THC Total Health Care

A comprehensive encyclopedia of THC related medical research articles

Sativex® as Add-on therapy Vs. further optimized first-line ANTispastics (SAVANT) in resistant multiple sclerosis spasticity: a double-blind, placebo-controlled randomised clinical trial.

Posted on May 26, 2018 by David Worrell

“Purpose/aim: To evaluate the efficacy of tetrahydrocannabinol [THC]:cannabidiol [CBD] oromucosal spray (Sativex®) as add-on therapy to optimized standard antispasticity treatment in patients with moderate to severe multiple sclerosis (MS) spasticity.

RESULTS:

Of 191 patients who entered Phase A, 106 were randomised in Phase B to receive add-on THC:CBD spray (n = 53) or placebo (n = 53). The proportion of clinically-relevant responders after 12 weeks (≥ 30% NRS improvement; primary efficacy endpoint) was significantly greater with THC:CBD spray than placebo (77.4 vs 32.1%; P < 0.0001). Compared with placebo, THC:CBD spray also significantly improved key secondary endpoints: changes in mean spasticity NRS (P < 0.0001), mean pain NRS (P = 0.0013), and mean modified Ashworth’s scale (P = 0.0007) scores from Phase B baseline to week 12. Adverse events, when present, were mild/moderate and without new safety concerns.

CONCLUSIONS:

Add-on THC:CBD oromucosal spray provided better and clinically relevant improvement of resistant MS spasticity compared with adjusting first-line antispasticity medication alone.” https://www.ncbi.nlm.nih.gov/pubmed/29792372 https://www.tandfonline.com/doi/abs/10.1080/00207454.2018.1481066]]>

Review of the neurological benefits of phytocannabinoids.

Posted on May 18, 2018 by David Worrell

“Numerous physical, psychological, and emotional benefits have been attributed to marijuana since its first reported use in 2,600 BC in a Chinese pharmacopoeia. The phytocannabinoids, cannabidiol (CBD), and delta-9-tetrahydrocannabinol (Δ9-THC) are the most studied extracts from cannabis sativa subspecies hemp and marijuana. CBD and Δ9-THC interact uniquely with the endocannabinoid system (ECS). Through direct and indirect actions, intrinsic endocannabinoids and plant-based phytocannabinoids modulate and influence a variety of physiological systems influenced by the ECS.

METHODS:

In 1980, Cunha et al. reported anticonvulsant benefits in 7/8 subjects with medically uncontrolled epilepsy using marijuana extracts in a phase I clinical trial. Since then neurological applications have been the major focus of renewed research using medical marijuana and phytocannabinoid extracts.

RESULTS:

Recent neurological uses include adjunctive treatment for malignant brain tumors, Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, neuropathic pain, and the childhood seizure disorders Lennox-Gastaut and Dravet syndromes. In addition, psychiatric and mood disorders, such as schizophrenia, anxiety, depression, addiction, postconcussion syndrome, and posttraumatic stress disorders are being studied using phytocannabinoids.

CONCLUSIONS:

In this review we will provide animal and human research data on the current clinical neurological uses for CBD individually and in combination with Δ9-THC. We will emphasize the neuroprotective, antiinflammatory, and immunomodulatory benefits of phytocannabinoids and their applications in various clinical syndromes.” https://www.ncbi.nlm.nih.gov/pubmed/29770251 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938896/]]>

The influence of THC:CBD oromucosal spray on driving ability in patients with multiple sclerosis-related spasticity.

Posted on May 16, 2018 by David Worrell

“Driving ability is a key function for the majority of patients with multiple sclerosis (MS) to help maintain daily interactions. Both physical and cognitive disability, as well as treatments, may affect the ability to drive. Spasticity is a common symptom associated with MS, and it may affect driving performance either directly or via the medications used to treat it. In this article, we review the evidence relating the antispasticity medicine, Δ⁹-tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray (Sativex^®), and its potential impact on driving performance. The results from THC:CBD oromucosal spray driving studies and real-world registries did not show any evidence of an increase in motor vehicle accidents associated with THC:CBD oromucosal spray. The majority of patients reported an improvement in driving ability after starting THC:CBD oromucosal spray, and it was speculated that this may be related to reduced spasticity and/or better cognitive function. THC:CBD oromucosal spray was shown not to impair driving performance.” https://www.ncbi.nlm.nih.gov/pubmed/29761015 https://onlinelibrary.wiley.com/doi/abs/10.1002/brb3.962

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Palatability and oral cavity tolerability of THC:CBD oromucosal spray and possible improvement measures in multiple sclerosis patients with resistant spasticity: a pilot study.

Posted on April 24, 2018 by David Worrell

“Complaints about Δ⁹-tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray (Sativex^®; GW Pharma Ltd, Sailsbury, UK) in the management of multiple sclerosis spasticity include unpleasant taste and oral mucosal anomalies. This pilot study assessed the use of sugar-free chewing gum and/or a refrigerated bottle of THC:CBD oromucosal spray to mitigate these effects.

RESULTS:

Taste perception in patients receiving chewing gum ± cold bottle intervention (Groups A and C combined) was significantly (p = 0.0001) improved from baseline to week 4 while maintaining spasticity control.

CONCLUSION:

Patient comfort, satisfaction and treatment adherence may benefit from these interventions.” https://www.ncbi.nlm.nih.gov/pubmed/29683408 https://www.futuremedicine.com/doi/10.2217/nmt-2017-0056

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Therapeutic cannabinoids in multiple sclerosis: immunomodulation revisited.

Posted on April 12, 2018 by David Worrell

“Cannabinoids are compounds with pleiotropic properties that act on the cannabinoid receptors, CB1 and CB2, and are divided into endocannabinoids, the endogenous ligands of these receptors, synthetic cannabinoids and phytocannabinoids. The latter are derived from the plant Cannabis sativa. The therapeutic and psychoactive properties of this plant have been observed and used for centuries. Of the over 60 compounds that are unique to Cannabis sativa, the substances that have been attributed the greatest therapeutic potential are Δ⁹ – tetrahydrocannabinol (THC) and cannabidiol (CBD), both of which, used alone or combined with each other, have become approved drugs.” https://www.ncbi.nlm.nih.gov/pubmed/29633480 https://onlinelibrary.wiley.com/doi/abs/10.1111/ene.13658]]>

The therapeutic effects of Cannabis and cannabinoids: An update from the National Academies of Sciences, Engineering and Medicine report

Posted on April 8, 2018 by David Worrell

“The National Academies of Sciences, Engineering and Medicine conducted a rapid turn-around comprehensive review of recent medical literature on The Health Effects of Cannabis and Cannabinoids. In the Therapeutics chapter reviewed here, the report concluded that there was conclusive or substantial evidence that Cannabis or cannabinoids are effective for the treatment of pain in adults; chemotherapy-induced nausea and vomiting and spasticity associated with multiple sclerosis. Moderate evidence was found for secondary sleep disturbances. The evidence supporting improvement in appetite, Tourette syndrome, anxiety, posttraumatic stress disorder, cancer, irritable bowel syndrome, epilepsy and a variety of neurodegenerative disorders was described as limited, insufficient or absent. A chapter of the NASEM report enumerated multiple barriers to conducting research on Cannabis in the US that may explain the paucity of positive therapeutic benefits in the published literature to date. The 2017 National Academies of Sciences, Engineering and Medicine report, like the 1999 Institute of Medicine publication before it, did conclude that there is evidence to support the therapeutic effect of Cannabis and cannabinoids in a number of conditions. Although it is well appreciated that the plural of anecdote is not evidence, it must also be remembered that in the case of evaluating the therapeutic effects of Cannabis as published in the medical literature, the absence of evidence is not necessarily indicative of evidence of the absence of effectiveness. ” http://www.ejinme.com/article/S0953-6205(18)30003-7/fulltext

“Researchers claim that medicinal cannabis is safe and effective for pain relief, and are calling for the treatment to be properly established in our modern medical arsenal” https://www.drugtargetreview.com/news/30737/medicinal-cannabis-safe-effective/

“Medicinal cannabis is safe and effective – it’s time to reboot research” https://www.elsevier.com/about/press-releases/research-and-journals/medicinal-cannabis-is-safe-and-effective-its-time-to-reboot-research

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Cannabidiol to Improve Mobility in People with Multiple Sclerosis

Posted on April 7, 2018 by David Worrell

“Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that affects an estimated 2.3 million people worldwide. The symptoms of MS are highly varied but frequently include pain, muscle spasticity, fatigue, inflammation, and depression. These symptoms often lead to reduced physical activity, negatively impact functional mobility, and have a detrimental impact on patients’ quality of life.

Although recent years have seen significant advances in disease modifying therapy, none of the current treatments halts or cures MS related symptoms. As a consequence, many people with MS (PwMS) look for alternative and complementary therapies such as cannabis.

The cannabis plant contains many biologically active chemicals, including ~60 cannabinoids. Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are typically the most concentrated chemical components of cannabis and believed to primarily drive therapeutic benefit.

There is evidence that CBD has a number of beneficial pharmacological effects. It is anti-inflammatory, antioxidative, antiemetic, antipsychotic, and neuroprotective. The review of 132 original studies by Bergamaschi et al. describes the safety profile of CBD by highlighting that catalepsy is not induced and physiological parameters (heart rate, blood pressure, and body temperature) are not altered. Moreover, psychomotor and psychological functions are not negatively affected. High doses of up to 1,500 mg per day and chronic use have been repeatedly shown to be well tolerated by humans.

Additionally, there is also evidence that CBD may reduce the negative psychotropic effects, memory impairment, and appetite stimulation, anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions.

Anecdotal reports indicate that an increasing number of PwMS use cannabis (medical marijuana) as a supplement to improve their mobility.

Based on the following considerations, it is our opinion that CBD supplementation maybe advisable for PwMS to reduce fatigue, pain, spasticity, and ultimately improve mobility. “

https://www.frontiersin.org/articles/10.3389/fneur.2018.00183/full]]>

Clinical response to Nabiximols correlates with the down-regulation of immune pathways in Multiple Sclerosis.

Posted on March 13, 2018 by David Worrell

“Nabiximols (Sativex^® ) is a cannabinoid-based compound used for the treatment of moderate to severe spasticity in multiple sclerosis (MS). The aim of the study is to investigate the effect of the administration of Nabiximols on blood transcriptome profile of MS patients and to interpret it in the context of pathways and networks.

Our findings support the immunomodulatory activity of cannabinoids in MS patients. Further studies in more specific cell types are needed to refine these results.” https://www.ncbi.nlm.nih.gov/pubmed/29528549 http://onlinelibrary.wiley.com/doi/10.1111/ene.13623/abstract

“Cannabinoid compounds suppress immune function, and while this could compromise one’s ability to fight infections, immune suppression is the desired effect for therapies for autoimmune diseases.” https://www.ncbi.nlm.nih.gov/pubmed/29512125

“Cannabinoids have emerged as powerful drug candidates for the treatment of inflammatory and autoimmune diseases due to their immunosuppressive properties.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923447/

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Evaluation of Marijuana Compounds on Neuroimmune Endpoints in Experimental Autoimmune Encephalomyelitis.

Posted on March 8, 2018 by David Worrell

“Cannabinoid compounds refer to a group of more than 60 plant-derived compounds in Cannabis sativa, more commonly known as marijuana. Exposure to marijuana and cannabinoid compounds has been increasing due to increased societal acceptance for both recreational and possible medical use. Cannabinoid compounds suppress immune function, and while this could compromise one’s ability to fight infections, immune suppression is the desired effect for therapies for autoimmune diseases. It is critical, therefore, to understand the effects and mechanisms by which cannabinoid compounds alter immune function, especially immune responses induced in autoimmune disease. Therefore, this unit will describe induction and assessment of the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS), and its potential alteration by cannabinoid compounds. The unit includes three approaches to induce EAE, two of which provide correlations to two forms of MS, and the third specifically addresses the role of autoreactive T cells in EAE.” https://www.ncbi.nlm.nih.gov/pubmed/29512125 http://onlinelibrary.wiley.com/doi/10.1002/cptx.43/abstract]]>

The inhibition of CB1 receptor accelerates the onset and development of EAE possibly by regulating microglia/macrophages polarization.

Posted on March 5, 2018 by David Worrell

“Cannabinoid 1 receptor (CB₁R) regulates the neuro-inflammatory and neurodegenerative damages of experimental autoimmune encephalomyelitis (EAE) and of multiple sclerosis (MS). The mechanism by which CB₁R inhibition exerts inflammatory effects is still unclear. Here, we explored the cellular and molecular mechanisms of CB₁R in the treatment of EAE by using a specific and selective CB₁R antagonist SR141716A. Our study demonstrated that SR141716A accelerated the clinical onset and development of EAE, accompanied by body weight loss. SR141716A significantly up-regulated the expression of toll like receptor-4 (TLR-4) and nuclear factor-kappaB/p65 (NF-κB/p65) on microglia/macrophages of EAE mice as well as levels of inflammatory factors (TNF-α, IL-1β, IL-6) and chemokines (MCP-1, CX3CL1), accompanied by the shifts of cytokines from Th2 (IL-4, IL-10) to Th1 (IFN-γ)/Th17 (IL-17) in the spinal cords of EAE mice. Similar changes happened on splenic mononuclear cells (MNCs) except chemokine CX3CL1. Consistently, SR141716A promoted BV-2 microglia to release inflammatory factors (TNF-α, IL-1β, IL-6) while inhibited the production of IL-10 and chemokines (MCP-1, CX3CL1). Furthermore, when splenic CD4⁺ T cells co-cultured with SR141716A-administered BV-2 microglia, the levels of IL-4 and IL-10 were decreased while production of IL-17 and IFN-γ increased significantly. Our research indicated that inhibition of CB₁R induced M1 phenotype-Th17 axis changed of microglia/macrophages through TLR-4 and NF-κB/p65 which accelerated the onset and development of EAE. Therefore, CB₁R may be a promising target for the treatment of MS/EAE, but its complexity remains to be carefully considered and studied in further clinical application.” https://www.ncbi.nlm.nih.gov/pubmed/29501084 http://www.jni-journal.com/article/S0165-5728(17)30467-8/fulltext]]>