[The endocannabinoid system role in the pathogenesis of obesity and depression].

“Excessive consumption and obesity do not always have to be strictly pathological. The adjustment of food intake as well as the pleasure of eating are the results of the circulation of neurotransmitters, hormones and glucocorticoids which have an ability to regulate the activity of many receptors connected with G protein, including endocannabinoid receptors.

The key role of endocannabinoids in pathogenesis of obesity is their overproduction by adipose cells.

Endocannabinoids (eCBs) affect CB1 receptors and increase hunger, willingness to intake food, decrease peristalsis and delay stomach emptying.

In obese people increased levels of both central and peripheral endocannabinoids are observed. It may be connected with higher availability of endocannabinoid precursors to synthesis from adipose tissue and lipids.

Raised concentration of eCBs in the body may be the consequence of their catabolism dysfunction. There is a positive correlation between amount the number of receptors in the peripheral tissues and obesity increase.

It is thought that expression of CB1 receptors in mesolimbic system is connected with motivation to consume food in response to rewarding factor.

The appetite increase after cannabinoids use is probably caused by rewarding action of the consumed food and it results from excessive dopaminergic transmission in award system.

The pharmacological inhibition of endocannabinoids activity leads to weight loss, but may also have negative consequences such as decreased mood, reduced tolerance of pain, intensified anxiety, anhedonia, depressive symptoms, even suicidal thoughts.

In post mortem examinations a decrease in CB1 receptor density in grey matter of glial cells in patients with major depression was identified. The pleiotropic and extensive activity of endocannabinoid system can influence a range of neurotransmitters thereby modulating the psychiatric life phenomena, simultaneously being involved in metabolism control and energetic system of human body.

Hence it is a link between metabolic disorders and depression and anxiety disorders. Therefore, in obese people depressive comorbidity is higher and it significantly worsens prognosis and decreases life quality.”

http://www.ncbi.nlm.nih.gov/pubmed/26277182

Anxiety, Stress, and Fear Response in Mice with Reduced Endocannabinoid Levels.

Disruption of the endocannabinoid system through pharmacological or genetic invalidation of cannabinoid CB1 receptors has been linked to depression in humans and depression-like behaviors in mice.

We generated and used knockout mice lacking DAGL-α (Dagla-/-) to assess the behavioral consequences of reduced endocannabinoid levels in the brain…

Our findings demonstrate that the deletion of Dagla adversely affects the emotional state of animals and results in enhanced anxiety, stress, and fear responses.”

http://www.ncbi.nlm.nih.gov/pubmed/25981172

[Cannabinoids in medicine].

“Cannabinoids have been known for many centuries because of their various effects in healthcare. They are primarily effective in reducing nausea, vomiting, pain, anorexia, spasticity and depression. Some other effects are known, all seem to be mediated by cannabinoid receptors in the central nervous system. In the past years, medical use has been proven in several studies. Today, the therapeutical use of cannabinoids in medicine is increasing, and access was made easier. Especially in pain-management and palliative care, they seem to be a valuable therapeutic option.”

http://www.ncbi.nlm.nih.gov/pubmed/19165445

For whom the endocannabinoid tolls: Modulation of innate immune function and implications for psychiatric disorders.

“Over the past decade, there has been increasing evidence demonstrating that the endocannabinoid system can elicit potent modulatory effects on inflammatory processes, with clinical and preclinical evidence demonstrating beneficial effects on disease severity and symptoms in several inflammatory conditions.

This review examines the evidence supporting a modulatory effect of endocannabinoids on TLR-mediated immune responses both peripherally and centrally, and the implications for psychiatric disorders such as depression and schizophrenia.

CLASSES OF CANNABINOID-BASED PHARMACOLOGICAL AGENTS CITED IN THE REVIEW: Nonselective CB1/CB2 agonists: Δ9-THC, HU210, CP55940, WIN55,212-2 Selective CB2 agonists: JWH-015 FAAH inhibitors: URB597, AA-5HT MAGL/ABHD6 inhibitors: JZL184, MJN110, KML129, WWL70 Endocannabinoid reuptake inhibitors: UCM707, OMDM1/2, AM404.”

http://www.ncbi.nlm.nih.gov/pubmed/25794989

The potential of inhibitors of endocannabinoid metabolism as anxiolytic and antidepressive drugs-A practical view.

“The endocannabinoid system, comprising cannabinoid CB1 and CB2 receptors, their endogenous ligands anandamide and 2-arachidonoylglyerol, and their synthetic and metabolic enzymes, are involved in many biological processes in the body, ranging from appetite to bone turnover.

Compounds inhibiting the breakdown of anandamide and 2-arachidonoylglycerol increase brain levels of these lipids and thus modulate endocannabinoid signalling.

In the present review, the preclinical evidence that these enzymes are good targets for development of novel therapies for anxiety and depression are discussed from a practical, rather than mechanistic, point of view.

It is concluded that the preclinical data are promising, albeit tempered by problems of tolerance as well as effects upon learning and memory for irreversible monoacylglycerol lipase inhibitors, and limited by a focus upon male rodents alone.

Clinical data so far has been restricted to safety studies with inhibitors of anandamide hydrolysis and a hitherto unpublished study on such a compound in elderly patients with major depressive disorders, but under the dose regimes used, they are well tolerated and show no signs of “cannabis-like” behaviours.”

http://www.ncbi.nlm.nih.gov/pubmed/25791296

Interactions of the opioid and cannabinoid systems in reward: Insights from knockout studies.

“The opioid system consists of three receptors, mu, delta, and kappa, which are activated by endogenous opioid peptides (enkephalins, endorphins, and dynorphins).

The endogenous cannabinoid system comprises lipid neuromodulators (endocannabinoids), enzymes for their synthesis and their degradation and two well-characterized receptors, cannabinoid receptors CB1 and CB2.

These systems play a major role in the control of pain as well as in mood regulation, reward processing and the development of addiction.

Both opioid and cannabinoid receptors are coupled to G proteins and are expressed throughout the brain reinforcement circuitry.

A better understanding of opioid-cannabinoid interactions may provide novel strategies for therapies in addicted individuals.”

http://www.ncbi.nlm.nih.gov/pubmed/25698968

Antidepressant-like effects of the cannabinoid receptor ligands in the forced swimming test in mice: Mechanism of action and possible interactions with cholinergic system.

“The purpose of the experiments was to explore the role of the endocannabinoid system, through cannabinoid (CB) receptor ligands, nicotine and scopolamine, in the depression-related responses using the forced swimming test (FST) in mice…

Our results provide clear evidence that the endocannabinoid system participates in the depression-related behavior and through interactions with cholinergic system modulate these kind of responses.”

http://www.ncbi.nlm.nih.gov/pubmed/25660201

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

University Of Saskatchewan Research Suggests Marijuana Analogue Stimulates Brain Cell Growth

ScienceDaily: Your source for the latest research news

“A synthetic substance similar to ones found in marijuana stimulates cell growth in regions of the brain associated with anxiety and depression, pointing the way for new treatments for these diseases, according to University of Saskatchewan medical research published today in The Journal of Clinical Investigation.

Xia Zhang, an associate professor in the U of S neuropsychiatry research unit, led the team that tested the effects of HU-210, a potent synthetic cannabinoid similar to a group of compounds found in marijuana. The synthetic version is about 100 times as powerful as THC, the compound responsible for the high experienced by recreational users.

The team found that rats treated with HU-210 on a regular basis showed neurogenesis – the growth of new brain cells in the hippocampus. This region of the brain is associated with learning and memory, as well as anxiety and depression.

The effect is the opposite of most legal and illicit drugs such as alcohol, nicotine, heroin, and cocaine.

“Most ‘drugs of abuse’ suppress neurogenesis,” Zhang says. “Only marijuana promotes neurogenesis.””

http://www.sciencedaily.com/releases/2005/10/051016083817.htm

“Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects… In summary, since adult hippocampal neurogenesis is suppressed following chronic administration of opiates, alcohol, nicotine, and cocaine, the present study suggests that cannabinoids are the only illicit drug that can promote adult hippocampal neurogenesis following chronic administration.”  http://www.jci.org/articles/view/25509

Medical Marijuana Helps Cure Chronic Disease

Medical Marijuana Helps Cure Chronic Disease

“The medicinal power of Marijuana is well documented throughtout history

Back in 2700 BC, According to Chinese lore, the Emperor Shen Nung, considered the Father of Chinese medicine, in 2700 BC ,discovered the healing properties of Marijuana as well as Ginseng and Ephedra.

Throughout recorded history, the use of Medical Marijuana  has been linked to the ancient Egyptians, Persians, Greek civilizations, George Washington, Queen Victoria and even mainstream medicine by the 1840s.

From the 1850s to Y 1942, Marijuana was listed in the United States Pharmacopeia, an official public standards-setting authority for all prescription and over-the counter medicines, as a treatment for tetanus, cholera, rabies, dysentery, alcoholism, opiate addiction, convulsive disorders, insanity, excessive menstrual bleeding and many other health problems. My father was a Dental doctor and had a license to dispense the drug, pharmacies carried it back then.

During that same time frame prohibition gained popularity, that along with a growing “faith” in federal government.

By Y 1937, the United States passed its 1st federal law against Marijuana despite objections by the American Medical Association (AMA).

In fact, Dr. William C. Woodward, testifying on behalf of the AMA, told the US Congress:

“The American Medical Association knows of no evidence that Marijuana is a dangerous drug.”

He warned that a prohibition “loses sight of the fact that future investigation may show that there are substantial medical uses for Cannabis.”

Today, we see a growing trend of acceptance of Marijuana for its medicinal purposes.

Dr. Sanjay Gupta, CNN’s chief medical correspondent, reversed his Y 2009 opinion against Marijuana when he said, “We have been terribly and systematically misled for nearly 70 yrs in the United States, and I apologize for my own role in that.”

Now people including lawmakers are seeing the legalization of Marijuana in states like Colorado and Washington for “recreational” purposes. Most Americans are in favor of Medical Marijuana,  and the legalization of this drug.

The Big Q: why does the federal government want to ban its usage?

The Big A: it is all about control and money, and there is a major market for it, plus it poses a major threat to the pharmaceutical industry.

Below are just a few of the many health benefits associated with Medical Marijuana:

1. It can stop HIV from spreading throughout the body.
2. It slows the progression of Alzheimer’s.
3. It slows the spread of cancer cells.
4. It is an active pain reliever.
5. It can prevent or help with opiate addiction.
6. It combats depression, anxiety and ADHD.
7. It can treat epilepsy and Tourette’s.
8. It can help with other neurological damage, such as concussions and strokes.
9. It can prevent blindness from glaucoma.
10. Its connected to lower insulin levels in diabetics.

Contrary to popular notions, many patients  experience health benefits from Medical Marijuana without “getting stoned.””

http://www.livetradingnews.com/medical-marijuana-helps-cure-chronic-disease-55569.htm#.U6VjgZRX-uY

Towards a personalized treatment in depression: endocannabinoids, inflammation and stress response.

“The complex nature of depression is mirrored by difficulties in tailoring its treatment. Key underlying mechanisms of this mental disorder include elevated inflammation and a dysregulated hypothalamic-pituitary-adrenal (HPA) axis. More recently, the endocannabinoid system has been proposed as another important component in the pathogenesis of depression, and strong evidence suggests that all three systems communicate with each other. A growing number of genetic studies have investigated polymorphisms in depression in each of these systems separately. However, no study to date has looked at these genes in conjunction. In this article we will review the crosstalk between the endocannabinoid system, immune system and HPA axis; and discuss the evidence of gene polymorphisms and their relation to the risk of depression and its treatment. We propose future directions where genes of these three systems are considered from a joint perspective to improve prediction of treatment response, taking into account potentially overlooked genetic variations.”

http://www.ncbi.nlm.nih.gov/pubmed/24798725

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