Cannabidiol as potential treatment in refractory pediatric epilepsy.

Posted on November 17, 2015 by David

“In recent years there has been great scientific and public interest focused on the therapeutic potential of compounds derived from cannabis for the treatment of refractory epilepsy in children.

From in vitro and in vivo studies on animal models, cannabidiol (CBD) appears to be a promising anticonvulsant drug with a favorable side-effect profile.

In humans, CBD efficacy and safety is not supported by well designed trials and its use has been described by anecdotal reports.

It will be necessary to investigate CBD safety, pharmacokinetics and interaction with other antiepileptic drugs alongside performing double-blinded placebo-controlled trials in order to obtain conclusive data on its efficacy and safety in children.”

http://www.ncbi.nlm.nih.gov/pubmed/26567560

http://www.thctotalhealthcare.com/category/epilepsy-2/

Cannabidiol-2′,6′-dimethyl ether stimulates body weight gain in apolipoprotein E-deficient BALB/c. KOR/Stm Slc-Apoe(shl) mice.

Posted on November 13, 2015 by David

“The biological activities of cannabidiol (CBD), a major non-psychotropic constituent of the fiber-type cannabis plant, have been examined in detail (e.g., CBD modulation of body weight in mice and rats).

However, few studies have investigated the biological activities of cannabidiol-2′,6′-dimethyl ether (CBDD), a dimethyl ether derivative of the parent CBD.

We herein focused on the effects of CBDD on body weight changes in mice, and demonstrated that it stimulated body weight gain in apolipoprotein E (ApoE)-deficient BALB/c. KOR/Stm Slc-Apoe(shl) mice, especially between 10 and 20 weeks of age.”

http://www.ncbi.nlm.nih.gov/pubmed/26558454

The neuroprotection of cannabidiol against MPP+-induced toxicity in PC12 cells involves trkA receptors, upregulation of axonal and synaptic proteins, neuritogenesis, and might be relevant to Parkinson’s disease.

Posted on November 12, 2015 by David

“Cannabidiol (CBD) is a non-psychoactive constituent of Cannabis sativa with potential to treat neurodegenerative diseases.

Its neuroprotection has been mainly associated with anti-inflammatory and antioxidant events; however, other mechanisms might be involved.

We investigated the involvement of neuritogenesis, NGF receptors (trkA), NGF, and neuronal proteins in the mechanism of neuroprotection of CBD against MPP+ toxicity in PC12 cells…

This is the first study to report the involvement of neuronal proteins and trkA in the neuroprotection of CBD.

Our findings suggest that CBD has a neurorestorative potential independent of NGF that might contribute to its neuroprotection against MPP+, a neurotoxin relevant to Parkinson’s disease.”

http://www.ncbi.nlm.nih.gov/pubmed/26556726

Anti-inflammatory effects of the cannabidiol derivative dimethylheptyl-cannabidiol – studies in BV-2 microglia and encephalitogenic T cells.

Posted on November 6, 2015 by David

“Dimethylheptyl-cannabidiol (DMH-CBD), a non-psychoactive, synthetic derivative of the phytocannabinoid cannabidiol (CBD), has been reported to be anti-inflammatory in RAW macrophages.

Here, we evaluated the effects of DMH-CBD at the transcriptional level in BV-2 microglial cells as well as on the proliferation of encephalitogenic T cells…

The results show that DMH-CBD has similar anti-inflammatory properties to those of CBD.

DMH-CBD downregulates the expression of inflammatory cytokines and protects the microglial cells by inducing an adaptive cellular response against inflammatory stimuli and oxidative injury.”

http://www.ncbi.nlm.nih.gov/pubmed/26540221

Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis.

Posted on November 1, 2015 by David

“Current arthritis treatments often have side-effects attributable to active compounds as well as route of administration.

Cannabidiol(CBD) attenuates inflammation and pain without side-effects…

These data indicate that topical CBD application has therapeutic potential for relief of arthritis pain-related behaviours and inflammation without evident side-effects.”

http://www.ncbi.nlm.nih.gov/pubmed/26517407

Inhibiting Heat Shock Proteins Can Potentiate the Cytotoxic Effect of Cannabidiol in Human Glioma Cells.

Posted on October 28, 2015 by David

“Cannabinoids possess a number of characteristics that make them putative anticancer drugs, and their value as such is currently being explored in a number of clinical studies.

To further understand the roles that cannabinoids may have, we performed gene expression profiling in glioma cell lines cultured with cannabidiol (CBD) and/or Δ9-tetrahydrocannabinol (THC), and pursued targets identified by this screening.

Results showed that a large number of genes belonging to the heat shock protein (HSP) super-family were up-regulated following treatment, specifically with CBD. Increases were observed both at the gene and protein levels and arose as a consequence of increased generation of ROS by CBD, and correlated with an increase in a number of HSP client proteins. Furthermore, increases impeded the cytotoxic effect of CBD; an effect that was improved by co-culture with pharmacalogical inhibitors of HSPs. Similarly, culturing glioma cells with CBD and HSP inhibitors increased radiosensitivity when compared to CBD-alone.

Taken together, these data indicate that the cytotoxic effects of CBD can be diminished by HSPs that indirectly rise as a result of CBD use, and that the inclusion of HSP inhibitors in CBD treatment regimens can enhance the overall effect.”

http://www.ncbi.nlm.nih.gov/pubmed/26504004

Cannabidiol protects an in vitro model of the blood brain barrier (BBB) from oxygen-glucose deprivation via PPARγ and 5-HT1A.

Posted on October 27, 2015 by David

“In vivo and in vitro studies have demonstrated a protective effect of cannabidiol (CBD) in reducing infarct size in stroke models, and against epithelial barrier damage in numerous disease models.

We aimed to investigate whether CBD also affects blood-brain barrier (BBB) permeability following ischaemia.

These data suggest that activity at the BBB could represent an as yet unrecognised mechanism of CBD-induced neuroprotection in ischaemic stroke, mediated by PPARγ and 5-HT1A .”

http://www.ncbi.nlm.nih.gov/pubmed/26497782

Addressing the stimulant treatment gap: A call to investigate the therapeutic benefits potential of cannabinoids for crack-cocaine use.

Posted on October 27, 2015 by David

“Crack-cocaine use is prevalent in numerous countries, yet concentrated primarily – largely within urban contexts – in the Northern and Southern regions of the Americas. It is associated with a variety of behavioral, physical and mental health and social problems which gravely affect users and their environments. Few evidence-based treatments for crack-cocaine use exist and are available to users in the reality of street drug use. Numerous pharmacological treatments have been investigated but with largely disappointing results.

An important therapeutic potential for crack-cocaine use may rest in cannabinoids, which have recently seen a general resurgence for varied possible therapeutic usages for different neurological diseases.

Distinct potential therapeutic benefits for crack-cocaine use and common related adverse symptoms may come specifically from cannabidiol (CBD) – one of the numerous cannabinoid components found in cannabis – with its demonstrated anxiolytic, anti-psychotic, anti-convulsant effects and potential benefits for sleep and appetite problems.

The possible therapeutic prospects of cannabinoids are corroborated by observational studies from different contexts documenting crack-cocaine users’ ‘self-medication’ efforts towards coping with crack-cocaine-related problems, including withdrawal and craving, impulsivity and paranoia.

Cannabinoid therapeutics offer further benefits of being available in multiple formulations, are low in adverse risk potential, and may easily be offered in community-based settings which may add to their feasibility as interventions for – predominantly marginalized – crack-cocaine user populations.

Supported by the dearth of current therapeutic options for crack-cocaine use, we are advocating for the implementation of a rigorous research program investigating the potential therapeutic benefits of cannabinoids for crack-cocaine use.

Given the high prevalence of this grave substance use problem in the Americas, opportunities for such research should urgently be created and facilitated there.”

http://www.ncbi.nlm.nih.gov/pubmed/26500166

http://www.thctotalhealthcare.com/category/addiction/

A new formulation of cannabidiol in cream shows therapeutic effects in a mouse model of experimental autoimmune encephalomyelitis.

Posted on October 23, 2015 by David

“The present study was designed to investigate the efficacy of a new formulation of alone, purified cannabidiol (CBD) (>98 %), the main non-psychotropic cannabinoid of Cannabis sativa, as a topical treatment in an experimental model of autoimmune encephalomyelitis (EAE), the most commonly used model for multiple sclerosis (MS)…

All these data suggest an interesting new profile of CBD that could lead to its introduction in the clinical management of MS and its associated symptoms at least in association with current conventional therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/26489494

“Summarizing, we have shown that the topical administration of CBD can protect against the cascade of events (inflammation, oxidative injury and neuronal cell death) associated to the induction of EAE. Of note, topical CBD application was able to recover the hind limb lost sensitivity. This observation provides a rationale for evaluating its clinical translation that might represent a new concept in the management of MS. Finally, we suggest that CBD, devoid of psychoactive activity, could be potentially, safe and effective non invasive alternatives for alleviating neuroinflammation and neurodegeneration.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618347/

GPR55 promotes migration and adhesion of colon cancer cells indicating a role in metastasis.

Posted on October 7, 2015 by David

“Tumor cell migration and adhesion constitute essential features of metastasis. G protein-coupled receptor 55 (GPR55), a lysophospholipid receptor, has been shown to play an important role in carcinogenesis. Here, we investigated the involvement of GPR55 in migration and metastasis of colon cancer cells.

GPR55 antagonist CID16020046, cannabidiol, a putative GPR55 antagonist, and GPR55 siRNA were used to block GPR55 activity in HCT116 colon cancer cells.

In a mouse model of metastasis, the arrest of HCT116 cancer cells in the liver was reduced after treatment with CID16020046 or cannabidiol.

CONCLUSIONS AND IMPLICATIONS:

GPR55 is involved in the migratory behavior of colon carcinoma cells and may serve as a pharmacological target for the prevention of metastasis.”

http://www.ncbi.nlm.nih.gov/pubmed/26436760

“Pharmacological Characterization of GPR55, A Putative Cannabinoid Receptor” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874616/