Single center experience with medical cannabis in Gilles de la Tourette syndrome.

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“Patients with Gilles de la Tourette syndrome (GTS) experience reduced function and impaired quality of life. The current medical treatments for this syndrome can cause significant side effects and offer partial symptomatic relief.

In a few small trials medical cannabis (MC) has been suggested to offer symptomatic relief with a relatively benign side effect profile.

We conducted a real-life assessment of clinical benefit and adverse effects of chronic MC treatment among patients with GTS.

CONCLUSION:

MC seems to hold promise in the treatment of GTS as it demonstrated high subjective satisfaction by most patients however not without side effects and should be further investigated as a treatment option for this syndrome.”

https://www.ncbi.nlm.nih.gov/pubmed/30292733

https://www.prd-journal.com/article/S1353-8020(18)30429-2/fulltext

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Cannabidiol prevents haloperidol-induced vacuos chewing movements and inflammatory changes in mice via PPARγ receptors.

Brain, Behavior, and Immunity

“The chronic use of drugs that reduce the dopaminergic neurotransmission can cause a hyperkinetic movement disorder called tardive dyskinesia (TD). The pathophysiology of this disorder is not entirely understood but could involve oxidative and neuroinflammatory mechanisms.

Cannabidiol (CBD), the major non-psychotomimetic compound present in Cannabis sativa plant, could be a possible therapeutic alternative for TD. This phytocannabinoid shows antioxidant, anti-inflammatory and antipsychotic properties and decreases the acute motor effects of classical antipsychotics.

The present study investigated if CBD would attenuate orofacial dyskinesia, oxidative stress and inflammatory changes induced by chronic administration of haloperidol in mice. Furthermore, we verified in vivo and in vitro (in primary microglial culture) whether these effects would be mediated by PPARγ receptors.

The results showed that the male Swiss mice treated daily for 21 days with haloperidol develop orofacial dyskinesia. Daily CBD administration before each haloperidol injection prevented this effect.

Mice treated with haloperidol showed an increase in microglial activation and inflammatory mediators in the striatum. These changes were also reduced by CBD. On the other hand, the levels of the anti-inflammatory cytokine IL-10 increased in the striatum of animals that received CBD and haloperidol.

Regarding oxidative stress, haloperidol induced lipid peroxidation and reduced catalase activity. This latter effect was attenuated by CBD. The combination of CBD and haloperidol also increased PGC-1α mRNA expression, a co-activator of PPARγ receptors. Pretreatment with the PPARγ antagonist, GW9662, blocked the behavioural effect of CBD in our TD model. CBD also prevented LPS-stimulated microglial activation, an effect that was also antagonized by GW9662.

In conclusion, our results suggest that CBD could prevent haloperidol-induced orofacial dyskinesia by activating PPARγ receptors and attenuating neuroinflammatory changes in the striatum.”

“Haloperidol, marketed under the trade name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndromemania in bipolar disorder, nausea and vomiting, delirium, agitation, acute psychosis, and hallucinations in alcohol withdrawal”  https://en.wikipedia.org/wiki/Haloperidol
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A Brief Background on Cannabis: From Plant to Medical Indications.

 Ingenta Connect

“Cannabis has been used as a medicinal plant for thousands of years.

As a result of centuries of breeding and selection, there are now over 700 varieties of cannabis that contain hundreds of compounds, including cannabinoids and terpenes.

Cannabinoids are fatty compounds that are the main biological active constituents of cannabis. Terpenes are volatile compounds that occur in many plants and have distinct odors.

Cannabinoids exert their effect on the body by binding to receptors, specifically cannabinoid receptors types 1 and 2. These receptors, together with endogenous cannabinoids and the systems for synthesis, transport, and degradation, are called the Endocannabinoid System.

The two most prevalent and commonly known cannabinoids in the cannabis plant are delta-9-tetrahydrocannabinol (THC) and cannabidiol.

The speed, strength, and type of effects of cannabis vary based on the route of administration. THC is rapidly distributed through the body to fatty tissues like the brain and is metabolized by the cytochrome P450 system to 11-hydroxy-THC, which is also psychoactive.

Cannabis and cannabinoids have been indicated for several medical conditions.

There is evidence of efficacy in the symptomatic treatment of nausea and vomiting, pain, insomnia, post-traumatic stress disorder, anxiety, loss of appetite, Tourette’s syndrome, and epilepsy. Cannabis has also been associated with treatment for glaucoma, Huntington’s Disease, Parkinson’s Disease, and dystonia, but there is not good evidence to support its efficacy. Side effects of cannabis include psychosis and anxiety, which can be severe.

Here, we provided a summary of the history of cannabis, its pharmacology, and its medical uses.”

https://www.ncbi.nlm.nih.gov/pubmed/30139415

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A Systematic Review of the Effectiveness of Medical Cannabis for Psychiatric, Movement and Neurodegenerative Disorders.

“The discovery of endocannabinoid’s role within the central nervous system and its potential therapeutic benefits have brought forth rising interest in the use of cannabis for medical purposes. The present review aimed to synthesize and evaluate the available evidences on the efficacy of cannabis and its derivatives for psychiatric, neurodegenerative and movement disorders. A systematic search of randomized controlled trials of cannabis and its derivatives were conducted via databases (PubMed, Embase and the Cochrane Central Register of Controlled Trials). A total of 24 reports that evaluated the use of medical cannabis for Alzheimer’s disease, anorexia nervosa, anxiety, dementia, dystonia, Huntington’s disease, Parkinson’s disease, post-traumatic stress disorder (PTSD), psychosis and Tourette syndrome were included in this review. Trial quality was assessed with the Cochrane risk of bias tool. There is a lack of evidence on the therapeutic effects of cannabinoids for amyotrophic lateral sclerosis and dystonia. Although trials with positive findings were identified for anorexia nervosa, anxiety, PTSD, psychotic symptoms, agitation in Alzheimer’s disease and dementia, Huntington’s disease, and Tourette syndrome, and dyskinesia in Parkinson’s disease, definitive conclusion on its efficacy could not be drawn. Evaluation of these low-quality trials, as rated on the Cochrane risk of bias tools, was challenged by methodological issues such as inadequate description of allocation concealment, blinding and underpowered sample size. More adequately powered controlled trials that examine the long and short term efficacy, safety and tolerability of cannabis for medical use, and the mechanisms underpinning the therapeutic potential are warranted.”

https://www.ncbi.nlm.nih.gov/pubmed/29073741

http://www.cpn.or.kr/journal/view.html?doi=10.9758/cpn.2017.15.4.301

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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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Medicinal Uses of Marijuana and Cannabinoids

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“In the past two decades, there has been increasing interest in the therapeutic potential of cannabis and single cannabinoids, mainly cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC). THC and cannabis products rich in THC exert their effects mainly through the activation of cannabinoid receptors (CB1 and CB2). Since 1975, 140 controlled clinical trials using different cannabinoids or whole-plant preparations for the treatment of a large number of disorders and symptoms have been conducted. Results have led to the approval of cannabis-based medicines [dronabinol, nabilone, and the cannabis extract nabiximols (Sativex®, THC:CBD = 1:1)] as well as cannabis flowers in several countries. Controlled clinical studies provide substantial evidence for the use of cannabinoid receptor agonists in cancer chemotherapy induced nausea and vomiting, appetite loss and cachexia in cancer and HIV patients, neuropathic and chronic pain, and in spasticity in multiple sclerosis. In addition, there is also some evidence suggesting a therapeutic potential of cannabis-based medicines in other indications including Tourette syndrome, spinal cord injury, Crohn’s disease, irritable bowel syndrome, and glaucoma. In several other indications, small uncontrolled and single-case studies reporting beneficial effects are available, for example in posttraumatic stress disorder, attention deficit hyperactivity disorder, and migraine. The most common side effects of THC and cannabis-based medicines rich in THC are sedation and dizziness (in more than 10% of patients), psychological effects, and dry mouth. Tolerance to these side effects nearly always develops within a short time. Withdrawal symptoms are hardly ever a problem in the therapeutic setting. In recent years there is an increasing interest in the medical use of CBD, which exerts no intoxicating side effects and is usually well-tolerated. Preliminary data suggest promising effects in the treatment of anxiety disorders, schizophrenia, dystonia, and some forms of epilepsy. This review gives an overview on clinical studies which have been published over the past 40 years.”

http://www.tandfonline.com/doi/abs/10.1080/07352689.2016.1265360?needAccess=true&journalCode=bpts20

“Review Identifies 140 Controlled Clinical Trials Related to Cannabis”  http://blog.norml.org/2017/06/04/review-identifies-140-controlled-clinical-trials-related-to-cannabis/

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Preliminary Evidence on Cannabis Effectiveness and Tolerability for Adults With Tourette Syndrome.

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“The authors retrospectively evaluated effectiveness and tolerability of cannabis in 19 adults with Tourette syndrome.

Tics scores decreased by 60%, and 18 of the 19 participants were at least “much improved.”

Cannabis was generally well tolerated, although most participants reported side effects.”

https://www.ncbi.nlm.nih.gov/pubmed/28464701

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Significant Tic Reduction in An Otherwise Treatment-Resistant Patient with Gilles de la Tourette Syndrome Following Treatment with Nabiximols.

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“Early anecdotal reports and preliminary studies suggested that cannabinoid-based medicines such as delta-9-tetrahydrocannabinol (THC) are effective in the treatment of Gilles de la Tourette syndrome (TS).

We report a single case study of a patient with otherwise treatment-resistant TS successfully treated with nabiximols.

Our results provide further evidence that treatment with nabiximols may be effective in the treatment of patients with TS.

Given the positive response exhibited by the patient highlighted in this report, further investigation of the effects of nabiximols is proposed on a larger group of patients in a clinical trial setting.”

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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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A frequent polymorphism in the coding exon of the human cannabinoid receptor (CNR1) gene.

“The central cannabinoid receptor (CB1) mediates the pharmacological activities of cannabis, the endogenous agonist anandamide and several synthetic agonists.

The cloning of the human cannabinoid receptor (CNR1) gene facilitates molecular genetic studies in disorders like Gilles de la Tourette syndrome (GTS), obsessive compulsive disorder (OCD), Parkinsons disease, Alzheimers disease or other neuro psychiatric or neurological diseases, which may be predisposed or influenced by mutations or variants in the CNR1 gene.

We detected a frequent silent mutation (1359G–>A) in codon 453 (Thr) of the CNR1 gene that turned out to be a common polymorphism in the German population. Allele frequencies of this polymorphism are 0.76 and 0.24, respectively.

We developed a simple and rapid polymerase chain reaction (PCR)-based assay by artificial creation of a Msp I restriction site in amplified wild-type DNA (G-allele), which is destroyed by the silent mutation (A-allele).

The intragenic CNR1 polymorphism 1359(G/A) should be useful for association studies in neuro psychiatric disorders which may be related to anandamide metabolism disturbances.”

http://www.ncbi.nlm.nih.gov/pubmed/10441206

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