Tag Archives: THC

Advances in the management of multiple sclerosis spasticity: recent clinical trials.

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“Most patients with multiple sclerosis (MS) experience spasticity as the clinical course evolves. Associated symptoms include (often painful) spasms, urinary dysfunction and sleep disturbances. THC:CBD oromucosal spray (Sativex®) is approved for symptom improvement in adult patients with moderate to severe MS-related spasticity who have not responded adequately to other antispasticity medication and who demonstrate clinically significant improvement in spasticity-related symptoms during an initial trial of therapy.

SUMMARY:

In pivotal clinical trials of THC:CBD oromucosal spray, a meaningful proportion of patients with treatment-resistant MS spasticity achieved clinically relevant improvement with active treatment versus placebo. The utility of a 4-week trial of therapy to identify patients who respond to treatment was demonstrated in an enriched-design study.

THC:CBD oromucosal spray was well tolerated in these studies, with no evidence of effects typically associated with recreational cannabis use.

In a subsequent post approval clinical trial, THC:CBD oromucosal spray had no statistically significant effect on cognition and mood compared with placebo.

Moreover, after 50 weeks’ treatment, approximately two-thirds of patients, physicians and caregivers reported improvement from baseline in spasticity based on global impressions of change.

In phase III clinical trials, approximately one-third of MS patients with treatment-resistant spasticity had a clinically relevant and statistically significant response to THC:CBD oromucosal spray.

In addition to a reduction in spasticity, responders experienced meaningful relief from associated symptoms.

THC:CBD oromucosal spray was generally well tolerated and efficacy was maintained over the longer term.

A post-approval clinical trial indicated no effect of THC:CBD oromucosal spray on cognition or mood after 50 weeks of use.”

http://www.ncbi.nlm.nih.gov/pubmed/25278117

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

Advances in the management of multiple sclerosis spasticity: multiple sclerosis spasticity nervous pathways.

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“Involvement of the endocannabinoid system in pathophysiological mechanisms responsible for spasticity has been demonstrated in animal models of MS…

Evidence indicates that the antispasticity effects of THC:CBD oromucosal spray (Sativex®) are associated with enhanced cortical long-term potentiation.

CB1 receptors, which are associated with movement, postural control, and pain and sensory perception, influence glutamatergic pathways.

THC:CBD oromucosal spray was shown to reverse motor cortex plasticity from long-term depression through long-term potentiation of synaptic transmission, thereby restoring, at least in part, effective corticospinal inputs to spinal circuits.”

http://www.ncbi.nlm.nih.gov/pubmed/25278116

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

A multicentre, open-label, follow-on study to assess the long-term maintenance of effect, tolerance and safety of THC/CBD oromucosal spray in the management of neuropathic pain.

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“Peripheral neuropathic pain (PNP) poses a significant clinical challenge.

The long-term efficacy of delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray was investigated…

THC/CBD spray was well tolerated for the study duration and patients did not seek to increase their dose with time, with no new safety concerns arising from long-term use.

In this previously difficult to manage patient population, THC/CBD spray was beneficial for the majority of patients with PNP associated with diabetes or allodynia.”

http://www.ncbi.nlm.nih.gov/pubmed/25270679

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

Δ(9)-tetrahydrocannabinol targeting estrogen receptor signaling: the possible mechanism of action coupled with endocrine disruption.

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“Δ(9)-Tetrahydrocannabinol (Δ(9)-THC), a biologically active constituent of marijuana, possesses a wide variety of pharmacological and toxicological effects (e.g., analgesia, hypotension, reduction of inflammation, and anti-cancer effects).

Among Δ(9)-THC’s biological activities, its recognized anti-estrogenic activity has been the subject of investigations.

… Δ(9)-THC is used as both a drug of abuse (marijuana) and as a preventive therapeutic to treat pain and nausea in cancer patients undergoing chemotherapy…

…important to investigate the mechanistic basis underlying the anti-estrogenic activity of Δ(9)-THC…

We have recently reported that ERβ, a second type of ER, is involved in the Δ(9)-THC abrogation of E2/ERα-mediated transcriptional activity. Here we discuss the possible mechanism(s) of the Δ(9)-THC-mediated disruption of E2/ERα signaling by presenting our recent findings as well.”

http://www.ncbi.nlm.nih.gov/pubmed/25177025

 

Engineering of Δ9-tetrahydrocannabinol delivery systems based on surface modified-PLGA nanoplatforms.

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“The objective of this work is to develop a nanoplatform that can potentiate the oral administration of Δ9-tetrahidrocannabinol, a highly lipophilic active agent with very promising antiproliferative and antiemetic activities…

Results were satisfactorily used to define the optimum engineering conditions to formulate surface modified nanoparticles for the efficient oral administration of Δ9-tetrahydrocannabinol.

To the best of our knowledge, this is the first time that biocompatible polymeric nanoparticles have been formulated for Δ9-tetrahydrocannabinol delivery.”

http://www.ncbi.nlm.nih.gov/pubmed/25262411

Effect of Marijuana Use on Outcomes in Traumatic Brain Injury.

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“Traumatic brain injury (TBI) is associated with significant morbidity (sickness) and mortality (death).

Several studies have demonstrated neuroprotective effects of cannabinoids.

The objective of this study was to establish a relationship between the presence of a positive toxicology screen for tetrahydrocannabinol (THC) and mortality after TBI…

After adjusting for differences between the study cohorts on logistic regression, a THC(+) screen was independently associated with survival after TBI.

A positive THC screen is associated with decreased mortality in adult patients sustaining TBI.”

http://www.ncbi.nlm.nih.gov/pubmed/25264643

http://www.thctotalhealthcare.com/category/brain-trauma/

Drug-resistant MS spasticity treatment with Sativex® add-on and driving ability.

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“The aim of the present observational study was to determine the effects of a delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) oromucosal spray (Sativex® spray), brand name Sativex® , indicated for drug-resistant MS spasticity, on the driving ability of treated MS patients…

Treatment of MS patients with Sativex® does not negatively impact on driving ability and may improve moderate to severe treatment-resistant MS spasticity.”

http://www.ncbi.nlm.nih.gov/pubmed/25208898

Impact of efficacy at the mu opioid receptor on antinociceptive effects of combinations of mu opioid receptor agonists and cannabinoid receptor agonists.

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“Cannabinoid receptor agonists, such as delta-9-tetrahydrocannabinol (Δ9-THC),  have antinociceptive effects and, are increasingly used to treat pain, and medications including cannabinoid receptor agonists are approved for use in humans.

Cannabinoid receptor agonists [e.g. Δ9-tetrahydrocannabinol (Δ9-THC)] enhance the antinociceptive effects of mu opioid receptor agonists, suggesting that combining cannabinoids with opioids would improve pain treatment.

…these results provide additional support for combining opioids with cannabinoids to treat pain.”

http://jpet.aspetjournals.org/content/early/2014/09/05/jpet.114.216648.long

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

Oxidative stress and cannabinoid receptor expression in type-2 diabetic rat pancreas following treatment with Δ9 -THC.

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“We can suggest that Δ9 -THC may be an important agent for the treatment of oxidative damages induced by diabetes…

Furthermore, the present study for the first time emphasizes that Δ9 -THC may improve pancreatic cells via cannabinoid receptors in diabetes.

The aim of present study was to elucidate the effects of Δ9 -THC, a natural cannabinoid receptor agonist, on the expression and localization of cannabinoid receptors, and oxidative stress statue in type-2 diabetic rat pancreas.

Results demonstrate that the cannabinoid receptors are presented in both Langerhans islets and duct regions.

The curative effects of Δ9 -THC can be occurred via activation of cannabinoid receptors in diabetic rat pancreas.

Moreover, it may provide a protective effect against oxidative damage induced by diabetes.

Thus, it is suggested that Δ9 -THC can be a candidate for therapeutic alternatives of diabetes symptoms.”

http://www.ncbi.nlm.nih.gov/pubmed/25187240

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

Cannabinoid CB2 receptor agonists protect the striatum against malonate toxicity: relevance for Huntington’s disease.

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“Cannabinoid agonists might serve as neuroprotective agents in neurodegenerative disorders… Cannabinoids may also offer neuroprotection in Huntington’s disease (HD)…

Here, we examined this hypothesis in a rat model ofHuntington’s disease (HD)…

Our results showed that only compounds able to activate CB2 receptors were capable of protecting striatal projection neurons from malonate-induced death. That CB2 receptor agonists are neuroprotective was confirmed…

…neuroprotection was attained exclusively with antioxidant cannabinoids like Δ9-tetrahydrocannabinol (Δ9-THC; or cannabidiol (CBD)…

In summary, our results demonstrate that stimulation of CB2 receptors protect the striatum against malonate toxicity, likely through a mechanism involving glial cells, in particular reactive microglial cells in which CB2 receptors would be upregulated in response to the lesion. Activation of these receptors would reduce the generation of proinflammatory molecules like TNF-alpha.

Altogether, our results support the hypothesis that CB2 receptors could constitute a therapeutic target to slowdown neurodegeneration in HD.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2706932/

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