The biology that underpins the therapeutic potential of cannabis-based medicines for the control of spasticity in multiple sclerosis.

Posted on April 18, 2015 by David

“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/

The role of cannabinoids and leptin in neurological diseases.

Posted on April 17, 2015 by David

“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.”

http://www.ncbi.nlm.nih.gov/pubmed/25880465

Drug repurposing and emerging adjunctive treatments for schizophrenia.

Posted on April 14, 2015 by David

“Schizophrenia is a frequent disorder, which substantially impairs patients’ quality of life. Moreover, the burden of illness for patients, their families and for the society, in general, is substantial.

Given the current failure of a number of mechanistically new drugs, repurposed compounds may serve as alternative and/or adjunctive agents for schizophrenic patients and for treatment refractory patients in particular. Anti-inflammatory drugs, as well as N-acetylcysteine, a precursor of the major antioxidant glutathione, hormones, glutamatergic and nicotinergic compounds, ‘nutraceuticals’ (e.g., ω-3 fatty acids) and cannabidiol, an endocannabinoid modulator, represent promising agents in this field.”

http://www.ncbi.nlm.nih.gov/pubmed/25866122

The multidrug transporter ABCG2 (BCRP) is inhibited by plant-derived cannabinoids.

Posted on April 11, 2015 by David

“Multiple drug resistance (MDR) is one of the principal causes of chemotherapeutic treatment failure in malignant disease…

Cannabinoids are used therapeutically for the palliation of the adverse side effects associated with cancer chemotherapy. However, cannabinoids also inhibit both the activity and expression of the multidrug transporter…

Cannabinoids are novel Abcg2/ABCG2 inhibitors, reversing the Abcg2-mediated multidrug-resistant phenotype in vitro. This finding may have implications for the co-administration of cannabinoids with pharmaceuticals that are ABCG2 substrates…

Cannabis and cannabinoid preparations are used as therapeutic agents.

One of the many applications of cannabinoids is in the palliation of cancer chemotherapy-induced nausea, vomiting and anorexia. Indeed, the commercial preparations, Marinol and Cesamet, containing the synthetic Δ9-tetrahydrocannabinol (THC) analogue, dronabinol (or nabilone), are approved in some countries for this use.

Interestingly, in the future, cannabinoids might be co-administered with conventional cancer chemotherapies not only in a palliative capacity but also as primary anticancer medications. Accordingly, cannabinoids have demonstrated antiproliferative actions on cancer cells in vitro and in vivo…

To conclude, this is the first study to address the interaction of cannabinoids with the multidrug transporter ABCG2/Abcg2. The results presented here indicate that plant-derived cannabinoids are a novel class of ABCG2/Abcg2 inhibitors. Our results may have important implications for the use of cannabinoid compounds with therapeutic drugs that are substrates for ABCG2.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2190019/

Role of the endogenous cannabinoid system in nicotine addiction: novel insights.

Posted on April 11, 2015 by David

“Several lines of evidence have shown that the endogenous cannabinoids are implicated in several neuropsychiatric diseases. Notably, preclinical and human clinical studies have shown a pivotal role of the cannabinoid system in nicotine addiction.

The CB1 receptor inverse agonist/antagonist rimonabant (also known as SR141716) was effective to decrease nicotine-taking and nicotine-seeking in rodents, as well as the elevation of dopamine induced by nicotine in brain reward area. Rimonabant has been shown to improve the ability of smokers to quit smoking in randomized clinical trials. However, rimonabant was removed from the market due to increased risk of psychiatric side-effects observed in humans.

Recently, other components of the endogenous cannabinoid system have been explored. Here, we present the recent advances on the understanding of the role of the different components of the cannabinoid system on nicotine’s effects.

Those recent findings suggest possible alternative ways of modulating the cannabinoid system that could have implication for nicotine dependence treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/25859226

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

A sativex-like combination of phytocannabinoids as a disease-modifying therapy in a viral model of multiple sclerosis.

Posted on April 11, 2015 by David

“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/

Parental reporting of response to oral cannabis extracts for treatment of refractory epilepsy.

Posted on April 9, 2015 by David

“Oral cannabis extracts (OCEs) have been used in the treatment of epilepsy; however, no studies demonstrate clear efficacy. We report on a cohort of pediatric patients with epilepsy who were given OCE and followed in a single tertiary epilepsy center…

Seventy-five patients were identified of which 57% reported any improvement in seizure control and 33% reported a >50% reduction in seizures (responders).

Our retrospective study of OCE use in pediatric patients with epilepsy demonstrates that some families reported patient improvement with treatment;

We strongly support the need for controlled, blinded studies to evaluate the efficacy and safety of OCE for treatment of pediatric epilepsies using accurate seizure counts, formal neurocognitive assessments, as well as EEG as a biomarker.

This study provides Class III evidence that OCE is well tolerated by children and adolescents with epilepsy.”

http://www.ncbi.nlm.nih.gov/pubmed/25845492

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

Activation of Cannabinoid CB2 receptors Reduces Hyperalgesia in an Experimental Autoimmune Encephalomyelitis Mouse Model of Multiple Sclerosis.

Posted on April 8, 2015 by David

“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.”

http://www.ncbi.nlm.nih.gov/pubmed/25849525

Efficacy of Inhaled Cannabis on Painful Diabetic Neuropathy.

Posted on April 7, 2015 by David

“A randomized, double-blinded, placebo controlled crossover study was conducted in 16 patients with painful diabetic peripheral neuropathy to assess the short-term efficacy and tolerability of inhaled cannabis.

In a cross-over design, each participant was exposed to a single dosing session of placebo, low (1% tetrahydrocannabinol, THC), medium (4% THC), or high (7% THC) doses of cannabis…

This small, short-term, placebo-controlled trial of inhaled cannabis demonstrated a dose dependent reduction in diabetic peripheral neuropathy pain in patients with treatment-refractory pain.

This adds preliminary evidence to support further research on the efficacy of the cannabinoids in neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/25843054

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

Increased Cerebral Cannabinoid-1 Receptor Availability Is a Stable Feature of Functional Dyspepsia: A [F]MK-9470 PET Study.

Posted on April 3, 2015 by David

“Functional dyspepsia (FD) is a prevalent functional gastrointestinal disorder (FGID) defined by chronic epigastric symptoms in the absence of organic abnormalities likely to explain them. Comorbidity with mood and anxiety disorders as well as with other FGIDs and functional somatic syndrome (FSS) is high. FD is characterized by abnormal regional cerebral activity in cognitive/affective pain modulatory circuits, but it is unknown which neurotransmitter systems are involved.

The authors aimed to assess and compare in vivo cerebral cannabinoid-1 (CB1) receptor availability between FD patients and age-, gender- and BMI-matched healthy controls (HC).

FD patients had significantly higher CB1 receptor availability in the cerebral regions involved in (visceral) nociception (brainstem, insula, anterior cingulate cortex) as well as in the homeostatic and hedonic regulation of food intake [hypothalamus, (ventral) striatum]….

Although these findings need replication in larger samples, they suggest that the abnormal brain activity in several of these regions, previously demonstrated in FD, may be due to a sustained endocannabinoid system dysfunction, identifying it as a potential novel target for treatment and warranting further studies to elucidate whether it is also a feature of other FGIDs or FSSs.”

http://www.ncbi.nlm.nih.gov/pubmed/25833408