Trial Outcomes & Findings for A Study of Tolerability and Efficacy of Cannabidiol on Motor Symptoms in Parkinson's Disease (NCT NCT03582137)

NCT ID: NCT03582137

Last Updated: 2024-07-23

Results Overview

Movement Disorders Society-Unified Parkinson's disease rating scale(MDS UPDRS) Part III assesses the motor signs of PD. There are 33 scores based on 18 items, several with right, left or other body distribution scores.Each question is anchored with five responses that are linked to commonly accepted clinical terms: 0=normal, 1=slight, 2=mild, 3=moderate, and 4=severe. The possible change may be the scores of the total 33 scores. Scores ranges 0 -132. Higher values represent a worse outcome.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 74 participants
• Primary outcome timeframe: From baseline to the end of 2.5 mg/kg/day of CBD, through 3 weeks
• Results posted on: 2024-07-23

Participant Flow

Between 9/5/2018 and 1/4/2022, 74 participants were screened, 61 randomized and 31 assigned to the CBD/THC drug and 30 to placebo. 13 participants were excluded: 8 participants not meeting inclusion criteria, and 5 declined to participate after screening.

Participant milestones

Measure	CBD Cannabis Extract Oral Solution Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Overall Study STARTED	31	30
Overall Study COMPLETED	30	30
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Measure	CBD Cannabis Extract Oral Solution Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Overall Study Adverse Event	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo	Total n=61 Participants Total of all reporting groups
Age, Continuous	70.4 years STANDARD_DEVIATION 6.2 • n=5 Participants	68.6 years STANDARD_DEVIATION 7.6 • n=7 Participants	69.5 years STANDARD_DEVIATION 6.9 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	7 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	23 Participants n=7 Participants	41 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	30 Participants n=5 Participants	29 Participants n=7 Participants	59 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	31 Participants n=5 Participants	28 Participants n=7 Participants	59 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	31 participants n=5 Participants	30 participants n=7 Participants	61 participants n=5 Participants
Disease duration	7.0 years STANDARD_DEVIATION 6.8 • n=5 Participants	4.5 years STANDARD_DEVIATION 3.9 • n=7 Participants	5.8 years STANDARD_DEVIATION 5.7 • n=5 Participants
Modified Hoehn & Yahr	2.47 units on a scale STANDARD_DEVIATION 0.69 • n=5 Participants	2.30 units on a scale STANDARD_DEVIATION 0.48 • n=7 Participants	2.39 units on a scale STANDARD_DEVIATION 0.61 • n=5 Participants
Baseline • Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) Part III	34.6 units on a scale STANDARD_DEVIATION 9.1 • n=5 Participants	30.9 units on a scale STANDARD_DEVIATION 9.0 • n=7 Participants	32.8 units on a scale STANDARD_DEVIATION 9.3 • n=5 Participants
Baseline total Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS)	56.7 units on a scale STANDARD_DEVIATION 17.9 • n=5 Participants	48.8 units on a scale STANDARD_DEVIATION 15.5 • n=7 Participants	52.8 units on a scale STANDARD_DEVIATION 17.4 • n=5 Participants
Levodopa-equivalent daily dosage	417.9 mg/day STANDARD_DEVIATION 440.3 • n=5 Participants	427.5 mg/day STANDARD_DEVIATION 292.8 • n=7 Participants	422.7 mg/day STANDARD_DEVIATION 370.7 • n=5 Participants
Montreal Cognitive Assessment (MoCA)	26.9 units on a scale STANDARD_DEVIATION 3.6 • n=5 Participants	27.1 units on a scale STANDARD_DEVIATION 2.2 • n=7 Participants	27.0 units on a scale STANDARD_DEVIATION 3.0 • n=5 Participants
Married	25 Participants n=5 Participants	23 Participants n=7 Participants	48 Participants n=5 Participants
Retired	25 Participants n=5 Participants	24 Participants n=7 Participants	49 Participants n=5 Participants
Education, >=college educated	23 Participants n=5 Participants	27 Participants n=7 Participants	50 Participants n=5 Participants
Income >$75,000	17 Participants n=5 Participants	18 Participants n=7 Participants	35 Participants n=5 Participants
Body weight	79.0 kg STANDARD_DEVIATION 16.2 • n=5 Participants	82.1 kg STANDARD_DEVIATION 12.4 • n=7 Participants	80.5 kg STANDARD_DEVIATION 14.4 • n=5 Participants

PRIMARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day of CBD, through 3 weeks

Movement Disorders Society-Unified Parkinson's disease rating scale(MDS UPDRS) Part III assesses the motor signs of PD. There are 33 scores based on 18 items, several with right, left or other body distribution scores.Each question is anchored with five responses that are linked to commonly accepted clinical terms: 0=normal, 1=slight, 2=mild, 3=moderate, and 4=severe. The possible change may be the scores of the total 33 scores. Scores ranges 0 -132. Higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III (Motor Examination) Scores	-4.5714 units on a scale Interval -8.1126 to -1.0302	-2.7665 units on a scale Interval -4.9213 to -0.6118

SECONDARY outcome

Timeframe: Every 3-5 days at each dose level, assessed up to 3 weeks

Adverse events (AEs) are collected at each dose level. AEs collection include Serious Adverse Events (SAE), withdrawal symptoms and common AEs. SAE is an undesirable medical occurrence that results in death, or life-threatening, or inpatient hospitalization or prolongation of existing hospitalization or significant disability or incapacity or in a congenital anomaly/birth defect. Withdrawal and common AEs include headache, anxiety, nausea/vomiting, tremor, chills, decreased concentration, increased concentration, agitation, irritability, sleep disturbances, mood changes, somnolence, fatigue, anorexia, appetite changes, weight loss or gain, diarrhea, convulsion, abdominal pain, weakness, fever and other unexpected AEs. All of the these AEs will be recorded and counted.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
The Number of Participants Wtih Treatment-related Adverse Events	26 Participants	25 Participants

SECONDARY outcome

Timeframe: Baseline; at the end of 2.5 mg/kg/day; and every 3-5 days at each dose level, through 3 weeks.

Liver function tests will be performed and evaluated at each clinic visit from baseline through 3 weeks. The result is reported as the number of participants that had a clinically significant change in the values of the liver function test, including aspartate aminotransferase (AST), Alanine transaminase (ALT), Gamma-glutamyl transferase (GGT), Alkaline phosphatase (Alk Phos), Total Bilirubin (TB).

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Liver Function Monitoring --Liver Function Test	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline; at the end of 2.5 mg/kg/day; and every 3-5 days at each dose level, through 3 weeks.

Liver function impairment will be evaluated and then related to adverse events and documented at each clinic visit. The change may be the frequency and severity of liver function impairment related AEs, including nausea/vomiting, diarrhea, abdominal pain, fatigue, weakness, chills, appetite changes, weight loss or gain, fever, etc.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
The Number of Participants Wtih Liver Function Impairment Related Adverse Events nausea	6 Participants	3 Participants
The Number of Participants Wtih Liver Function Impairment Related Adverse Events diarrhea	2 Participants	4 Participants
The Number of Participants Wtih Liver Function Impairment Related Adverse Events fatigue	10 Participants	6 Participants
The Number of Participants Wtih Liver Function Impairment Related Adverse Events abdominal pain	1 Participants	3 Participants
The Number of Participants Wtih Liver Function Impairment Related Adverse Events anorexia	2 Participants	3 Participants
The Number of Participants Wtih Liver Function Impairment Related Adverse Events weight loss	1 Participants	2 Participants
The Number of Participants Wtih Liver Function Impairment Related Adverse Events not applicable	9 Participants	9 Participants

SECONDARY outcome

Timeframe: Baseline; at the end of 2.5 mg/kg/day, through 3 weeks

Standing systolic blood pressure measurements will be assessed through 3 weeks. The change may be the value of systolic blood pressure.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=30 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Blood Pressure (Systolic)	-5.4145 change in mmHg Interval -11.4569 to 0.6279	-0.9891 change in mmHg Interval -6.4615 to 4.4833

SECONDARY outcome

Timeframe: Baseline; at the end of 2.5 mg/kg/day, through 3 weeks

The change may be Heart rate (beat/minute) while standing.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=30 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Vital Signs-heart Rate	0.9459 change in beats per minute Interval -3.164 to 5.0559	0.6326 change in beats per minute Interval -2.1185 to 3.3838

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

The change may be weight in kilograms or lbs.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=30 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Vital Signs--weight	0.07389 change in kilograms Interval -0.2163 to 0.3641	-0.07658 change in kilograms Interval -0.4177 to 0.2645

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

The change may be temperature in Fahrenheit degree

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=30 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Vital Signs--temperature (Fahrenheit Degree)	-0.3069 change in degrees Fahrenheit Interval -0.6335 to 0.01972	-0.1882 change in degrees Fahrenheit Interval -0.5579 to 0.1816

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

The result is reported as the number of participants that had a clinically significant change in the physical exam findings, including allergic immunologic, cardiovascular, constitutional symptoms, ENT, endocrine, eyes, gastrointestinal, genitourinary, hematologic, integumentary, musculoskeletal, neurological, psychiatric, respiratory and other symptoms clinical significant findings.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Physical Exam	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

The result is reported as the number of participants that had a clinically significant change in the general neurological exam clinical significant findings, including cranial nerves, motor strength, sensation, reflexes, gait, and other movements.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Neurological Exam	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

The result is reported as the number of participants that had a clinically significant change in the EKG.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Electrocardiograms	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

The result is reported as the number of participants that had a clinically significant change in the values of Hematology parameters, including RBC, WBC, HB, PLT, et al.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Laboratory Values--hematology	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

The result is reported as the number of participants that had a clinically significant change in the values of the Chemistry profile, including BUN, CR, Electrolyte, glucose, liver function, etc.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Laboratory Values--chemistry	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Montreal Cognitive Assessment (MoCA) is a rapid screening instrument for mild cognitive dysfunction. The change may be the scores of MoCA, which is ranging from 0-30. Higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Montreal Cognitive Assessment (MoCA)	-0.8341 change in units on a scale Interval -1.7743 to 0.1062	-0.5000 change in units on a scale Interval -1.3489 to 0.3489

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Population: Out of the total study population, 25 participants took the cognitive test from CBD group, and 26 from placebo group.

The change may be the scores of Wechsler test for Adult Reading. Wechsler Test of Adult Reading (WTAR) - Word reading tests are an established method of establishing a premorbid estimate of verbal intellectual functioning, which will serve as an estimate of premorbid cognitive reserve. The WTAR comprises 50 words with irregular pronunciations that participants read aloud. The raw score can be transformed to an age-adjusted standard score, which is used to predict IQ (M = 100; SD = 15). Scores higher means better.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=25 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=26 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Wechsler Test for Adult Reading	0.4421 change in units on a scale Interval -1.6349 to 2.5192	-1.4931 change in units on a scale Interval -3.0859 to 0.09972

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Population: Out of the total study population, 15 participants performed the cognitive test from CBD group, and 14 from placebo group.

The change are the scores of Grooved Pegboard Test for the dominant affected hand. Manipulative dexterity, including finger speed, is assessed. Scoring is the time it took the participant to complete the task. Start the clock once the participant starts and stop it once the task has been completed. If after five minutes the participant has not completed the pegboard, stop the participant. The score the higher the worse.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=15 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=14 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Grooved Pegboard Test	5.3406 change in seconds Interval -12.2701 to 22.9514	-14.3454 change in seconds Interval -27.0367 to -1.654

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Population: Out of the total study population, 29 participants performed the cognitive test from CBD group, and 29 from placebo group.

The change may be the scores of Intellectual functioning estimate, Symbol digit modalities test (SDMT). The SDMT is a measure of processing speed and working memory that has proven to be sensitive to cognitive impairment in MS that has both oral and written trials (only the oral trial will be administered given the anticipated difficulty patients will have with tremor). Participants are presented with a key at the top of a page pairing unique symbols with single digits. Participants are required to provide the correct digit with symbols that are presented on the rest of the page. The score is the number of correctly coded items from 0-110. The number of correct responses provided in 90 seconds on the oral trial is recorded. Scores range 0-110 items. The higher the score the better.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=29 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=29 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Symbol Digit Modalities Test	0.6143 change in units on a scale Interval -2.0546 to 3.2832	3.8357 change in units on a scale Interval 1.1306 to 6.5408

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Population: Out of the total study population, 27 participants performed the cognitive test from CBD group, and 25 from placebo group.

The change may be the scores of Intellectual functioning estimate, Paced auditory serial addition test. Paced Auditory Serial Addition Test (PASAT) - The PASAT is a more complex measure of processing speed and working memory in which a series of digits is presented to participants at varying intervals (i.e., 2 seconds, 3 seconds). Participants must add each digit to the immediately preceding digit for the duration of each trial. The number of correct responses for each trial is recorded. The score for the PASAT is the total number correct out of 60 possible answers. The higher, the better.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=27 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=25 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Paced Auditory Serial Addition Test	6.9653 change in units on a scale Interval -0.04668 to 13.9773	11.9489 change in units on a scale Interval 5.576 to 18.3219

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Population: Out of the total study population, 29 participants performed the cognitive test from CBD group, and 29 from placebo group.

The change may be the scores of Intellectual functioning estimate, Controlled oral word association test (COWAT). The COWAT is a measure of speeded verbal fluency and word retrieval in which participants are asked to say as many words as they can that begin with each of three letters for 60 seconds. The total number of words generated across all three trials is recorded. The higher, the better.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=29 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=29 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Controlled Oral Word Association Test	3.1675 change in units on a scale Interval 1.0881 to 5.247	2.5916 change in units on a scale Interval -0.843 to 6.0262

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Population: Out of the total study population, 26 participants performed the cognitive test from CBD group, and 25 from placebo group.

The change may be the scores of Intellectual functioning estimate, Hopkins verbal learning test-revised. Hopkins Verbal Learning Test-Revised (HVLT-R) - The HVLT-R is a measure of verbal learning and memory in which participants are asked to learn a 12-item word list over three trials (total immediate learning). When scoring, the three leaning trials are combined to calculate a total recall score. Score ranges 0-36. The higher, the better. The outcoe measure is reporting the change from baseline in the total leaning score across all three trials.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=26 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=25 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Hopkins Verbal Learning Test-total Learning	-2.03 change in units on a scale Standard Error 1.06	-1.30 change in units on a scale Standard Error 1.15

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Population: Out of the total study population, 26 participants performed the cognitive test from CBD group, and 25 from placebo group.

Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed recall trial. The participant is asked to recall as many words as they can 20-25 minutes after being presented the word list. The range is 0-12; the higher, the better.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=26 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=25 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change From Baseline for the Delayed Recall Trials Score of HVLT-R	-1.16 change in units on a scale Standard Error 0.60	-0.28 change in units on a scale Standard Error 0.26

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Population: Out of the total study population, 26 participants performed the cognitive test from CBD group, and 25 from placebo group.

The change may be the scores of Intellectual functioning estimate, Hopkins verbal learning test-revised. Hopkins Verbal Learning Test-Revised (HVLT-R) is a measure of verbal learning and memory in which participants are asked to learn a 12-item word list over three trials (total immediate learning). Delayed recognition trials is composed of 24 words, including the 12 target words and 12 false-positives, 6 semantically related, and 6 semantically unrelated. Retention % = percentage retained or delayed recall divided by better score on trial 2 or 3. Range 0-1. The higher, the better.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=26 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=25 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change From Baseline in Hopkins Verbal Learning Test-Delayed Recognition Trial	0.54 units on a scale Standard Error 0.48	0.55 units on a scale Standard Error 0.27

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Population: Out of the total study population, 26 participants performed the cognitive test from CBD group, and 25 from placebo group.

The change may be the scores of Intellectual functioning estimate, Judgment of line orientation. Judgment of Line Orientation (JOLO) - The JOLO is test of visuospatial functioning which measures a person's ability to match the angle and orientation of lines in space. Patients are asked to match two angled lines to a set of 11 lines that are arranged in a semicircle and separated 18 degrees from each other. Score ranges 0-30. The higher, the better.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=26 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=25 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Judgment of Line Orientation	0.1367 change in units on a scale Interval -1.0173 to 1.2907	-1.1626 change in units on a scale Interval -2.6697 to 0.3446

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Population: Out of the total study population, 29 participants performed the cognitive test from CBD group, and 29 from placebo group.

The change may be the scores of Semantic verbal fluency. Semantic Verbal Fluency - Semantic Verbal fluency is a measure of speeded verbal fluency and word retrieval in which participants are asked to say as many animal names/fruits and vegetables for 60 seconds. The total number of words generated across all three trials is recorded. The higher the score is, the better.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=29 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=29 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Semantic Verbal Fluency	0.7153 change in units on a scale Interval -0.7948 to 2.2253	2.4672 change in units on a scale Interval 0.8614 to 4.0729

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Comprised of 8 items which has five response options. Anxiety short form - is component of the Neurol-QOL (Quality of Life in Neurological Disorders) Measurement System, which is a collaborative effort of the National Institute of Neurological Disorders and Stroke and a number of partnering institutions. This measurement system was designed to be responsive to the needs of researchers in a variety of neurological disorders and to facilitate comparisons of data across clinical trials in different diseases. The short form is comprised of eight items that were selected from the respective item bank. Items have five response options (e.g., 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always). Respondents generally can answer five questions per minute. The change may be the total scores of the 8 items. Higher values represent a worse outcome. Scores range 8-40.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Anxiety Short Form Response	-2.1001 change in units on a scale Interval -3.6111 to -0.5891	-3.4533 change in units on a scale Interval -4.8327 to -2.074

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Valid and reliable scale to provide a means of assessing neuropsychiatric symptoms and psychopathology of patients. The change may be the scores of NPI. Neuropsychiatric Inventory (NPI) - is a valid and reliable scale. It was developed to provide a means of 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. The NPI is administered to a caregiver/significant other who has detailed knowledge of the participant's behavior. Higher values represent a worse outcome. Score ranges 0-12.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=30 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Neuropsychiatric Inventory (NPI)	-0.3000 change in units on a scale Interval -0.9611 to 0.3611	-1.2667 change in units on a scale Interval -2.7392 to 0.2058

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Population: 31 patients from CBD group and 30 from placebo group conducted the SCOPA DS scales.

Scales for Outcomes in Parkinson's disease (SCOPA)sleep - is a valid, reliable, short scale for assessing daytime sleepiness (DS) and nighttime sleep problems (NS) in patients with PD. The DS sub scale evaluates daytime sleepiness and includes six items with four response options, ranging from 0 (never) to 3 (often). The score ranges 0-18. The higher the worse. The other

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Scales of Outcomes in Parkinson's Disease (SCOPA) Sleep-daytime Sleepiness	-0.5280 change in units on a scale Interval -1.2572 to 0.2012	-0.2667 change in units on a scale Interval -1.0365 to 0.5031

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Comprised of 8 items which item has five response options. Depression short form - is a component of the Neurol-QOL (Quality of Life in Neurological Disorders) Measurement System, which is a collaborative effort of the National Institute of Neurological Disorders and Stroke and a number of partnering institutions. This measurement system was designed to be responsive to the needs of researchers in a variety of neurological disorders and to facilitate comparisons of data across clinical trials in different diseases. The short form is comprised of eight items that were selected from the respective item bank. Items have five response options (e.g., 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always). Respondents generally can answer five questions per minute.

The change may be the scores of the total 8 items. Score ranges 0-40. Higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=30 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Depression Short Form	-1.7300 change in units on a scale Interval -3.9531 to 0.4931	-2.0367 change in units on a scale Interval -4.1183 to 0.045

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Comprised of 8 items which item has 5 response options. Emotional and behavioral dyscontrol short form - is a component of the Neurol-QOL Measurement System, which is a collaborative effort of the National Institute of Neurological Disorders and Stroke and a number of partnering institutions. This measurement system was designed to be responsive to the needs of researchers in a variety of neurological disorders and to facilitate comparisons of data across clinical trials in different diseases. The short form is comprised of eight items that were selected from the respective item bank. Items have five response options (e.g., 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always). Respondents generally can answer five questions per minute.

The change may be the total scores of the 8 items. Score ranges 0-40. Higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Emotional and Behavioral Dyscontrol Short Form	-3.9870 change in units on a scale Interval -6.3219 to -1.6522	-4.2733 change in units on a scale Interval -6.8021 to -1.7445

SECONDARY outcome

Timeframe: Pre- and 3 hours post- dose at baseline visit

Is a quick and easy way to assess how the participant is feeling. The change may be the scores of the scale 3 hours after dosing compared to pre-dosing.

Stanford Sleepiness Scale (SSS): The Stanford Sleepiness Scale is a quick and easy way to assess how alert the participant is feeling. SSS is validated and probably the most widely used instrument for the assessment of participant's sleepiness.

Score ranges 0-7. Higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Stanford Sleepiness Scale	0.2903 change in units on a scale Interval -0.138 to 0.7187	-0.03333 change in units on a scale Interval -0.3298 to 0.2631

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Assess how much a person hurts. The change may be the score of the short form. Pain Intensity 3a short form - components of the Patient Reported Outcome Measurement Information System (PROMIS), which was developed by the NIH to provide a standardized metric for measuring physical, mental, and social health across chronic diseases. PROMIS instruments were developed using item response theory and have been tested in more than 20,000 individuals drawn from the general US population. The Pain Intensity instrument assesses how much a person hurts. This includes the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities. Each question has five response options ranging in value from one to five.

Score ranges 0-15. Higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Pain Intensity 3a Short Form	-3.1209 change in units on a scale Interval -4.9451 to -1.2968	-2.6169 change in units on a scale Interval -4.8111 to -0.4226

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Self-reported consequences of pain on relevant aspects of one's life. The change may be the scores of the short form.

The Pain Interference instrument measures the self-reported consequences of pain on relevant aspects of one's life. This includes the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities. Each question has five response options ranging in value from one to five.

Score ranges 0-20. Higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Pain Interference 4a Short Form	-0.1543 change in units on a scale Interval -2.1498 to 1.8412	-2.7701 change in units on a scale Interval -4.8473 to -0.6929

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Self-report 9-item questionnaire with questions related to how fatigue interferes with certain activities and rates its severity. The change may be the total scores of the 9 items, ranging from 9-63. Higher values represent worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Fatigue Severity Scale	1.4224 change in units on a scale Interval -2.2727 to 5.1175	-1.3667 change in units on a scale Interval -4.3254 to 1.592

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Movement Disorder Society Unified Parkinson Disease Rating Scale. There are four parts, non-motor experiences of daily living, motor experiences of daily living, motor examination, and motor complications. The change may be the total scores of the four parts. Total score ranges 0-260. Higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Movement Disorder Society Unified Parkinson Disease Rating Scale	-6.2798 change in units on a scale Interval -11.5293 to -1.0303	-7.2333 change in units on a scale Interval -10.5756 to -3.8911

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Population: In CBD group, 31 patients at baseline and 29 patients at 2.5 mg/kg/day were testes. In Placebo group, 30 at baseline and 28 at 2.5 mg/kg/day were tested.

To evaluate involuntary movements often associated with treated PD. The change may be the total scores of the scale, including historical sub-score (0-60) and objective sub-score (0-44). The total score is historical sub score plus objective sub score, ranged from 0- 104. Higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Unified Dyskinesia Rating Scale	1.4704 score on a scale Interval -1.4078 to 4.3487	-1.4270 score on a scale Interval -3.2753 to 0.4214

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

The Timed Up & Go (TUG) test is a physical performance measure in which the ability to rise up from a seated chair position, walk 3m, turn, walk back, and sit down is timed. This measure is useful in an outpatient setting, because it requires only a few minutes, is easy to administer, and requires little equipment. Importantly, the TUG test is highly correlated with functional mobility, gait speed, and falls in older adults. The change may be the time duration (seconds) of performing the task. The higher, the worse.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=30 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in the Timed UP&GO (TUG)	-0.5409 seconds Interval -1.378 to 0.2962	-0.5922 seconds Interval -1.0932 to -0.09113

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

International restless legs syndrome (IRLS) study group rating scale for restless legs syndrome. The change may be the scores of the IRLS, ranged from 0-40. Higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in IRLS	-1.2366 change in units on a scale Interval -3.344 to 0.8709	-0.5667 change in units on a scale Interval -2.2772 to 1.1439

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

REM sleep behavior disorder screening questionnaire (RBDSQ). The change may be the total scores of RBDSQ.

REM sleep behavior disorder screening questionnaire (RBDSQ) - is a 10-item, patient self-rating instrument assessing the participant's sleep behavior with short questions that have to be answered by either "yes" or "no". Items 1 to 4 address the frequency and content of dreams and their relationship to nocturnal movements and behavior. Item 5 asks about self-injuries and injuries of the bed partner. Item 6 consists of four sub items assessing nocturnal motor behavior more specifically, e.g., questions about nocturnal vocalization, sudden limb movements, complex movements, or bedding items that fell down. Items 7 and 8 deal with nocturnal awakenings. Item 9 focuses on disturbed sleep in general and item 10 on the presence of any neurological disorder. The maximum total score of the RBDSQ is 13 points.

Score ranges 0-13 points. Higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ)	-0.4692 change in units on a scale Interval -1.0392 to 0.1009	-0.3333 change in units on a scale Interval -1.0095 to 0.3429

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

A validated self-administered questionnaire consisting of 7 questions on a 5-point Likert scale. The change may be the scores of the scale, ranged from 0-35. Higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Overactive Bladder Symptom Score	-0.09605 change in units on a scale Interval -1.0385 to 0.8464	0 change in units on a scale Interval -1.2663 to 1.2663

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

A reliable valid responsive acceptable and feasible tool for assessment of quality of life in PD, including 39 multiple-choice items covering 8 dimensions: mobility (#1-10), activities of daily living (#11-16), emotional well-being (#17-22), stigma (#23-26), social support (#27-29), cognition (#30-33), communication (#34-36), and bodily discomfort (#37-39). 5-point ordinal scoring system: 0=never, 1= occasionally, 2=sometimes, 3=often, 4=always. The change may be the total scores of PDQ-39, ranged from 0-156. Higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Parkinson's Disease Questionnaire (PDQ-39)	-4.8005 change in units on a scale Interval -10.0155 to 0.4145	-4.4788 change in units on a scale Interval -8.6298 to -0.3278

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Consists of 2 pages-the EuroQol-5 Dimension-5 level (EQ-5D-5L) descriptive system and the EuroQol (EQ) Visual analogue scale. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The VAS records the patient's self-rated health on a vertical visual analogue-scale, where the endpoints are labelled the best health you can imagine and the worst health you can imagine. The change may be the scales of EQ-5D. Score ranges 11111-55555. The higher, the worse.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in EuroQol-5 Dimension-5 Level	0.05364 change in units on a scale Interval 0.009875 to 0.09741	0.02467 change in units on a scale Interval -0.01451 to 0.06384

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Difference in Proportion of participants that discontinue the study due to study drug intolerance. The change may be the number of patients dropped out.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Difference in Proportion of Participants That Discontinue the Study Due to Study Drug Intolerance	1 Participants	0 Participants

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Rest tremor amplitude and constancy of rest tremor scores in MDS UPDRS. The change may be the sum scores of 3.17 and 3.18. Score ranged from 0-24. Higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Total Scores on Items 3.17 and 3.18 in MDS-UPDRS	-1.1570 change in units on a scale Interval -2.0377 to -0.2763	-0.1000 change in units on a scale Interval -0.7625 to 0.5625

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Patient's tremor experience. The change may be the scores of item 2.10. Score ranged from 0-4. Higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Item 2.10 in MDS UPDRS	-0.2280 change in units on a scale Interval -0.4929 to 0.0368	-0.100 change in units on a scale Interval -0.3008 to 0.1008

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Postural tremor of the hands and kinetic tremor of the hand. The change may be the sum scores of item 3.15 and 3.16. Score ranged from 0-16. Higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Item 3.15 and 3.16 in MDS UPDRS	-0.4291 change in units on a scale Interval -0.9259 to 0.0677	-0.6667 change in units on a scale Interval -1.1317 to -0.2016

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Rigidity sub scores in MDS UPDRS. The change may be the sub scores of rigidity related item in MDS UPDRS (item 3.3). Score ranged from 0-20. Higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Rigidity Sub Scores in MDS UPDRS	-0.3742 change in units on a scale Interval -1.6096 to 0.8612	-0.6030 change in units on a scale Interval -1.5951 to 0.3891

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Bradykinesia sub scores in MDS UPDRS. The change may be the sub scores of bradykinesia related items in MDS UPDRS, including items 3.4-3.8, and 3.14. The scores ranged from 0-44. Higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Bradykinesia Sub Scores in MDS UPDRS	-1.6787 change in units on a scale Interval -3.6134 to 0.256	-0.8666 change in units on a scale Interval -2.6253 to 0.8921

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Axial sub scores in MDS UPDRS. The change may be the sub scores of axial related items in MDS UPDRS, including items 3.9, 3.13, 3.10, 3.11, and 3.12. The sub scores ranged from 0-20. Higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Axial Sub Scores in MDS UPDRS	-0.2919 change in units on a scale Interval -0.8076 to 0.2237	-0.2667 change in units on a scale Interval -0.8275 to 0.2941

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Bulbar sub scores in MDS UPDRS (item 3.1 and 3.2). The change may be the sub scores of bulbar related items in MDS UPDRS, ranged from 0-8. Higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Bulbar Sub Scores in MDS UPDRS	-0.3376 change in units on a scale Interval -0.8015 to 0.1263	-0.03333 change in units on a scale Interval -0.6754 to 0.6088

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Insomnia Severity Index (ISI): ISI is a verified seven-item self-report questionnaire assessing the nature, severity, and impact of insomnia. A five-point Likert scale is used to rate each item (e.g., 0=no problem; 4=very severe problem), yielding a total score ranging from 0 to 28. The total score is interpreted as follows: absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); and severe insomnia (22-28).

A total score ranging from 0 to 28. Higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Insomnia Severity Index	-1.6982 change in units on a scale Interval -2.8162 to -0.5803	-1.6333 change in units on a scale Interval -2.7246 to -0.5421

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

To measure the quality and patterns of sleep in adults. It differentiates "poor" from "good" sleep quality by measuring seven areas (components): subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction. The change may be the total scores, ranged from 0 to 42. The higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Pittsburgh Sleep Quality Index	-0.8226 change in units on a scale Interval -1.7676 to 0.1225	-1.5000 change in units on a scale Interval -2.1722 to -0.8278

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Dermatology quality of life index. The change may be the scores of the questionnaire. The scoring of each question is as follows: very much=3, a lot =2, a little=1, not at all=0, not relevant =0. Question 7, prevented work or studying =3. The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Dermatology Quality of Life Index	-0.1763 change in units on a scale Interval -0.7571 to 0.4044	0.1000 change in units on a scale Interval -0.3343 to 0.5343

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Dermatology photography evaluation. The change in number of participants with a presence of seborrheic dermatitis from baseline to final visit. Dermatology photography: take a picture of the central face, as this is the most common area of seborrhea, and send it, with appropriate privacy safeguards, to dermatologists, Dr. Robert Dellavalle, MD., and Dr. Andrea Steel.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=29 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=29 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in the Number of Participants With Presence of Seborrheic Dermatitis From Baseline to Final Visit.	2 participants	3 participants

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Validated 30-item scale for the assessment of NMS in PD. Each symptom scored with respect to severity (0=none, 1=mild, 2=moderate, 3=severe), frequency (1=rarely, 2=often, 3=frequent, 4=very frequent). Each NMSS item score is calculated by multiplying the severity and frequency score. The final score is the sum of the total 30-item scores. The change may be the total scores of NMSS, ranged from 0 to 360. The higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Non-motor Symptoms Scale for Parkinson's Disease (NMSS)	-5.8652 change in units on a scale Interval -11.6281 to -0.1023	-5.0333 change in units on a scale Interval -8.9647 to -1.102

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Population: 31 patients from CBD group and 30 from placebo group conducted the SCOPA DS scales.

Scales for Outcomes in Parkinson's disease (SCOPA) sleep DS subscale is a valid, reliable, short scale for assessing daytime sleep problems (DS) in patients with PD. The sub scale includes six items with four response options, ranging from 0 (never) to 3 (often). The score ranges 0-18. The higher the worse.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Scales of Outcomes in Parkinson's Disease (SCOPA) - Daytime Sleep (DS) Problems.	-0.5280 change in units on a scale Standard Error 0.3575	-0.2667 change in units on a scale Standard Error 0.3769

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Population: 31 patients from CBD group and 30 from placebo group conducted the SCOPA NS scales.

Scales for Outcomes in Parkinson's disease (SCOPA) sleep NS subscale - is a valid, reliable, short scale for assessing nighttime sleep problems (NS) in patients with PD. The NS sub scale includes five items with four response options, ranging from 0 (never) to 3 (often). The score ranges 0-15. The higher the worse.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=31 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Scales of Outcomes in Parkinson's Disease (SCOPA) - Nighttime Sleep (NS) Problems.	-1.2066 change in units on a scale Standard Error 0.5075	-1.2333 change in units on a scale Standard Error 0.4074

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Modified Dysfunctional Beliefs and Attitudes about Sleep Questionnaire (DBAS-16): A validated self-reported questionnaire designed to identify and assess various sleep/insomnia-related cognitions (e.g., beliefs, attitudes, expectations, appraisals, attributions). range is 0-160; the higher numbers are worse.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=30 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Modified Dysfunctional Beliefs and Attitudes About Sleep Questionnaire (DBAS-16)	-2.70 units on a scale Standard Error 3.40	-4.57 units on a scale Standard Error 3.30

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

WASO, the total number of minutes that a person is awake after having initially fallen asleep; higher numbers are worse.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=21 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=25 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Wake After Sleep Onset	-48.89 change in minutes Interval -80.25 to -17.53	-1.97 change in minutes Interval -53.29 to 49.35

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

Population: PD participants who took either cannabidiol cannabis extract oral solution or placebo.

Interleukin 6 is an inflammatory cytokine, and is measured in the blood. Whole bold was collected into tubes containing anticoagulant; tubes were inverted gently 3-4 times. Blood was allowed to clot at room temperature for 30 to 45 min, centrifuged at 1,000 x g for 15 min at 4°C and serum was transferred to a clean polypropylene tube. To completely remove platelets and precipitates, the tubes were centrifuge again at 10,000 x g for 10 min at 4°C. Processed samples were stored at -80°F, and cytokine levels measured using the Bio-Plex ProTM Human Cytokine Assay.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=17 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=19 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Difference of Plasma Interleukin 6 Level Between PD and Healthy Control Population	2.99 ng/mL Interval 0.61 to 14.66	1.59 ng/mL Interval 0.33 to 7.66

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

To measure severity of symptoms and support a diagnosis of impulse control disorders and related disorders in PD. The result is the difference of the change of the total scores of QUIP-RS (excessive hobbies-punding and dopamine dysregulation syndrome) between groups. The total QUIP-RS scores is 0-112. Higher values represent a worse outcome.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=29 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale (QUIP-RS) - Total Scores	-0.24 score on a scale Interval -12.0 to 4.0	0.43 score on a scale Interval 0.0 to 8.0

SECONDARY outcome

Timeframe: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks

C-SSRS is a suicidal ideation rating scale. The change may be the answers to the questions of C-SSRS. There are five questions and have binary responses (yes/no). Assign a score of 1 if answer yes and score of 0 if no . Higher values represent a worse outcome.The mximum score is 5.

Outcome measures

Measure	CBD Cannabis Extract Oral Solution n=30 Participants Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 Participants Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Change in The Columbia-Suicide Severity Rating Scale (C-SSRS)	0 score on a scale Interval 0.0 to 0.0	0 score on a scale Interval 0.0 to 0.0

Adverse Events

CBD Cannabis Extract Oral Solution

Serious events: 1 serious events

Other events: 26 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Measure	CBD Cannabis Extract Oral Solution n=31 participants at risk Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 participants at risk Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Respiratory, thoracic and mediastinal disorders pneumonia	3.2% 1/31 • Number of events 1 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	0.00% 0/30 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.

Other adverse events

Measure	CBD Cannabis Extract Oral Solution n=31 participants at risk Cannabidiol (CBD) Cannabis extract oral solution Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution	Placebo n=30 participants at risk Placebo oral solution Placebo: Subjects randomized to this arm will receive Placebo
Nervous system disorders dizziness	58.1% 18/31 • Number of events 18 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	20.0% 6/30 • Number of events 6 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Nervous system disorders feeling of relaxation	41.9% 13/31 • Number of events 13 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	23.3% 7/30 • Number of events 7 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Nervous system disorders fatigue	32.3% 10/31 • Number of events 10 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	20.0% 6/30 • Number of events 6 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Nervous system disorders decreased concentration	32.3% 10/31 • Number of events 10 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	13.3% 4/30 • Number of events 4 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Nervous system disorders headache	29.0% 9/31 • Number of events 9 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	33.3% 10/30 • Number of events 10 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Nervous system disorders somnolence	25.8% 8/31 • Number of events 8 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	26.7% 8/30 • Number of events 8 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Nervous system disorders feeling abnormal	25.8% 8/31 • Number of events 8 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	6.7% 2/30 • Number of events 2 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Nervous system disorders feeling drunk	22.6% 7/31 • Number of events 7 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	6.7% 2/30 • Number of events 2 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Gastrointestinal disorders nausea	19.4% 6/31 • Number of events 6 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	10.0% 3/30 • Number of events 3 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Nervous system disorders confusion	16.1% 5/31 • Number of events 5 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	3.3% 1/30 • Number of events 1 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Nervous system disorders thinking abnormal	16.1% 5/31 • Number of events 5 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	0.00% 0/30 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Nervous system disorders disorientation	12.9% 4/31 • Number of events 4 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	0.00% 0/30 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
General disorders dry mouth	12.9% 4/31 • Number of events 4 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	3.3% 1/30 • Number of events 1 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
General disorders fall	12.9% 4/31 • Number of events 4 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	10.0% 3/30 • Number of events 3 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Nervous system disorders increased concentration	12.9% 4/31 • Number of events 4 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	3.3% 1/30 • Number of events 1 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
General disorders weakness	12.9% 4/31 • Number of events 4 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	3.3% 1/30 • Number of events 1 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Nervous system disorders agitation	9.7% 3/31 • Number of events 3 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	3.3% 1/30 • Number of events 1 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Nervous system disorders elevated mood	9.7% 3/31 • Number of events 3 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	10.0% 3/30 • Number of events 3 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Gastrointestinal disorders diarrhea	6.5% 2/31 • Number of events 2 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	13.3% 4/30 • Number of events 4 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Metabolism and nutrition disorders anorexia	6.5% 2/31 • Number of events 2 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	10.0% 3/30 • Number of events 3 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Nervous system disorders anxiety	6.5% 2/31 • Number of events 2 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	10.0% 3/30 • Number of events 3 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Nervous system disorders insomnia	6.5% 2/31 • Number of events 2 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	10.0% 3/30 • Number of events 3 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Gastrointestinal disorders abdominal pain	3.2% 1/31 • Number of events 1 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	10.0% 3/30 • Number of events 3 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Nervous system disorders sleep disturbance	3.2% 1/31 • Number of events 1 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	6.7% 2/30 • Number of events 2 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
General disorders weight loss	3.2% 1/31 • Number of events 1 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	6.7% 2/30 • Number of events 2 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Respiratory, thoracic and mediastinal disorders cold	0.00% 0/31 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	6.7% 2/30 • Number of events 2 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Respiratory, thoracic and mediastinal disorders cough	0.00% 0/31 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	6.7% 2/30 • Number of events 2 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Nervous system disorders depression	0.00% 0/31 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	6.7% 2/30 • Number of events 2 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Gastrointestinal disorders constipation	6.5% 2/31 • Number of events 2 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	0.00% 0/30 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
General disorders chills	6.5% 2/31 • Number of events 2 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	0.00% 0/30 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Metabolism and nutrition disorders increased appetite	12.9% 4/31 • Number of events 4 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	0.00% 0/30 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Psychiatric disorders irritability	6.5% 2/31 • Number of events 2 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	0.00% 0/30 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Renal and urinary disorders urinary tract infection	6.5% 2/31 • Number of events 2 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	0.00% 0/30 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.
Gastrointestinal disorders vomiting	6.5% 2/31 • Number of events 2 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.	0.00% 0/30 • 9 weeks Adverse events are collected at all contacts with participants: primarily and formally at scheduled study visits (using a form) and phone calls (using a script), but also informally at any unscheduled contacts.

Additional Information

Maureen Leehey, MD

University of Colorado

Phone: 3037248288

Email: maureen.leehey@cuanschutz.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place