Quais são e pra que servem os medicamentos à base de Cannabis?

The Cannabis is constituted by compounds with therapeutic properties, obsered in distinct contexts. Some Cannabis-based products are already available in the international market, and here we will highlight those already in use, which are supported by solid scientific evidence, including phytocannabinoids, synthetic cannabinoids and herbal extracts. The biggest challenge is to balance the beneficial effects of Cannabis and the potential adverse effects, which may happen after chronic high-dose use. Despite the equivalente efficacy, smoked Cannabis is not well tolerated by patients without previous recreative use. On the other hand, the herbal product is preferred by recreative users that become patients. In this case, one should vaporize the plant, to avoid the harms caused by the smoke. Considering cost-effectiveness, therapeutic efficacy and quality control, the standardized herbal extracts seem to be the best option, so far available.A Cannabis possui compostos com propriedades terapêuticas observadas em diferentes contextos. Alguns produtos à base de Cannabis já estão disponíveis no mercado internacional. Aqui iremos destacar as preparações que já estão em uso, para os quais há sólidas evidências científicas incluindo canabinoides de origem natural, sintéticos e extratos vegetais. O grande desafio é encontrar um equilíbrio entre os efeitos benéficos da Cannabis e os efeitos adversos, que podem ocorrer em uso crônico e altas doses. Apesar da similaridade de eficácia com os produtos farmacêuticos, a maconha fumada não é bem aceita por pacientes que não fazem uso recreativo. O produto herbal tende a ser preferido por usuários com experiência recreacional prévia. Neste caso, deve-se optar pela vaporização, para evitar os danos causados pela fumaça. Considerando um equilíbrio entre custo, eficácia e garantia de qualidade, os extratos padronizados parecem ser a melhor opção atualmente disponível

Corrigendum: Potential Clinical Benefits of CBD-Rich Cannabis Extracts Over Purified CBD in Treatment-Resistant Epilepsy: Observational Data Meta-analysis

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Potential Clinical Benefits of CBD-Rich Cannabis Extracts Over Purified CBD in Treatment-Resistant Epilepsy: Observational Data Meta-analysis

This meta-analysis paper describes the analysis of observational clinical studies on the treatment of refractory epilepsy with cannabidiol (CBD)-based products. Beyond attempting to establish the safety and efficacy of such products, we also investigated if there is enough evidence to assume any difference in efficacy between CBD-rich extracts compared to purified CBD products. The systematic search took place in February/2017 and updated in December/2017 using the keywords “epilepsy” or “Dravet” or “Lennox-Gastaut” or “CDKL5” combined with “Cannabis,” “cannabinoid,” “cannabidiol,” or “CBD” resulting in 199 papers. The qualitative assessment resulted in 11 valid references, with an average impact factor of 8.1 (ranging from 1.4 to 47.8). The categorical data of a total of 670 patients were analyzed by Fischer test. The average daily dose ranged between 1 and 50 mg/kg, with treatment length from 3 to 12 months (mean 6.2 months). Two thirds of patients reported improvement in the frequency of seizures (399/622, 64%). There were more reports of improvement from patients treated with CBD-rich extracts (318/447, 71%) than patients treated with purified CBD (81/175, 46%), with statistical significance (p < 0.0001). Nevertheless, when the standard clinical threshold of a “50% reduction or more in the frequency of seizures” was applied, only 39% of the individuals were considered “responders,” and there was no difference (p = 0.52) between treatments with CBD-rich extracts (122/330, 37%) and purified CBD (94/223, 42%). Patients treated with CBD-rich extracts reported lower average dose (6.0 mg/kg/day) than those using purified CBD (25.3 mg/kg/day). The reports of mild (158/216, 76% vs. 148/447, 33%, p < 0.001) and severe (41/155, 26% vs. 23/328, 7%, p < 0.0001) adverse effects were more frequent in products containing purified CBD than in CBD-rich extracts. CBD-rich extracts seem to present a better therapeutic profile than purified CBD, at least in this population of patients with refractory epilepsy. The roots of this difference is likely due to synergistic effects of CBD with other phytocompounds (aka Entourage effect), but this remains to be confirmed in controlled clinical studies

Friend engine framework:A real time neuro feedback client-server system for neuro imaging studies

In this methods article, we present a new implementation of a recently reported FSL-integrated neurofeedback tool, the standalone version of Functional Real-time Interactive Endogenous Modulation and Decoding (FRIEND). We will refer to this new implementation as the FRIEND Engine Framework. The framework comprises a client-server cross-platform solution for real time fMRI and fMRI/EEG neurofeedback studies, enabling flexible customization or integration of graphical interfaces, devices and data processing. This implementation allows a fast setup of novel plug-ins and frontends, which can be shared with the user community at large. The FRIEND Engine Framework is freely distributed for non-commercial, research purposes

Age-Dependent Relevance of Endogenous 5-Lipoxygenase Derivatives in Anxiety-Like Behavior in Mice

<div><p>When 5-lipoxygenase (5-LO) is inhibited, roughly half of the CNS effect of the prototypic endocannabinoid anandamide (AEA) is lost. Therefore, we decided to investigate whether inhibiting this enzyme would influence physiological functions classically described as being under control of the endocannabinoid system. Although 5-LO inhibition by MK-886 reduced lipoxin A₄ levels in the brain, no effect was found in the elevated plus maze (EPM), even at the highest possible doses, via i.p. (10 mg/kg,) or i.c.v. (500 pmol/2 µl) routes. Accordingly, no alterations in anxiety-like behavior in the EPM test were observed in 5-LO KO mice. Interestingly, aged mice, which show reduced circulating lipoxin A₄ levels, were sensitive to MK-886, displaying an anxiogenic-like state in response to treatment. Moreover, exogenous lipoxin A₄ induced an anxiolytic-like profile in the EPM test. Our findings are in line with other reports showing no difference between FLAP KO or 5-LO KO and their control strains in adult mice, but increased anxiety-like behavior in aged mice. We also show for the first time that lipoxin A₄ affects mouse behavior. In conclusion, we propose an age-dependent relevancy of endogenous 5-LO derivatives in the modulation of anxiety-like behavior, in addition to a potential for exogenous lipoxin A₄ in producing an anxiolytic-like state.</p></div

Anxiolytic-like effect of exogenous Lipoxin A₄ in the EPM test.

<p>After a single dose of Lipoxin A₄ (10 ug/kg, i.p.), adult Swiss mice showed a significant increase in (A) open arm time. No difference was observed in (B) entries in open arms, (C) time in closed arms or (D) entries in closed arms. Data are presented as mean ± SEM (n = 9). Statistical Analysis was performed by ANOVA followed by Newman-Keuls post hoc test. *p<0.05 vs vehicle.</p

MK-886 induced anxiogenic-like behavior in 12-month-old Swiss mice in the EPM test.

<p>After treatment with MK-886 (10 mg/kg, i.p.) aged mice displayed a tendency toward reduced (A) open arm time and a significant decrease in the number of (B) entries in open arms, while no changes were observed in (C) entries in closed arms (n = 4). (D) Twelve-month-old mice also show reduced lipoxin A₄ levels in plasma compared to 3-month-old mice (n = 12−15). Data are presented as mean ± SEM, statistical analysis was carried out by two-tailed Student’s t test. *p<0.05 vs vehicle. mo: months.</p

5-LO knockout mice exhibit unaltered anxiety-like behavior in the EPM test.

<p>No difference was observed between control and 5-LO knockout mice as to (A) open arm time, (B) open arm entries or (C) closed arm entries (n = 8−12). (D) 5-LO knockout mice show significantly reduced lipoxin A₄ in plasma (n = 8−10). Data are expressed as mean ± SEM and statistical analysis was performed by two-tailed or one-tailed Student’s t test, respectively. KO: knockout, 5-LO: 5-lipoxygenase enzyme.</p

Cellular prion protein (PrPC) modulates ethanol-induced behavioral adaptive changes in mice

Chronic consumption of drugs with addictive potential induces profound synaptic changes in the dopaminergic mesocorticolimbic pathway that underlie the long-term behavioral alterations seen in addicted subjects. Thus, exploring modulation systems of dopaminergic function may reveal novel targets to interfere with drug addiction. We recently showed that cellular prion protein (PrPC) affects the homeostasis of the dopaminergic system by interfering with dopamine synthesis, content, receptor density and signaling pathways in different brain areas. Here we report that the genetic deletion of PrPC modulates ethanol (EtOH)-induced behavioral alterations including the maintenance of drug seeking, voluntary consumption and the development of EtOH tolerance, all pivotal steps in drug addiction. Notably, these behavioral changes were accompanied by a significant depletion of dopamine levels in the prefrontal cortex and reduced dopamine D-1 receptors in PrPC knockout mice. Furthermore, the pharmacological blockade of dopamine D-1 receptors, but not D-2 receptors, attenuated the abnormal EtOH consumption in PrPC knockout mice. Altogether, these findings provide new evidence that the PrPC/dopamine interaction plays a pivotal role in EtOH addictive properties in mice. (C) 2014 Elsevier B.V. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Programa de Apoio aos Nucleos de Excelencia (PRONEX-NENASC Project)Fundacao de Apoio a Pesquisa do Estado de Santa Catarina (FAPESC)Fundacao para a Ciencia e Tecnologia (Portugal)Univ Fed Santa Catarina, Ctr Ciencias Biol, Dept Farmacol, Florianopolis, SC, BrazilUniv Coimbra, CNC Ctr Neurosci & Cell Biol, P-3000 Coimbra, PortugalUniv Fed Fluminense, Inst Biol, Dept Neurobiol, Niteroi, RJ, BrazilDOr Inst Res & Educ, Rio de Janeiro, BrazilUniversidade Federal de São Paulo, UNIFESP, Dept Psicobiol, São Paulo, BrazilUniv Fed Parana, UFPR, Dept Farmacol, BR-80060000 Curitiba, Parana, BrazilUniv Fed Santa Catarina, Univ Hosp, Ctr Neurociencias Aplicadas CeNAp, Florianopolis, SC, BrazilUniv Coimbra, FMUC Fac Med, P-3000 Coimbra, PortugalUniversidade Federal de São Paulo, UNIFESP, Dept Psicobiol, São Paulo, BrazilFundacao para a Ciencia e Tecnologia (Portugal): PTDC/SAU-NMC/114810/2009Web of Scienc