“Sustained administration of cannabinoid agonists acting on neuronal CB1 receptors (CB1Rs) are proposed for treating spasticity and chronic pain…
Our data suggest that CB1Rs may control the circuit gateway regulating the inflow of sensory afferent inputs into the locomotor circuits, indicating a potential site of action for restricting peripheral signals disruptive for locomotor activity.”
“Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear.
To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids.
There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome.
Cannabinoids were associated with an increased risk of short-term AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination.”
“Cannabis-based medicines have recently been approved for the treatment of pain and spasticity in multiple sclerosis (MS).
This supports the original perceptions of people with MS, who were using illegal street cannabis for symptom control and pre-clinical testing in animal models of MS.
This activity is supported both by the biology of the disease and the biology of the cannabis plant and the endocannabinoid system.
MS results from disease that impairs neurotransmission and this is controlled by cannabinoid receptors and endogenous cannabinoid ligands. This can limit spasticity and may also influence the processes that drive the accumulation of progressive disability.”
http://www.ncbi.nlm.nih.gov/pubmed/25876933
http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/
“Cannabinoids exert a neuroprotective influence on some neurological diseases, including Alzheimer’s, Parkinson’s, Huntington’s, multiple sclerosis and epilepsy.
Synthetic cannabinoid receptor agonists/antagonists or compounds can provide symptom relief or control the progression of neurological diseases. However, the molecular mechanism and the effectiveness of these agents in controlling the progression of most of these diseases remain unclear.
Cannabinoids may exert effects via a number of mechanisms and interactions with neurotransmitters, neurotropic factors and neuropeptides.
Leptin is a peptide hormone involved in the regulation of food intake and energy balance via its actions on specific hypothalamic nuclei. Leptin receptors are widely expressed throughout the brain, especially in the hippocampus, basal ganglia, cortex and cerebellum. Leptin has also shown neuroprotective properties in a number of neurological disorders, such as Parkinson’s and Alzheimer’s.
Therefore, cannabinoid and leptin hold therapeutic potential for neurological diseases.
Further elucidation of the molecular mechanisms underlying the effects on these agents may lead to the development of new therapeutic strategies for the treatment of neurological disorders.”
“Sativex® is an oromucosal spray, containing equivalent amounts of Δ9 -tetrahydrocannabinol (Δ9 -THC) and cannabidiol (CBD)-botanical drug substance (BDS), and which has been approved for the treatment of spasticity and pain associated to multiple sclerosis (MS).
In this study, we investigated whether Sativex® may also serve as a disease-modifying agent in the Theiler’s murine encephalomyelitis virus induced demyelinating disease model of MS…
The data support the therapeutic potential of Sativex® to slow MS progression and its relevance in CNS repair.”
http://www.ncbi.nlm.nih.gov/pubmed/25857324
http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/
“Clinical trials investigating the analgesic efficacy of cannabinoids in multiple sclerosis have yielded mixed results, possibly due to psychotropic side effects mediated by cannabinoid CB1 receptors. We hypothesized that a CB2-specific agonist (JWH-133) would decrease hyperalgesia in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis…
Our results suggest that JWH-133 acts at CB2 receptors, most likely within the dorsal horn of the spinal cord, to suppress the hypersensitivity associated with experimental autoimmune encephalomyelitis.
These are the first pre-clinical studies to directly promote CB2 as a promising target for the treatment of central pain in an animal model of multiple sclerosis.”
“Since the identification of the endocannabinoid system, two G protein-coupled receptors (GPCRs) of this complex system were identified and characterized: cannabinoid receptors type 1 (CB1R) and type 2 (CB2R).
In addition to orthosteric and subsequently allosteric ligands, new strategies have been used to target CBRs.
Bivalent ligands and multifunctional ligands acting at diverse biological targets have been designed, synthesized, and characterized for both CBRs. Due to their altered receptor binding and pharmacological profiles, they are interesting tools to explore CBR functions and their interactions with other physiological systems.
Moreover, this approach may bear therapeutic advantages in the therapy of CBR-related disorders, especially multifactorial diseases.
Promising prospects include anorectics with fewer side effects, analgesics with decreased tolerance, and therapeutics with multiple pharmacological activities for the treatment of cancer, inflammation, multiple sclerosis, Huntington’s and Alzheimer’s diseases.”
“This study aims to evaluate the cost-effectiveness of Sativex® (9-delta-tetrahydrocannabinol plus cannabidiol oromucosal spray) when used as add-on therapy for management of resistant MS-related spasticity in the context of the Italian healthcare system…
Sativex can be regarded as a cost-effective treatment option for patients with MS-related spasticity in Italy.”
http://www.ncbi.nlm.nih.gov/pubmed/25771713
http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/
“Sativex is an emergent treatment option for spasticity in patients affected by multiple sclerosis (MS).
This oromucosal spray, acting as a partial agonist at cannabinoid receptors, may modulate the balance between excitatory and inhibitory neurotransmitters, leading to muscle relaxation that is in turn responsible for spasticity improvement.
The aim of our study was to investigate the role of Sativex in improving spasticity and related symptomatology in MS patients by means of an extensive neurophysiological assessment of sensory-motor circuits…
Our data showed an increase of intracortical inhibition, a significant reduction of spinal excitability, and an improvement in spasticity and associated symptoms.
Thus, we can speculate that Sativex could be effective in reducing spasticity by means of a double effect on intracortical and spinal excitability.”
“To investigate the regulation of cannabinoid receptors CB1 and CB2 on immune cells by proinflammatory cytokines and its potential relevance to the inflammatory neurological disease, multiple sclerosis (MS).
CB1 and CB2 signalling may be anti-inflammatory and neuroprotective in neuroinflammatory diseases.
Cannabinoids can suppress inflammatory cytokines…
The levels of CB1 and CB2 can be up-regulated by inflammatory cytokines, which can explain their increase in inflammatory conditions including MS”
http://www.ncbi.nlm.nih.gov/pubmed/25704169
http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/