The Effect of Medical Cannabis on Tics, Premonitory Urge and Psychiatric Comorbidity in Adults With Tourette Syndrome

Study Overview
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Brief Summary
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Medical cannabis (MC) is a standard treatment in Israel to adults with resistant Gilles de la Tourette syndrome (GTS). While small randomized control trials assessed THC efficacy on tics and premonitory urge, only small retrospective studies assessed MC efficacy and tolerability in GTS. Herein, By using an open-label, prospective design, our aim is to determine the preferred method of use, efficacy and tolerability of 12 weeks of treatment with MC in adult patients with GTS.

Detailed Description
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Gilles de la Tourette syndrome (GTS) is a childhood onset neuropsychiatric disorder characterized by the presence of multiple motor and one or more phonic tics continuing for at least one year. In Israel, although consumption of cannabis is outlawed, there is an option to allow patients to consume the drug under supervision. Medical Cannabis (MC) consumed by inhalation of smoked or vaporized dried female buds, or subligual oil extract of whole plant, has been an approved treatment by the Ministry of Health (MOH) for resistant GTS since 2013. Previous studies suggested that MC has a good effect on tics, quality of like and with good tolerability among patients with resistant GTS. In the current study, we prospectively followed-up patients eligible for MC according to MOH restrictions, at our GTS clinic at the Tel-Aviv Sourasky Movement Disorders Unit (MDU). Each subject signed a written informed consent before inclusion in the trial. Also, since driving under the influence of cannabis is forbidden by the Israeli law, patients were instructed and gave their oral commitment to avoid driving. The study was approved by the research ethics (Helsinki) committee at our center. MC was consumed as oil extract, vaporized, or smoked dried buds. The treating neurologist (S.A.) and patient together decided on the method of consumption during the visit before initiating treatment. Patients were assessed 4 and 12-weeks following treatment initiation to gather data regarding treatment efficacy, tolerability and SEs.

Official Title
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The Effect of Medical Cannabis on Tics, Premonitory Urge and Psychiatric Comorbidity in Adults With Tourette Syndrome

Conditions
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Tourette Syndrome, Cannabis

Intervention / Treatment
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* Drug: Medical Cannabis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 - 65 years Diagnosis of GTS confirmed by the treating neurologist based on the DSM-V criteria Eligibility to receive MOH MC license for GTS Provided written informed consent Exclusion Criteria: Regularly use cannabis in any form for self-medication prior to entering the study Pregnant or lactating women Have a tic disorder other than GTS Have concurrent physical or mental disease that could interfere with the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adult Tourette syndrome patients<br>Patients will be assessed before (baseline), 4 (visit 2) and 12 weeks (visit 3) after use of Medical cannabis via inhaled dried buds or sublingual oil extract. The percentage of THC and CBD were pre-set to 10% and 2%, respectively. All patients received the same general instructions for treatment titration, which was to start with 1 drop or puff a day and increase by 1 drop or puff as needed. There was no fixed schedule for the incremental increases, thus each patient freely raised the dose as well as number of daily consumptions until clinical benefit was achieved or SE emerged over a follow-up period of 12 weeks. | Drug: Medical Cannabis<br>* Patients with GTS were assessed before, 4 and 12 weeks after Medical cannabis initiation for consumption habits, efficacy and side effect profile<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in vocal and motor tics and disease burden | Using Yale Global Tic Severity Scale (YGTSS), range 0-100, higher scores mean a worse outcome | Baseline, after 4 and 12 weeks since treatment initiation | 
| Change in premonitory urge | using Premonitory Urge for Tic Scale (PUTS), range 0-36, higher scores mean a worse outcome | Baseline, after 4 and 12 weeks since treatment initiation | 
| Subjective improvement of tics and Quality of life | Using a 7-point Likert-type scale, range 1-7, higher scores mean a better outcome | Baseline, after 4 and 12 weeks since treatment initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Examine patient's tetrahydrocannabinol-9-delta (THC) and Cannabidiol (CBD) consumption per month | Measuring total THC and CBD consumption per month in grams | After 12 weeks since treatment initiation | 
| Assessment of major side effects of treatment | report (yes/no) on side effects from list and (free text) to add notes on side effect. List: Anxiety, Cognitive, Dizziness, Sedation, Fatigue, Red eyes , Dry mouth, Gastrointestinal | After 4 and 12 weeks since treatment initiation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cannabidiol, Cannabis, Medical Cannabis, delta(9)-Tetrahydrocannabinol, Tourette Syndrome