The Resurgence of Hallucinogen Drugs in Clinical Research

ABSTRACT Since the dawn of civilization, ancient cultures have utilized hallucinogens from plants and fungi in the context of religious and healing practices. Recently, their use has expanded to other cultures. Hallucinogens are natural or synthetic substances that alter the perception of reality at nontoxic doses, producing intense psychological and physiological effects. The initial research on hallucinogens began in the 1950s. However, their non-medical use, studies without proper controls, and negative social opinion resulted in legal restrictions that limited their use for clinical and preclinical research for more than two decades. A renewed interest in studying hallucinogens as potential therapeutic agents for treating different psychiatric conditions has recently re-emerged. This review summarizes the effects of main hallucinogen drugs and their therapeutic potential. Classic hallucinogens such as LSD, dimethyltryptamine, psilocin, and mescaline have chemical structures similar to serotonin and directly activate 5-hydroxy-tryptamine (5-HT2A) receptors. Ketamine is a dissociative anesthetic with antagonist effects at the glutamatergic N-methyl-D-aspartate receptor, indirectly activating 5-HT2A receptors. Ketamine has rapid antidepressant effects and reduces suicidal ideation, but its effects are short-lasting. Other hallucinogens are under study. It is necessary to continue this research with a more rigorous methodology and include studying the long-term effects of psychedelics use.

Promising natural lysine specific demethylase 1 inhibitors for cancer treatment: advances and outlooks / 中国天然药物

Lysine specific demethylase 1 (LSD1), a transcriptional corepressor or coactivator that serves as a demethylase of histone 3 lysine 4 and 9, has become a potential therapeutic target for cancer therapy. LSD1 mediates many cellular signaling pathways and regulates cancer cell proliferation, invasion, migration, and differentiation. Recent research has focused on the exploration of its pharmacological inhibitors. Natural products are a major source of compounds with abundant scaffold diversity and structural complexity, which have made a major contribution to drug discovery, particularly anticancer agents. In this review, we briefly highlight recent advances in natural LSD1 inhibitors over the past decade. We present a comprehensive review on their discovery and identification process, natural plant sources, chemical structures, anticancer effects, and structure-activity relationships, and finally provide our perspective on the development of novel natural LSD1 inhibitors for cancer therapy.

O renascimento dos psicodélicos como potenciais agentes psicoterapêuticos: trajetória, avanços recentes e perspectivas / The renaissance of psychedelics as potential psychotherapeutic agents: trajectory, recent advances and perspectives

Utilizados em vários contextos pela humanidade desde tempos imemoriais até os dias atuais, os psicodélicos despertaram a atenção dos pesquisadores na primeira metade do século passado. Desde então, mesmo com o longo período de restrições às pesquisas científicas devido à implementação da Controlled Substance Act em 1970, inúmeras investigações, principalmente nos últimos anos, vêm indicando o renascimento dos psicodélicos como importantes ferramentas em psicoterapia assistida. Esta revisão narrativa pretende divulgar a trajetória de pesquisa de psicodélicos selecionados (LSD, psilocibina, ayahuasca e MDMA), lançando luz sobre estudos clínicos que indicam a eficácia e a segurança médica dessas substâncias no tratamento de distúrbios mentais como depressão, ansiedade, dependência química e transtorno de estresse pós-traumático. Adicionalmente, também são apontados alguns eventos históricos e culturais relevantes que, de alguma forma, dialogam com esta trajetória.(AU)

Used in various contexts by mankind from immemorial time to nowadays, psychedelics aroused the attention of researchers in the first half of last century. Since then, even with the long period of restrictions on scientific research due to the implementation of the Controlled Substance Act in 1970, accumulated investigations, especially in recent years, have been indicating the renaissance of psychedelics as important tools in assisted psychotherapy. This narrative review intends to disclose the research trajectory of selected psychedelics (LSD, psilocybin, ayahuasca and MDMA) shedding light on clinical studies which support medical efficacy and safety of these substances to treat mental diseases such as depression, anxiety, substance use disorder and post-traumatic stress disorder. Additionally, some relevant historical and cultural events that somehow had dialogued with this trajectory are also approached.(AU)

Utilizados en diversos contextos por la humanidad desde tiempos inmemoriales hasta nuestros días, los psicodélicos despertaron la atención de los investigadores en la primera mitad del siglo pasado. Desde entonces, incluso con el largo período de restricciones en las investigaciones científicas debido a la implementación de la Controlled Substance Act en 1970, numerosas investigaciones, principalmente en los últimos años, han indicado el resurgimiento de los psicodélicos como herramientas importantes en la psicoterapia asistida. Esta revisión narrativa tiene como objetivo dar a conocer la trayectoria de investigación de psicodélicos seleccionados (LSD, psilocibina, ayahuasca y MDMA), arrojando luz sobre estudios clínicos que demuestran la eficacia médica y la seguridad de estas sustancias en el tratamiento de desordenes mentales como la depresión, la ansiedad, dependencia química y trastorno de estrés postraumático. Adicionalmente, también se señalan algunos hechos históricos y culturales relevantes que, de alguna manera, dialogan con esta trayectoria.(AU)

Uso de club drugs entre estudantes de graduação: prevalência, características associadas e a influência dos pares / Club drugs use among undergraduate students: prevalence, associated characteristics and peer influence

OBJETIVO: Medir a prevalência do uso na vida, no último ano e no último mês de duas club drugs ­ o ecstasy e o LSD ­, bem como as características associadas ao uso dessas substâncias, no último mês, entre estudantes de graduação de uma universidade no Sul do Brasil. MÉTODOS: Trata-se de um estudo transversal conduzido no ano de 2015 com amostragem aleatória sistemática por conglomerados. Participaram 1.423 estudantes de graduação. Foi utilizado um modelo de análise multivariável em três níveis hierárquicos por meio da regressão de Poisson com ajuste robusto da variância. RESULTADOS: As prevalências de uso na vida, no último ano e no último mês de club drugs foram de 12,7%, 7,8% e 3,8%, respectivamente. Indivíduos do sexo masculino, com orientação sexual homossexual ou bissexual, mais jovens, que moravam com seus pares, solteiros, e que relataram uso no último mês de tabaco e maconha apresentaram maior probabilidade de ter feito uso no último mês de alguma club drug. Entretanto, a variável mais fortemente associada a esse desfecho foi ter algum amigo que já fez uso de alguma droga ilícita na vida (RP = 19,54). CONCLUSÕES: O ambiente universitário parece ser um terreno fértil para a difusão do uso de club drugs. O fortalecimento de uma rede de apoio institucional da universidade, capaz de propor atividades de prevenção, bem como de identificar, acolher e encaminhar casos em que haja abuso e dependência dessas substâncias, pode ser uma estratégia importante para lidar com essa problemática.

OBJECTIVE: To measure the prevalence of lifetime, last-year, and last-month use of two club drugs ­ ecstasy and LSD ­, as well as the characteristics associated with the last-month use of these substances among undergraduate students at a university in southern Brazil. METHODS: This was a cross-sectional study conducted in 2015 with a clustered systematic sampling strategy. Overall, 1,423 undergraduate students participated. A three-level hierarchical multivariate analysis model was used through Poisson regression with robust adjustment of variance. RESULTS: Prevalence of lifetime, last-year, and lastmonth use of club drugs were 12.7%, 7.8% and 3.8%, respectively. Male participants, with homosexual or bisexual sexual orientation, younger, who lived with their peers, who were single, and who reported last-month use of tobacco and marijuana had higher probability of last-month use club drugs. However, the variable most strongly associated with this outcome was having a friend with lifetime use of illicit drugs (PR = 19.54). CONCLUSIONS: University environment seems to be a fertile ground for the spread of the use of club drugs. The strengthening of the university's institutional assistance network, capable of proposing prevention activities, as well as identifying, supporting and referring cases where there is abuse and dependence on these substances can be an important strategy to deal with this problem.

Inibidores de Desmetilase Lisina-Específica 1 (LSD1) como candidatos a agentes antineoplásicos / Lysine-Specif Demethylase 1 (LSD1) inhibitors as candidates for antineoplastic agents

O câncer é uma das principais causas de morte no mundo sendo, atualmente, a segunda principal causa de morte, perdendo apenas para as doenças cardiovasculares, tornando-se um grande desafio para as autoridades de saúde pública. No Brasil são estimados 625000 novos casos desta enfermidade para o triênio de 2020-2022. Nesse cenário, vários alvos epigenéticos são considerados alternativas no desenvolvimento de inibidores para a terapia do câncer devido serem identificados e relacionados com a carcinogênese, incluindo modificações no perfil de metilação do DNA e modificações de histonas como a metilação, acetilação e fosforilação. Dentre estas modificações, a metilação de histonas é regulada reversivelmente por histonas metiltransferases e desmetilases. A enzima desmetilase lisina-específica 1 (LSD1) foi a primeira histona desmetilase caracterizada e catalisa a remoção de grupos metila das lisinas 4 e 9 da histona H3 (H3K4 e H3K9), utilizando o FAD como cofator. Superexpressa em vários tumores de alto risco e tendo seus níveis correlacionados com a reincidência do tumor durante o tratamento, a LSD1 apresenta papel fundamental na tumorgênese. Portanto, tem sido considerado um alvo biológico promissor no desenvolvimento de novos fármacos para terapêutica contra o câncer. Sendo assim, neste trabalho, a partir de dados de triagem virtual baseado neste alvo biológico, selecionou-se um hit, o qual foi utilizado como protótipo para o planejamento de análogos visando melhorar as características farmacológicas, pois possuem grupos químicos passíveis das mesmas interações com o alvo. Foram sintetizadas 16 moléculas, sendo 7 compostos finais inéditos derivados carboxamídicos e 9 derivados sulfonamídicos. Todos os compostos foram caracterizados por RMN (1H e 13C), espectrometria de massas de alta resolução, espectroscopia de infravermelho, ponto de fusão, polarímetro e a pureza dos compostos foi avaliada por CLAE. Os compostos finais foram submetidos ao ensaio enzimático frente à LSD1, acoplado a Enzima Horseradish Peroxidase (EHP), mostrando que apenas o composto 4g apresentou atividade inibitória de 64% e 57% em 50 µM e 500 µM respectivamente. No ensaio de viabilidade celular na linhagem HEL (linhagem leucêmica) os 16 compostos (4a- 4g, 5a-5d e 6a-6d) apresentaram-se ativos com valores de CI50 na faixa de 5,3 µM a 20,25 µM. Os compostos mais potentes foram os 4e (CI50 = 6,9 µM), 5d (CI50 =5,30 µM) e 6ª (CI50 =6,61 µM), evidenciando que os compostos possuem elevada potência, tornando-se moléculas promissoras em linhagens leucêmicas. Os estudos de ancoramento molecular com a LSD1 sugeriram que a mudança de orientação do composto 4g, permitiu que o grupo benzila da porção benzilamida faça interação com os resíduos PHE560 e TYR807 no bolso hidrofóbico, o que possivelmente acarretou um bloqueio na entrada da cavidade, permitindo a inibição pelo composto

Cancer is one of the leading causes of death in the world and is currently the second leading cause of death, second only to cardiovascular disease, making it a major challenge for public health authorities. In Brazil, approximately, 625000 new cases of this disease are estimated for the 2020-2022 period. In this scenario, several epigentic targets are considered alternatives in the development of inhibitors in cancer therapy, since they are identified and related to carcinogenesis, including changes in the DNA methylation profile and changes in histones such as methylation, acetylation and phosphorylation. Among these modifications, histone methylation is reversibly regulated by histones methyltransferases and demethylases. Lysine-specific demethylase1 (LSD1) was the first histone demethylase characterized and catalyzes the removal of methyl groups from lysines 4 and 9 of histone H3 (H3K4 and H3K9), using FAD as a cofactor. LSD1 has been found to be overexpressed in several high-risk tumors and these levels are correlated with tumor recurrence during treatment. Therefore, it has been considered a promising biological target in the development of new drugs with therapeutic potential against cancer. Thus, in this work, the virtual screening technique based on the biological target was used to discover LSD1 interactions, and then based on the hit found, we propose to synthesize compounds that have chemical groups susceptible to such interactions, seeking to evaluate the enzymatic activity in LSD1 enzyme. Were synthesized 16 molecules, 7 of which are unpublished final compound derived from carboxamides and 9 sulfonamide derivatives. All compounds were characterized by NMR (1H and 13C), high resolution mass spectrometry, infrared spectroscopy, melting point, polarimeter and the purity of the compounds was assessed by CLAE. The final compounds were subjected to enzymatic assays Against LSD1, coupled with enzime Horseradish Peroxidase (HRP), showing that only the 4g compound showed 64% and 57% inhibitory activity in 50 µM and 500 µM respectively. In the cell viability assay in the HEL line (Leukemic line) the 16 compounds (4a-4g, 5a-5d and 6a-6d) were active with IC 50 values in the range of 5.3 µM to 20.25 µM. The most potent compounds were 4e (CI50 = 6.9 µM), 5d (CI50 = 5.30 µM) and 6a (CI50 = 6.61 µM), showing that the compounds have high potency, becoming promising molecules in leukemic lines. Docking studies with LSD1 suggested, that the change in orientation of the 4g compound allows the benzyl group of the benzylamide portion to interact with the PHE560 and TYR807 residues in the hydrophobic pocket, which possibly cause a block in the entrance of the cavity, allowing the inhibition by the compound. Thus, the results obtained indicate that the class of compounds described is likely to continue to be investigated, both in the search for new LSD1 inhibitory hits based on the structure of the 4g compound, how to deepen the studies with 16 compounds of the present work in the performance of more specific tests in leukemic cells, in order to unravel the mechanism of action and possible targets

Effect of glaucocalyxin A on proliferation and cell cycle of triple-negative breast cancer MDA-MB-231 cells / 中草药

Objective: To investigate the effect of glaucocalyxin A on proliferation and cell cycle of triple-negative breast cancer MDA-MB-231 cells and its mechanism. Methods The proliferation inhibition rates of MDA-MB-231 cells were measured by MTT assay. The cell cycle was analyzed by flow cytometry, and the expression of the protein cyclin B1, cyclin D1, CDK2, CDK4, p53, p21, p27, LSD1, H3K4me2, and H3K9me2 was detected by Western blotting. Results Growth of MDA-MB-231 cells was significantly inhibited by glaucocalyxin A in a dose-dependent and time-dependent manner. Flow cytometric analysis indicated that the percentage of MDA-MB-231 cells at G2/M phase was increased significantly. As the results of Western blotting, the protein expression levels of p53, p21, p27, H3K4me2, and H3K9me2 in MDA-MB-231 cells were increased, while that of cyclin B1, cyclin D1, CDK2, CDK4, and LSD1 were decreased after treated with glaucocalyxin A. Conclusion Glaucocalyxin A could inhibit the proliferation of MDA-MB-231 cells and induce cell cycle arrest at the G2/M phase, and the mechanism may be related to the activation of p53 protein expression and the regulation of histone methylation.

LSD1 inhibition suppresses the growth of clear cell renal cell carcinoma upregulating P21 signaling

Histone lysine-specific demethylase 1 (LSD1) has been implicated in the disease progression of several types of solid tumors. This study provides the first evidence showing that LSD1 overexpression occurred in 62.6% (224/358) of clear cell renal cell carcinomas (ccRCC). LSD1 expression was associated with the progression of ccRCC, as indicated by TNM stage (=0.006), especially tumor stage (=0.017) and lymph node metastasis (=0.030). High LSD1 expression proved to be an independent prognostic factor for poor overall survival (<0.001) and recurrence-free survival (<0.001) of ccRCC patients. We further show that LSD1 inhibition by siRNA knockdown or using the small molecule inhibitor SP2509 suppressed the growth of ccRCC and . Mechanistically, inhibition of LSD1 decreased the H3K4 demethylation at the gene promoter, which was associated with P21 upregulation and cell cycle arrest at G1/S in ccRCC cells. Our findings provide new mechanistic insights into the role of LSD1 in ccRCC and suggest the therapeutic potential of LSD1 inhibitors in ccRCC treatment.

The deubiquitinase USP38 affects cellular functions through interacting with LSD1

BACKGROUND: Deubiquitination is a posttranslational protein modification prevalent in mammalian cells. Deubiquitinases regulate the functions of the target protein by removing its ubiquitin chain. In this study, the effects of the deubiquitinase USP38's functions on the LSD1 protein and on cell physiology were investigated. MATERIALS AND METHODS: Western blotting, real-time quantitative PCR, immunoprecipitation, denaturing immunoprecipitation and luciferase reporter assays were used to analyze the protein stability, protein interactions and changes in the ubiquitin chain. Cell proliferation assays, colony formation assays, drug treatments and western blotting were used to explore the functions of USP38 in cells. RESULTS: The deubiquitinase USP38 stabilizes protein LSD1 in cells by binding LSD1 and cleaving its ubiquitin chain to prevent the degradation of LSD1 by the intracellular proteasome. USP38 enhances the ability of LSD1 to activate signaling pathways and hence promotes cellular abilities of proliferation and colony formation through interacting with LSD1. Furthermore, USP38 enhances the drug tolerance of human colon cancer cells. CONCLUSIONS: USP38 is an LSD1-specific deubiquitinase that affects cellular physiology through interacting with LSD1.

Effect of LSD1 knock-down by small hairpin RNA on the apoptosis and cell cycle of human acute myelogenous leukemia cells / 实用医学杂志

Objective To investigate the effect of down-regulation of lysine specific demethylase 1 (LSD1) by shRNA on the apoptosis and cell cycle of human acute myelogenous leukemia cells.Methods The lentiviral vector-mediated LSD1-shRNA was transfected into human acute promyelocytic leukemia HL-60 cells and acute monocytic leukemia SHI-1 cells.The expressions of LSD1 mRNA and protein were examined by real time quantitative PCR and Western blot,respectively.The flow cytometry was applied to detect the apoptosis and cell cycle distribution after AnnexinV-PE/7-AAD and PI dying,respectively.Results The expressions of LSD1 mRNA and protein in HL-60 and SHI-1 LSD1-shRNA group were significantly decreased compared with the blank control group and the negative shRNA group (P ＜ 0.01,respectively).The apoptosis levels of HL-60 and SHI-1 cells were significantly increased after knockdown of LSD1 (P ＜ 0.01).Moreover,the cell cycle distribution in the G0/G1 phases was also significantly increased(P ＜ 0.01).Conclusion LSDI-shRNA promotes cell apoptosis and increases the percentage of cells in the G0/G1 phases of human acute myelogenous leukemia cells.

Effects of neural stem cell LSD1 conditional knockout on the mood and memory in mice / 中国实验动物学报

Objective To study the function of LSD1 in the development of neurons and the influence of LSD1 on mood and memory-related behavior in mice. Methods The LSD1(flox / flox) transgenic mice were crossed with Nestin?cre(Tg) transgenic mice, using Cre?LoxP recombination system, to generate LSD1 conditional knockout of neural stem cell ( LSD1?CKO) mice, LSD1(flox/ flox) Nestin?cre(Tg) mice, and LSD1(flox/ flox) mice as control. The neuron proliferation in LSD1?CKO mice was further detected by immunofluorescence staining. At the same time, the mood and memory?related behavior of LSD1?CKO mice were examined using several methods:sucrose preference test ( SPT) , forced swimming test ( FST) and novel?object recognition ( NOR) assay. Results In the LSD1 brain?specific CKO mice, the neuron proliferation rate in the hippocampus was significantly reduced ( P=0. 023 ) , the preference for sucrose was reduced ( P =0. 0075 ) , immobility duration during the forced swimming test was increased (P<0. 05), and LSD1?CKO mice also exhibits memory?decline (P=0. 0019) during the novel?object recognition test. Conclusions Depletion of LSD1 in mouse brain neural stem cells leads to significant reduction of the neuron proliferation in the hippocampus. LSD1?CKO mice show more negative emotions and memory impairment.

The Role of Next-Generation Sequencing in the Diagnosis of Lysosomal Storage Disorders

Abstract Next-generation sequencing (NGS) panels are used widely in clinical diagnostics to identify genetic causes of various monogenic disease groups including neurometabolic disorders and, more recently, lysosomal storage disorders (LSDs). Many new challenges have been introduced through these new technologies, both at the laboratory level and at the bioinformatics level, with consequences including new requirements for interpretation of results, and for genetic counseling. We review some recent examples of the application of NGS technologies, with purely diagnostic and with both diagnostic and research aims, for establishing a rapid genetic diagnosis in LSDs. Given that NGS can be applied in a way that takes into account the many issues raised by international consensus guidelines, it can have a significant role even early in the course of the diagnostic process, in combination with biochemical and clinical data. Besides decreasing the delay in diagnosis for many patients, a precise molecular diagnosis is extremely important as new therapies are becoming available within the LSD spectrum for patients who share specific types of mutations. A genetic diagnosis is also the prerequisite for genetic counseling, family planning, and the individual choice of reproductive options in affected families.

Effects of silencing LSD1 gene on Molt-4 cells apoptosis / 中国药理学通报

Aim To observe the effect of the LSD1 gene on the proliferation and apoptosis of Molt-4 cells, a kind of human acute T-lymphoblastic leukemia cells. Methods siRNA fragment based on LSD1 gene was designed, filtered out and then transfected into Molt-4 cells. The effects of LSD 1 siRNA on Molt-4 cell prolif-eration were observed by the method of MTS. The cell apoptosis was analyzed by flow cytometry. The states of histone H3K4, H3K9 methylation, histone H3 acetyla-tion, p15, DNA methyltransferase 1 (DNMT1), and apoptosis-related proteins like Bcl-2 , procaspase-3 were evaluated by Western blot. Results Silencing LSD1 gene inhibited cell proliferation. Molt-4 cell pro-liferation rate was ( 99. 65 ± 1. 21 )%, ( 83. 02 ± 1. 69)%, (65. 72 ± 2. 16)%,and (41. 15 ± 2. 23)%respectively after the treatment of Molt-4 cells with 0 , 30, 60, 120 nmol·L-1 of LSD1 siRNA after 48 hours ( P < 0. 05 ) . Cell proliferation rate was ( 99. 86 ± 1. 35)%,(65. 72 ± 2. 16)%,(48. 26 ± 1. 92)%,and ( 37. 86 ± 1. 66 )% respectively after the transfection of Molt-4 cells with 60 nmol · L-1 of LSD1 siRNA after 0 , 24 , 48 , 72 hours ( P<0. 05 ) . Cell apoptosis rate was ( 3. 35 ± 1. 26 )%, ( 12. 16 ± 1. 74 )%, ( 32. 74 ± 2. 47 )%, ( 54. 64 ± 2. 58 )% respectively after transfection of LSD1 siRNA in indicated concentrations for 48 hours ( P <0. 05 ) . At the same time, the ex-pression levels of apoptosis-related proteins like Bcl-2 , procaspase-3 decreased. LSD1 siRNA inhibited LSD1 and LSD1 mRNA, and accumulated histone mono-, and di-methylation H3K4 and histone H3 acetylation. However, alteration of H3K4 trimethylation, H3K9 methylation was not detected. LSD1 siRNA downregu-lated DNA demethylase DNMT1 and upregulated p15 . Conclusions LSD1 siRNA can inhibit Molt-4 cell proliferation and induce apoptosis. Its mechanism may be associated with epigenetic regulation. In addition, it is expected to become a new target for leukemia treat-ment.

The research progress of LSD1 in malignant tumors / 实用肿瘤学杂志

Lysine specific demethylase 1( LSD1) is a kind of flavin adenine dinucleotid ( FAD) dependent amine oxidase and can specifically demethylate H 3K4me2/me1 and H3K9me2/mel, thus it can regulate gene transcriptional activity .LSD1 is essential for mammalian development and is involved in many biological proces-ses,including cell differentiation,gene activation,and gene repression.Nowadays,it is demonstrated that LSD1 might promote cell phase transition(deficiency in LSD1 leads to partial cell cycle arrest in G2/M)and cell prolif-eration,suggesting that the over -expression of LSD1 might promote tumorigenesis.LSD1,as a demethylase,may be a new target for anti -cancer therapy.Hereby,we review on the structure,action mode of LSD1 and its rela-tionship with oncogenesis .

Usos terapéuticos de sustancias prohibidas: LSD, MDMA, THC, GHB, DMT, psilocybina y mescalina / Therapeutic uses of prohibited substances: LSD, MDMA, THC, GHB, DMT, psilocybin, mescaline

El presente texto hace un breve recorrido sobre los usos terapéuticos que han tenido la LSD, MDMA, THC, GHB, DMT, Psilocybina y Mescalina en la historia, así como también refiere algunos de los beneficios para la salud física y mental que se considera tienen en la actualidad. Esta información científica se contrapone a la normativa internacional en materia de drogas, que las clasifica como sustancias prohibidas en la Lista I, debido a su falta de uso médico aceptado por Estados Unidos y a su alto potencial de abuso. En este trayecto también se intenta comprender a qué hace referencia dicho potencial, así como las motivaciones que podrían existir detrás de la prohibición del uso terapéutico de estas drogas. En este marco, se consideran consecuencias para la salud de la población, las que atentan contra los Derechos Humanos de las personas que podrían requerir alguna de estas sustancias.

This paper makes a brief of the therapeutic uses have had the LSD, MDMA, THC, GHB, DMT, Psilocybin and Mescaline in history, as well as some of the benefits referred to physical and mental health that are considered today. This scientific information seems contrary to international legislation on drugs, which classifies as prohibited substances in Schedule I, due to its lack of acceptance medical use by the United States and its high potential for abuse. In this way also try to understand what makes this potential reference, and the reasons that could be behind the ban on therapeutic use of these drugs. In this framework, we consider health consequences of the population, which violate the human rights of people who may require some of these substances.

El LSD y su impacto en el movimiento hippie: a 105 años del nacimiento de su descubridor, el químico Dr. Albert Hofmann / LSD and Its Impact on the Hippie Movement: 105th Anniversary of the Birth of Its Finder, Dr. Albert Hofmann

Durante la mitad de la década de 1960 surgieron en San Francisco, California, USA, las primeras comunidades del movimiento hippie. La ideología hippie nació como una oposición al materialismo, al conformismo, a la burocracia, a las prohibiciones, a la discriminación racial. La droga que se puso “de moda” en aquellos años fue el LSD, sustancia descubierta accidentalmente por el químico Albert Hofmann cuando investigaba los alcaloides de un hongo que atacaba al cornezuelo del centeno. Esta droga, que es capaz de inducir estados alterados de conciencia, comparados en ocasiones con los de la esquizofrenia o la experiencia mística, forma parte de las llamadas “drogas psicodélicas”. Si bien durante los primeros años a partir de su descubrimiento el LSD se empleó casi exclusivamente con fines médicos en psiquiatría, psicoterapia e investigaciones sobre el cerebro, su consumo masivo politizó la droga, transformándola en un acto de resistencia antiestablishment. Más aún, tuvo un fuerte impacto en las distintas disciplinas del arte: la pintura, la escultura, la vestimenta y la música. En conclusión, una sustancia química inadvertidamente absorbida por su descubridor adquirió posteriormente, una masividad tal que llegó a tener influencias muy profundas sobre distintos aspectos de la vida del ciudadano común ya que, en poco tiempo, tanto la vestimenta como la música de estilo hippie, así como las distintas formas del arte, se extendieron más allá del movimiento y llegaron a todos los grupos sociales

During the mid 1960's the first communities of the hippie movement arouse in San Francisco, California, U.S.A. The hippie ideology emerged in opposition to materialism, conformism, bureaucracy, prohibitions and racial discrimination. The drug "in fashion" at that time was LSD, a substance which was accidentally discovered by the Chemist, Albert Hofmann, while conducting research on the alkaloids of the ergot fungus that grows on rye. This substance, which is capable of inducing an altered state of consciousness, as occacionally opposed to shizophrenia and mystical exprience, is part of the so called "psychedelic drugs". Although during the first years following its discovery, LSD was almost exclusively used for medical purposes in Psychiatry, Psychotherapy, and research conducted on the brain, its massive consumpltion has caused this substance to become politicized, turning into an act of resistance known as "anti-establishment". It is so much so that it has had a strong impact on the different disciplines of art: painting and sculpture, clothing and music. To sum up, LSD, a chemical substance which was inadvertently discovered by its finder became so widespread that caused very deep impact on the different aspects of life of the regular citizen since in a very short lapse, both the hippie clothing and music, as well as the different forms of art, went beyond the movement to reach every social group

Quantification of LSD in illicit samples by high performance liquid chromatography

In the present study, a method using high performance liquid chromatography to quantify LSD, in blotter papers seized in Minas Gerais, was optimized and validated. Linearity, precision, recovery, limits of detection and quantification, and selectivity were the parameters used to evaluate performance. The samples were extracted with methanol:water (1: 1) in an ultra-sound bath. The linearity between 0.05 and 20.00 μg/mL (0.5 and 200.0μg of LSD/blotter) was observed with satisfactory mean intra and inter assay precision (RSDr = 4.4% and RSD R = 6.4%, respectively) and with mean recoveries of 83.4% and 84.9% to the levels of 1.00 and 20.00 μg/mL (10 and 200μg LSD/blotter). The limits of detection and quantification were 0.01 and 0.05 μg/mL, respectively (0.1 and 0.5 μg of LSD/blotter). The samples of blotters (n =22) were analyzed and the mean value of 67.55 μg of LSD/blotter (RSD=27.5%) was found. Thus, the method used showed satisfactory analytical performance, and proved suitable as an analytical tool for LSD determination in illicit samples seized by police forces.

No presente trabalho, um método utilizando cromatografia líquida de alta eficiência foi otimizado e validado para quantificar o LSD em selos apreendidos em Minas Gerais. A linearidade, precisão, recuperação, limites de detecção e quantificação e seletividade foram os parâmetros de desempenho avaliados. As amostras foram extraídas com metanol: água (1:1) em banho de ultra-som. A linearidade entre 0,05 a 20,00 mg/mL (0,5 a 200 μg LSD/blotter) foi observada com precisão média, intra e inter ensaio, satisfatória (RSDr = 4,4% e RSD R = 6,4%, respectivamente) e com recuperações médias de 83,4% e 84,9% para os níveis de LSD de 1,00 e 20,00 mg/mL (10 e 200 μg LSD/selo). Os limites de detecção e quantificação encontrados foram de 0,01 e 0,05 mg/mL, respectivamente (0,1 e 0,5 μg LSD/selo). As amostras de selos (n = 22) foram analisadas e o valor médio encontrado foi de 67,55 μg de LSD/selo (RSD% = 27,5). Desta forma, o método analítico apresentou desempenho satisfatório, capaz de ser utilizado como instrumento de análise para a determinação do LSD em amostras ilícitas apreendidas pelas forças policiais.

Uso y abuso de drogas durante el embarazo / Illicit drug use and abuse during pregnancy

El consumo y dependencia de sustancias, es un serio problema social con alta morbilidad materno-fetal. El aumento de la oferta y el contexto social favorecedor, permitió que la difusión del consumo sustancias tóxicas ilícitas, conlleve una incidencia creciente en gestantes consumidoras de sustancias y aumento de recién nacidos afectados por las prácticas tóxicas de sus madres. La evaluación del riesgo cuando la gestación es expuesta a las drogas es difícil, los resultados pueden estar sesgados por el consumo concomitante de otros tóxicos o por factores sicológicos y socio-sanitarios desfavorables. Aunque tampoco se definió un patrón específico de anomalías congénitas, se considera que el abuso de drogas, en general, comporta mayor riego de desenlace anómalo del embarazo, por un incremento del riesgo de malformaciones congénitas, debido a la probable teratogenicidad de algunas sustancias o de la morbilidad perinatal afectando el crecimiento fetal o el normal desarrollo del embarazo. También existen posibles repercusiones a largo plazo en la capacidad de aprendizaje y comportamiento de los niños expuestos intraútero, aunque no demostró efectivamente. Por lo tanto, todo embarazo en el que se detecto un hábito tóxico se debe considerar de mayor riesgo, tomando las medidas oportunas para lograr que las pacientes se alejen de éstas prácticas, apoyadas por un equipo multidisciplinario, idealmente antes del inicio del embarazo, lo que implica la adopción de medidas profilácticas de información y concienciación de las mujeres en edad fértil y de apoyo durante el embarazo y la lactancia para el abandono de la dependencia

Illicit drug use and dependence is a serious social problem with high maternal and fetal morbidity. Supply increase and propitious social context allowed that the diffusion of the use of illicit toxic substances entails a growing incidence in pregnant women who use illicit drugs and an increase of newborns affected by the practices of their mothers. Risk evaluation is difficult when gestation is exposed to illicit drugs because the results could be biased by the concomitant consumption of others toxic substances or by psychological and socio-sanitary unfavorable factors. Though a specific pattern of congenital anomalies has not been defined, in general it is considered that drug abuse has an increased risk of anomalous outcomes in pregnancies. This risk is caused by an increase in the risk of congenital malformations due to the probable teratogenicity of some substances or the perinatal morbility affecting the fetal growth or normal pregnancy development. Although it has not been demonstrated effectively, there are also possible long-term repercussions in the learning capacity and behavior of the children exposed intra uterus. In conclusion, all pregnancies exposed to illicit drugs must be considered high risk pregnancies and measures should be taken so that the patients avoid these practices supported by a multidisciplinary team. Ideally, this team should start working before pregnancy implying the adoption of preventive measures such as information and public awareness of women in fertile age and support during pregnancy and maternal lactation

Uso y abuso de drogas durante el embarazo: [revisión] / Illicit drug use and abuse during pregnancy: [review]

El consumo y dependencia de sustancias, es un serio problema social con alta morbilidad materno-fetal. El aumento de la oferta y el contexto social favorecedor, permitió que la difusión del consumo sustancias tóxicas ilícitas, conlleve una incidencia creciente en gestantes consumidoras de sustancias y aumento de recién nacidos afectados por las prácticas tóxicas de sus madres. La evaluación del riesgo cuando la gestación es expuesta a las drogas es difícil, los resultados pueden estar sesgados por el consumo concomitante de otros tóxicos o por factores sociológicos y socio-sanitarios desfavorables. Aunque tampoco se definió un patrón específico de anomalías congénitas, se considera que el abuso de drogas, en general, comporta mayor riego de desenlace anómalo del embarazo, por un incremento del riesgo de malformaciones congénitas, debido a la probable teratogenicidad de algunas sustancias o de la morbilidad perinatal afectando el crecimiento fetal o el normal desarrollo del embarazo. También existen posibles repercusiones a largo plazo en la capacidad de aprendizaje y comportamiento delos niños expuestos intraútero, aunque no demostró efectivamente. Por lo tanto, todo embarazo en el que se detecto un hábito tóxico se debe considerar de mayor riesgo, tomando las medidas oportunas para lograr que las pacientes se alejen de éstas prácticas, apoyadas por un equipo multidisciplinario, idealmente antes del inicio del embarazo, lo que implica la adopción de medidas profilácticas de información y concienciación de las mujeres en edad fértil y de apoyo durante el embarazo y la lactancia para el abandono de la dependencia.

Illicit drug use and dependence is a serious social problem with high maternal and fetal morbidity. Supply increase and propitious social context allowed that the diffusion of theuse of illicit toxic substances entails a growing incidence in pregnant women who use illicit drugs and an increase of newborns affected by the practices of their mothers. Risk evaluation is difficult when gestation is exposed to illicit drugs because the results could be biased by the concomitant consumption of others toxic substances or by psychological and socio-sanitary unfavorable factors. Though a specific pattern of congenital anomalies has not been defined, in general it is considered that drug abuse has an increased risk ofanomalous outcomes in pregnancies. This risk is caused by an increase in the risk of congenital malformations due to the probable teratogenicity of some substances or the perinatal morbility affecting the fetal growth or normal pregnancy development. Although it has not been demonstrated effectively, there are also possible long-term repercussions in the learning capacity and behavior of the children exposed intra uterus. In conclusion, all pregnancies exposed to illicit drugs must be considered high risk pregnancies and measures should be taken so that the patients avoid these practices supported by a multidisciplinary team. Ideally, this team should start working before pregnancy implying the adoption of preventive measures such as information and public awareness of women in fertile age and support during pregnancy and maternal lactation.

ANALGESIC ACTION OF LITHIUM SALT IN RAT CAUDATE-PUTAMEN NUCLEUS / 重庆医科大学学报

Effect of lithium salt(Li)administnation to caudate-putamen nucleus (CPN) on pain response in the rat was studied by chronic cannula implantation and direct injection of drugs into the brain structurementioned above. The results were as follows:( 1 ) The injection of Li into anterior part of the head of CPN of rats produced significantly the analgesic effect that could be antagonized by naloxone, atropine,phento-lamine.propranolol, lysergic acid diethylamide and bicuculline, but not by haloperidol.(2) The injection of Li into central part of the head of CPN of rats did not produce analgesic effect.The results above showed that microinjection of Li into different parts of the head of CPN could give rise to different effects on pain response and the analgesic effect of Li could be related to metabolic changes of endogenous opioid peptides, acetylcholine, noradrenaline, gama aminobutyric acid and 5-hydroXytryptamin aad mediated by their receptors respectively