Cannabinoids and Epilepsy.

Posted on August 19, 2015 by David

“Cannabis has been used for centuries to treat seizures.

Recent anecdotal reports, accumulating animal model data, and mechanistic insights have raised interest in cannabis-based antiepileptic therapies.

In this study, we review current understanding of the endocannabinoid system, characterize the pro- and anticonvulsive effects of cannabinoids [e.g., Δ9-tetrahydrocannabinol and cannabidiol (CBD)], and highlight scientific evidence from pre-clinical and clinical trials of cannabinoids in epilepsy.

These studies suggest that CBD avoids the psychoactive effects of the endocannabinoid system to provide a well-tolerated, promising therapeutic for the treatment of seizures, while whole-plant cannabis can both contribute to and reduce seizures.

Finally, we discuss results from a new multicenter, open-label study using CBD in a population with treatment-resistant epilepsy. In all, we seek to evaluate our current understanding of cannabinoids in epilepsy and guide future basic science and clinical studies.”

http://www.ncbi.nlm.nih.gov/pubmed/26282273

Cannabinoids: is there a potential treatment role in epilepsy?

Posted on August 4, 2015 by David

“Cannabinoids have been used medicinally for centuries, and in the last decade, attention has focused on their broad therapeutic potential particularly in seizure management.

While some cannabinoids have demonstrated anticonvulsant activity in experimental studies, their efficacy for managing clinical seizures has not been fully established.

This commentary will touch on our understanding of the brain endocannabinoid system’s regulation of synaptic transmission in both physiological and pathophysiological conditions, and review the findings from both experimental and clinical studies on the effectiveness of cannabinoids to suppress epileptic seizures.

At present, there is preliminary evidence that non-psychoactive cannabinoids may be useful as anticonvulsants, but additional clinical trials are needed to fully evaluate the efficacy and safety of these compounds for the treatment of epilepsy.”

http://www.ncbi.nlm.nih.gov/pubmed/26234319

ACEA (a highly selective cannabinoid CB1 receptor agonist) stimulates hippocampal neurogenesis in mice treated with antiepileptic drugs.

Posted on August 1, 2015 by David

“Hippocampal neurogenesis plays a very important role in learning and memory functions.

In a search for best neurological drugs that protect neuronal cells and stimulate neurogenesis with no side effects, cannabinoids proved to be a strong group of substances having many beneficial properties.

The aim of this study was to evaluate the impact of ACEA (arachidonyl-2′-chloroethylamide – a highly selective cannabinoid CB1 receptor agonist) combined with a classical antiepileptic drug sodium valproate (VPA) on neural precursor cells’ proliferation and differentiation in the mouse brain.

VPA administered alone decreased the number of newly born neurons with no significant impact on neurogenesis.

These data provide substantial evidence that VPA administered chronically slightly decreases the proliferation and differentiation of newly born cells while combination of VPA+ACEA significantly increases the level of newborn neurons in the dentate subgranular zone.”

http://www.ncbi.nlm.nih.gov/pubmed/26225920

Therapeutic potential of cannabis-related drugs.

Posted on July 29, 2015 by David

“In this review, I will consider the dual nature of Cannabis and cannabinoids.

The duality arises from the potential and actuality of cannabinoids in the laboratory and clinic and the ‘abuse’ of Cannabis outside the clinic.

The therapeutic areas currently best associated with exploitation of Cannabis-related medicines include pain, epilepsy, feeding disorders, multiple sclerosis and glaucoma.

As with every other medicinal drug of course, the ‘trick’ will be to maximise the benefit and minimise the cost.

After millennia of proximity and exploitation of the Cannabis plant, we are still playing catch up with an understanding of its potential influence for medicinal benefit.”

http://www.ncbi.nlm.nih.gov/pubmed/26216862

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