Fatty acids, endocannabinoids and inflammation.

“From their phylogenetic and pharmacological classification it might be inferred that cannabinoid receptors and their endogenous ligands constitute a rather specialised and biologically distinct signalling system.

However, the opposite is true and accumulating data underline how much the endocannabinoid system is intertwined with other lipid and non-lipid signalling systems.

Endocannabinoids per se have many structural congeners, and these molecules exist in dynamic equilibria with different other lipid-derived mediators, including eicosanoids and prostamides.

With multiple crossroads and shared targets, this creates a versatile system involved in fine-tuning different physiological and metabolic processes, including inflammation.

A key feature of this ‘expanded’ endocannabinoid system, or ‘endocannabinoidome’, is its subtle orchestration based on interactions between a relatively small number of receptors and multiple ligands with different but partly overlapping activities.

Following an update on the role of the ‘endocannabinoidome’ in inflammatory processes, this review continues with possible targets for intervention at the level of receptors or enzymes involved in formation or breakdown of endocannabinoids and their congeners.

Although its pleiotropic character poses scientific challenges, the ‘expanded’ endocannabinoid system offers several opportunities for prevention and therapy of chronic diseases.

In this respect, successes are more likely to come from ‘multiple-target’ than from ‘single-target’ strategies.”

http://www.ncbi.nlm.nih.gov/pubmed/26325095

Medical Marijuana: Reducing Spasticity in Multiple Sclerosis Patients

 

“Medical marijuana is a justifiable treatment for spasticity in patients with MS.

Interviews indicate that many patients choose marijuana over other medicines because they experience minimal side effects and rapid improvements in motor functioning…

Compared to the steroids, tranquilizers, and sedatives usually prescribed for MS patients, marijuana is remarkably safe and benign…

There is a lack of evidence for long-term risks associated with marijuana use. The short-term risks are minimal and short-lived.

Studies verify the positive relationship between medical marijuana use and reduced spasticity.

Voters are realizing the cruelty associated with robbing a terminally or chronically ill patient from the medicine that most relieves their pain.

MS is a chronic disease that can lead to severe pain and disability if untreated. For these reasons, medical marijuana should be available to patients who understand the risks associated with its use.

Until medical research develops an equally effective oral drug, marijuana will remain a reasonable option for patients suffering from MS.”

http://www.vanderbilt.edu/AnS/psychology/health_psychology/medicalmarijuana.htm

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

Increasing levels of the endocannabinoid 2-AG is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease.

“Parkinson’s disease (PD) is a common chronic neurodegenerative disorder, usually of idiopathic origin. Symptoms including tremor, bradykinesia, rigidity and postural instability are caused by the progressive loss of dopaminergic neurons in the nigrostriatal region of the brain.

Symptomatic therapies are available but no treatment slows or prevents the loss of neurons.

Neuroinflammation has been implicated in its pathogenesis.

To this end, the present study utilises the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin to reproduce the pattern of cell death evident in PD patients.

Herein, the role of a potential regulator of an immune response, the endocannabinoid system (ECS), is investigated.

The most prevalent endocannabinoid, 2-arachidonoylglycerol (2-AG) (3 and 5mg/kg), was added exogenously and its enzymatic degradation inhibited to provide protection against MPTP-induced cell death.

Furthermore, the addition of DFU (25mg/kg), a selective inhibitor of inflammatory mediator cyclooxygenase-2 (COX-2), potentiated these effects.

Levels of 2-AG were shown to be upregulated in a time- and region-specific manner following MPTP administration, indicating that the ECS represents a natural defence mechanism against inflammation, potentiation of which could provide therapeutic benefits.

The results expand the current understanding of the role that this signalling system has and its potential influence in PD.”

Age-related changes in the endocannabinoid system in the mouse hippocampus.

“Previous studies have demonstrated that the endocannabinoid system significantly influences the progression of brain ageing, and the hippocampus is one of the brain regions most vulnerable to ageing and neurodegeneration.

We have further examined age-related changes in the hippocampalendocannabinoid system by measuring the levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in young and old mice from two different mouse strains.

We found a decrease in 2-AG but not AEA levels in aged mice.

In order to identify the cause for 2-AG level changes, we investigated the levels of several enzymes that contribute to synthesis and degradation of 2-AG in the hippocampus.

We found a selective decrease in DAGLα mRNA and protein levels as well as an elevated MAGL activity during ageing.

We hypothesize that the observed decrease of 2-AG levels is probably caused by changes in DAGLα expression and MAGL activity.

This finding can contribute to the existing knowledge about the processes underlying selective vulnerability of the hippocampus to ageing and age-related neurodegeneration.”

http://www.ncbi.nlm.nih.gov/pubmed/26278494

Effect of anandamide on endometrial adenocarcinoma (Ishikawa) cell numbers: implications for endometrial cancer therapy.

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“We have previously shown that patients with endometrial carcinoma express elevated concentrations of the endocannabinoid, anandamide (AEA), in both their plasma and their endometrial tissue and that the endometrial carcinoma cell line, Ishikawa, contains the receptors to which AEA binds.

Several studies have reported that human and rodent cancer cell lines die in response to high AEA concentrations.

The incidence of endometrial carcinoma continues to escalate and, although surgical treatment has improved, morbidity and mortality rates have not. A move towards a novel non-surgical therapeutic option is thus required, and the endocannabinoid system provides a good candidate target.

We aimed to investigate the effects of AEA on the survival and proliferation of an endometrial carcinoma cell model.

Our results show that AEA induces a decrease in Ishikawa cell number probably through inhibition of cell proliferation rather than cell death.

These data suggest that the increased plasma and tissue AEA concentrations observed in patients with endometrial cancer is a counter mechanism against further cancer growth and points to the endocannabinoid system as a potentially new therapeutic target.”

http://www.ncbi.nlm.nih.gov/pubmed/26312842

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60335-X/fulltext

Cannabinoids and Schizophrenia: Risks and Therapeutic Potential.

“The endocannabinoid system has been implicated in psychosis both related and unrelated to cannabis exposure, and studying this system holds potential to increase understanding of the pathophysiology of schizophrenia.

Anandamide signaling in the central nervous system may be particularly important.

Δ9-Tetrahydrocannabinol in cannabis can cause symptoms of schizophrenia when acutely administered, and cannabidiol (CBD), another compound in cannabis, can counter many of these effects.

CBD may have therapeutic potential for the treatment of psychosis following cannabis use, as well as schizophrenia, possibly with better tolerability than current antipsychotic treatments. CBD may also have anti-inflammatory and neuroprotective properties.

Establishing the role of CBD and other CBD-based compounds in treating psychotic disorders will require further human research.”

http://www.ncbi.nlm.nih.gov/pubmed/26311150

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

High dosage of cannabidiol (CBD) alleviates pentylenetetrazole-induced epilepsy in rats by exerting an anticonvulsive effect.

“The study was designed to investigate the effect of various concentrations of cannabidiol (CBD) in rats with chronic epilepsy.

The results revealed a significant decrease in the daily average grade of epileptic seizures on treatment with CBD (50 mg/kg).

The neuronal loss and astrocyte hyperplasia in the hippocampal area were also decreased.

CBD treatment did not affect the expression of iNOS in the hippocampus; however, the expression of NR1 was decreased significantly.

Thus, CBD administration inhibited the effect of pentylenetetrazole in rats, decreased the astrocytic hyperplasia, decreased neuronal damage in the hippocampus caused by seizures and selectively reduced the expression of the NR1 subunit of NMDA.

Therefore, CBD exhibits an anticonvulsive effect in the rats with chronic epilepsy.”

http://www.ncbi.nlm.nih.gov/pubmed/26309534

“Epilepsy is one of the most common diseases of the brain, affecting at least 50 million people globally… Despite development of a number of new antiepileptic drugs, epilepsy could not be significantly reduced and is a challenge to the clinicians… Many plants, known for their anticonvulsant activity are subjected to phytochemical and pharmacological studies. Cannabidiol (CBD) a constituent of the hemp seed exhibits potent anticonvulsant activity…  The CBD possess anticonvulsive, anti-epileptic, and antimicrobial properties… The present study was performed to examine the anticonvulsive effects of CBD in pentylenetetrazole-induced chronic epilepsy rat models… The present study demonstrates that CBD protects against pentylenetetrazole-induced chronic seizures, decreases astrocytic hyperplasia, decreases neuronal cell loss and selectively suppresses NMDA1 receptor in the hippocampus… Therefore, CBD exhibits an anticonvulsive effect in the rats with chronic epilepsy.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537971/

The Genetic Structure of Marijuana and Hemp.

“Despite its cultivation as a source of food, fibre and medicine, and its global status as the most used illicit drug, the genus Cannabis has an inconclusive taxonomic organization and evolutionary history.

Drug types of Cannabis (marijuana), which contain high amounts of the psychoactivecannabinoid Δ9-tetrahydrocannabinol (THC), are used for medical purposes and as a recreational drug.

Hemp types are grown for the production of seed and fibre, and contain low amounts of THC.

Two species or gene pools (C. sativa and C. indica) are widely used in describing the pedigree or appearance of cultivated Cannabis plants.

Using 14,031 single-nucleotide polymorphisms (SNPs) genotyped in 81 marijuana and 43 hemp samples, we show that marijuana and hemp are significantly differentiated at a genome-wide level, demonstrating that the distinction between these populations is not limited to genes underlying THC production.

We find a moderate correlation between the genetic structure of marijuana strains and their reported C. sativa and C. indica ancestry and show that marijuana strain names often do not reflect a meaningful genetic identity.

We also provide evidence that hemp is genetically more similar to C. indica type marijuana than to C. sativa strains.”

http://www.ncbi.nlm.nih.gov/pubmed/26308334

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0133292

Pregnenolone can protect the brain from cannabis intoxication.

“Pregnenolone is considered the inactive precursor of all steroid hormones, and its potential functional effects have been largely uninvestigated.

The administration of the main active principle of Cannabis sativa (marijuana), Δ(9)-tetrahydrocannabinol (THC), substantially increases the synthesis of pregnenolone in the brain via activation of the type-1 cannabinoid (CB1) receptor.

Pregnenolone then, acting as a signaling-specific inhibitor of the CB1 receptor, reduces several effects of THC.

This negative feedback mediated by pregnenolone reveals a previously unknown paracrine/autocrine loop protecting the brain from CB1 receptor overactivation that could open an unforeseen approach for the treatment of cannabis intoxication and addiction.

These data indicate that THC increases pregnenolone through activation of the CB1 receptor…

In conclusion, this new understanding of the role of pregnenolone has the potential to generate new therapies for cannabis dependence.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057431/

Marijuana Use in Epilepsy: The Myth and the Reality.

“Marijuana has been utilized as a medicinal plant to treat a variety of conditions for nearly five millennia.

Over the past few years, there has been an unprecedented interest in using cannabis extracts to treat epilepsy, spurred on by a few refractory pediatric cases featured in the media that had an almost miraculous response to cannabidiol-enriched marijuana extracts.

This review attempts to answer the most important questions a clinician may have regarding the use of marijuana in epilepsy. First, we review the preclinical and human evidences for the anticonvulsant properties of the different cannabinoids, mainly tetrahydrocannabinol (THC) and cannabidiol (CBD).

Then, we explore the safety data from animal and human studies. Lastly, we attempt to reconcile the controversy regarding physicians’ and patients’ opinions about whether the available evidence is sufficient to recommend the use of marijuana to treat epilepsy.”

http://www.ncbi.nlm.nih.gov/pubmed/26299273

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