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

“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.

“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?

“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.”

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

“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.

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.

“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

Medicinal Marijuana May Help Cure Children With Severe Epilepsy

A marijuana plant

“Recent research found that a liquid form of therapeutic marijuana can provide cure to children with treatment-resistant epilepsy.

The said study will be presented at the American Academy of Neurology’s 67th Annual Meeting in Washington, DC in late April.”

http://au.ibtimes.com/medicinal-marijuana-may-help-cure-children-severe-epilepsy-1440398

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

Weeding out bad waves: towards selective cannabinoid circuit control in epilepsy.

“Endocannabinoids are lipid-derived messengers, and both their synthesis and breakdown are under tight spatiotemporal regulation. As retrograde signalling molecules, endocannabinoids are synthesized postsynaptically but activate presynaptic cannabinoid receptor 1 (CB1) receptors to inhibit neurotransmitter release. In turn, CB1-expressing inhibitory and excitatory synapses act as strategically placed control points for activity-dependent regulation of dynamically changing normal and pathological oscillatory network activity. Here, we highlight emerging principles of cannabinoid circuit control and plasticity, and discuss their relevance for epilepsy and related comorbidities. New insights into cannabinoid signalling may facilitate the translation of the recent interest in cannabis-related substances as antiseizure medications to evidence-based treatment strategies.”

http://www.ncbi.nlm.nih.gov/pubmed/25891509

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

Pure cannabidiol in the treatment of malignant migrating partial seizures in infancy: a case report.

“Malignant migrating partial seizures in infancy is a devastating pharmacoresistent epileptic encephalopathy of unknown etiology characterized by onset in the first 6 months of life, continuous migrating focal seizures with corresponding multifocal electroencephalographic discharges, developmental deterioration, and early mortality.

Recent widespread interest in the nonpsychoactive component of the cannabis plant, cannabidiol, as a potential treatment for refractory devastating epilepsies has led to individual trials initiated by families or physicians in states that have legalized medical marijuana with anecdotal success.

We describe a now 10-month-old boy with malignant migrating partial seizures in infancy who made developmental gains and demonstrated sustained seizure reduction with the addition of cannabidiol to his antiepileptic regimen.

This report supports a role for cannabidiol in the treatment of malignant migrating partial seizures in infancy.”

http://www.ncbi.nlm.nih.gov/pubmed/25882081

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

The role of cannabinoids and leptin in neurological diseases.

“Cannabinoids exert a neuroprotective influence on some neurological diseases, including Alzheimer’s, Parkinson’s, Huntington’s, multiple sclerosis and epilepsy.

Synthetic cannabinoid receptor agonists/antagonists or compounds can provide symptom relief or control the progression of neurological diseases. However, the molecular mechanism and the effectiveness of these agents in controlling the progression of most of these diseases remain unclear.

Cannabinoids may exert effects via a number of mechanisms and interactions with neurotransmitters, neurotropic factors and neuropeptides.

Leptin is a peptide hormone involved in the regulation of food intake and energy balance via its actions on specific hypothalamic nuclei. Leptin receptors are widely expressed throughout the brain, especially in the hippocampus, basal ganglia, cortex and cerebellum. Leptin has also shown neuroprotective properties in a number of neurological disorders, such as Parkinson’s and Alzheimer’s.

Therefore, cannabinoid and leptin hold therapeutic potential for neurological diseases.

Further elucidation of the molecular mechanisms underlying the effects on these agents may lead to the development of new therapeutic strategies for the treatment of neurological disorders.”