenéticos que afectan al sistema endocanabinérgico (seCB) e interfieren con la función del sistema de inhibición de la conducta.

Abstract The proportion of drug abuse users that develop dependence does not represent the totality of users. Therefore, there is a substantial proportion of users that does not develop a substance use disorder (SUD). For example, in Mexico, only 15% of all alcohol consumers develop alcohol use disorder (AUD). Determining the mechanisms that predispose individuals to AUD or SUD is crucial for its prevention or rehabilitation. The involvement of genetic and environmental factors to the development of SUD has been suggested. For example, psychopaths or sociopaths that have a strong genetic predisposition have comorbidity with SUD. On the other hand, a relationship between adverse experiences in the early years of and substance abuse has been documented. In pre-clinical studies, we have shown that rats deprived of maternal care from postnatal day (PND)2 to PND16, and tested once they reach adulthood (PND90) consume more alcohol than those that were under materna care at all times. In addition, we observed a dysregulation in the expression of cannabinoid receptors type 1 (CBIR)in some areas of the brain, i.e. nucleus acumens and prefrontal cortex. In short, we presume that a subject who is vulnerable to addiction has either been born with a psychopathic disorder, developed an antisocial personality, experienced adverse situations such as neglected parental care, or verbal, physical or sexual abuse. These are not the only factors that have been associated with SUD, but for the purposes of this review we will discuss vulnerability based only on epigenetic mechanisms affecting the endocannabinergic system and interfering with the functioning of the behavior inhibition system.

Potential Therapeutic Targets of the Endocannabinoid System in Common Neurodegenerative Disorders and Organic Acidemias

Abstract The cannabinoid chemistry is currently being addressed in preclinical approaches as a viable therapeutic alternative for the management of a wide range of signs, symptoms, and some biochemical hallmarks of many neurological pathologies (such as neuroinflammation and neurodegeneration). This clinical orientation is grounded on the consistent promissory profile that cannabinoid compounds have shown, and the great necessity of feasible options to undergo such disorders. Even though at early research stages, metabolic disorders are starting to rise as potential targets of cannabinoid alternatives; approaches in this term could, in turn, aim to modulate the endocannabinoid response for therapeutic purposes. This review recalls the pathologic scenarios endured in the course of neurological diseases of high occurrence and the most typical metabolic disorders, while discussing the neuroprotective mechanisms of cannabinoid agonists in the central nervous system, and the potential targets of the endocannabinoid system and metabolic disorders.