Cannabidivarin is anticonvulsant in mouse and rat in vitro and in seizure models

Summary Background and purpose: Phytocannabinoids in Cannabis sativa have diverse pharmacological targets extending beyond cannabinoid receptors and several exert notable anticonvulsant effects. For the first time, we investigated the anticonvulsant profile of the phytocannabinoid cannabidivarin (CBDV) in vitro and in in vivo seizure models. Experimental approach: The effect of CBDV (1-100μM) on epileptiform local field potentials (LFPs) induced in rat hippocampal brain slices by 4-AP application or Mg2+-free conditions was assessed by in vitro multi-electrode array recordings. Additionally, the anticonvulsant profile of CBDV (50-200 mg kg-1) in vivo was investigated in four rodent seizure models: maximal electroshock (mES) and audiogenic seizures in mice, and pentylenetetrazole (PTZ) and pilocarpine-induced seizures in rat. CBDV effects in combination with commonly-used antiepileptic drugs were investigated in rat seizures. Finally, the motor side effect profile of CBDV was investigated using static beam and gripstrength assays. Key results: CDBV significantly attenuated status epilepticus-like epileptiform LFPs induced by 4-AP and Mg2+-free conditions. CBDV had significant anticonvulsant effects in mES (≥100 mg kg-1), audiogenic (≥50 mg kg-1) and PTZ-induced seizures (≥100 mg kg-1). CBDV alone had no effect against pilocarpine-induced seizures, but significantly attenuated these seizures when administered with valproate or phenobarbital at 200 mg kg-1 CBDV. CBDV had no effect on motor function. Conclusions and Implications: These results indicate that CBDV is an effective anticonvulsant across a broad range of seizure models, does not significantly affect normal motor function and therefore merits further investigation in chronic epilepsy models to justify human trials

The effect of CBD(BDS) botanical cannabinoid extraction on MCF-7 human breast carcinoma cells.

The use of cannabinoids in cancer treatment has recently attracted attention (Alexander et al., 2009). A number of studies have shown that the apoptosis or reduced growth induced in tumour cells by cannabinoids involves an increase in the expression of CB2 receptors (Alexander et al., 2009; Pisanti et al., 2009). The aim of the present study was to investigate the potential anti-tumour activity of CBD (BDS), a botanical cannabinoid extract on breast tumour cells. MCF-7 cells (American Type Culture Collection) were grown and maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum at 37oC, 5% CO2 .The cells were plated in 96-well culture plates at a density of 1x104 cells/well and allowed to adhere at 37oC for 24 hours. The following day, various doses of extract in the absence and presence of AM251, SR144528 and capsazepine, were added to the cells and further incubated for 4 days. Then the supernatant was removed and MTT (3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) was added for 4 hours. The ability of cells to form formazan crystals by active mitochondrial respiration was determined by using a Microplate reader after dissolving the crystals in DMSO. Cytotoxicity was expressed as a relative percentage of the absorbance measured at 540 nm in the control and extract-treated cells. CBD (BDS) extract induced dose-dependent cytotoxic effects on MCF-7 cells with an IC50 of 0.046 mg/ml. Pre-treatment with AM251, SR144528 and Capsazepine, CB1, CB2 and TRPV1 receptor antagonists, respectively, did not reverse the cytotoxicity afforded by CBD (BDS). Single application of antagonists alone or vehicle did not affect the survival rate of the MCF7 cells. The data suggest the unlikely involvement of CB1, CB2 and TRPV1 receptors in mediating CBD (BDS)-induced apoptosis in MCF-7 tumour cells. Further experiments are required to investigate the receptor type/subtypes involvement and the mechanism of cell death

One Hundred Questions of Importance to the Conservation of Global Biological Diversity

We identified 100 scientific questions that, if answered, would have the greatest impact on conservation practice and policy. Representatives from 21 international organizations, regional sections and working groups of the Society for Conservation Biology, and 12 academics, from all continents except Antarctica, compiled 2291 questions of relevance to conservation of biological diversity worldwide. The questions were gathered from 761 individuals through workshops, email requests, and discussions. Voting by email to short-list questions, followed by a 2-day workshop, was used to derive the final list of 100 questions. Most of the final questions were derived through a process of modification and combination as the workshop progressed. The questions are divided into 12 sections: ecosystem functions and services, climate change, technological change, protected areas, ecosystem management and restoration, terrestrial ecosystems, marine ecosystems, freshwater ecosystems, species management, organizational systems and processes, societal context and change, and impacts of conservation interventions. We anticipate that these questions will help identify new directions for researchers and assist funders in directing funds