A Study of Tolerability and Efficacy of Cannabidiol on Tremor in Parkinson's Disease

• ClinicalTrials.gov Identifier: NCT02818777
• Recruitment Status: Completed
• First Posted: June 30, 2016
• Results First Posted: February 19, 2019
• Last Update Posted: February 19, 2019
• Sponsor: University of Colorado, Denver
• Collaborators: Colorado Department of Public Health and Environment; Jazz Pharmaceuticals
• Information provided by (Responsible Party): University of Colorado, Denver

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Parkinson's Disease
• Intervention: Drug: cannabidiol
• Enrollment: 13

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Cannabidiol
Arm/Group Description	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day. cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.
Period Title: Overall Study
Started	13 [1]
Completed	10
Not Completed	3
Reason Not Completed
Adverse Event	3
[1] The number of baseline participants was 13.

Baseline Characteristics

Arm/Group Title		Cannabidiol
Arm/Group Description		GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day. cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.
Overall Number of Baseline Participants		13
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	13 participants
		68.15 (6.05)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	13 participants
	Female	3 23.1%
	Male	10 76.9%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	13 participants
	Hispanic or Latino	0 0.0%
	Not Hispanic or Latino	13 100.0%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	13 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	13 100.0%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	13 participants
		13 100.0%

Outcome Measures

1. Primary Outcome

Title	Severity of Participants Reporting Study-related Adverse Events at Each Dose Level
Description	Severity of each specific adverse event was scored as 0=no adverse event, 1=mild adverse event, 2=moderate adverse event, and 3=sever adverse event. The range of severity is 0-3. Higher scores mean a worse outcome. The severity was expressed as mean (standard deviation).
Time Frame	Every 3rd day on each dose level, assessed up to 5 weeks

Outcome Measure Data

Analysis Population Description

13 PD patients were included in safety analysis group because they were all treated with study drug.

Arm/Group Title	Cannabidiol 5 mg/kg/Day	Cannabidiol 7.5 mg/kg/Day	Cannabidiol 10 mg/kg/Day	Cannabidiol 15 mg/kg/Day	Cannabidiol 20 mg/kg/Day	Cannabidiol 25 mg/kg/Day
Arm/Group Description:	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Dosage: 5 mg/kg/day cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Dosage: 7.5 mg/kg/day cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Dosage: 10 mg/kg/day cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Dosage: 15 mg/kg/day cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Dosage: 20 mg/kg/day cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Dosage: 25 mg/kg/day cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.
Overall Number of Participants Analyzed	13	8	12	10	8	3
Mean (Standard Deviation); Unit of Measure: units on a scale
Somnolence	1 (0)	1 (0)	1 (0)	1.25 (0.5)	1.143 (0.345)	1.25 (0.5)
Fatigue	1 (0)	1 (0)	1 (0)	1.667 (0.577)	1.25 (0.5)	1 (0)
Weight gain	1.333 (0.577)	0 (0)	1 (0)	1 (0)	1 (0)	0 (0)
increased appetite	1 (0)	0 (0)	0 (0)	1 (0)	0 (0)	0 (0)
Diarrhea	1 (0)	1 (0)	1 (0)	1.667 (0.842)	1 (0)	1.4 (0.775)
Weight loss	0 (0)	1 (0)	0 (0)	1 (0)	0 (0)	0 (0)
Abdominal pain	0 (0)	0 (0)	1 (0)	1 (0)	0 (0)	1 (0)
Nausea	0 (0)	0 (0)	1 (0)	2 (0)	1 (0)	0 (0)
Diziness	0 (0)	0 (0)	1 (0)	1 (0)	1 (0)	0 (0)
Weakness	0 (0)	0 (0)	1 (0)	2 (0)	0 (0)	0 (0)
Anorexia	0 (0)	0 (0)	0 (0)	2 (0)	0 (0)	2 (0)
Vomiting	0 (0)	0 (0)	0 (0)	0 (0)	1 (0)	0 (0)
Fever	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	1 (0)

2. Primary Outcome

Title	Number of Participants Had Changes in Orthostatic Blood Pressure
Description	Orthostatic blood pressure will be monitored at each study visit.
Time Frame	Baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cannabidiol
Arm/Group Description:	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day. cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.
Overall Number of Participants Analyzed	13
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%

3. Primary Outcome

Title	Number of Participants Had Changes in Physical Exam
Description	A physical exam will be performed at each study visit.
Time Frame	Baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cannabidiol
Arm/Group Description:	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day. cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.
Overall Number of Participants Analyzed	13
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%

4. Primary Outcome

Title	Number of Participants Had Changes in EKG
Description	EKG will be performed at each study visit.
Time Frame	Baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cannabidiol
Arm/Group Description:	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day. cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.
Overall Number of Participants Analyzed	13
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%

5. Primary Outcome

Title	Number of Participants Had Changes in Laboratory Values
Description	Laboratory tests (hematology, serum chemistry, and urinalysis) will be evaluated at each study visit.
Time Frame	Baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cannabidiol
Arm/Group Description:	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day. cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.
Overall Number of Participants Analyzed	13
Measure Type: Count of Participants; Unit of Measure: Participants
	5 38.5%

6. Primary Outcome

Title	Proportion of Subjects That Drop Out of the Study Due to Study Drug Intolerance
Description	Assessing the proportion of subjects that drop out of the study due to study drug intolerance.
Time Frame	Baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cannabidiol
Arm/Group Description:	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day. cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.
Overall Number of Participants Analyzed	13
Measure Type: Count of Participants; Unit of Measure: Participants
	3 23.1%

7. Primary Outcome

Title	Change in Movement Disorder Society-Unified Parkinsons Disease Rating Scale Total Score
Description	There are four parts: Part I (Non-motor experiences of daily living, scores range 0-52), Part II (motor experiences of daily living, scores range 0-52), Part III (motor examination, scores range 0-132) and Part IV (motor complications scores range 0-24). Subscales are summed to a total score, ranging 0-260. Higher scores mean a worse outcome.
Time Frame	Baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

10 Participants completed the study drug treatment and were included in the efficacy analysis group.

Arm/Group Title	Cannabidiol
Arm/Group Description:	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day. cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: score on a scale
	-7.70 (9.393)

8. Primary Outcome

Title	Change in Montreal Cognitive Assessment (MoCA)
Description	MoCA - is designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visual -constructional skills, conceptual thinking, calculation. Scores range 0-30. Higher values represent a better outcome.
Time Frame	Baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

10 Participants completed the study drug treatment and were included in efficacy analysis group.

Arm/Group Title	Cannabidiol
Arm/Group Description:	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day. cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: score on a scale
	1.0 (1.491)

9. Primary Outcome

Title	Change in Anxiety Short Form
Description	This includes 8 items that assess severity of anxiety. Scores range 8-40. Higher values represent a worse outcome.
Time Frame	Baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

10 participants completed the study drug treatment and were included in efficacy analysis group.

Arm/Group Title	Cannabidiol
Arm/Group Description:	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day. cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: score on a scale
	0.33 (3.5668)

10. Primary Outcome

Title	Change in Neuropsychiatric Inventory (NPI)
Description	Assessing neuropsychiatric symptoms and psychopathology of patients with Alzheimer's disease and other neurodegenerative disorders. It has proven to be sensitive to change and has been employed to capture treatment related behavioral.Total NPI scores range 0-120. Higher values represent a worse outcome.
Time Frame	Baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cannabidiol
Arm/Group Description:	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day. cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: score on a scale
	-0.125 (1.5526)

11. Primary Outcome

Title	Change in Depression Short Form
Description	This includes 8 items that assess severity of depression. Score range 8-40. Higher values represent a worse outcome.
Time Frame	Baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

10 Participants completed the study drug treatment and were included in the efficacy analysis group.

Arm/Group Title	Cannabidiol
Arm/Group Description:	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day. cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: score on a scale
	-0.85 (3.132)

12. Primary Outcome

Title	Change in Scales for Outcomes in Parkinson's Disease (SCOPA)-Sleep-night Time Sleep
Description	A valid, reliable, short scale that is used to evaluate night time sleep problems in PD. Scores range 0-18. Higher values represent a worse outcome.
Time Frame	Baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

10 Participants completed the study drug treatment and were included in the efficacy analysis group.

Arm/Group Title	Cannabidiol
Arm/Group Description:	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day. cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: score on a scale
	-2.80 (3.91)

13. Primary Outcome

Title	Change From Baseline of REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ)
Description	10-item, patient self-rating instrument assessing the subject's sleep behavior with short questions that have to be answered by either "yes" or "no". Scores range 0-13. Higher values represent a worse outcome.
Time Frame	Baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

10 Participants completed the study drug treatment and were included in the efficacy analysis group.

Arm/Group Title	Cannabidiol
Arm/Group Description:	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day. cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: score on a scale
	-0.7 (1.767)

14. Primary Outcome

Title	Change in Emotional and Behavioral Dyscontrol Short Form
Description	8 items that assess severity of emotional and behavioral dyscontrol. Scores range 8-40. Higher values represent a worse outcome.
Time Frame	Baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

10 Participants completed the study drug treatment and were included in the efficacy analysis group.

Arm/Group Title	Cannabidiol
Arm/Group Description:	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day. cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: score on a scale
	-4.69 (6.144)

15. Primary Outcome

Title	Change in Pain Severity Form
Description	This will assess severity of pain. Scores range 3-15. Higher scores represent a worse outcome.
Time Frame	Baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

10 Participants completed the study drug treatment and were included in the efficacy analysis group.

Arm/Group Title	Cannabidiol
Arm/Group Description:	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day. cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: score on a scale
	-1.86 (4.711)

16. Primary Outcome

Title	Change in Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS)
Description	To measure severity of symptoms and support a diagnosis of impulse control disorders and related disorders in PD. Total QUIP-RS scores were summed by 6 subscores (gambling 0-16, Sex 0-16, Buying 0-16, Eating 0-16, Hobbyism-punding 0-32, and PD Medication use 0-16), range 0-112. Higher scores represent a worse outcome.
Time Frame	Baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

10 Participants completed the study drug treatment and were included in the efficacy analysis group.

Arm/Group Title	Cannabidiol
Arm/Group Description:	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day. cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: score on a scale
	0 (0)

17. Primary Outcome

Title	Change in Fatigue Severity Scale
Description	A self-report 9-item questionnaire with questions related to how fatigue interferes with certain activities and rates its severity. Scores range 9-63. Higher values represent a worse outcome.
Time Frame	Baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

10 Participants completed the study drug treatment and were included in the efficacy analysis group.

Arm/Group Title	Cannabidiol
Arm/Group Description:	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day. cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: score on a scale
	-0.5 (11.4625)

18. Primary Outcome

Title	Change in International Restless Legs Syndrome Study Group Rating Scale for Restless
Description	This encompasses a ten-question instrument for measuring severity of restless legs syndrome (RLS). Score range 0-40. Higher values represent a worse outcome.
Time Frame	Baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

10 Participants completed the study drug treatment and were included in the efficacy analysis group.

Arm/Group Title	Cannabidiol
Arm/Group Description:	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day. cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: score on a scale
	-1.2 (4.517)

19. Primary Outcome

Title	Change in Unified Dyskinesia Rating Scale (UDysRS)
Description	To evaluate involuntary movements often associated with treated Parkinson's disease. Total UDysRS scores is the sum of historical sub-scores (0-60) and objective sub-score (0-44). Total scores range 0-104. Higher values represent a worse outcome.
Time Frame	Baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

10 Participants completed the study drug treatment and were included in the efficacy analysis group.

Arm/Group Title	Cannabidiol
Arm/Group Description:	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day. cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: score on a scale
	1.0 (3.887)

20. Secondary Outcome

Title	Change in MDS-UPDRS Tremor Score (Total of Items 3.17 and 3.18) in the ON State
Description	Sum of items 3.17 and 3.18 of Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) evaluates the rest tremor amplitude (3.17, score range 0-20) and constancy of rest tremor (3.18 score range 0-4). The sum scores of 3.17 and 3.18 range 0-24. Higher values represent a worse outcome.
Time Frame	Baseline and 5 weeks

Outcome Measure Data

Analysis Population Description

10 Participants completed the study drug treatment and were included in the efficacy analysis group.

Arm/Group Title	Cannabidiol
Arm/Group Description:	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day. cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: score on a scale
	-0.4 (1.2649)

Adverse Events

Time Frame	1 year
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Cannabidiol
Arm/Group Description	GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day. cannabidiol: Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.
All-Cause Mortality
	Cannabidiol
	Affected / at Risk (%)
Total	0/13 (0.00%)
Serious Adverse Events
	Cannabidiol
	Affected / at Risk (%)
Total	0/13 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Cannabidiol
	Affected / at Risk (%)
Total	13/13 (100.00%)
Gastrointestinal disorders
Diarrhea * 1	11/13 (84.62%)
Abdominal pain * 1	3/13 (23.08%)
nausea * 1	2/13 (15.38%)
anorexia * 1	2/13 (15.38%)
increased appetite * 1	2/13 (15.38%)
vomiting * 1	1/13 (7.69%)
flatulence * 1	1/13 (7.69%)
gastroesophageal reflux * 1	1/13 (7.69%)
General disorders
Fatigue * 1	8/13 (61.54%)
fever * 1	1/13 (7.69%)
Hepatobiliary disorders
Elevated liver function tests * 1	5/13 (38.46%)
Metabolism and nutrition disorders
Weight gain * 1	4/13 (30.77%)
weight loss * 1	2/13 (15.38%)
Musculoskeletal and connective tissue disorders
spasm * 1	1/13 (7.69%)
Nervous system disorders
Somnolence * 1	9/13 (69.23%)
Dizziness * 1	3/13 (23.08%)
headache * 1	2/13 (15.38%)
weakness * 1	1/13 (7.69%)
Skin and subcutaneous tissue disorders
allergic reaction * 1	1/13 (7.69%)
1 Term from vocabulary, CTCAE (Unspecified); * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dr. Maureen Anne Leehey
• Organization: University of Colorado
• Phone: 303-724-2194
• EMail: maureen.leehey@ucdenver.edu

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT02818777
• Other Study ID Numbers: 15-0929
• First Submitted: May 6, 2016
• First Posted: June 30, 2016
• Results First Submitted: October 23, 2018
• Results First Posted: February 19, 2019
• Last Update Posted: February 19, 2019