Interaction between Cannabinoid Compounds and Capsazepine in Protection against Acute Pentylenetetrazole-induced Seizure in Mice.

Posted on July 19, 2015 by David

“The pharmacological interaction between cannabinoidergic system and vanilloid type 1 (TRPV1) channels has been investigated in various conditions such as pain and anxiety.

In some brain structure including hippocampus, CB1 and TRPV1 receptors coexist and their activation produces opposite effect on excitability of neurons.

In this study, we tested the hypothesis that TRPV1 channel is involved in the modulation of cannabinoid effects on pentylenetetrazole (PTZ)-induced seizure threshold…

The anticonvulsant actions of both capsazepine and ACEA were attenuated after co-administration of these compounds. Moreover, the anticonvulsant action of capsazepine was attenuated after co-administration with VDM11.

The results suggest an interaction between cannabinoidergic system and TRPV1 receptors in protection against acute PTZ-induced seizure in mice.”

http://www.ncbi.nlm.nih.gov/pubmed/26185513

[Changes over time of cannabinoid receptor 1 in hippocampus of status epilepticus rats].

Posted on July 15, 2015 by David

To explore the changes over time of cannabinoid receptor 1 (CB1R) in hippocampus of status epilepticus (SE) rats…

There is a protective increase of CB1R in hippocampus of SE rats and then it returns to normal.

Thus CB1R may he involved in the occurrences and terminations of seizures.”

http://www.ncbi.nlm.nih.gov/pubmed/26168676

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

Cannabinoid and nitric oxide signalling interplay in the modulation of hippocampal hyperexcitability: study on electrophysiological and behavioural models of temporal lobe epilepsy in the rat.

Posted on July 3, 2015 by David

“A growing bulk of evidence suggests that cannabinoid system plays a pivotal role in the control of hyperexcitability phenomena.

Notwithstanding, the anticonvulsant action of cannabinoids has not been fully addressed, in particular the involvement of potential cellular neuromodulators, for instance nitric oxide.

In the current study, we focused on two distinct rat models of temporal lobe epilepsy, the Maximal Dentate Activation and the Pilocarpine-induced acute seizures, providing both electrophysiological and behavioural data on cannabinoid and nitrergic system interplay.

MDA study showed that these drugs protected animals in a dose-dependent manner from electrically-induced epileptiform discharges.

In the light of this, our findings suggest a putative antagonism between CBr-activated pathway and NO signalling in the context of neuronal hyperexcitability and contribute to elucidate possible synaptic processes underlying neuroprotective properties of cannabinoids, with a view to better integrate antiepileptic therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/26135674

Colocalization of cannabinoid receptor 1 with somatostatin and neuronal nitric oxide synthase in rat brain hippocampus.

Posted on June 28, 2015 by David

“Somatostatin (SST), a growth hormone inhibitory peptide, is expressed in different parts of the brain and functions as a neurotransmitter and neuromodulator. In the central nervous system (CNS), SST inhibits Ca2+ influx and regulates neuronal excitability in the hippocampus, the brain region which plays a major role in seizure, as well as cognitive and memory function.

Much like SST, cannabinoid receptor 1 (CB1 receptor) is also widely distributed in the CNS, associated with memory function ad exerts inhibitory effects on seizure.

It is unknown whether overlapping functional activities of SST and CB1 receptor are also associated with coexpression in the hippocampus.

In the present study, we determined the colocalization between SST and CB1 receptor in adult rat brain hippocampus. In the CNS, the majority of SST positive interneurons coexpress neuronal nitric oxide synthase (nNOS). Accordingly, colocalization studies were also performed to determine whether nNOS positive neurons display comparable colocalization with CB1 receptor.

The findings suggested that SST and nNOS are expressed in most interneurons whereas CB1 receptor is present in both interneurons and projection neurons in hippocampal regions. The distinct neuronal populations either expressing CB1 receptor, SST and nNOS alone or colocalization were observed in a region specific manner.

Taken together, the observations described here anticipate the possibility of crosstalk between somatostatin subtypes and CB1 receptor in regulation of physiological activities in the hippocampus.”

http://www.ncbi.nlm.nih.gov/pubmed/26115586

Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy.

Posted on June 27, 2015 by David

“Under an expanded access investigational new drug (IND) trial, cannabidiol (CBD) is being studied as a possible adjuvant treatment of refractory epilepsy in children.

Of the 25 subjects in the trial, 13 were being treated with clobazam (CLB). Because CLB and CBD are both metabolized in the cytochrome P450 (CYP) pathway, we predicted a drug-drug interaction, which we evaluate in this article…

Monitoring of CLB and nCLB levels is necessary for clinical care of patients concomitantly on CLB and CBD.

Nonetheless, CBD is a safe and effective treatment of refractory epilepsy in patients receiving CLB treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/26114620

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

Biomedical benefits of cannabinoids?

Posted on June 24, 2015 by David

“Cannabinoids appear to be of therapeutic value as antiemetics, antispasmodics, analgesics and appetite stimulants and may have potential uses in epilepsy, glaucoma and asthma.

This paper reviews the clinical trials which have been carried out with cannabinoids including Δ⁹-tetrahydrocannabinol (THC) and synthetic cannabinoids such as nabilone and levonantradol, and discusses the advantages and adverse effects of cannabinoids in clinical use.

The place of cannabinoids in modern medicine remains to be properly evaluated, but present evidence suggests that they could be valuable, particularly as adjuvants, for symptom control in a range of conditions for which standard drugs are not fully satisfactory.”

http://www.ncbi.nlm.nih.gov/pubmed/20575778

Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: A potential role for infantile spasms and Lennox-Gastaut syndrome.

Posted on May 6, 2015 by David

“There is a great need for safe and effective therapies for treatment of infantile spasms (IS) and Lennox-Gastaut syndrome (LGS). Based on anecdotal reports and limited experience in an open-label trial, cannabidiol (CBD) has received tremendous attention as a potential treatment for pediatric epilepsy, especially Dravet syndrome.

We sought to document the experiences of children with IS and/or LGS who have been treated with CBD-enriched cannabis preparations.

Perceived efficacy and tolerability were similar across etiologic subgroups.

Eighty-five percent of all parents reported a reduction in seizure frequency, and 14% reported complete seizure freedom.

Reported side effects were far less common during CBD exposure, with the exception of increased appetite (30%).

A high proportion of respondents reported improvement in sleep (53%), alertness (71%), and mood (63%) during CBD therapy… this study suggests a potential role for CBD in the treatment of refractory childhood epilepsy including IS and LGS…”

http://www.ncbi.nlm.nih.gov/pubmed/25935511

“Safety and side effects of cannabidiol, a Cannabis sativa constituent.” http://www.ncbi.nlm.nih.gov/pubmed/22129319

“Cannabidiol, a safe and non-psychotropic ingredient of the marijuana plant Cannabis sativa…” http://www.ncbi.nlm.nih.gov/pubmed/19690824

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

Long-term disease-modifying effect of the endocannabinoid agonist WIN55,212-2 in a rat model of audiogenic epilepsy.

Posted on May 3, 2015 by David

Modulation of the endocannabinoid (eCB) transmission is a promising approach to treating epilepsy.

Animal models can be used to investigate this approach. Krushinsky-Molodkina (KM) rats have, genetically, audiogenic epilepsy. Moreover, in these animals, repeated induction of audiogenic seizures results in a progressive prolongation of the seizures, known as audiogenic kindling.

Administration of the single dose of WIN55,212-2 one hour before the 4th seizure delayed the kindling process by two weeks, without any acute effect on the audiogenic seizures.

CONCLUSIONS:

This result suggests that short-term potentiation of the eCB system might modify the epileptogenic disease process in patients with a progressive course of epilepsy.”

http://www.ncbi.nlm.nih.gov/pubmed/25933961

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

Cannabidiol in medicine: a review of its therapeutic potential in CNS disorders.

Posted on April 27, 2015 by David

“Cannabidiol (CBD) is the main non-psychotropic component of the glandular hairs of Cannabis sativa.

It displays a plethora of actions including anticonvulsive, sedative, hypnotic, antipsychotic, antiinflammatory and neuroprotective properties.

However, it is well established that CBD produces its biological effects without exerting significant intrinsic activity upon cannabinoid receptors.

For this reason, CBD lacks the unwanted psychotropic effects characteristic of marijuana derivatives, so representing one of the bioactive constituents of Cannabis sativa with the highest potential for therapeutic use.

The present review reports the pharmacological profile of CBD and summarizes results from preclinical and clinical studies utilizing CBD, alone or in combination with other phytocannabinoids, for the treatment of a number of CNS disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/18844286