The influence of cannabinoids on generic traits of neurodegeneration

“In an increasingly ageing population, the incidence of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease are rising. While the aetiologies of these disorders are different, a number of common mechanisms that underlie their neurodegenerative components have been elucidated; namely neuroinflammation, excitotoxicity, mitochondrial dysfunction and reduced trophic support. Current therapies focus on treatment of the symptoms and attempt to delay the progression of these diseases but there is currently no cure.

Modulation of the endogenous cannabinoid system is emerging as a potentially viable option in the treatment of neurodegeneration. Endocannabinoid signalling has been found to be altered in many neurodegenerative disorders. To this end, pharmacological manipulation of the endogenous cannabinoid system, as well as application of phytocannabinoids and synthetic cannabinoids have been investigated. Signalling from the CB1 and CB2 receptors are known to be involved in the regulation of Ca2+ homeostasis, mitochondrial function, trophic support and inflammatory status, respectively, while other receptors gated by cannabinoids such as PPARγ, are gaining interest in their anti-inflammatory properties.

Through multiple lines of evidence, this evolutionarily conserved neurosignalling system has shown neuroprotective capabilities and is therefore a potential target for neurodegenerative disorders. This review details the mechanisms of neurodegeneration and highlights the beneficial effects of cannabinoid treatment.”

http://onlinelibrary.wiley.com/doi/10.1111/bph.12492/full

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/

Experimental cannabinoid 2 receptor-mediated immune modulation in sepsis.

“Sepsis is a complex condition that results from a dysregulated immune system in response to a systemic infection. Current treatments lack effectiveness in reducing the incidence and mortality associated with this disease. The endocannabinoid system offers great promise in managing sepsis pathogenesis due to its unique characteristics.

The present study explored the effect of modulating the CB2 receptor pathway in an acute sepsis mouse model.

Using various compounds we have shown different mechanisms of activating CB2 receptors to reduce leukocyte endothelial interactions in order to prevent further inflammatory damage during sepsis.”

http://www.ncbi.nlm.nih.gov/pubmed/24803745

[Tetrahydrocannabinol for treatment of chronic pain].

“Even in the last century cannabis was used in the treatment of chronic pain. The main active component of cannabis Delta-9-Tetrahydrocannabinol (THC) has been increasingly used in the treatment of nausea, vomiting, loss of appetite and depression. It is also recommended in the treatment of chronic pain. We present our first experiences with THC in the treatment of patients with chronic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/11810357

http://www.thctotalhealthcare.com/category/chronic-pain/

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

No Relief Yet for Brutal Oral Cancer Pain, but Cannabinoids May Offer Some Hope

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“Many cancer patients endure severe pain and, by far, one of the most excruciating pain conditions is caused by oral cancer, for which even the strongest available pain medications are largely ineffective. One of the nation’s leading oral cancer treating clinicians, speaking at the American Pain Society’s annual meeting, said he believes that while prospects for major treatment advances remain bleak, a new cannabinoid-based medication may have some promise for providing meaningful pain relief.”  http://www.newswise.com/articles/no-relief-yet-for-brutal-oral-cancer-pain-but-cannabinoids-may-offer-some-hope

Marijuana Rated Most Effective for Treating Fibromyalgia

marijuana graph

“Medical marijuana is far more effective at treating symptoms of fibromyalgia than any of the three prescription drugs approved by the Food and Drug Administration to treat the disorder.

That is one of the surprise findings in an online survey of over 1,300 fibromyalgia patients conducted by the National Pain Foundation and National Pain Report.”

Cymbalta graph

Lyrica graph

Savella graph.”

“The FDA has approved only three drugs – Cymbalta, Lyrica and Savella — for the treatment of fibromyalgia.”

http://americannewsreport.com/nationalpainreport/marijuana-rated-most-effective-for-treating-fibromyalgia-8823638.html

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

 

Therapeutic benefits of cannabis: a patient survey.

“Clinical research regarding the therapeutic benefits of cannabis (“marijuana”) has been almost non-existent in the United States since cannabis was given Schedule I status in the Controlled Substances Act of 1970.

In order to discover the benefits and adverse effects perceived by medical cannabis patients, especially with regards to chronic pain, we hand-delivered surveys to one hundred consecutive patients who were returning for yearly re-certification for medical cannabis use in Hawai’i. The response rate was 94%. Mean and median ages were 49.3 and 51 years respectively. Ninety-seven per cent of respondents used cannabis primarily for chronic pain. Average pain improvement on a 0-10 pain scale was 5.0 (from 7.8 to 2.8), which translates to a 64% relative decrease in average pain. Half of all respondents also noted relief from stress/anxiety, and nearly half (45%) reported relief from insomnia. Most patients (71%) reported no adverse effects, while 6% reported a cough or throat irritation and 5% feared arrest even though medical cannabis is legal in Hawai’i.

No serious adverse effects were reported.

These results suggest that Cannabis is an extremely safe and effective medication for many chronic pain patients. Cannabis appears to alleviate pain, insomnia, and may be helpful in relieving anxiety.

Cannabis has shown extreme promise in the treatment of numerous medical problems and deserves to be released from the current Schedule I federal prohibition against research and prescription.”

http://www.ncbi.nlm.nih.gov/pubmed/24765558

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998228/

Cannabinoid inhibits HIV-1 Tat-stimulated adhesion of human monocyte-like cells to extracellular matrix proteins.

“The aim of this study was to assess the effect of select cannabinoids on human immunodeficiency virus type 1 (HIV-1) transactivating (Tat) protein-enhanced monocyte-like cell adhesion to proteins of the extracellular matrix (ECM)…

KEY FINDINGS:

THC and CP55,940 inhibited Tat-enhanced attachment of U937 cells to ECM proteins in a mode that was linked to the cannabinoidreceptor type 2 (CB2R). The cannabinoid treatment of Tat-activated U937 cells was associated with altered β1-integrin expression and distribution of polymerized actin, suggesting a modality by which these cannabinoids inhibited adhesion to the ECM.

SIGNIFICANCE:

The blood-brain barrier (BBB) is a complex structure that is composed of cellular elements and an extracellular matrix (ECM). HIV-1 Tat promotes transmigration of monocytes across this barrier, a process that includes interaction with ECM proteins.

The results indicate that cannabinoids that activate the CB2R inhibit the ECM adhesion process. Thus, this receptor has potential to serve as a therapeutic agent for ablating neuroinflammation associated with HIV-elicited influx of monocytes across the BBB.”

http://www.ncbi.nlm.nih.gov/pubmed/24742657

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

Prophylactic cannabinoid administration blocks the development of paclitaxel-induced neuropathic nociception during analgesic treatment and following cessation of drug delivery.

“Chemotherapeutic treatment results in chronic pain in an estimated 30-40 percent of patients. Limited and often ineffective treatments make the need for new therapeutics an urgent one. We compared the effects of prophylactic cannabinoids as a preventative strategy for suppressing development of paclitaxel-induced nociception…

Our results support the therapeutic potential of cannabinoids for suppressing chemotherapy-induced neuropathy in humans.”

http://www.ncbi.nlm.nih.gov/pubmed/24742127

http://www.thctotalhealthcare.com/category/neuropathic-pain/

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