Treatment of Tourette's syndrome with Delta 9-tetrahydrocannabinol (THC): a randomized crossover trial. Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial. Haloperidol addition in fluvoxamine-refractory obsessive-compulsive disorder. A double-blind, placebo-controlled study in patients with and without tics. Controlled stimulant treatment of ADHD and comorbid Tourette's syndrome: effects of stimulant and dose. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. The treatment of attention-deficit hyperactivity disorder in Tourette's syndrome: a double-blind placebo-controlled study with clonidine and desipramine. The effect of cannabis on tremor in patients with multiple sclerosis. Safety, tolerability, and efficacy of orally administered cannabinoids in MS. A comparison of pimozide and haloperidol in the treatment of Gilles de la Tourette's syndrome.
Anecdotal reports in Tourette's syndrome (TS) have suggested that marijuana (cannabis sativa) and delta-9-tetrahydrocannabinol (Delta(9)-THC), the major psychoactive ingredient of marijuana, reduce tics and associated behavioral disorders. We performed a randomized double-blind placebo-controlled crossover single-dose trial of Delta(9)-THC (5.0, 7.5 or 10.0 mg) in 12 adult TS patients. Tic severity was assessed using a self-rating scale (Tourette's syndrome Symptom List, TSSL) and examiner ratings (Shapiro Tourette's syndrome Severity Scale, Yale Global Tic Severity Scale, Tourette's syndrome Global Scale). Using the TSSL, patients also rated the severity of associated behavioral disorders. Clinical changes were correlated to maximum plasma levels of THC and its metabolites 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) and 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid (THC-COOH). Using the TSSL, there was a significant improvement of tics (p=0.015) and obsessive-compulsive behavior (OCB) (p = 0.041) after treatment with Delta(9)-THC compared to placebo. Examiner ratings demonstrated a significant difference for the subscore "complex motor tics" (p = 0.015) and a trend towards a significant improvement for the subscores "motor tics" (p = 0.065), "simple motor tics" (p = 0.093), and "vocal tics" (p = 0.093). No serious adverse reactions occurred. Five patients experienced mild, transient side effects. There was a significant correlation between tic improvement and maximum 11-OH-THC plasma concentration. Results obtained from this pilot study suggest that a single-dose treatment with Delta(9)-THC is effective and safe in treating tics and OCB in TS. It can be speculated that clinical effects may be caused by 11-OH-THC. A more long-term study is required to confirm these results. Preliminary studies suggested that delta-9-tetrahydrocannabinol (THC), the major psychoactive ingredient of Cannabis sativa L., might be effective in the treatment of Tourette syndrome (TS). This study was performed to investigate for the first time under controlled conditions, over a longer-term treatment period, whether THC is effective and safe in reducing tics in TS.
                In this randomized, double-blind, placebo-controlled study, 24 patients with TS, according to DSM-III-R criteria, were treated over a 6-week period with up to 10 mg/day of THC. Tics were rated at 6 visits (visit 1, baseline; visits 2-4, during treatment period; visits 5-6, after withdrawal of medication) using the Tourette Syndrome Clinical Global Impressions scale (TS-CGI), the Shapiro Tourette-Syndrome Severity Scale (STSSS), the Yale Global Tic Severity Scale (YGTSS), the self-rated Tourette Syndrome Symptom List (TSSL), and a videotape-based rating scale.
                Seven patients dropped out of the study or had to be excluded, but only 1 due to side effects. Using the TS-CGI, STSSS, YGTSS, and video rating scale, we found a significant difference (p <.05) or a trend toward a significant difference (p <.10) between THC and placebo groups at visits 2, 3, and/or 4. Using the TSSL at 10 treatment days (between days 16 and 41) there was a significant difference (p <.05) between both groups. ANOVA as well demonstrated a significant difference (p =.037). No serious adverse effects occurred.
                Our results provide more evidence that THC is effective and safe in the treatment of tics. It, therefore, can be hypothesized that the central cannabinoid receptor system might play a role in TS pathology. To determine the efficacy of adding haloperidol to the treatment of patients with obsessive-compulsive disorder (OCD), with or without a comorbid chronic tic disorder, who were refractory to adequate treatment with the serotonin-uptake inhibitor fluvoxamine alone. It was hypothesized that OCD patients with a concurrent chronic tic disorder would preferentially respond to this treatment.
                Sixty-two patients with a primary DSM-III-R diagnosis of OCD received placebo fluvoxamine for 1 week, followed by 8 weeks of active fluvoxamine. Thirty-four of these patients were refractory to fluvoxamine and were randomized in a double-blind fashion to 4 weeks of treatment with either haloperidol (n = 17) or placebo (n = 17) added to ongoing fluvoxamine treatment. The placebo-treated group included five women and 12 men, six inpatients and 11 outpatients, and eight patients with a comorbid chronic tic disorder. The haloperidol-treated group consisted of two women and 15 men, three inpatients and 14 outpatients, and seven patients with a comorbid chronic tic disorder. All 34 patients completed the entire study. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Clinical Global Impression scale were the principal measures of treatment outcome.
                Haloperidol addition was significantly better than placebo in reducing the severity of obsessive-compulsive symptoms as measured by the Y-BOCS. Eleven of 17 patients responded to the haloperidol, compared with none of 17 patients given placebo. Eight of eight patients with comorbid chronic tic disorders, such as Tourette's disorder, responded to double-blind haloperidol addition to ongoing fluvoxamine treatment. Haloperidol addition was of little benefit in treating OCD patients without tics. Fluvoxamine blood levels were not related to treatment response.
                The results of this study suggest that OCD patients with a comorbid chronic tic disorder constitute a clinically meaningful subtype of OCD that might require conjoint serotonin-uptake inhibitor/neuroleptic therapy for effective symptom reduction. To determine the effects of methylphenidate (MPH) and dextroamphetamine (DEX) on tic severity in boys with attention-deficit/hyperactivity disorder (ADHD) comorbid with Tourette's syndrome.
                A 9-week, placebo-controlled, double-blind crossover using a wide range of doses was completed by 20 subjects in three cohorts.
                Relatively high doses of MPH and DEX in the first cohort produced significant increases in tic severity which were sustained on higher doses of DEX but which attenuated on MPH. Overall, 14 of 20 subjects continued stimulant treatment for 1 to 3 years, generally in combination with other psychotropics. Stimulant-associated adverse effects, including tic exacerbations, were reversible in all cases.
                A substantial minority of comorbid subjects had consistent worsening of tics on stimulants, although the majority experienced improvement in ADHD symptoms with acceptable effects on tics. MPH was better tolerated than DEX. To determine whether plant-derived cannabis medicinal extracts (CME) can alleviate neurogenic symptoms unresponsive to standard treatment, and to quantify adverse effects.
                A consecutive series of double-blind, randomized, placebo-controlled single-patient cross-over trials with two-week treatment periods.
                Patients attended as outpatients, but took the CME at home.
                Twenty-four patients with multiple sclerosis (18), spinal cord injury (4), brachial plexus damage (1), and limb amputation due to neurofibromatosis (1).
                Whole-plant extracts of delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), 1:1 CBD:THC, or matched placebo were self-administered by sublingual spray at doses determined by titration against symptom relief or unwanted effects within the range of 2.5-120 mg/24 hours. Measures used: Patients recorded symptom, well-being and intoxication scores on a daily basis using visual analogue scales. At the end of each two-week period an observer rated severity and frequency of symptoms on numerical rating scales, administered standard measures of disability (Barthel Index), mood and cognition, and recorded adverse events.
                Pain relief associated with both THC and CBD was significantly superior to placebo. Impaired bladder control, muscle spasms and spasticity were improved by CME in some patients with these symptoms. Three patients had transient hypotension and intoxication with rapid initial dosing of THC-containing CME.
                Cannabis medicinal extracts can improve neurogenic symptoms unresponsive to standard treatments. Unwanted effects are predictable and generally well tolerated. Larger scale studies are warranted to confirm these findings. Because psychostimulants can exacerbate preexisting motor/phonic tics in individuals with Tourette's syndrome (TS), a clinical trial was performed to examine the ability of clonidine and desipramine to modify attention-deficit hyperactivity disorder (ADHD) behaviors in children with TS + ADHD.
                A double-blind, placebo-controlled protocol was used in which each subject served as his or her own control and received, in a randomly assigned fashion, 6-week medication cycles with clonidine (0.05 mg four times daily), desipramine (25 mg four times daily), and placebo.
                Thirty-seven children with TS+ADHD between the ages 7 to 13 years and of normal intellect were recruited, and 34 (31 males, 3 females) completed the entire protocol. Outcome measures for ADHD included Parent and Teacher Child Behavior Checklists (CBCL), continuous performance tests, and neuropsychologic tests of executive function. Several markers for ADHD were shown to improve significantly (P < .05) after treatment with desipramine (parent linear analogue rating, parent CBCL "hyperactivity" subscale, and teacher CBCL subscales "nervous/overactive," "anxious," and "unpopular"). Improvement with desipramine was always superior to that noted with clonidine. Clinical improvement did not correlate with drug blood levels. On measures of tic severity, neither drug made tics worse. Desipramine showed a statistically significant improvement on a global linear analogue scale, but not on the Hopkins Motor/Vocal Tic Severity Scale, the Tourette Syndrome Severity Scale, or the Yale Global Tic Severity Scale. Clonidine did not significantly alter tic severity on any measure.
                The results of this study suggest that desipramine may be a useful alternative for the treatment of symptoms of ADHD in children with TS. Disabling tremor is common in patients with multiple sclerosis (MS). Data from animal model experiments and subjective and small objective studies involving patients suggest that cannabis may be an effective treatment for tremor associated with MS. To our knowledge, there are no published double-blind randomized controlled trials of cannabis as a treatment for tremor in MS patients.
                The authors conducted a randomized double-blind placebo-controlled crossover trial to examine the effect of oral cannador (cannabis extract) on 14 patients with MS with upper limb tremors. There were eight women and six men, with a mean age of 45 years and mean Expanded Disability Status Scale score of 6.25. Patients were randomly assigned to receive each treatment and the doses escalated over a 2-week period before each assessment. The primary outcome was change on a tremor index, measured using a validated tremor rating scale. The study was powered to detect a functionally significant 50% improvement in the tremor index. Secondary outcomes included accelerometry, an ataxia scale, spiral drawing, finger tapping, and nine-hole pegboard test performance.
                Analysis of the data showed no significant improvement in any of the objective measures of upper limb tremor with cannabis extract compared to placebo. Finger tapping was faster on placebo compared to cannabis extract (p < 0.02). However, there was a nonsignificant trend for patients to experience more subjective relief from their tremors while on cannabis extract compared to placebo.
                Cannabis extract does not produce a functionally significant improvement in MS-associated tremor. The authors conducted a randomized, double-blind, placebo-controlled, twofold crossover study in 16 patients with MS who presented with severe spasticity to investigate safety, tolerability, and efficacy of oral Delta(9)-Tetrahydrocannabinol (THC) and Cannabis sativa plant extract. Both drugs were safe, but adverse events were more common with plant-extract treatment. Compared with placebo, neither THC nor plant-extract treatment reduced spasticity. Both THC and plant-extract treatment worsened the participant's global impression. In a double-blind placebo-controlled study, both pimozide and haloperidol significantly decreased tic frequency in nine patients with Gilles de la Tourette's syndrome. These findings are consistent with the catecholamine hypothesis of tic generation. Pimozide was associated with significantly fewer complaints of lethargy. Follow-up 4-20 months later showed that six of seven patients receiving pimozide and one of two receiving haloperidol had had greater than 75% improvement in symptoms.
Not enough evidence to support the use of cannabinoids in treating tics and obsessive compulsive behaviour in people with Tourette's syndrome.