Reversal effect of simvastatin on the decrease in cannabinoid receptor 1 density in 6-hydroxydopamine lesioned rat brains.

“Cannabinoid 1(CB1) receptors are closely correlated to the dopaminergic system and involved in cognitive function. Since statins have been used to regulate the progression of Parkinson’s disease (PD) via its anti-inflammation and neuroprotective effects, we asked if statins affect the CB1 receptors in the 6-hydroxydopamine (6-OHDA) lesioned rat.

Our data suggest a critical role of CB1 receptors in treating PD with simvastatin, and implicate CB1 receptors as a potential therapeutic target in the treatment of PD.”

http://www.ncbi.nlm.nih.gov/pubmed/27155397

Cannabinoid receptor genes.

“Cannabinoids are the constituents of the marijuana plant (cannabis sativa) of which the major active ingredient is delta-9-tetrahydrocannabinol (delta 9-THC). Rapid progress has been achieved in marijuana research in the last five years than in the thousands of years that marijuana has been used in human history.

For many decades therefore, research on the molecular and neurobiological bases of the physiological and neurobehavioral effects of marijuana was hampered by the lack of specific research tools and technology. The situation has started to change with the availability of molecular probes and other recombinant molecules that have led to major advances.

Recent advances include the cloning of the cDNA sequences encoding the rat, human and the mouse peripheral and CNS cannabinoid receptors. In addition a putative ligand, anandamide, thought to represent the endogenous cannabis-like substance that binds the cannabinoid receptors, has been isolated from the brain.

This achievement has opened a whole new neurochemical system particularly as the physiological and pharmacological properties of anandamide indicate a possible neuromodulatory or neurotransmitter role.

The recent demonstration of a potent and selective antagonist for CBl receptors may become an important and powerful investigative tool. Future progress on the neurobiology of cannabinoid research may include data on the use of antisense strategies and gene targeting approach to further understand the mechanism(s) of action of cannabinoids which has been slow to emerge.

We conclude that these are exciting times for cannabis research which has given us anandamide–a substance of inner bliss.”

http://www.ncbi.nlm.nih.gov/pubmed/8804112

The in vitro GcMAF effects on endocannabinoid system transcriptionomics, receptor formation, and cell activity of autism-derived macrophages

Logo of jneuro

“Immune system dysregulation is well-recognized in autism and thought to be part of the etiology of this disorder.

The endocannabinoid system is a key regulator of the immune system via the cannabinoid receptor type 2 (CB2R) which is highly expressed on macrophages and microglial cells.

The use of the Gc protein-derived Macrophage Activating Factor (GcMAF), an endogenous glycosylated vitamin D binding protein responsible for macrophage cell activation has demonstrated positive effects in the treatment of autistic children.

In this current study, we investigated the in vitro effects of GcMAF treatment on the endocannabinoid system gene expression, as well as cellular activation in blood monocyte-derived macrophages (BMDMs) from autistic patients compared to age-matched healthy developing controls.

This study presents the first observations of GcMAF effects on the transcriptionomics of the endocannabinoid system and expression of CB2R protein. These data point to a potential nexus between endocannabinoids, vitamin D and its transporter proteins, and the immune dysregulations observed with autism.

This study demonstrates a biomolecular effect of GcMAF in BMDMs from autistic patients, providing further evidence for a positive use of this molecule in autism treatment. It also seems likely that the CB2R is a potential therapeutic target for Autism and autism spectrum disorders (ASDs) interventions.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996516/

Cannabidiol Counteracts Amphetamine-Induced Neuronal and Behavioral Sensitization of the Mesolimbic Dopamine Pathway through a Novel mTOR/p70S6 Kinase Signaling Pathway.

“Schizophrenia-related psychosis is associated with disturbances in mesolimbic dopamine (DA) transmission, characterized by hyperdopaminergic activity in the mesolimbic pathway. Currently, the only clinically effective treatment for schizophrenia involves the use of antipsychotic medications that block DA receptor transmission. However, these medications produce serious side effects leading to poor compliance and treatment outcomes.

Emerging evidence points to the involvement of a specific phytochemical component of marijuana called cannabidiol (CBD), which possesses promising therapeutic properties for the treatment of schizophrenia-related psychoses.

Our findings demonstrate a novel mechanism for the putative antipsychotic-like properties of CBD in the mesolimbic circuitry. We identify the molecular signaling pathways through which CBD may functionally reduce schizophrenia-like neuropsychopathology.

SIGNIFICANCE STATEMENT:

The cannabis-derived phytochemical, cannabidiol (CBD), has been shown to have pharmacotherapeutic efficacy for the treatment of schizophrenia.

However, the mechanisms by which CBD may produce antipsychotic effects are entirely unknown. Using preclinical behavioral procedures combined with molecular analyses and in vivo neuronal electrophysiology, our findings identify a functional role for the nucleus accumbens as a critical brain region whereby CBD can produce effects similar to antipsychotic medications by triggering molecular signaling pathways associated with the effects of classic antipsychotic medications.

Specifically, we report that CBD can attenuate both behavioral and dopaminergic neuronal correlates of mesolimbic dopaminergic sensitization, via a direct interaction with mTOR/p70S6 kinase signaling within the mesolimbic pathway.”

http://www.ncbi.nlm.nih.gov/pubmed/27147666

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

The Influence of Biomechanical Properties and Cannabinoids on Tumor Invasion.

Image result for Cell Adhesion & Migration journal

“Cannabinoids are known to have an anti-tumorous effect, but the underlying mechanisms are only sparsely understood. Mechanical characteristics of tumor cells represent a promising marker to distinguish between tumor cells and the healthy tissue.

We tested the hypothesis whether cannabinoids influence the tumor cell specific mechanical and migratory properties and if these factors are a prognostic marker for the invasiveness of tumor cells.

Here we could show that a “generalized stiffness” is a profound marker for the invasiveness of a tumor cell population in our model and thus might be of high clinical relevance for drug testing.

Additionally cannabinoids were shown to be of potential use for therapeutic approaches of glioblastoma.”

http://www.ncbi.nlm.nih.gov/pubmed/27149140

“Glioblastomas (GBM) are tumors that arise from astrocytes—the star-shaped cells that make up the “glue-like,” or supportive tissue of the brain. These tumors are usually highly malignant (cancerous) because the cells reproduce quickly and they are supported by a large network of blood vessels. Glioblastomas are generally found in the cerebral hemispheres of the brain, but can be found anywhere in the brain or spinal cord.”  http://www.abta.org/brain-tumor-information/types-of-tumors/glioblastoma.html?referrer=https://www.google.com/

Marihuana as Medicine

“BETWEEN 1840 and 1900, European and American medical journals published more than 100 articles on the therapeutic use of the drug known then as Cannabis indica (or Indian hemp) and now as marihuana.

It was recommended as an appetite stimulant, muscle relaxant, analgesic, hypnotic, and anticonvulsant. As late as 1913 Sir William Osler recommended it as the most satisfactory remedy for migraine.

Today the 5000-year medical history of cannabis has been almost forgotten.

Its use declined in the early 20th century because the potency of preparations was variable, responses to oral ingestion were erratic, and alternatives became available—injectable opiates and, later, synthetic drugs such as aspirin and barbiturates.

In the United States, the final blow was struck by the Marihuana Tax Act of 1937. Designed to prevent nonmedical use, this law made cannabis so difficult to obtain for medical purposes that it was removed from the pharmacopeia.”

http://jama.jamanetwork.com/article.aspx?articleid=388943#Abstract

The use of cannabis as a mood stabilizer in bipolar disorder: anecdotal evidence and the need for clinical research.

“The authors present case histories indicating that a number of patients find cannabis (marihuana) useful in the treatment of their bipolar disorder.

Some used it to treat mania, depression, or both. They stated that it was more effective than conventional drugs, or helped relieve the side effects of those drugs.

One woman found that cannabis curbed her manic rages; she and her husband have worked to make it legally available as a medicine. Others described the use of cannabis as a supplement to lithium (allowing reduced consumption) or for relief of lithium’s side effects.

Another case illustrates the fact that medical cannabis users are in danger of arrest, especially when children are encouraged to inform on parents by some drug prevention programs.

An analogy is drawn between the status of cannabis today and that of lithium in the early 1950s, when its effect on mania had been discovered but there were no controlled studies.

In the case of cannabis, the law has made such studies almost impossible, and the only available evidence is anecdotal. The potential for cannabis as a treatment for bipolar disorder unfortunately can not be fully explored in the present social circumstances.”

http://www.ncbi.nlm.nih.gov/pubmed/9692379

[Study on the extraction process for cannabinoids in hemp seed oil by orthogonal design].

“OBJECTIVE: To select the optimum extracting procedure for cannabinoids from hemp seed oil.

METHODS: The optimum extracting procedure was selected with the content of cannabinol and delta9-tetrehydrocannabinol from hemp seed oil by orthogonal test design. We have examined three factors that may influence the extraction rate: the time of extraction, the times of extraction and the amount of methanol.

RESULTS: The optimum extraction condition was adding 5 ml, two times amount of methanol into hemp seed oil for 15 min.

CONCLUSION: The above extraction process gave the most rational, stable, feasible and satisfactory results. The method is convenient.”

http://www.ncbi.nlm.nih.gov/pubmed/16131037

Stimulated CB1 Cannabinoid Receptor Inducing Ischemic Tolerance and Protecting Neuron from Cerebral Ischemia.

“Anandamide system is mainly made up of cannabinoid receptors, their endogenous ligands and some related enzymes. Activation of the system mediates various molecular events, thereafter leading to vasodilation, bradycardia and anti-inflammation.

The stimulated cannabinoid receptors may take part in protection of endothelial cells from injury and therefore can be potential targets in therapy for some diseases, especially cardio or cerebral vascular disturbances.

Cerebral ischemia is a deadly disease that modern people have to face and will probably face for a long period of time. Ischemic tolerance has the protective effect of brain as an endogenous event in cerebral ischemia, in which variety of inducers such as transient cerebral ischemia, hypoxia, hypothermia and drug agents are involved.

Most of cannabinoid 1 receptors (CB1Rs), a member in G protein-coupled receptor family, exist in central nervous systems.

Mechanism of neuroprotection mediated by the receptor is considered through facilitating neurotransmitter release and regulating other molecular events. In this review, advance of the neuroprotection against cerebral ischemia and the mechanism of the action are overviewed.”

http://www.ncbi.nlm.nih.gov/pubmed/27142423

“Cerebral ischemia or brain ischemia, is a condition that occurs when there isn’t enough blood flow to the brain to meet metabolic demand. This leads to limited oxygen supply or cerebral hypoxia and leads to the death of brain tissue, cerebral infarction, or ischemic stroke. It is a sub-type of stroke along with subarachnoid hemorrhage and intracerebral hemorrhage. There are two kinds of ischemia: focal ischemia: confined to a specific region of the brain; global ischemia: encompasses wide areas of brain tissue.”  http://www.columbianeurosurgery.org/conditions/cerebral-ischemia/

Cannabis May Cure Celiac Disease

Evidence suggests that there is a natural plant treatment that can mitigate or even cure celiac disease: cannabis.

“Celiac disease can be devastating to those who suffer from it, but evidence suggests that there is a natural plant treatment that can mitigate or even cure the ailment: cannabis.

People who have celiac suffer from autoimmune attacks on their small intestine after eating gluten, which can lead to pain and an inability to absorb nutrients, as well as diabetes, multiple sclerosis and cancer over the long term.

Gluten is ubiquitous in the Western diet and people who take pains to avoid eating it are still likely to consume some by accident on occasion, and even in small amounts gluten can lead to extremely painful and embarrassing episodes.

Fortunately, marijuana may be able to help.

A study published in the PLOS One journal in 2013 suggests that cannabis could play a key role in taming the ravages of celiac. The study, conducted by researchers at the University of Teramo in Italy, took intestinal biopsies from celiac patients and looked at the cannabinoid receptors in the gut, which play a role in controlling inflammation and dysfunction. The results showed significantly more receptors in people with an active disease than those who had been treating it with at least 12 months of a gluten-free diet, leading the scientists to suggest that the data “points to the therapeutic potential of targeting [cannabinoid receptors] in patients with celiac disease.”

Anecdotal reports corroborate the study’s findings. Some patients believe that marijuana has actually helped them cure celiac outright.”

http://reset.me/story/cannabis-may-cure-celiac-disease/

“Altered Expression of Type-1 and Type-2 Cannabinoid Receptors in Celiac Disease” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631143/