Peripheral cannabinoid receptor, CB2, regulates bone mass.

“Here we show that CB2-deficient mice have a markedly accelerated age-related trabecular bone loss and cortical expansion, although cortical thickness remains unaltered.

These changes are reminiscent of human osteoporosis and may result from differential regulation of trabecular and cortical bone remodeling…

These results demonstrate that the endocannabinoid system is essential for the maintenance of normal bone mass by osteoblastic and osteoclastic CB2 signaling.

Hence, CB2 offers a molecular target for the diagnosis and treatment of osteoporosis, the most prevalent degenerative disease in developed countries.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1334629/

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

 

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

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/

Activation of Cannabinoid Receptor 2 Enhances Osteogenic Differentiation of Bone Marrow Derived Mesenchymal Stem Cells.

“Bone marrow derived mesenchymal stem cells (BM-MSCs) are considered as the most promising cells source for bone engineering.

Cannabinoid(CB) receptors play important roles in bone mass turnover.

The aim of this study is to test if activation of CB2 receptor by chemical agonist could enhance the osteogenic differentiation and mineralization in bone BM-MSCs…

Taken together, data from this study suggested that activation of CB2 receptor plays important role in osteogenic differentiation of BM-MSCs.

Lack of CB2 receptor may be related to osteoporosis.

These results demonstrate that the activation of CB2 signaling is essential for the maintenance of normal bone mass.

Manipulating CB2 signaling may offer a molecular tool for the increasing osteogenic differentiation of stem cells.”

http://www.hindawi.com/journals/bmri/2015/874982/

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

 

Cannabinoid Receptors as Target for Treatment of Osteoporosis: A Tale of Two Therapies

“This review summarises in vitro and in vivo findings relating to the influence of cannabinoid ligands on bone metabolism and argues in favour of the exploitation of cannabinoid receptors as targets for both anabolic and anti-resorptive therapy for treatment of complex multifaceted bone diseases such as osteoporosis.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001217/

The promise and dilemma of cannabinoid therapy: lessons from animal studies of bone disease.

“The endocannabinoid system plays an important role in numerous physiological processes and represents a potential drug target for diseases ranging from brain disorders to cancer…

In the aging skeleton, CB1 deficiency causes accelerated osteoporosis characterized mainly by a significant reduction in bone formation coupled to enhanced adipocyte accumulation in the bone marrow.

A similar acceleration of bone loss was also reported in aging CB2-deficient mice but found to be associated with enhanced bone turnover.

This perspective describes the role of cannabinoid ligands and their receptors in bone metabolism and highlights the promise and dilemma of therapeutic exploitation of the endocannabinoid system for treatment of bone disorders.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868875/

Increase of mesenchymal stem cell migration by Cannabidiol via activation of p42/44 MAPK.

“Migration and differentiation of mesenchymal stem cells (MSCs) are known to be involved in various regenerative processes such as bone healing.

The present study therefore focussed on cannabinoids which have been demonstrated to exhibit tissue healing properties…

Collectively, this study demonstrates CBD to promote the migration of MSCs via activation of the CB2 receptor and inhibition of GPR55 and to induce osteoblastic differentiation. CBD may therefore recruit MSCs to sites of calcifying tissue regeneration and subsequently support bone regeneration via an osteoanabolic action on MSCs.”

http://www.ncbi.nlm.nih.gov/pubmed/24304686

Therapeutic potential of cannabinoid medicines.

Drug Testing and Analysis

“Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines.

The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology.

In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24006213

http://onlinelibrary.wiley.com/doi/10.1002/dta.1529/abstract

The endocannabinoid system and its therapeutic exploitation.

Image result for Nat Rev Drug Discov.

“The term ‘endocannabinoid’ – originally coined in the mid-1990s after the discovery of membrane receptors for the psychoactive principle in Cannabis, Delta9-tetrahydrocannabinol and their endogenous ligands – now indicates a whole signalling system that comprises cannabinoid receptors, endogenous ligands and enzymes for ligand biosynthesis and inactivation. This system seems to be involved in an ever-increasing number of pathological conditions. With novel products already being aimed at the pharmaceutical market little more than a decade since the discovery of cannabinoid receptors, the endocannabinoid system seems to hold even more promise for the future development of therapeutic drugs. We explore the conditions under which the potential of targeting the endocannabinoid system might be realized in the years to come.”  http://www.ncbi.nlm.nih.gov/pubmed/15340387

http://www.nature.com/nrd/journal/v3/n9/full/nrd1495.html

From cannabis to the endocannabinoid system: refocussing attention on potential clinical benefits.

Image result for West Indian Med J

“Cannabis sativa is one of the oldest herbal remedies known to man. Over the past four thousand years, it has been used for the treatment of numerous diseases but due to its psychoactive properties, its current medicinal usage is highly restricted. In this review, we seek to highlight advances made over the last forty years in the understanding of the mechanisms responsible for the effects of cannabis on the human body and how these can potentially be utilized in clinical practice. During this time, the primary active ingredients in cannabis have been isolated, specific cannabinoid receptors have been discovered and at least five endogenous cannabinoid neurotransmitters (endocannabinoids) have been identified. Together, these form the framework of a complex endocannabinoid signalling system that has widespread distribution in the body and plays a role in regulating numerous physiological processes within the body. Cannabinoid ligands are therefore thought to display considerable therapeutic potential and the drive to develop compounds that can be targeted to specific neuronal systems at low enough doses so as to eliminate cognitive side effects remains the ‘holy grail’ of endocannabinoid research.”

http://www.ncbi.nlm.nih.gov/pubmed/23155985

Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities.

Philosophical Transactions of the Royal Society B: Biological Sciences: 367 (1607)

“Human tissues express cannabinoid CB(1) and CB(2) receptors that can be activated by endogenously released ‘endocannabinoids’ or exogenously administered compounds in a manner that reduces the symptoms or opposes the underlying causes of several disorders in need of effective therapy. Three medicines that activate cannabinoid CB(1)/CB(2) receptors are now in the clinic: Cesamet (nabilone), Marinol (dronabinol; Δ(9)-tetrahydrocannabinol (Δ(9)-THC)) and Sativex (Δ(9)-THC with cannabidiol). These can be prescribed for the amelioration of chemotherapy-induced nausea and vomiting (Cesamet and Marinol), stimulation of appetite (Marinol) and symptomatic relief of cancer pain and/or management of neuropathic pain and spasticity in adults with multiple sclerosis (Sativex). This review mentions several possible additional therapeutic targets for cannabinoid receptor agonists. These include other kinds of pain, epilepsy, anxiety, depression, Parkinson’s and Huntington’s diseases, amyotrophic lateral sclerosis, stroke, cancer, drug dependence, glaucoma, autoimmune uveitis, osteoporosis, sepsis, and hepatic, renal, intestinal and cardiovascular disorders. It also describes potential strategies for improving the efficacy and/or benefit-to-risk ratio of these agonists in the clinic. These are strategies that involve (i) targeting cannabinoid receptors located outside the blood-brain barrier, (ii) targeting cannabinoid receptors expressed by a particular tissue, (iii) targeting upregulated cannabinoid receptors, (iv) selectively targeting cannabinoid CB(2) receptors, and/or (v) adjunctive ‘multi-targeting’.”  https://www.ncbi.nlm.nih.gov/pubmed/23108552

“Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities”  http://rstb.royalsocietypublishing.org/content/367/1607/3353.long