Speechlessness in Gilles de la Tourette Syndrome: Cannabis-Based Medicines Improve Severe Vocal Blocking Tics in Two Patients.

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“We report the cases of two young German male patients with treatment-resistant Tourette syndrome (TS), who suffer from incapacitating stuttering-like speech disfluencies caused by vocal blocking tics and palilalia. Case 1: a 19-year old patient received medical cannabis at a dose of 1 × 0.1 g cannabis daily. Case 2: a 16-year old patient initially received dronabinol at a maximum dose of 22.4-33.6 mg daily. Both treatments provided significant symptom improvement of vocal blocking tics as well as of comorbid conditions and were well tolerated. Thus, cannabis-based medicine appears to be effective in treatment-resistant TS patients with vocal blocking tics.”

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Cannabidiol reduces seizure frequency in Dravet syndrome

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“Cannabidiol is effective in treating drug-resistant seizures in Dravet syndrome, according to a new clinical trial. For the first time, a multinational, randomized, double-blind, placebo-controlled trial has confirmed controversial anecdotal evidence supporting the efficacy of cannabinoids in epilepsy.” https://www.nature.com/nrneurol/journal/v13/n7/full/nrneurol.2017.86.html

“Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome”  http://www.nejm.org/doi/10.1056/NEJMoa1611618

“Cannabinoids for Epilepsy — Real Data, at Last”  http://www.nejm.org/doi/full/10.1056/NEJMe1702205

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Cannabis and intractable chronic pain: an explorative retrospective analysis of Italian cohort of 614 patients.

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“Despite growing interest in the therapeutic use of cannabis to manage chronic pain, only limited data that address these issues are available. In recent years, a number of nations have introduced specific laws to allow patients to use cannabis preparations to treat a variety of medical conditions. In 2015, the Italian government authorized the use of cannabis to treat several diseases, including chronic pain generally, spasticity in multiple sclerosis, cachexia and anorexia among AIDS and cancer patients, glaucoma, Tourette syndrome, and certain types of epilepsy. We present the first snapshot of the Italian experience with cannabis use for chronic pain over the initial year of its use.

METHODS:

This is a retrospective case series analysis of all chronic pain patients treated with oral or vaporized cannabis in six hubs during the initial year following the approval of the new Italian law (December 2015 to November 2016). We evaluated routes of administration, types of cannabis products utilized, dosing, and effectiveness and safety of the treatment.

RESULTS:

As only one of the six centers has extensively used cannabinoids for intractable chronic pain (614 patients of 659), only the population from Azienda Ospedaliero Universitaria Pisana (Pisa) was considered. Cannabis tea was the primary mode of delivery, and in almost all cases, it was used in association with all the other pain treatments. Initial and follow-up cannabinoid concentrations were found to vary considerably. At initial follow-up, 76.2% of patients continued the treatment, and <15% stopped the treatment due to side effects (none of which were severe).

CONCLUSION:

We present the first analysis of Italian clinical practice of the use of cannabinoids for a large variety of chronic pain syndromes. From this initial snapshot, we determined that the treatment seems to be effective and safe, although more data and subsequent trials are needed to better investigate its ideal clinical indication.”

https://www.ncbi.nlm.nih.gov/pubmed/28579820

https://www.dovepress.com/cannabis-and-intractable-chronic-pain-an-explorative-retrospective-ana-peer-reviewed-article-JPR

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Cannabinoids for treating neurogenic lower urinary tract dysfunction in patients with multiple sclerosis: a systematic review and meta-analysis.

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“To systematically review all available evidence on efficacy and safety of cannabinoids for treating neurogenic lower urinary tract dysfunction (NLUTD) in patients with multiple sclerosis (MS).

:Preliminary data imply, that cannabinoids might be an effective and safe treatment option for NULTD in patients with MS.”

https://www.ncbi.nlm.nih.gov/pubmed/28058780

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InMed Announces Progress on COPD Treatment Using Cannabinoids

InMed Announces Progress on COPD Treatment Using Cannabinoids

“Recent research has indicated that cannabinoid-based therapies might be effective in ameliorating the most important symptoms of COPD.”

“Researchers have observed that cannabinoids can be bronchodilatory, immunosuppressive, and anti-inflammatory, suggesting that cannabinoid-based therapies might offer safer and more effective treatment options for COPD.”

“Additionally, studies have suggested that cannabinoids might help promote better sleep, support the immune system, work as an expectorant, relieve pain, and have anti-microbial properties.”

https://copdnewstoday.com/2016/12/08/inmed-announces-progress-copd-treatment-using-cannabinoids/

http://www.thctotalhealthcare.com/category/copd-chronic-obstructive-pulmonary-disease/

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Severe motor and vocal tics controlled with Sativex®.

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“A single case report on cannabinoid treatment for treatment-resistant Tourette syndrome (TS).

METHOD:

Our subject received 10.8 mg Tetrahydocannabinol and 10 mg cannabidiol daily, in the form of two oro-mucosal sprays of ‘Sativex®‘, twice daily. Assessment was pre-treatment and at week one, two, and four during treatment. He completed the Yale Global Tic Severity Scale as a subjective measure, and was videoed at each stage. The videos were objectively rated by two assessors, blind to the stage of treatment, using the Original Rush Videotape Rating Scale.

RESULTS:

Both subjective and objective measures demonstrated marked improvement in the frequency and severity of motor and vocal tics post-treatment. There was good interrater reliability of results.

CONCLUSIONS:

Our results support previous research suggesting that cannabinoids are a safe and effective treatment for TS and should be considered in treatment-resistant cases.

Further studies are needed to substantiate our findings.”

http://www.ncbi.nlm.nih.gov/pubmed/27558217

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The therapeutic potential of the phytocannabinoid cannabidiol for Alzheimer’s disease.

“Alzheimer’s disease (AD) is the most common neurodegenerative disorder, characterized by progressive loss of cognition. Over 35 million individuals currently have AD worldwide. Unfortunately, current therapies are limited to very modest symptomatic relief.

The brains of AD patients are characterized by the deposition of amyloid-β and hyperphosphorylated forms of tau protein. AD brains also show neurodegeneration and high levels of oxidative stress and inflammation.

The phytocannabinoid cannabidiol (CBD) possesses neuroprotective, antioxidant and anti-inflammatory properties and reduces amyloid-β production and tau hyperphosphorylation in vitro.

CBD has also been shown to be effective in vivo making the phytocannabinoid an interesting candidate for novel therapeutic interventions in AD, especially as it lacks psychoactive or cognition-impairing properties.

CBD treatment would be in line with preventative, multimodal drug strategies targeting a combination of pathological symptoms, which might be ideal for AD therapy.

Thus, this review will present a brief introduction to AD biology and current treatment options before outlining comprehensively CBD biology and pharmacology, followed by in-vitro and in-vivo evidence for the therapeutic potential of CBD. We will also discuss the role of the endocannabinioid system in AD before commenting on the potential future of CBD for AD therapy (including safety aspects).”

http://www.ncbi.nlm.nih.gov/pubmed/27471947

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New Study Finds Marijuana To Be Effective Against Depression, Migraine and Anxiety

“Research has suggested that cannabis may be a promising treatment option for a number of different physical and mental health conditions, from post-traumatic stress disorder to chronic pain. A study released this week suggests that depression , anxiety and migraine can be added to that list.

Neuroscientists from the University of Buffalo’s Research Institute on Addictions found that endocannabinoids — chemical compounds in the brain that activate the same receptors as THC, an active compound in marijuana — may be helpful in treating depression, anxiety and migraine that results from chronic stress.

In studies on rats, the researchers found that chronic stress reduced the production of endocannabinoids, which affect our cognition, emotion and behavior, and have been linked to reduced feelings of pain and anxiety, increases in appetite and overall feelings of well-being. The body naturally produces these compounds, which are similar to the chemicals in cannabis. Reduction of endocannabinoid production may be one reason that chronic stress is a major risk factor in the development of depression.

Then, the research team administered marijuana cannabinoids to the rats, finding it to be an effective way to restore endocannabinoid levels in their brains — possibly, thereby, alleviating some symptoms of depression.

“Using compounds derived from cannabis — marijuana — to restore normal endocannabinoid function could potentially help stabilize moods and ease depression,” lead researcher Dr. Samir Haj-Dahmane said in a university press release.

Recent research around marijuana’s effect on symptoms of post-traumatic stress disorder further bolsters the Buffalo neuroscientists’ findings, since both disorders involve the way the brain responds to stress. A study published last year in the journal Neuropsychopharmacology, for instance, found synthetic cannabinoids triggered changes in brain centers associated with traumatic memories in rats, preventing some of the behavioral and physiological symptoms of PTSD. Another study published last year found that patients who smoked cannabis experienced a 75 percent reduction in PTSD symptoms.

However, it’s important to note that the relationship between marijuana and depression  is complex. Some research has suggested that regular and heavy marijuana smokers are at a higher risk for depression, although a causal link between cannabis use and depression has not been established. More studies are needed in order to determine whether, and how, marijuana might be used in a clinical context for patients with depression.”  http://painphysicianjournal.co/2016/06/30/new-study-finds-marijuana-to-be-effective-against-depression-migraine-and-anxiety/

New Study Finds Marijuana To Be Effective Against Depression, Migraine and Anxiety

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Hybrid inhibitor of peripheral cannabinoid-1 receptors and inducible nitric oxide synthase mitigates liver fibrosis

 

 

“Liver fibrosis, a consequence of chronic liver injury and a way station to cirrhosis and hepatocellular carcinoma, lacks effective treatment.

Endocannabinoids acting via cannabinoid-1 receptors (CB1R) induce profibrotic gene expression and promote pathologies that predispose to liver fibrosis. CB1R antagonists produce opposite effects, but their therapeutic development was halted due to neuropsychiatric side effects.

Inducible nitric oxide synthase (iNOS) also promotes liver fibrosis and its underlying pathologies, but iNOS inhibitors tested to date showed limited therapeutic efficacy in inflammatory diseases.

Here, we introduce a peripherally restricted, orally bioavailable CB1R antagonist, which accumulates in liver to release an iNOS inhibitory leaving group.

Additionally, it was able to slow fibrosis progression and to attenuate established fibrosis. Thus, dual-target peripheral CB1R/iNOS antagonists have therapeutic potential in liver fibrosis.

Regarding the pharmacodynamics of the hybrid CB1R/iNOS inhibitor, two important principles have emerged from efforts to develop effective antifibrotic therapies. First, antifibrotic treatment strategies could aim to control the primary disease, to inhibit fibrogenic gene expression and signaling, to promote molecular mechanisms involved in fibrosis regression, or a combination of these. Second, with multiple molecular mechanisms and signaling pathways involved in fibrosis, targeting more than one could increase antifibrotic efficacy, and the hybrid CB1R/iNOS inhibitor embodies optimal characteristics on both accounts.

As to the first principle, both the endocannabinoid/CB1R system and iNOS are ideal targets, as they are known to be involved directly in the fibrotic process and also in the conditions predisposing to liver fibrosis, as detailed in the Introduction. An emerging major predisposing factor to liver fibrosis is nonalcoholic fatty liver disease, and CB1R blockade has proven effective in mitigating obesity-related hepatic steatosis in both rodent models and humans. The other two major predisposing factors, alcoholic fatty liver disease and viral hepatitis, also involve increased CB1R activity. Hepatic CB1R expression is induced either by chronic ethanol intake or the hepatitis C virus, and CB1R blockade mitigates alcohol-induced steatosis and inhibits hepatitis C virus production.

The dual targeting of peripheral CB1R and iNOS demonstrated here exemplifies the therapeutic gain obtained by simultaneously hitting more than one molecule, which could then engage distinct as well as convergent cellular pathways. The advantage of such an approach is highlighted by emerging experience with recently developed antifibrotic medications, which indicates that targeting a single pathway has limited effect on fibrotic diseases.

Thus, the approach illustrated by the present study has promise as an effective antifibrotic strategy.”

http://insight.jci.org/articles/view/87336

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Effect of combined oral doses of Δ9-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models.

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“The purpose of this study was to evaluate the potential of oral combined cannabis constituents to reduce nausea.

The objective of this study was to determine the effect of combining subthreshold oral doses of Δ9-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models of conditioned gaping.

RESULTS:

For acute nausea, i.g. administration of subthreshold doses of THC (0.5 and 1 mg/kg) or CBDA (0.5 and 1 μg/kg) significantly suppressed acute nausea-induced gaping, whereas higher individual doses of both THC and CBDA were maximally effective. Combined i.g. administration of higher doses of THC and CBDA (2.5 mg/kg THC-2.5 μg/kg CBDA; 10 mg/kg THC-10 μg/kg CBDA; 20 mg/kg THC-20 μg/kg CBDA) also enhanced positive hedonic reactions elicited by saccharin solution during conditioning. For anticipatory nausea, combined subthreshold i.g. doses of THC (0.1 mg/kg) and CBDA (0.1 μg/kg) suppressed contextually elicited conditioned gaping. When administered i.g., THC was effective on its own at doses ranging from 1 to 10 mg/kg, but CBDA was only effective at 10 μg/kg. THC alone was equally effective by intraperitoneal (i.p.) and i.g. administration, whereas CBDA alone was more effective by i.p. administration (Rock et al. in Psychopharmacol (Berl) 232:4445-4454, 2015) than by i.g. administration.

CONCLUSIONS:

Oral administration of subthreshold doses of THC and CBDA may be an effective new treatment for acute nausea and anticipatory nausea and appetite enhancement in chemotherapy patients.”

http://www.ncbi.nlm.nih.gov/pubmed/27438607

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