“Cannabinoids produce analgesia through a variety of mechanisms.
It has been proposed that one mechanism is by modulating the release of CGRP in the spinal cord pain pathways.
Previous studies have reported that cannabinoids, particularly CB2 receptor agonists, can modulate CGRP release in the isolated rat spinal cord.
These results question the role of spinal cord cannabinoid receptors in the regulation of CGRP signalling.”
“Cannabinoids are involved in the regulation of neural stem cell biology and their receptors are expressed in the neurogenic niches of adult rodents.
In the spinal cord of rats and mice, neural stem cells can be found in the ependymal region, surrounding the central canal, but there is evidence that this region is largely different in adult humans: lacks a patent canal and presents perivascular pseudorosettes, typically found in low grade ependymomas.
Using Laser Capture Microdissection, Taqman gene expression assays and immunohistochemistry, we have studied the expression of endocannabinoid system components (receptors and enzymes) at the human spinal cord ependymal region.
We observe that ependymal region is enriched in CB1 cannabinoid receptor, due to high CB1 expression in GFAP+ astrocytic domains. However, in human spinal cord levels that retain central canal patency we found ependymal cells with high CB1 expression, equivalent to the CB1HIGH cell subpopulation described in rodents.
Our results support the existence of ependymal CB1HIGH cells across species, and may encourage further studies on this subpopulation, although only in cases when central canal is patent. In the adult human ependyma, which usually shows central canal absence, CB1 may play a different role by modulating astrocyte functions.”
“Increased matrix metalloproteinase (MMP) activity contributes to glial scar formation that inhibits the repair path after spinal cord injury (SCI). We examined whether treatment with N-(2-chloroethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (ACEA), a selective synthetic cannabinoid receptor (CB1R) agonist, inhibits MMP and improves functional and histological recovery in a mouse spinal cord compression injury model…
Collectively these data demonstrate that post-injury CB1R agonism can improve SCI outcome and also indicate marked attenuation of MMP-9 proteolytic enzyme activity as a biochemical mechanism.”
http://www.ncbi.nlm.nih.gov/pubmed/25881484
http://www.thctotalhealthcare.com/category/spinal-cord-injury/
“Spinal Cord Injury (SCI) is a devastating condition for which there is no standard treatment beyond rehabilitation strategies. In this review, we discuss the current knowledge on the use of cannabinoids to treat this condition.
The endocannabinoid system is expressed in the intact spinal cord, and it is dramatically upregulated after lesion. Endogenous activation of this system counteracts secondary damage following SCI, and treatments with endocannabinoids or synthetic cannabinoid receptor agonists promote a better functional outcome in experimental models.
The use of cannabinoids in SCI is a new research field and many questions remain open. Here, we discuss caveats and suggest some future directions that may help to understand the role of cannabinoids in SCI and how to take advantage of this system to regain functions after spinal cord damage.”
http://www.ncbi.nlm.nih.gov/pubmed/25805333
http://www.thctotalhealthcare.com/category/spinal-cord-injury/
“Disc degeneration is a multifactorial process that involves hypoxia, inflammation, neoinnervation, accelerated catabolism, and reduction in water and glycosaminoglycan content…
Cannabidiol (CBD) is the major nonpsychotropic phytocannabinoid of Cannabis sativa (up to 40% of Cannabis extracts). Contrary to most cannabinoids, CBD does not produce psychotomimetic or cognitive effects. Interesting, in the last years it has been suggest that CBD produces a plethora of others pharmacological effects, including antioxidant, neuroprotective, anti-proliferative, anti-anxiety, hypnotic and antiepileptic, anti-nausea, anti-ischemic, anti-hyperalgesic, and anti-inflammatory…
The present study investigated the effects of cannabidiol intradiscal injection in the coccygeal intervertebral disc degeneration induced by the needle puncture model using magnetic resonance imaging (MRI) and histological analyses…
Cannabidiol significantly attenuated the effects of disc injury induced by the needle puncture. Considering that cannabidiol presents an extremely safe profile and is currently being used clinically, these results suggest that this compound could be useful in the treatment of intervertebral disc degeneration.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269422/
http://www.thctotalhealthcare.com/category/spinal-cord-injury/
“Spinal cord injury (SCI) is a devastating condition… Modulation of the endocannabinoid system (ECS) counteracts neurodegeneration, and pharmacological modulation of type-2 cannabinoid receptor (CB2R) is a promising therapeutic target for several CNS pathologies, including SCI…
These findings implicate the ECS, particularly CB2R, as part of the endogenous neuroprotective response that is triggered after SCI.
Thus, CB2R modulation might represent a promising therapeutic target that lacks psychotropic effects and can be used to exploit ECS-based approaches to counteract neuronal degeneration.”
http://www.ncbi.nlm.nih.gov/pubmed/25188514
http://www.thctotalhealthcare.com/category/spinal-cord-injury/
1942-7611/asset/olalertbanner.jpg?v=1&s=4b27d6a6bed6b58a9935efe70e4f95efc39146bd)
“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 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
“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.”
“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