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Clinical data so far has been restricted to safety studies with inhibitors of anandamide hydrolysis and a hitherto unpublished study on such a compound in elderly patients with major depressive disorders, but under the dose regimes used, they are well tolerated and show no signs of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

Cannabinoid receptor type 1 receptors on GABAergic vs. glutamatergic neurons differentially gate sex-dependent social interest in mice.

“Abnormalities in social behavior are found in almost all psychiatric disorders, such as anxiety, depression, autism, and schizophrenia. Thus, comprehension of the neurobiological basis of social interaction is important for a better understanding of numerous pathologies and improved treatments.

Several findings have suggested that an alteration of cannabinoid receptor type 1 (CB1) receptor function could be involved in the pathophysiology of such disorders…

In conclusion, we provide evidence that CB1 receptors specifically modulate the social investigation of female mice in a neuronal subtype-specific manner.”

http://www.ncbi.nlm.nih.gov/pubmed/24698342

Intense exercise increases circulating endocannabinoid and BDNF levels in humans–possible implications for reward and depression.

“The endocannabinoid system is known to have positive effects on depression partly through its actions on neurotrophins, such as Brain-Derived Neurotrophic Factor (BDNF). As BDNF is also considered the major candidate molecule for exercise-induced brain plasticity, we hypothesized that the endocannabinoid system represents a crucial signaling system mediating the beneficial antidepressant effects of exercise…

These findings provide evidence in humans that acute exercise represents a physiological stressor able to increase peripheral levels of AEA and that BDNF might be a mechanism by which AEA influences the neuroplastic and antidepressant effects of exercise.”

http://www.ncbi.nlm.nih.gov/pubmed/22029953

“Neuroplasticity – exercise-induced response of peripheral brain-derived neurotrophic factor: a systematic review of experimental studies in human subjects. Exercise is known to induce a cascade of molecular and cellular processes that support brain plasticity. Brain-derived neurotrophic factor (BDNF) is an essential neurotrophin that is also intimately connected with central and peripheral molecular processes of energy metabolism and homeostasis, and could play a crucial role in these induced mechanisms… We can only speculate which central regions and peripheral sources in particular circulating BDNF originates from,…” http://www.ncbi.nlm.nih.gov/pubmed/20726622

“Preliminary evidence of cannabinoid effects on brain-derived neurotrophic factor (BDNF) levels in humans… cannabinoids modulate brain-derived neurotrophic factor (BDNF)… Delta(9)-THC increased serum BDNF levels…” http://www.ncbi.nlm.nih.gov/pubmed/18807247

“Antidepressant-like effects of Δ⁹-tetrahydrocannabinol…” http://www.ncbi.nlm.nih.gov/pubmed/22634064

“Antidepressant-like effects of cannabidiol… CBD treatment did not change hippocampal BDNF levels… CBD induces antidepressant-like effects…” http://www.ncbi.nlm.nih.gov/pubmed/20002102

Regulatory role of the Cannabinoid-2 receptor in stress-induced neuroinflammation in mice.

“Stress-exposure produces excitoxicity and neuroinflammation, contributing to the cellular damage observed in stress-related neuropathologies. The endocannabinoid system is present in stress-responsive neural circuits and it is emerging as a homeostatic system. The aim of this study was to elucidate the possible regulatory role of cannabinoid-2 receptor in stress-induced excitotoxicity and neuroinflammation.

CONCLUSIONS AND IMPLICATIONS:

These results suggest that pharmacological manipulation of CB2 receptor is a potential therapeutic strategy for the treatment of stress-related pathologies with a neuroinflammatory component, such as depression.”

http://www.ncbi.nlm.nih.gov/pubmed/24467609

Medical Marijuana Laws and Suicides by Gender and Age.

:American Journal of Public Health Logo

 

“We estimated the association between legalizing medical marijuana and suicides.

Legalization was associated with a 10.8%  and 9.4% reduction in the suicide rate of men aged 20 through 29 years and 30 through 39 years, respectively.

Suicides among men aged 20 through 39 years fell after medical marijuana legalization compared with those in states that did not legalize.

The negative relationship between legalization and suicides among young men is consistent with the hypothesis that marijuana can be used to cope with stressful life events.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232164/

http://www.ncbi.nlm.nih.gov/pubmed/24432945

http://ajph.aphapublications.org/doi/10.2105/AJPH.2013.301612

“Legalizing Medical Marijuana May Lead To Fewer Suicides”  https://www.huffingtonpost.com/2014/02/04/marijuana-legalization-suicide_n_4726390.html

“Medical Marijuana Cuts Suicide Rates By 10% In Years Following Legalization”  http://www.medicaldaily.com/medical-marijuana-cuts-suicide-rates-10-years-following-legalization-268472