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http://rollingstone.uol.com.br/noticia/capa-de-marco-maconha-no-brasil/ por REDAÇÃO 10 de Março de 2014 às 17:09 O Brasil, enfim, está pronto para discutir a legalização da maconha. E na reportagem de capa da edição de março da Rolling Stone Brasil, conversamos com especialistas sobre os prós e os contras de uma possível mudança na lei, as propostas de diversas frentes, os impactos na saúde do usuário e os mitos e verdades sobre a substância. Além disso, damos uma prévia, com exclusividade, do projeto de lei ainda inédito elaborado pelo deputado Jean Wyllys (PSOL-RJ). Segundo Wyllys, 40 anos, antes de ser apresentado no Congresso, o texto será submetido aos “grupos de interesse”. Ou seja: o setorial de drogas do PSOL, ativistas ligados à Marcha da Maconha e à Rede Pense Livre, policiais e advogados antiproibicionismo, além de cientistas e médicos que defendem o uso do THC na terapia de doenças. O PL de Wyllys propõe mudanças no sistema Nacional de Políticas Públicas sobre Drogas e regula a “produção, a industrialização e a comercialização da maconha”. O texto também prevê a autorização do uso da maconha para pesquisas e estudos científicos mediante prévia autorização da autoridade competente. A espinha dorsal teórica prega “o fortalecimento da autonomia e da responsabilidade individual em relação ao uso problemático de drogas”. O projeto, porém, vai além da maconha e prevê uma ideia polêmica: que o Brasil adote a política da redução de danos. Isso inclui, entre outras coisas, a “distribuição de seringas e/ou outros insumos e produtos para a redução do dano à saúde da pessoa que faz uso” e o acesso a dispositivos de controle de pureza e detecção da presença de aditivos perigosos em substâncias psicoativas lícitas ou ilícitas. Mas é no artigo 18 que o PL mostra a que veio: “Não comete crime quem, para uso ou consumo pessoal, com fim religioso, medicinal ou recreativo, adquire, guarda, transporta ou traz consigo plantas destinadas à preparação de drogas”. Salvo prova em contrário no sentido de que o agente se dedica à mercancia, presumiria-se de uso pessoal o cultivo e a colheita de até 12 plantas. “Nenhuma pessoa poderá ser presa, detida, privada de sua liberdade ou indicada em processo criminal nos casos acima citados”, define o projeto. No capítulo específico sobre a maconha, o projeto de Wyllys bebe na fonte das leis mais liberais da Europa, no caso da Espanha e da Holanda, e também do vizinho Uruguai: “Autoriza-se a produção e o comércio de Cannabis em todo o território nacional, e estabelece-se a obrigatoriedade de registro, da padronização, da classificação, da inspeção e da fiscalização de tais atividades”. A inspeção e a fiscalização ficariam sob a competência do Sistema Único de Saúde (SUS). As sementes estrangeiras poderão, caso o PL seja aprovado, “ser objeto de comércio ou entregues ao consumo”, mas só quando suas especificações atenderem aos padrões de “identidade e qualidade” previstos para os produtos nacionais. O exemplo espanhol também inspirou o Artigo 44, parágrafo único: “Os clubes de autocultivadores deverão ter um mínimo de 15 e o máximo de 45 sócios”, que poderão plantar um número de plantas proporcional ao número de sócios, o que equivale a um máximo de 180 plantas para clubes de 15 sócios, “sendo 90 plantas maduras e 90 imaturas”. A comercialização seria livre em todo o território nacional, mas a rotulagem deve informar o nome genérico e a matéria-prima. Caberia então ao poder executivo regulamentar o uso medicinal da Cannabis em todo o país. Leia a íntegra da reportagem “Um País Envolto em Fumaça”, escrita pelos repórteres Antonio Burani e Regiane de Oliveira, na edição 90 da Rolling Stone Brasil, nas bancas a partir de terça, 11 de março.

http://www.jci.org/articles/view/25509 Research Article Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects Wen Jiang1,2, Yun Zhang1, Lan Xiao1, Jamie Van Cleemput1, Shao-Ping Ji1, Guang Bai3 andXia Zhang1 1Neuropsychiatry Research Unit, Department of Psychiatry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. 2Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China. 3Department of Biomedical Sciences, Dental School, Program in Neuroscience, University of Maryland, Baltimore, Maryland, USA. Address correspondence to: Xia Zhang, Neuropsychiatry Research Unit, 103 Wiggins Road, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E4. Phone: (306) 966-2288; Fax: (306) 966-8830; E-mail: zhangxia@duke.usask.ca. First published October 1, 2005 Received for publication April 29, 2005, and accepted in revised form August 9, 2005. The hippocampal dentate gyrus in the adult mammalian brain contains neural stem/progenitor cells (NS/PCs) capable of generating new neurons, i.e., neurogenesis. Most drugs of abuse examined to date decrease adult hippocampal neurogenesis, but the effects of cannabis (marijuana or cannabinoids) on hippocampal neurogenesis remain unknown. This study aimed at investigating the potential regulatory capacity of the potent synthetic cannabinoid HU210 on hippocampal neurogenesis and its possible correlation with behavioral change. We show that both embryonic and adult rat hippocampal NS/PCs are immunoreactive for CB1 cannabinoid receptors, indicating that cannabinoids could act on CB1 receptors to regulate neurogenesis. This hypothesis is supported by further findings that HU210 promotes proliferation, but not differentiation, of cultured embryonic hippocampal NS/PCs likely via a sequential activation of CB1 receptors, Gi/o proteins, and ERK signaling. Chronic, but not acute, HU210 treatment promoted neurogenesis in the hippocampal dentate gyrus of adult rats and exerted anxiolytic- and antidepressant-like effects. X-irradiation of the hippocampus blocked both the neurogenic and behavioral effects of chronic HU210 treatment, suggesting that chronic HU210 treatment produces anxiolytic- and antidepressant-like effects likely via promotion of hippocampal neurogenesis. Introduction Cannabis (marijuana, hashish, or cannabinoids) has been used for medical and recreational purposes for many centuries and is likely the only medicine or illicit drug that has constantly evoked tremendous interest or controversy within both the public domain and medical research. Cannabinoids appear to be able to modulate pain, nausea, vomiting, epilepsy, ischemic stroke, cerebral trauma, multiple sclerosis, tumors, and other disorders in humans and/or animals (1–7). However, marijuana has been the most commonly used illicit drug in developed countries, producing acute memory impairment and dependence/withdrawal symptoms in chronic users and animal models (6, 8–10). Cannabis acts on 2 types of cannabinoid receptors, the CB1 and CB2 receptors, which are distributed mainly in the brain and immune system, respectively. In the brain, CB1 receptors are also targeted by endogenous cannabinoids (i.e., endocannabinoids) such as anandamide (AEA), 2-arachidonylglycerol, and arachidonylethanolamide (1, 6, 10,11). The recent discovery that the hippocampus is able to generate new neurons (i.e., neurogenesis) throughout the lifespan of mammals, including humans, has changed the way we think about the mechanisms of psychiatric disorders (12) and drug addiction (13). The subgranular zone of the dentate gyrus (SGZ) in the adult brain contains neural stem/progenitor cells (NS/PCs) capable of producing thousands of new granule cells per day (14). We, and others, have shown that these newborn hippocampal neurons are functionally integrated into the existing neuroanatomical circuitry (15, 16) and are positively correlated with hippocampus-dependent learning and memory processes (17) and the developmental mechanisms of stress and mood disorders (12). Recent studies have further shown that chronic fluoxetine treatment produced antidepressant and anxiolytic effects (18, 19) and the anxiolytic effects are likely achieved by promoting hippocampal neurogenesis (18). Chronic administration of the major drugs of abuse including opiates, alcohol, nicotine, and cocaine has been reported to suppress hippocampal neurogenesis in adult rats (20–23), suggesting a potential role of hippocampal neurogenesis in the initiation, maintenance, and treatment of drug addiction (13). The recent finding of prominently decreased hippocampal neurogenesis in CB1-knockout mice (24) suggests that CB1 receptor activation by endogenous, plant-derived, or synthetic cannabinoids may promote hippocampal neurogenesis. However, endogenous cannabinoids have been reported to inhibit adult hippocampal neurogenesis (25). Nevertheless, it is possible that exo- and endocannabinoids could differentially regulate hippocampal neurogenesis, as exo- and endocannabinoids act as full or partial agonists on CB1 receptors, respectively (11). The goal of the present study was to test the hypothesis that the potent synthetic cannabinoid HU210 is able to promote hippocampal neurogenesis, leading to the anxiolytic and antidepressant effects of cannabinoids. We demonstrate here that both HU210 and the endocannabinoid AEA promote proliferation of embryonic hippocampal NS/PCs without significant effects on their differentiation, resulting in more newborn neurons. The effects of HU210 on adult hippocampal neurogenesis were quantified in freely moving rats and were correlated with behavioral testing. We show that 1 month after chronic HU210 treatment, rats display increased newborn neurons in the hippocampal dentate gyrus and significantly reduced measures of anxiety- and depression-like behavior. Thus, cannabinoids appear to be the only illicit drug whose capacity to produce increased hippocampal newborn neurons is positively correlated with its anxiolytic- and antidepressant-like effects. Results Expression of CB1 receptors in embryonic and adult hippocampal NS/PCs. In the mammalian brain, the CB1 receptor is one of the most abundant G protein–coupled receptors, accounting for most, if not all, of the centrally mediated effects of cannabinoids (5). We reasoned that if cannabinoids were able to regulate neurogenesis, the NS/PCs capable of producing new neural cells would contain CB1 receptors. We therefore employed CB1 antibody immunocytochemistry, Western blotting, and PCR to examine CB1 protein and gene expression in cultured NS/PCs isolated from the hippocampus of E17 rat embryos. About 95% of the total neurosphere cells labeled with Hoeschst stain were also labeled with both CB1 and nestin (a marker for NS/PCs) antibodies (Figure1A). Some Hoechst-labeled cells in the neurospheres exhibited the shape of glial cells, with small round nuclei, and were CB1 immunoreactive but without nestin staining (Figure 1A). The staining of CB1 antibody appears specific for 2 reasons. First, Western blots with the same antibody and cultured NS/PC revealed a strong protein band with the molecular weight of 60 kDa (Figure 1 , which corresponds to the CB1 receptor (26). Second, we could not detect the positive immunostaining or 60-kDa protein band using the CB1 antibody preabsorbed with the antigen. Using PCR, we further identified a band of the predicted size (1,440 bp) corresponding to the full encoding region of CB1 (Figure 1C), suggesting the presence of CB1 transcripts in NS/PCs. Similar results, i.e., CB1 protein and gene expression, were seen in both second and sixth passages of NS/PCs. We then examined adult naive rats sacrificed 2 hours after receiving a single dose of BrdU to label dividing cells. We found that about 90% of BrdU-stained cells in the SGZ were also doubly labeled with CB1 (Figure 1D; n = 3). These results suggest that both embryonic and adult hippocampal NS/PCs express CB1 receptors. Figure 1 Expression of CB1 receptors in NS/PCs. (A) Coimmunofluorescent staining of CB1 and nestin in cultured hippocampal NS/PCs derived from E17 embryos. Hoechst staining was conducted to reveal the total cultured cells. The arrow indicates the glial-like cells, located in the center of a neurosphere, with CB1 staining and without nestin staining. Scale bar, 20 μm. (B) Western blot using cultured NS/PC reveals a 60-kDa protein band corresponding to CB1 receptor. (C) PCR indicates CB1 gene expression in NS/PCs (lane 2) using primers yielding a predicted product of 1,440 bp (i.e., the full encoding region of CB1 receptor) from embryonic NS/PCs. Lane 1: molecular weight standards; lane 2: CB1 receptor; lane 3: PCR reaction without sample added. (D) Confocal microscopic assessments of costaining of BrdU and CB1 receptors in the SGZ located between the hilus and the granule cell layer (granule) of the dentate gyrus in an adult rat. Scale bar, 10 μm. Increased proliferation of embryonic NS/PCs by HU210 and AEA. To examine the effects of HU210 on NS/PC proliferation, cultured embryonic NS/PCs were incubated with different concentrations of HU210. With the WST-8 assay, changes in NS/PC proliferation between HU210- and vehicle-treated culture were significant at some concentrations of HU210, as evidenced by significant group effects with 1-way ANOVA (F5,18 = 513.129, P < 0.01). Specifically, when 10 nM to 1 μM of HU210 were added to the culture medium containing the mitogenic growth factors bFGF and EGF, the WST-8 assay showed a significant increase in NS/PC proliferation (Tukey post-hoc tests, P < 0.05); 1 nM of HU210 exerted no significant effects (P = 0.072); 10 μM produced profound toxic effects on cultured NS/PCs (Figure 2A). Because HU210 can activate both CB1 and CB2 receptors, we next used the selective CB1 receptor antagonist AM281 to identify the possible involvement of CB1 in the action of HU210 on NS/PC proliferation. Although 1 nM to 1 μM of AM281 alone produced no significant effects on NS/PC proliferation, 10 nM to 1 μM of AM281 blocked the promoting effects of 10 nM to 1 μM of HU210 on NS/PC proliferation (1-way ANOVA for repeated measures, F2,25.713 = 16.792, P < 0.01; pairwise comparisons, HU210-treated cells with or without AM281: P < 0.01) (Figure 2A), suggesting that HU210 specifically acts on CB1 receptors to promote NS/PC proliferation. While 10 μM of AM281 alone significantly inhibited NS/PC proliferation (P < 0.01), this concentration of AM281 did not exert significant effects in preventing the lethal effects of 10 μM of HU210 on NS/PCs (Figure 2A), indicating that the lethal effects of 10 μM of HU210 on NS/PC cells were caused nonspecifically or by another receptor. Figure 2

Já disse pro Pedreiro, mas como vai ser meu mantra pra esse ano e pro ano que vem, vou repetir: "Eu já sabia". NPD, como tenho orgulho do passado, mesmo que eu tenha contribuído pouco, repito tb: "nossa vitória não será por acidente". "a questão não é se vai se legalizar a maconha, mas quando". Porra, Guns é maneiro e rock tá em falta hoje em dia, não dá pra negar... Tive um bro, cujo sonho era ser o Axl, que foi pra Califa e conheceu os feras e tudo. Tem doido pra tudo e a RS, afinal de conta, é um veículo de imprensa internacional... no BR G'n'R continua top... Eu, pessoalmente, curto de Paradise City até http://www.youtube.com/watch?v=u8X76NRiQLQ Tamo junto! Zil, Zil, Zil... Todas! Aqui a questão não é se, é "quando" parceiro! AI AI AI!!! =~'>

Zeitgeist a nosso favor!

É galera, essa reportagem me surpreendeu! Foi bem mais positiva que eu esperava ao ver a capa! E mais uma vez o GR ta lá contribuindo para mostrar a realidade dura do cultivador de maconha!

Muito bom é esta avalanche de matérias,sinal que o sininho já esta chegando na mesa dos Homi de Gravata. Quando regulamentar, vamos fazer uma Festa com toda Galera do GR reunida em algum lugar de cada cidade.

http://www.jci.org/articles/view/25509 Research Article Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects Wen Jiang1,2, Yun Zhang1, Lan Xiao1, Jamie Van Cleemput1, Shao-Ping Ji1, Guang Bai3 andXia Zhang1 1Neuropsychiatry Research Unit, Department of Psychiatry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. 2Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China. 3Department of Biomedical Sciences, Dental School, Program in Neuroscience, University of Maryland, Baltimore, Maryland, USA. Address correspondence to: Xia Zhang, Neuropsychiatry Research Unit, 103 Wiggins Road, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E4. Phone: (306) 966-2288; Fax: (306) 966-8830; E-mail: zhangxia@duke.usask.ca. First published October 1, 2005 Received for publication April 29, 2005, and accepted in revised form August 9, 2005. The hippocampal dentate gyrus in the adult mammalian brain contains neural stem/progenitor cells (NS/PCs) capable of generating new neurons, i.e., neurogenesis. Most drugs of abuse examined to date decrease adult hippocampal neurogenesis, but the effects of cannabis (marijuana or cannabinoids) on hippocampal neurogenesis remain unknown. This study aimed at investigating the potential regulatory capacity of the potent synthetic cannabinoid HU210 on hippocampal neurogenesis and its possible correlation with behavioral change. We show that both embryonic and adult rat hippocampal NS/PCs are immunoreactive for CB1 cannabinoid receptors, indicating that cannabinoids could act on CB1 receptors to regulate neurogenesis. This hypothesis is supported by further findings that HU210 promotes proliferation, but not differentiation, of cultured embryonic hippocampal NS/PCs likely via a sequential activation of CB1 receptors, Gi/o proteins, and ERK signaling. Chronic, but not acute, HU210 treatment promoted neurogenesis in the hippocampal dentate gyrus of adult rats and exerted anxiolytic- and antidepressant-like effects. X-irradiation of the hippocampus blocked both the neurogenic and behavioral effects of chronic HU210 treatment, suggesting that chronic HU210 treatment produces anxiolytic- and antidepressant-like effects likely via promotion of hippocampal neurogenesis. Introduction Cannabis (marijuana, hashish, or cannabinoids) has been used for medical and recreational purposes for many centuries and is likely the only medicine or illicit drug that has constantly evoked tremendous interest or controversy within both the public domain and medical research. Cannabinoids appear to be able to modulate pain, nausea, vomiting, epilepsy, ischemic stroke, cerebral trauma, multiple sclerosis, tumors, and other disorders in humans and/or animals (1–7). However, marijuana has been the most commonly used illicit drug in developed countries, producing acute memory impairment and dependence/withdrawal symptoms in chronic users and animal models (6, 8–10). Cannabis acts on 2 types of cannabinoid receptors, the CB1 and CB2 receptors, which are distributed mainly in the brain and immune system, respectively. In the brain, CB1 receptors are also targeted by endogenous cannabinoids (i.e., endocannabinoids) such as anandamide (AEA), 2-arachidonylglycerol, and arachidonylethanolamide (1, 6, 10,11). The recent discovery that the hippocampus is able to generate new neurons (i.e., neurogenesis) throughout the lifespan of mammals, including humans, has changed the way we think about the mechanisms of psychiatric disorders (12) and drug addiction (13). The subgranular zone of the dentate gyrus (SGZ) in the adult brain contains neural stem/progenitor cells (NS/PCs) capable of producing thousands of new granule cells per day (14). We, and others, have shown that these newborn hippocampal neurons are functionally integrated into the existing neuroanatomical circuitry (15, 16) and are positively correlated with hippocampus-dependent learning and memory processes (17) and the developmental mechanisms of stress and mood disorders (12). Recent studies have further shown that chronic fluoxetine treatment produced antidepressant and anxiolytic effects (18, 19) and the anxiolytic effects are likely achieved by promoting hippocampal neurogenesis (18). Chronic administration of the major drugs of abuse including opiates, alcohol, nicotine, and cocaine has been reported to suppress hippocampal neurogenesis in adult rats (20–23), suggesting a potential role of hippocampal neurogenesis in the initiation, maintenance, and treatment of drug addiction (13). The recent finding of prominently decreased hippocampal neurogenesis in CB1-knockout mice (24) suggests that CB1 receptor activation by endogenous, plant-derived, or synthetic cannabinoids may promote hippocampal neurogenesis. However, endogenous cannabinoids have been reported to inhibit adult hippocampal neurogenesis (25). Nevertheless, it is possible that exo- and endocannabinoids could differentially regulate hippocampal neurogenesis, as exo- and endocannabinoids act as full or partial agonists on CB1 receptors, respectively (11). The goal of the present study was to test the hypothesis that the potent synthetic cannabinoid HU210 is able to promote hippocampal neurogenesis, leading to the anxiolytic and antidepressant effects of cannabinoids. We demonstrate here that both HU210 and the endocannabinoid AEA promote proliferation of embryonic hippocampal NS/PCs without significant effects on their differentiation, resulting in more newborn neurons. The effects of HU210 on adult hippocampal neurogenesis were quantified in freely moving rats and were correlated with behavioral testing. We show that 1 month after chronic HU210 treatment, rats display increased newborn neurons in the hippocampal dentate gyrus and significantly reduced measures of anxiety- and depression-like behavior. Thus, cannabinoids appear to be the only illicit drug whose capacity to produce increased hippocampal newborn neurons is positively correlated with its anxiolytic- and antidepressant-like effects. Results Expression of CB1 receptors in embryonic and adult hippocampal NS/PCs. In the mammalian brain, the CB1 receptor is one of the most abundant G protein–coupled receptors, accounting for most, if not all, of the centrally mediated effects of cannabinoids (5). We reasoned that if cannabinoids were able to regulate neurogenesis, the NS/PCs capable of producing new neural cells would contain CB1 receptors. We therefore employed CB1 antibody immunocytochemistry, Western blotting, and PCR to examine CB1 protein and gene expression in cultured NS/PCs isolated from the hippocampus of E17 rat embryos. About 95% of the total neurosphere cells labeled with Hoeschst stain were also labeled with both CB1 and nestin (a marker for NS/PCs) antibodies (Figure1A). Some Hoechst-labeled cells in the neurospheres exhibited the shape of glial cells, with small round nuclei, and were CB1 immunoreactive but without nestin staining (Figure 1A). The staining of CB1 antibody appears specific for 2 reasons. First, Western blots with the same antibody and cultured NS/PC revealed a strong protein band with the molecular weight of 60 kDa (Figure 1 , which corresponds to the CB1 receptor (26). Second, we could not detect the positive immunostaining or 60-kDa protein band using the CB1 antibody preabsorbed with the antigen. Using PCR, we further identified a band of the predicted size (1,440 bp) corresponding to the full encoding region of CB1 (Figure 1C), suggesting the presence of CB1 transcripts in NS/PCs. Similar results, i.e., CB1 protein and gene expression, were seen in both second and sixth passages of NS/PCs. We then examined adult naive rats sacrificed 2 hours after receiving a single dose of BrdU to label dividing cells. We found that about 90% of BrdU-stained cells in the SGZ were also doubly labeled with CB1 (Figure 1D; n = 3). These results suggest that both embryonic and adult hippocampal NS/PCs express CB1 receptors. Figure 1 Expression of CB1 receptors in NS/PCs. (A) Coimmunofluorescent staining of CB1 and nestin in cultured hippocampal NS/PCs derived from E17 embryos. Hoechst staining was conducted to reveal the total cultured cells. The arrow indicates the glial-like cells, located in the center of a neurosphere, with CB1 staining and without nestin staining. Scale bar, 20 μm. (B) Western blot using cultured NS/PC reveals a 60-kDa protein band corresponding to CB1 receptor. (C) PCR indicates CB1 gene expression in NS/PCs (lane 2) using primers yielding a predicted product of 1,440 bp (i.e., the full encoding region of CB1 receptor) from embryonic NS/PCs. Lane 1: molecular weight standards; lane 2: CB1 receptor; lane 3: PCR reaction without sample added. (D) Confocal microscopic assessments of costaining of BrdU and CB1 receptors in the SGZ located between the hilus and the granule cell layer (granule) of the dentate gyrus in an adult rat. Scale bar, 10 μm. Increased proliferation of embryonic NS/PCs by HU210 and AEA. To examine the effects of HU210 on NS/PC proliferation, cultured embryonic NS/PCs were incubated with different concentrations of HU210. With the WST-8 assay, changes in NS/PC proliferation between HU210- and vehicle-treated culture were significant at some concentrations of HU210, as evidenced by significant group effects with 1-way ANOVA (F5,18 = 513.129, P < 0.01). Specifically, when 10 nM to 1 μM of HU210 were added to the culture medium containing the mitogenic growth factors bFGF and EGF, the WST-8 assay showed a significant increase in NS/PC proliferation (Tukey post-hoc tests, P < 0.05); 1 nM of HU210 exerted no significant effects (P = 0.072); 10 μM produced profound toxic effects on cultured NS/PCs (Figure 2A). Because HU210 can activate both CB1 and CB2 receptors, we next used the selective CB1 receptor antagonist AM281 to identify the possible involvement of CB1 in the action of HU210 on NS/PC proliferation. Although 1 nM to 1 μM of AM281 alone produced no significant effects on NS/PC proliferation, 10 nM to 1 μM of AM281 blocked the promoting effects of 10 nM to 1 μM of HU210 on NS/PC proliferation (1-way ANOVA for repeated measures, F2,25.713 = 16.792, P < 0.01; pairwise comparisons, HU210-treated cells with or without AM281: P < 0.01) (Figure 2A), suggesting that HU210 specifically acts on CB1 receptors to promote NS/PC proliferation. While 10 μM of AM281 alone significantly inhibited NS/PC proliferation (P < 0.01), this concentration of AM281 did not exert significant effects in preventing the lethal effects of 10 μM of HU210 on NS/PCs (Figure 2A), indicating that the lethal effects of 10 μM of HU210 on NS/PC cells were caused nonspecifically or by another receptor. Figure 2 Effects of the cannabinoid HU210 on proliferation of cultured hippocampal NS/PCs. (A) In the WST-8 assay, incubation of NS/PCs with 10 nM to 1 μM of HU210 for 48 hours significantly promoted NS/PC proliferation, which was blocked by the CB1 receptor antagonist AM281. AM281 alone significantly decreased NS/PC proliferation only with 10 μM, but this concentration of AM281 was not able to block the lethal effects of 10 μM of HU210 on NS/PCs. (B) BrdU incorporation assay confirmed the results obtained with the WST-8 assay shown in A. (C) Incubation of NS/PCs with 1 μM to 10 μM of AEA for 48 hours significantly promoted NS/PC proliferation in the WST-8 assay. (D) Application of 10 nM to 1 μM of HU210 significantly promoted NS/PC proliferation in both the presence and absence of the growth factors bFGF and EGF in the culture medium. (E) Pertussis (PTX; 100 ng/ml), a selective blocker for Gi/o protein activation, prevented the effects of 10 nM to 1 μM of HU210 on promoting NS/PC proliferation. (F) Incubation of NS/PCs with 1 mg/ml of cholera toxin, a selective Gs activator, stimulated a profound increase in cAMP accumulation in NS/PCs 0.5, 1, 2, and 24 hours after the addition of cholera toxin. (G) Incubation of NS/PCs with 1 mg/ml of cholera toxin for 0.5, 1, 2, 24, or 48 hours did not induce significant change in NS/PC proliferation. Error bars represent SEM. *P < 0.05 and **P < 0.01 by Tukey post-hoc tests after 1-way ANOVA. To confirm the effects of 10 nM to 1 μM of HU210 on promoting NS/PC proliferation as previously assessed by the WST-8 assay, the BrdU incorporation assay was used. It measures cell proliferation by detecting dividing cells. Similar to the results of the WST-8 assay, 1-way ANOVA showed significant group effects (F5,18 = 176.004; P < 0.01); Tukey post-hoc tests revealed that 10 nM to 1 μM of HU210 significantly increased NS/PC proliferation (P < 0.05), which was blocked by 10 nM to 1 μM of the selective CB1 receptor antagonist AM281 (1-way ANOVA for repeated measures, F2,36 = 19.081, P < 0.01; pairwise comparisons, HU210-treated cells with or without AM281: P < 0.01) (Figure 2 . To determine the effects of the endogenous cannabinoid AEA on NS/PC proliferation, cultured NS/PCs were incubated with different concentrations of AEA. The WST-8 assay showed significant group effects with 1-way ANOVA (F5,18 = 61.585, P < 0.01). Tukey post-hoc tests further showed that 1 μM to 10 μM of AEA significantly increased NS/PC proliferation (P < 0.05) in the presence of bFGF and EGF; 100 μM produced toxic effects (Figure 2C). To explore the possibility of whether HU210 itself is able to produce mitogenic effects, we further examined NS/PC proliferation by adding different concentrations of HU210 to the culture medium with or without the mitogenic growth factors bFGF and EGF. When bFGF and EGF were absent from the culture medium, a significant overall change in NS/PC proliferation was observed following HU210 application (F5,30 = 219.076, P < 0.01) (Figure 2D). Specifically, 10 nM to 1 μM of HU210 without growth factors produced significant mitogenic effects on NS/PCs (Tukey post-hoc tests, P < 0.05), whereas 10 μM of HU210 killed the cells. Similar results were observed in the control culture when different concentrations of HU210 were added to the culture medium containing the mitogenic growth factors (F5,30 = 194.429, P < 0.01; Tukey post-hoc tests, P < 0.05) (Figure 2D). Nevertheless, the basal proliferation levels with bFGF and EGF were significantly higher than those without bFGF and EGF (1-way ANOVA for repeated measures, F1,30 = 214.703, P < 0.01; pairwise comparisons: P < 0.01) (Figure 2D). Intracellular signaling involved in HU210-induced NS/PC proliferation. To investigate the mechanisms underlying the action of HU210 on NS/PC proliferation, we examined the intracellular signaling pathways. CB1 receptor stimulation activates Gi/o or Gsproteins (27, 28). To examine whether Gi/o protein mediates the effects of HU210, we added pertussis toxin, a selective blocker for Gi/o protein activation, to the culture medium 4 hours prior to HU210 treatment. Again, 10 nM to 1 μM of HU210 significantly increased NS/PC proliferation (1-way ANOVA, F5,18 = 880.629, P < 0.01; post-hoc tests, P < 0.01 between control and each of the 3 concentrations of HU210), which was completely blocked by 100 ng/ml of pertussis (1-way ANOVA for repeated measures, F1,18 = 41.64, P < 0.01; pairwise comparisons, HU210-treated cells with or without pertussis: P < 0.01) (Figure 2E). It has been shown that HU210 activates Gs proteins when Gi/o proteins are inhibited by pertussis toxin (27). Therefore, to determine whether the blockade effects of HU210-induced NS/PC proliferation following pertussis treatment is achieved by activation of Gs proteins, we examined the effects of cholera toxin, a Gs protein activator, on NS/PC proliferation. Incubation of NS/PCs with 1 mg/ml of cholera toxin stimulated about 14-, 80-, 90-, and 13-fold increase in cAMP accumulation in NS/PCs 0.5, 1, 2, and 24 hours after the addition of cholera toxin; cAMP production returned to the basal levels 48 hours after cholera toxin (1-way ANOVA, F5,18 = 93.341,P < 0.01) (Figure 2F). These results indicate the effective activation of Gs proteins in NS/PCs by cholera toxin. However, there was no significant change in NS/PC proliferation 0.5, 1, 2, 24, and 48 hours after the addition of cholera toxin (1-way ANOVA, F5,18 = 76.562, P = 0.86) (Figure 2G). These results together suggest the involvement of Gi/o proteins, but not Gs proteins, in HU210-induced NS/PC proliferation. Since Gi/o protein activates PI3K/Akt and ERK signaling (29), which are well known to play an important role in cell growth and cell death, we studied whether HU210 could activate Akt and ERK1/2. There was no significant change in phosphorylation of phospho-Akt during the first 1 hour after HU210 application (F4,10 = 1.693, P = 0.228) (Figure 3A), indicating that the PI3K/Akt signaling pathway is not involved in the action of HU210 on NS/PC proliferation. In contrast, changes in phosphorylation of phospho-ERK1/2 (pERK1/2) during the first 1 hour after HU210 application were dramatic at specific time points, as shown by 1-way ANOVA (with growth factors, F4,15 = 33.698, P < 0.01; without growth factors, F4,15 = 23.513, P < 0.01). As early as 5 minutes after addition of HU210 to culture medium with (Figure 3 or without bFGF and EGF (Figure 3C), a 2.5-fold increase in phosphorylation of pERK1/2 was observed (P < 0.05). At 15 minutes after HU210 application, phosphorylation of pERK1/2 reached the peak level, which was about a 4-fold (with growth factors) or 7-fold increase (without growth factors) relative to control (P < 0.01). By 60 minutes after addition of HU210, phosphorylation of pERK1/2 either significantly decreased (P < 0.05) (Figure 3 or returned to the pretreatment level (Figure 3C). We did not observe any significant changes in the total ERK1/2 during the first 1 hour after HU210 application. Thus, the significant increase in pERK1/2 in this period suggests an important involvement of ERK signaling pathway in the action of HU210 in promoting NS/PC proliferation. This hypothesis was supported by further experiments in which U0126, a specific inhibitor of the ERK pathway, was employed. Figure 3D shows an overall significant difference in pERK1/2 phosphorylation after application of vehicle or 100 nM of HU210 with or without 10 μM of U0126 (F3,8 = 60.769, P < 0.01). Specifically, HU210 profoundly increased phosphorylation of pERK1/2 (P < 0.01), which was almost completely blocked by U0126 (P < 0.01). A parallel experiment demonstrated that U0126 blocked the promoting effects of 100 nM of HU210 on NS/PC proliferation (1-way ANOVA for repeated measures, F1,17 = 6.356, P < 0.05; pairwise comparisons, HU210-treated cells with or without U0126: P < 0.05) (Figure3E). Figure 3 Effects of the cannabinoid HU210 on PI3K/Akt and ERK signaling in cultured hippocampal NS/PCs. (A) There was no significant change in pAkt or actin in NS/PCs within the first hour after addition of 100 nM of HU210 to culture medium. (B) Application of 100 nM of HU210 rapidly induced phosphorylation of pERK1/2 in NS/PCs in the presence of bFGF and EGF in culture medium. (C) Application of 100 nM of HU210 3 hours after removal of bFGF and EGF from culture medium also induced phosphorylation of pERK1/2 in NS/PCs. (D) Application of the ERK signaling inhibitor U0126 blocked the promoting effects of 100 nM of HU210 on phosphorylation of pERK1/2 in NS/PCs 5 minutes after addition of HU210 to culture medium. (E) Addition of U0126 (10 μM) to the culture medium 1 hour before HU210 antagonized the promoting effects of 10 nM to 1 μM of HU210 on NS/PC proliferation. Error bars represent SEM. *P < 0.05 and **P < 0.01 by Tukey post-hoc tests after 1-way ANOVA. tERK1/2, total ERK1/2. HU210 and AEA do not affect neuronal differentiation of cultured NS/PCs. To examine the effects of HU210 on neuronal differentiation of cultured NS/PCs, neurospheres were dissociated, plated, and cultured in the medium containing bFGF and EGF for 1 day and then in another medium containing different concentrations of HU210 without bFGF or EGF for 8 days. After fixation, immunofluorescence staining was performed using antibodies against the neuronal marker β-tubulin III (TuJ1), followed by Hoechst staining that detects all the cultured cells. Cell counting revealed no significant difference among the ratios of TuJ1-labeled neurons and Hoechst-labeled total cells following treatment with vehicle or 10 nM, 100 nM, or 1 μM of HU210 (1-way ANOVA, F4,20 = 3.307,P = 0.324) (Figure 4), suggesting that HU210 exerts no significant effects on neuronal differentiation of cultured NS/PCs. Similarly to HU210, AEA (1 and 5 μM) did not produce significant effects on neuronal differentiation of cultured NS/PCs (1-way ANOVA, F2,9= 0.177, P = 0.840) (Figure 4 . Figure 4 Effects of HU210 and AEA on neuronal differentiation of cultured hippocampal NS/PCs. (A) Incubation of NS/PCs with the culture medium containing either vehicle or 100 nM of HU210 without growth factors for 8 days produced similar density of neurons (pink cells) stained with TuJ1 antibody. The total cultured cells are labeled deep blue by Hoechst staining. (B) There was no significant difference in the ratio of TuJ1-labeled neurons to total cells following application of HU210 (10 nM to 1 μM) or AEA (1 or 5 μM) to culture medium. Increased hippocampal cell proliferation following HU210 treatment in adult rats. BrdU labeling of dividing cells was used to test the acute effects of HU210 treatment on cell proliferation in adult hippocampus. Adult rats received a single dose of vehicle, AM281 (3 mg/kg, i.p.), or HU210 (25 or 100 μg/kg, i.p.), followed 2 hours later by BrdU administration and then perfusion 1 day later. BrdU-labeled cells showed fusiform or irregular shape and were clustered or aggregated in the SGZ (Figure 5A) throughout the whole hippocampus in all rats examined. Cell counting revealed no significant change in the number of BrdU-positive cells in the SGZ among rats treated with vehicle, AM281, or HU210 (1-way ANOVA, F3,16 = 52.784, P = 0.58; n = 5) (Figure 5 . We then examined the effects of chronic HU210 injection on cell proliferation in adult hippocampus. Two hours after receiving the last dose of twice-daily injections of vehicle, AM281 (3 mg/kg, i.p.), or HU210 (25 or 100 μg/kg, i.p.) for 10 days, adult Long-Evans rats received BrdU administration and then were perfused 1 day later. Immunohistochemical staining showed an apparent increase in the density of BrdU-labeled cells in the SGZ following chronic administration of 100 μg/kg of HU210 (Figure 5C). One-way ANOVA revealed a significant overall difference in the mean ± SEM number of BrdU-positive cells in the SGZ (F3,16 = 11.504, P < 0.001; n= 5) (Figure 5D). Tukey post-hoc test showed a significant increase (about 40%) in the number of BrdU-labeled cells following 100 μg/kg of HU210 (P < 0.05) but not 25 μg/kg of HU210 (P = 0.979), relative to vehicle (Figure 5D). AM281 injection seemingly decreased the number of BrdU-positive cells in the SGZ, but there was no significant difference relative to control (P = 0.099). Figure 5 Effects of HU210 treatment on cell proliferation in the dentate gyrus in adult rats (n = 5–7 rats in each group). Cell proliferation was assessed by BrdU labeling of dividing cells. (A) Representative microphotographs of the dentate gyrus show BrdU-positive cells clustered or aggregated in the SGZ in rats receiving an acute injection of vehicle or 100 μg/kg of HU210. Scale bar, 60 μm. (B) There was no significant difference in the average number of BrdU-stained cells in the dentate gyrus per section following 1 dose of acute vehicle, 100 and 25 μg/kg of HU210, and 3 mg/kg of AM281. (C) Representative microphotographs of the dentate gyrus show that twice-daily injections of 100 μg/kg of HU210 for 10 days apparently increased the density of BrdU-positive cells in the SGZ relative to chronic vehicle injection. Scale bar, 60 μm. (D) Relative to vehicle injection, there was a significant increase in the number of BrdU-immunoreactive cells in the dentate gyrus following chronic treatment with 100 μg/kg of HU210, but not 25 μg/kg of HU210 or 3 mg/kg of AM281. Error bars represent SEM. *P < 0.05 by Tukey post-hoc tests after 1-way ANOVA. Increased newborn hippocampal neurons following chronic HU210 treatment in adult rats. A recent study has demonstrated that newborn neurons in the dentate granule cell layer that had survived 4 weeks were stably integrated into the granule cell layer (30). To examine the survival, migration, and differentiation of HU210-induced newborn cells in the SGZ, we injected rats twice daily with HU210 (100 μg/kg, i.p.), AM281 (3 mg/kg), or vehicle for 10 days, followed 12 hours later by 4 BrdU injections at 12 hours intervals. One month after the last HU210, AM281, or vehicle injection, the majority of BrdU-labeled cells migrated and dispersed into the granule cell layer and showed size and morphology indistinguishable from both their neighboring granule neurons and from different treatment (Figure 6A). The number of BrdU-labeled dentate cells in HU210-treated rats was significantly higher than that in vehicle-treated rats (Student’s t test, P < 0.01; n = 5) (Figure 6 , indicating that most of chronic HU210–induced newborn cells survived. Immunofluorescence staining revealed that HU210- and vehicle-treated rats exhibited a similar proportion of BrdU/neuronal nuclear antigen (BrdU/NeuN) double-labeling cells to the total BrdU-labeled cells (Student’s ttest, P = 0.977) (Figure 6C), suggesting that chronic HU210-induced newborn cells in the SGZ have neuronal differentiation ratio similar to that of vehicle-induced newborn cells in the SGZ. Nevertheless, because chronic HU210 treatment significantly increased the number of BrdU-labeled newborn cells in the dentate gyrus (Figure 6 , the total number of newborn neurons doubly labeled with BrdU/NeuN in the dentate gyrus also significantly increased following chronic HU210. Figure 6 Fate and migration of BrdU-labeled cells in the dentate gyrus following chronic HU210 treatment. After receiving twice-daily injections of vehicle or 100 μg/kg of HU210 for 10 days, rats were given 4 BrdU injections, followed 1 month later by perfusion. (A) Representative confocal microscopic images show costaining (yellow) of BrdU (green) and NeuN (red) in the dentate granule cell layer. The majority of BrdU-stained cells are doubly labeled with the neuronal marker NeuN and located within the granule cell layer. 3D, 3 dimensional photograph of doubly stained neurons indicated with arrows. Scale bar, 20 μm. (B) Chronic HU210 significantly increased the number of BrdU-stained cells in the dentate gyrus (n = 5 in each group). (C) There was no significant difference in the proportion of cells doubly labeled with BrdU and NeuN to the total cells singly labeled with BrdU. Error bars represent SEM. **P < 0.01 by Student’s t test. No hippocampal neuronal death following chronic HU210 treatment in adult rats. Ample evidence has illustrated the increased hippocampal neurogenesis following ischemia, epileptic status, enriched environment, or exercise (15). It is therefore possible that increased hippocampal neurogenesis following chronic HU210 treatment in adult rats may result from the toxic effects of chronic HU210 treatment on hippocampal neurons. To explore this possibility, we examine the total number of the dentate granule and CA3 pyramidal neurons following twice-daily injections of HU210 (100 μg/kg) for 10 days. As depicted in Figure 7A, HU210-treated rats did not show detectable loss of NeuN-immunopositive neurons in the hippocampus, relative to naive control rats. Stereological cell counting confirmed that no significant difference in the total number of the dentate granule cells (F1,4 = 1.443, P = 0.782) and CA3 pyramidal neurons (F1,4 = 5.099, P = 0.553) between naive and HU210-treated rats (Figure 7 . These results, however, do not exclude the possibility that some of NeuN-stain neurons following chronic HU210 treatment shown in Figure 7A are dying. Accordingly, we used TUNEL stain and Fluoro-Jade B stain to examine the degenerating hippocampal neurons (31) in rats receiving chronic HU210 treatment, with the naive rats as negative control and kainic acid–treated rats as positive control (31). We failed to detect any TUNEL- or Fluoro-Jade B–stained degenerating cells throughout the whole hippocampus in both naive rats and HU210-treated rats, whereas kainic acid–injected rats showing epileptic status exhibited numerous dying cells in the CA3 pyramidal cell layer and even dentate granule cell layer (Figure 7, C and D). Figure 7 Effects of chronic HU210 on neuronal survival. (A) Both naive control rats and rats receiving twice-daily injections of HU210 (100 μg/kg) for 10 days showed similar density of NeuN-stained neurons in the dentate granule cell layer and CA3 pyramidal cell layer. (B) There was no significant difference in the total number of NeuN-stained cells in the dentate granule cell layer and CA3 pyramidal layer between naive and HU210-treated rats (n = 3 for each group). (C) While naive rats and chronic HU210-treated rats showed no TUNEL-stained cells in the hippocampus, kainic acid–treated (KA-treated) rats exhibited numerous TUNEL-positive neurons in the CA3 pyramidal cell layer and dentate granule cell layer. (D) While naive rats and chronic HU210-treated rats showed no Fluoro-Jade B–stained (FJB-stained) cells in the hippocampus, kainic acid–treated rats exhibited numerous Fluoro-Jade B–positive neurons in the CA3 pyramidal cell layer (n = 3 for each group). Scale bar, 60 μm. Anxiolytic and antidepressant effects of chronic HU210. Two recent studies employing novelty-suppressed feeding (NSF) tests and forced swimming test (FSTs) as measures of anxiety and depression have shown that chronic treatment with the antidepressant fluoxetine produced anxiolytic and antidepressant effects (18, 19), and the anxiolytic effects are likely achieved by promoting hippocampal neurogenesis (18). Therefore, we employed the same behavioral tests to examine the effects of chronic HU210 treatment on measures of anxiety and depression. Rats received twice-daily injections of vehicle, AM281 (3 mg/kg), or HU210 (100 μg/kg) for 10 days, followed 12 hours later by 4 BrdU injections at 12-hour intervals. Rats were subjected to behavioral testing 1 month later, based on the recent finding that hippocampal newborn neurons need 4 weeks to become functional (32). In the NSF test, 1-way ANOVA showed an overall significant difference in the latency to eat in the novel environment among the 3 groups of rats deprived of food for 48 hours (F2,20 = 8.187, P < 0.01). As shown in Figure 8A, relative to vehicle treatment, chronic HU210 (but not AM281) treatment significantly reduced the latency to eat food in the novel environment (P < 0.01). However, when returned to their home cages immediately after the test, rats receiving vehicle, chronic AM281, and chronic HU210 showed no significant difference in the latency to eat food (F2,20 = 0.276, P = 0.762) (Figure 8A) or the amount of food consumed (F2,20 = 0.839, P = 0.447). In the FST, there was an overall significant difference in the duration of immobility among vehicle-, AM281-, and HU210-treated rats (F2,19 = 4.441, P < 0.05). Post-hoc test revealed that HU210 (but not AM281) significantly decreased immobility (P < 0.05) (Figure 8 , whereas neither AM281 nor HU210 produced significant effects on the number of rats climbing in the first 5 minutes in the pretest sessions of the FST (F2,19 = 7.552, P = 0.887) (Figure 8C). Rats were killed for immunohistochemical staining after behavioral tests. The majority of BrdU-positive cells in vehicle-, AM281-, or HU210-treated rats were located in the granule cell layer, suggesting that they became granule neurons. Cell counting revealed an overall significant difference in the number of BrdU-stained cells in the dentate gyrus (F2,19 = 3.896, P < 0.05). Post-hoc test showed results similar to those in Figure 5D: namely, relative to vehicle-treated rats, HU210-treated rats displayed a significant increase (P< 0.05) in the number of BrdU-positive cells in the dentate gyrus, whereas AM281-treated rats exhibited no significant difference (P = 0.165). Thus, these data together suggest that chronic HU210 treatment promoted hippocampal neurogenesis and exerted anxiolytic- and antidepressant-like effects. Figure 8 Effects of chronic HU210 on the NSF test, the FST, and cell proliferation in the dentate gyrus. After receiving chronic vehicle, AM281, or HU210 injections for 10 days, rats were injected with BrdU to label dividing cells, followed 1 month later by behavioral testing and 1 day later by perfusion (n = 7–8 for each group in A–C; n = 5 for each group in D–F). (A) In the NSF test, rats receiving chronic HU210 (but not AM281) showed significantly shortened latency to feed in a novel environment but not in their home cages, suggesting anxiolytic effects produced by HU210. (B) In the FST, chronic HU210 (but not AM281) significantly shortened the duration of immobility (i.e., antidepressant-like effects). (C) Among the rats receiving vehicle, AM281, and HU210, there was no significant difference in the number climbing in the first 5 minutes in the pretest sessions of the FST. (D) Irradiation of the hippocampus prominently reduced cell proliferation in the SGZ. (E) Irradiation of the hippocampus blocked chronic HU210–induced shortened latency of rats to feed in novel environment but not in their home cages in the NSF test. (F) Irradiation of the hippocampus prevented chronic HU210–induced shortened duration of immobility in the FST. Error bars represent SEM. *P < 0.05 and **P < 0.01 by Tukey post-hoc tests after 1-way ANOVA.

De olho na foto.

http://www.ncbi.nlm.nih.gov/pubmed/24577515 Chronic cannabidiol treatment improves social and object recognition in double transgenic APPswe/PS1∆E9 mice. Cheng D1, Low JK, Logge W, Garner B, Karl T. Author information Abstract RATIONALE: Patients suffering from Alzheimer's disease (AD) exhibit a decline in cognitive abilities including an inability to recognise familiar faces. Hallmark pathological changes in AD include the aggregation of amyloid-β (Aβ), tau protein hyperphosphorylation as well as pronounced neurodegeneration, neuroinflammation, neurotoxicity and oxidative damage. OBJECTIVES: The non-psychoactive phytocannabinoid cannabidiol (CBD) exerts neuroprotective, anti-oxidant and anti-inflammatory effects and promotes neurogenesis. CBD also reverses Aβ-induced spatial memory deficits in rodents. MATERIALS AND METHODS: Thus we determined the therapeutic-like effects of chronic CBD treatment (20 mg/kg, daily intraperitoneal injections for 3 weeks) on the APPswe/PS1∆E9 (APPxPS1) transgenic mouse model for AD in a number of cognitive tests, including the social preference test, the novel object recognition task and the fear conditioning paradigm. We also analysed the impact of CBD on anxiety behaviours in the elevated plus maze. RESULTS: Vehicle-treated APPxPS1 mice demonstrated impairments in social recognition and novel object recognition compared to wild type-like mice. Chronic CBD treatment reversed these cognitive deficits in APPxPS1 mice without affecting anxiety-related behaviours. CONCLUSIONS: This is the first study to investigate the effect of chronic CBD treatment on cognition in an AD transgenic mouse model. Our findings suggest that CBD may have therapeutic potential for specific cognitive impairments associated with AD.

Droga ou remédio? Em entrevista à CH On-line, neurocientista dinamarquesa fala sobre estudos que buscam compreender a ação do ‘ecstasy’ e de outros alucinógenos na química cerebral e no humor dos usuários e os potenciais benefícios de seu uso médico controlado. Fonte:http://cienciahoje.uol.com.br/noticias/2014/03/droga-ou-remedio Por: Sofia Moutinho, Ciência Hoje On-line Publicado em 10/03/2014 | Atualizado em 10/03/2014 O ‘ecstasy’ vem sendo alvo de pesquisas que propõem o seu uso em conjunto com a psicoterapia para tratar distúrbios psiquiátricos como o estresse pós-traumático. (foto: DEA/ Wikimedia Commons) Em 1914, pesquisadores alemães criaram uma pílula supressora de apetite para soldados em situação de fome em campos de batalha. O medicamento começou a mostrar que tinha efeitos sobre o humor e a consciência humana e passou a ser prescrito por psiquiatras como auxílio para terapias, até que se tornou ilegal em vários países a partir de década de 1980 sob a alegação de provocar dependência e problemas à saúde. Trata-se do ecstasy. Conhecida como a ‘droga do amor’ por deixar seus usuários felizes e empáticos, a substância, ilícita no Brasil, tem sido alvo de pesquisas que buscam reintroduzi-la no ambiente médico. Estudos que tentam compreender os possíveis efeitos benéficos desse e de outros alucinógenos vêm sendo conduzidos pela neurocientista dinamarquesa Gitte Knudesen, pesquisadora-chefe da Unidade de Pesquisa em Neurobiologia do Hospital da Universidade de Copenhague (Dinamarca) e representante da Fundação Europeia para Pesquisa do Cérebro Grete Lundbeck. Em entrevista à CH On-line, Knudesen comenta a possibilidade de uso médico do ecstasy e outras drogas – como a ayahuasca, bebida feita de plantas amazônicas cujo consumo está associado a algumas religiões no Brasil. Ela também fala sobre suas pesquisas mais recentes, que usam a neuroimagem para identificar a ação dessas substâncias no cérebro. A neurocientista Gitte Knusen. (foto: Andre Aron) Nos últimos anos, a senhora tem estudado a ação do ecstasy e de outras drogas alucinógenas no cérebro. Pode nos contar sobre sua pesquisa? Há indicações de que essas drogas podem ajudar pessoas que sofrem de depressão ou estresse pós-traumático, especialmente o ecstasy e o DMT, um dos compostos da ayahuasca, bebida bastante apreciada no Brasil. Encaramos essas substâncias como drogas recreacionais e não como relacionadas ao abuso de entorpecentes, pois elas não têm um efeito viciante forte. Estamos interessados em olhar para o seu potencial médico. Nos últimos anos, fizemos muitas pesquisas com usuários de ecstasy e agora estamos olhando para esses outros compostos alucinógenos. O ecstasy também atua como alucinógeno, mas de maneira muito leve. Sua principal ação é provocar a liberação de serotonina, um neurotransmissor associado à sensação de prazer, alegria e euforia. Como ele te faz sentir muito empático e inclinado a confiar em outras pessoas, os cientistas estão começando a olhar para seus potenciais benefícios. A maioria das pessoas pensa no ecstasy apenas como uma droga ruim. É claro que não é saudável para o cérebro tomar altas doses da droga, mas o que estamos interessados em olhar é o potencial benefício do uso controlado do ecstasy e de uma classe de componentes alucinógenos que se assemelham ao ecstasy, mas que não provocam a liberação de tanta serotonina. O que a senhora tem observado em suas pesquisas com o ecstasy? Quando você toma uma alta dose de ecstasy, uma quantidade muito grande de serotonina é liberada no seu cérebro, te deixando feliz, de maneira semelhante à ação de alguns antidepressivos. Mas o ecstasy também age sobre os receptores alucinógenos do cérebro chamados 5-HT2A, o que proporciona ‘experiências coloridas’ e a sensação de união com a natureza. Essas mudanças de consciência podem ser muito interessantes. Sabemos muito pouco sobre a consciência e sobre como o cérebro pode se aproveitar dos estados alterados de consciência. A literatura científica e a mídia geralmente focam mais os potenciais efeitos neurotóxicos do ecstasy e menos como ele funciona de verdade. Existe uma atitude muito política sobre o ecstasy, que acho que de certa forma se justifica, mas que tem sido exagerada. Existem muitos outros compostos, muitos deles lícitos, que são muito mais danosos ao cérebro que o ecstasy. Segundo a neurocientista Gitte Knusen, as drogas alucinógenas abrem caminho para o estudo da consciência e de seus estados alterados. (foto: Flickr/ nwe1iluminati – CC BY 2.0) Como esses efeitos do ecstasy poderiam ser aproveitados para fins médicos? Nossos estudos mostram que os usuários de ecstasy respondem de maneira mais ativa às emoções positivas que às negativas. Fizemos alguns testes em que demos imagens de expressões faciais a usuários de ecstasy e pedimos que eles as identificassem. Percebemos que eles se saíram melhor que o grupo controle (de não usuários de drogas) para reconhecer expressões positivas, como de alegria e de fantasia, e tiveram uma performance pior para identificar as expressões negativas, de raiva e desdém, por exemplo. Alguns cientistas pensam em combinar o ecstasy com a psicoterapia As pessoas reagem de modo diferente ao ecstasy, mas tudo tem a ver com a dosagem. Se você der a dose certa, a pessoa passa a responder mais a emoções positivas e confiar mais nas pessoas. Por isso, alguns cientistas pensam em combinar o ecstasy com a psicoterapia. Em uma sessão de psicoterapia, é muito importante que o paciente confie no pscioterapeuta e o ecstasy pode auxiliar nisso, ajudando o paciente a ter o sentimento certo para a terapia funcionar. Para fins de tratamento, a ação alucinógena do ecstasy poderia ser bloqueada, deixando apenas a ação da serotonina sobre o cérebro? Sim, podemos bloquear diferentes partes da droga ao combinar compostos diferentes. Mas o ecstasy não é tão alucinante quanto a ayahuasca, por exemplo. Ele é considerado um alucinógeno leve e não é conhecido por suas propriedades viciantes. Ele é, na verdade, um composto muito pouco viciante, diferentemente da cocaína, por exemplo. Então não precisamos nos preocupar com isso. O problema do ecstasy é que muitas vezes os seus usuários não usam somente essa droga, mas a combinam com álcool, maconha e outros – e essa não é uma boa mistura para o cérebro. Mas, de uma forma controlada, é absolutamente possível explorar os efeitos médicos do ecstasy. A senhora mesma comentou que o ecstasy é visto de forma negativa e não podemos negar que é uma droga que pode ter efeitos negativos no usuário. A senhora não enfrentou nenhum problema de ordem ética e legal para conduzir suas experiências? Eu, pessoalmente, só estudei usuários de ecstasy, não dei a droga a eles. Recentemente, conduzimos esse estudo para mapear a ação de compostos alucinógenos no cérebro de humanos, mas foram doses muito pequenas, cerca de 1,5 microgramas, só para ter a sua imagem no cérebro. Nós não tivemos nenhum problema com esse estudo. No meu país, não existe um entrave ético e, mesmo em outros países, como Reino Unido e Holanda, os pesquisadores têm recebido permissão dos comitês de ética para fazer isso, inclusive para dar ecstasy para pessoas em testes clínicos. Em relação às suas pesquisas sobre a atuação de outras drogas alucinógenas – como a ayahuasca – no cérebro, já há algum resultado? No momento, estamos conduzindo estudos de neuroimagem e tomografia para ver imagens do cérebro ao vivo e descobrir como essa segunda classe de drogas atua. Ainda é uma fase muito inicial, em que estamos simplesmente usando esses compostos alucinógenos como uma ferramenta para visualizar os receptores cerebrais. Por meio de exames de imagem, como tomografia, estamos tentando identificar a ação desses compostos no cérebro de pessoas que tomaram pequenas doses deles. É uma primeira etapa da pesquisa, em que temos que validar os compostos e descobrir como quantificá-los no cérebro e, para isso, precisamos criar alguns modelos de análise. Por meio de exames de imagem, como tomografia, estamos tentando identificar a ação desses compostos no cérebro de pessoas que tomaram pequenas doses deles Na segunda etapa, no mês que vem, vamos ver se esses compostos podem ser usados para medir mudanças nos níveis de serotonina no cérebro. Queremos saber se vai ser possível escanear o cérebro de uma pessoa que está tomando ayahuasca, por exemplo, e ver como as imagens cerebrais mudam quando essa pessoa está fazendo algum tipo de tarefa. Basicamente, ainda estamos desenvolvendo a ferramenta para analisar tudo isso e, quando tivermos validado nossos dados, vamos poder começar a usar em mais pessoas para ver como o cérebro delas está mudando. No Brasil, temos alguns grupos de estudo que também investigam a ação da ayahuasca como forma de terapia. A senhora tem algum contato ou pretende fazer algum tipo de colaboração com cientistas brasileiros? Ainda não, mas estamos pensando em estabelecer uma relação, porque o mais interessante sobre a ayahuasca é que é uma droga muito limpa, as pessoas que tomam não costumam usar outras drogas. Um dos maiores problemas que enfrentamos nos estudos sobre drogas é a grande dificuldade de achar pessoas que não combinem drogas. Na Dinamarca, por exemplo, parece haver dois tipos de pessoas que usam ecstasy. Um grupo são os jovens que tomam ecstasy e tudo mais que estiver à disposição. O segundo grupo, que geralmente usa o ecstasy em pó, toma menos de outras drogas, tem mais consciência do que a substância faz ao cérebro e a usa de forma mais espiritual. Mas sempre há mistura de drogas e fica difícil identificar em um estudo a ação de uma droga isolada se as pessoas combinam várias. Eu gostaria muito de trabalhar com pesquisadores brasileiros, eu ficaria feliz em oferecer esses métodos de neuroimagem que estamos desenvolvendo.

boa pro paulinhuuu... palestrino

Nao foi bem isso q eu kis Big. Ate pq, como falei, sou leigo na sua area de atuação. Oq ue sabia era que empresas (pessoa juridica, bem como vc falou) possuem sim advogados. Afinal, um funcionario pode prejudicar a empresa ao realizar a compra de um material roubado, como ja aconteceu inclusive na empresa a qual trabalho atualmente. Eu so achei estranho a pergunta do nosso amigo, justamente por nao conhecer essa tal Advocacia Preventiva e por pensar tb que "afinal de contas é muito melhor você evitar cometer um crime, do que ter que se defender numa acusação criminal." Toda profissão honesta, é digna. A nao ser que sua consciencia diga que nao. Mas isso é outro assunto. Obrigado pelos esclarecimentos.

show demais heim? Invertendo completamente para alguns o senso pretensamente epistêmico (sabemos que mais ideológico) de que maconha "queima" neurônios. Que loucura meu povo....por isso, gosto por demais de debater e aprender mais sobre C&T&I . Show o/ sinto que sou um jumento, uma mula perto da grandeza da cannabis . De fato, uma planta fantástica, por que não sagrada/medicinal/complexa. Nem todos merecem a cannabis. A canábis não precisa do homem para nada. É justamente ao contrário, é o homem quem precisa da canábis para tudo. obrigado pela info. fabrício.

Tenho fé que vai!

fiz um potinho de geleia recentemente...

Doidera hein floks ??? sei não hein.... 30 % a mais de alcatrão do que um beck normal ?? perder thc ?? jah vi altos maconhero véio passando mal de uma bôa bongada bem dada... Acho q não ..... acho que a galera deu uma viajada nessa info hein.. Opa amigo,ótimos bongs e preços interessantes,só o frete que achei que está tendo alguma coisa errada,por exemplo,achei o bong de R$ 115 muito bom,mas quando calculei o frete esta saindo por R$ 96,20 no PAC, quase o preço do bong... e por sedex sai R$ 279

Mó viaje véio,ñ sabia,fui dar uma procurada,ele era o gordinho que fazia o personagem macaco kkkkkkkkkk Momento nostalgia rsrsrsr

E fanatismo religioso atrofia o hipocampo cerebral. http://www.scientificamerican.com/article/religious-experiences-shrink-part-of-brain/ Tá explicado.

O que posso afirmar é que o exame realizado por perícia do juízo durante a instrução do processo judicial costuma ter maior credibilidade do que o exame realizado diretamente por uma das partes. Abs!

esse é só o começo de uma longa discussão (acho eu) em nosso país, hoje vivemos em um país o qual nossa realidade ("cabeça aberta") não é a realidade da grande maioria da população, mas para todo fim obrigatoriamente tem que existir um começo... salve jah e legalize já!

Pó de crê planta! Quando onde como... #tamojunto #simplesaasim alias... Fazer uma doação pro GR para o post ganhar opção de upload de fotos mais simples... Desconto nas revistas e acompanhamento dos potenciais clubs... Suas divisoes e relação mercadoxambiente

Que que isso, minha gente. Esses maconheiros não param de inventar história. E ainda tem gente que quer legalizar uma droga! Salvem-nos dela e destes que pregam a mentira por aí! MACONHA NÃO! CHOOOOOOOOOOOOOOOOOOORA PROIBASSSSSSSS DE MERDA!

Esse ano vai ser igualzinho da uma bicuda numa bola e jogar ela lá na frente. VAI BRASIIIIL!

Vamo q vamo que a causa nao para... :emoticon-0137-clapping:

Hot hot hot E se tu Plantas.club ... Plantas terás! "G_d save the stones" rs

... me admiro os cara ainda fala de guns'n'roses

Alá. Aí botei fé heim! VAI BRASIL, LEGALIZA!!!!

Legal que chegou aí deserteagle, chega de stress né... Eu tomei a decisão de importar umas seeds da Hiper, mesmo sabendo da encrenca que pode dar... Consegui meu auto sustento com sativa de prensado por algum tempo, mas esse feno produz muito pouco num indoor humilde como o meu e daí tinha que levar muitas plantas ao mesmo tempo...desanimador! O Jeito foi importar mesmo...mas pensando bem cheguei a conclusão que o risco que estou correndo também faz parte da minha ideologia: "faço isso para não financiar o tráfico de drogas , planto para o meu próprio sustento , sigo de cabeça erguida mesmo que a injustiça venha , mesmo que me tratem como criminoso e me julguem como o mal que eu tento combater." Em 42 anos de vida nunca vendi um baseado sequer , sempre trabalhei , nunca tive problemas com a justiça e sou radicalmente contra o tráfico , tanto que virei grower. Mas no último ano e meio tive que parar meu cultivo e fui obrigado a comprar prensado novamente e participar outra vez do círculo do tráfico que eu tanto abomino. Mas enfim , resolvi tomar uma atitude mesmo sabendo das possíveis consequências , não jogarei a responsabilidade do meu vício para uma sociedade que já está violenta demais. Se tudo der certo vou continuar cultivando canabis pro meu consumo e nunca mais dar um centavo pra traficante. Contando os dias com fé...

Mais um registro e contribuição, show de bola. As Marchas acontece 1 vez por ano, tipo, passamos 364 dias do ano pra todo trabalho se concentrar nas Marchas, e a Baixada tá no pique de se fortaceler em cima desse evento único. Quem é do Rio tem, no mínimo, 2 oportunidades de fato pra pedir por sua moral e dignidade: uma em Ipanema representando o Rio. E a outra em Nova Iguaçú representando a Baixada Fluminense. Abs. "ativismo começa em casa"