Cannabinoid Replacement Therapy (CRT): Nabiximols (Sativex) as a novel treatment for cannabis withdrawal.

Posted on March 18, 2015 by David

“Cannabis is a common recreational drug that is generally considered to have low addictive potential.

However an increasing number of cannabis users are seeking treatment for dependence on the drug.

There is interest in using agonist (substitution) pharmacotherapies to treat cannabis dependence and here we outline a novel approach involving a buccal spray (Nabiximols) that contains tetrahydrocannabinol (THC) and cannabidiol (CBD).

We review recent research with Nabiximols and highlight findings relevant to clinical practice.”

http://www.ncbi.nlm.nih.gov/pubmed/25777582

Identification of the CB1 cannabinoid receptor and fatty acid amide hydrolase (FAAH) in the human placenta.

Posted on March 4, 2015 by David

“Synthetic cannabinoids, the psychoactive components of the Cannabis sativa (marijuana) and their endogenous counterparts, act through two G protein-coupled receptors, CB1 and CB2.

The endocannabinoids are metabolized by fatty acid amide hydrolase (FAAH).

We have examined CB1 receptor and FAAH expression in human term placenta by immunohistochemistry.

CB1 receptor was found to be present in all layers of the membrane, with particularly strong expression in the amniotic epithelium and reticular cells and cells of the maternal decidua layer. Moderate expression was observed in the chorionic cytotrophoblasts. The expression of FAAH was the highest in amniotic epithelial cells, chorionic cytotrophoblast and maternal decidua layer.

Our results suggest that the human placenta is a likely target for cannabinoid action and metabolism. ”

http://www.ncbi.nlm.nih.gov/pubmed/12744923

Emerging targets and therapeutic approaches for the treatment of osteoarthritis pain.

Posted on March 3, 2015 by David

“Osteoarthritis is a complex and often painful disease that is inadequately controlled with current analgesics. This review discusses emerging targets and therapeutic approaches that may lead to the development of better analgesics…

Aberrant excitability in peripheral and central pain pathways drives osteoarthritis pain, reversing this via modulation of nerve growth factor, voltage-gated sodium channel, voltage-gated calcium channel and transient receptor potential vanilloid one activity, and increasing inhibitory mechanisms through modulation of cannabinoid and descending modulatory systems hold promise for osteoarthritis pain therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/25730180

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

Cannabinoid receptor type 1 protects against age-related osteoporosis by regulating osteoblast and adipocyte differentiation in marrow stromal cells.

Posted on February 28, 2015 by David

X-ray generic

“Age-related osteoporosis is characterized by reduced bone formation and accumulation of fat in the bone marrow compartment.

Here, we report that the type 1 cannabinoid receptor (CB1) regulates this process…

The CB1 receptor is therefore unique in that it regulates peak bone mass through an effect on osteoclast activity, but protects against age-related bone loss by regulating adipocyte and osteoblast differentiation of bone marrow stromal cells.”

http://www.ncbi.nlm.nih.gov/pubmed/19656492

“Cannabis may prevent osteoporosis” http://news.bbc.co.uk/2/hi/uk_news/scotland/edinburgh_and_east/8199007.stm

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

Influence of nitric oxide synthase or cyclooxygenase inhibitors on cannabinoids activity in streptozotocin-induced neuropathy.

Posted on February 27, 2015 by David

“The results of this study seemed to indicate that the interaction between cannabinoid, COX-2 and NOS(s) systems might exist…

Concomitant administration of small doses of CB1 and/or CB2 receptor agonists and COX-2 or NOS inhibitors can be effective in the alleviation of diabetic neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/25712641

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

Are Cannabinoids Effective for Orofacial Pain States?

Posted on February 27, 2015 by David

“…there is increasing attention being given in the media as well as in the biomedical sciences to the use as analgesic agents of the crude extracts of plants of the genus Cannabis (eg, marijuana) and their active ingredient delta 9-tetrahydrocannabinol (Δ9-THC).

These cannabinoid compounds have been reported in the biomedical literature to be beneficial in the treatment of some types of neuropathic pain and other pain states…

This review has found evidence indicating that they may be effective analgesic agents for neuropathic pain conditions refractory to other therapeutic approaches…

The clinical findings pointing to the usefulness of the cannabinoids for pain relief are supported by a growing body of evidence from basic science investigations addressing the possible efficacy and mechanisms of action of the cannabinoids in animal models of acute or chronic pain.

These preclinical findings add to the growing evidence that cannabinoid receptor agonists may be effective agents for the treatment of neuropathic pain and other types of pain.

They also point to their possible clinical utility in acute or chronic orofacial pain conditions, and thereby suggest an affirmative answer applies to the question posed in the title of this editorial.”

http://www.quintpub.com/journals/ofph/abstract.php?article_id=15025#.VPBsU033-iw

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

Molecular Mechanisms of Cannabinoid Protection from Neuronal Excitotoxicity

Posted on February 25, 2015 by David

“Cannabinoids protect neurons from excitotoxic injury…

Endogenous or exogenous cannabinoids have shown neuroprotective effects…

The main finding reported here is that cannabinoids protect neurons from excitotoxic injury by a mechanism that involves the activation of CB1R and inhibition of NOS and PKA….

Cannabinoid receptor agonist drugs protect neurons…

By identifying the signaling pathways responsible for cannabinoid effects in animal models of disease and their human counterparts, it may be possible to design more specific and therefore more efficacious cannabinoid-based therapies.”

http://molpharm.aspetjournals.org/content/69/3/691.long

“Delta9-tetrahydrocannabinol protects hippocampal neurons from excitotoxicity.” http://www.ncbi.nlm.nih.gov/pubmed/17140550

Cannabinoids & Stress: Impact of HU-210 on behavioral tests of anxiety in acutely stressed mice.

Posted on February 25, 2015 by David

“Anxiety disorders are one of the most prevalent classes of mental disorders affecting the general population, but current treatment strategies are restricted by their limited efficacy and side effect profiles.

Although the cannabinoid system is speculated to be a key player in the modulation of stress responses and emotionality, the vast majority of current research initiatives had not incorporated stress exposure into their experimental designs.

This study was the first to investigate the impact of exogenous cannabinoid administration in an acutely stressed mouse model, where CD1 mice were pre-treated with HU-210, a potent CB1R agonist, prior to acute stress exposure and subsequent behavioural testing.

Exogenouscannabinoid administration induced distinct behavioural phenotypes in stressed and unstressed mice…

These findings suggest that exogenous cannabinoids and acute stress act synergistically in an anxiogenic manner.

This study underlies the importance of including stress exposure into future anxiety-cannabinoid research due to the differential impact of cannabinoid administration on stressed and unstressed subjects.”

http://www.ncbi.nlm.nih.gov/pubmed/25707713

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

Effects of intra-infralimbic prefrontal cortex injections of cannabidiol in the modulation of emotional behaviors in rats: contribution of 5HT1A receptors and stressful experiences.

Posted on February 24, 2015 by David

“The infralimbic (IL) and prelimbic (PL) regions of the prefrontal cortex are involved in behavioral responses observed during defensive reactions.

Intra-PL or IL injections of cannabidiol (CBD), a major non-psychotomimetic cannabinoid present in the Cannabis sativa plant, result in opposite behavioral effects in the contextual fear conditioning (CFC) paradigm…

Together these results indicate that CBD effects in the IL depend on the nature of the animal model, being influenced by previous stressful experiences and mediated by facilitation of 5HT1A receptors-mediated neurotransmission.”

http://www.ncbi.nlm.nih.gov/pubmed/25701682

Cannabinoid signaling and liver therapeutics.

Posted on February 19, 2015 by David

Journal of Hepatology Home

“Over the last decade, the endocannabinoid system has emerged as a pivotal mediator of acute and chronic liver injury, with the description of the role of CB1 and CB2 receptors and their endogenous lipidic ligands in various aspects of liver pathophysiology.

A large number of studies have demonstrated that CB1 receptor antagonists represent an important therapeutic target, owing to beneficial effects on lipid metabolism and in light of its antifibrogenic properties.

Unfortunately, the brain-penetrant CB1 antagonist rimonabant, initially approved for the management of overweight and related cardiometabolic risks, was withdrawn because of an alarming rate of mood adverse effects.

However, the efficacy of peripherally-restricted CB1 antagonists with limited brain penetrance has now been validated in preclinical models of NAFLD, and beneficial effects on fibrosis and its complications are anticipated.

CB2 receptor is currently considered as a promising anti-inflammatory and antifibrogenic target, although clinical development of CB2 agonists is still awaited.

In this review, we highlight the latest advances on the impact of the endocannabinoid system on the key steps of chronic liver disease progression and discuss the therapeutic potential of molecules targeting cannabinoid receptors…

Overwhelming evidence supports the therapeutic potential of peripherally-restricted CB1 antagonists and CB2 agonists in the management of chronic liver diseases.”

http://www.journal-of-hepatology.eu/article/S0168-8278(13)00212-2/fulltext

http://www.thctotalhealthcare.com/category/liver-disease/