Table 4.

Clinical studies of cannabinoids for movement disorders

Movement disorder	Study Design	Sample Size	Intervention	Outcome	Reference
Parkinson’s disease	Randomized, double-blind, placebo-controlled crossover.	17	Cannador standardized to 2.5 mg of D9-THC and 1.25 mg of cannabidiol per capsule. 2 treatment phases, each of 4 weeks duration separated by a 2-week washout phase.	No improvement in LID, motor symptoms, quality of life or sleep.	59
	Case series.	5	One gram marijuana (2–9% THC) smoked as a cigarette on morning of testing.	None of the patients experienced relief or demonstrated improvement of tremor following marijuana.	138
	Case series.	22	After baseline assessment, patients were asked to smoke .5 g of cannabis. 30 minutes later the motor and non-motor battery was repeated.	Significant improvement in tremor and bradykinesia.	135
	Randomized, double-blind, placebo-controlled study.	8	Administered 20 mg rimonabant (CB1 antagonist) or placebo for 9 or 16 days and then gave levodopa challenge.	No effect on LID or motor disability in on or off state.	58
	Randomized, double-blind, placebo-controlled, crossover trial.	5	Nabilone or placebo was administered in 2 split doses 12 hours and 1 hour before levodopa challenges 2 weeks apart.	Rush Dyskinesia Disability Score and LID time was significantly reduced with nabilone vs. control.	60
	Cross-sectional survey.	84	PD registered at Prague Movement Disorders Centre were asked to anonymously complete a questionnaire about their possible experience with cannabis.	39 patients described mild or substantial improvement of PD symptoms, including resting tremor and LID.	61
	Open-label pilot study.	6	150 mg cannabidiol tablet was administered; the dose was increased weekly by 150 mg depending on the clinical response for 4 weeks.	Decreased psychotic symptoms.	57
	Open-label pilot study.	4	Patients administered 75–300 mg/day of cannabidiol.	Decreased REM Behavior disorder per patient and spouse report	139
	Randomized, double-blind, placebo-controlled study.	21	Patients randomized to placebo, 75mg/day cannabidiol or 300 mg/day cannabidiol for 6 weeks.	No change in total UPDRS or any subscales. Improvements were reported for total PDQ-39 score in 300 mg/day group.	140
Huntington’s disease	Randomized, double-blind, placebo-controlled crossover trial.	15	Cannabidiol (5 mg/kg) or placebo was given twice daily for 6 weeks.	No effect on chorea severity.	56
	Case study.	1	Self-administered smoked cannabis. Then, patient was administered 1 mg nabilone/day.	Reduction of chorea.	71
	Randomized, double-blind, placebo-controlled crossover study.	37	Four assessment visits were made to each patient at their residence at 5-week intervals. Administered nabilone (1 and 2 mg) versus placebo. For the last 10 days of each treatment block patients were taking nabilone 1 or 2 mg/day.	Improved motor coordination and chorea. Measures: Unified Huntington’s Disease Rating Scale (UHDRS): motor scale, cognitive assessment and behavioral assessment. No difference between taking 1 mg or 2 mg of nabilone.	70
	Case study.	1	Patient was treated once with 1.5 mg nabilone and 3 hours later was given an evaluation.	Increased chorea.	90
Tremor	Uncontrolled, open clinical trial.	8	Patients with multiple sclerosis, seriously disabled with tremor and ataxia, were given oral tetrahydrocannabinol.	Improved tremor in 2 out of 8 patients.	82
	Randomized, double-blind, placebo-controlled, parallel group.	337	Sativex (nabiximols) or placebo was administered daily for 6 weeks. Patients were assessed at weeks 2 and 6.	No improvement in tremor.	93
	Randomized, double-blind, placebo-controlled crossover.	13	Patients were randomly assigned to receive cannador (containing THC) orally either active treatment for the first 2 weeks followed by placebo for the second 2 weeks or vice versa.	No improvement in tremor.	95
	Randomized, double-blind, placebo-controlled crossover.	57	Group A started with drug escalation: 15–30 mg THC (2.5 mg tetrahydrocannabinol and 0.9 mg cannabidiol) by 5 mg per day for 14 days before placebo. Group B started with placebo for 7 days, crossed to the active period (14 days) and a three-day placebo period	No improvement in tremor.	94
Dystonia	Case study.	1	Smoked one ‘joint’ in the morning once a week for three weeks.	Self-reported improvement with dystonia.	96
	Case series.	5	Oral doses of cannabidiol rising from 100 to 600 mg/day over a 6 week period.	Dystonia assessed with a standard dystonia movement scale, ranging from 0 to 120. Dose-related improvement in dystonia. Cannabidiol at doses over 300 mg/day exacerbated the hypokinesia and resting tremor.	77
	Randomized, double-blind, placebo-controlled crossover.	15	A single dose of nabilone or placebo (0.03 mg/kg) was administered.	No significant reduction in dystonia. Measures: dystonia–movement scale portion of the Burke, Fahn, Marsden dystonia scale, adverse effects, and lying and standing blood pressure.	78
	Case study.	1	Smoked cannabis 3–4g/day. Patient was evaluated and reevaluated after 24 hour drug free period.	Significantly improved dystonia. Measures: Burke-Fahn-Marsden dystonia rating scale.	73
	Randomized, double-blind, placebo-controlled study.	7	Dronabinol or placebo was administered daily for 3 weeks.	No improvement in dystonia.	76
Tics	Case study.	1	Within 2 weeks, the daily dose was raised to 15 mg.	Improved tics by 75%. Measures: the Yale Global Tic Severity Scale.	79
	Case study.	1	Starting with a morning dose of 5 mg, increased D9-THC during the following 9 weeks.	Improved tic with no adverse effects. Measures: Yale Global Tic Severity Scale, Gilles de la Tourette Syndrome Quality of Life Scale, and the ADHD symptoms, on the Conners’ Teacher Rating Scale	81
	Case study.	1	Smoked cannabis (one “cone”) per night for 1 year.	Complete remission of tic. Measures: 1 hour examination.	84
	Cross-sectional structured interviews.	17	Prior cannabis use	(82%) experienced a marijuana-induced improvement of their symptoms. Measures: Shapiro Tourette Syndrome Severity Scale	80
	Case study	1	Administered THC once.	Tourette’s Syndrome Global Scale, revealed total tic severity score was 41 before treatment and was reduced to 7 just 2 hours after treatment.	86
	Randomized, double-blind, placebo-controlled crossover study.	12	Δ9-THC or placebo was administered once. After a 4 week washout period, patients were crossed over to receive other treatment.	Scores on Global Clinical Impression Scale, Shapiro Tourette-Syndrome Severity Scale, Yale Global Tic Severity Scale, and Tourette-Syndrome Symptom List revealed dose-dependent improvement in tics.	69
	Case study.	1	Combined treatment with risperidone and Δ9-THC	Scores on Global Clinical Impression Scale, Shapiro Tourette-Syndrome Severity Scale, Yale Global Tic Severity Scale, and Tourette-Syndrome Symptom List revealed significant improvement in tics.	87
	Randomized, double-blind, placebo-controlled.	17	During 6 weeks, patients treated with up to 10 mg/day of THC.	Improved tics. Measures: Tourette Syndrome Clinical Global Impressions scale, the Shapiro Tourette-Syndrome Severity Scale, the Yale Global Tic Severity Scale, the self- rated Tourette Syndrome Symptom List, and a videotape-based rating scale.	87
	Case study	3	a. Self-administered smoked cannabis (1–2 cigarettes/day) for four weeks. b. Self-administered smoked cannabis intermittently. 3. Self-administered smoked cannabis (1/2–1 cigarette/day).	Improved tics.	88