Trial Outcomes & Findings for Cannabidiol and CES1 Interactions in Healthy Subjects (NCT NCT04603391)

Results Overview

Plasma methylphenidate (MPH) concentrations for both arms were determined by using a liquid-liquid extraction method and LC-MS/MS analysis. Peak concentration (Cmax) was reported as observed for each subject. The geometric mean ratios (GMR) of the Cmax for MPH were compared between the two exposure conditions, i.e., MPH with CBD versus MPH with placebo. In brief, if the 90% confidence interval (CI) of GMR for Cmax between the CBD group and placebo group extend beyond the FDA's established bioequivalent limits of 0.8-1.25, the result was interpreted to represent a DDI. In our case, a GMR greater than 1.25 would be indicative of a DDI, since CBD would impair CES1's ability to efficiently metabolize MPH, thus a higher ratio of Cmax's of MPH in our CBD group relative to our placebo group.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

14 participants

Primary outcome timeframe

8 hours

Results posted on

2024-07-18

Participant Flow

After enrollment, subjects were assigned a screening visit date at the Clinical Research Center to obtain a medical history, physical, and routine lab tests including a complete blood count, comprehensive metabolic panel, urinalysis, and urine drug screen.

Participant milestones

Participant milestones
Measure	First Methylphenidate and CBD, Then Methylphenidate and Placebo Subjects received a three day run in of CBD 750 mg orally twice daily (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]). On day four, all subjects returned to the clinical research center to receive one oral dose of CBD 750 mg orally (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast). After a minimum washout period of five days, subjects received a three day run in of 7.5 ml of Epidiolex® placebo solution (no CBD) orally twice daily. On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® placebo solution (no CBD) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast).	First Methylphenidate and Placebo, Then Methylphenidate and CBD Subjects received a three day run in of 7.5 ml of Epidiolex® placebo solution (no CBD) orally twice daily. On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® placebo solution (no CBD) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast). After a minimum washout period of five days, subjects received a three day run in of CBD 750 mg orally twice daily (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]). On day four, all subjects returned to the clinical research center to receive one oral dose of CBD 750 mg orally (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast).
First Intervention (4 Days) STARTED	8	6
First Intervention (4 Days) COMPLETED	6	6
First Intervention (4 Days) NOT COMPLETED	2	0
Washout (Minimum 5 Days) STARTED	6	6
Washout (Minimum 5 Days) COMPLETED	6	6
Washout (Minimum 5 Days) NOT COMPLETED	0	0
Second Intervention (4 Days) STARTED	6	6
Second Intervention (4 Days) COMPLETED	6	6
Second Intervention (4 Days) NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	First Methylphenidate and CBD, Then Methylphenidate and Placebo Subjects received a three day run in of CBD 750 mg orally twice daily (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]). On day four, all subjects returned to the clinical research center to receive one oral dose of CBD 750 mg orally (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast). After a minimum washout period of five days, subjects received a three day run in of 7.5 ml of Epidiolex® placebo solution (no CBD) orally twice daily. On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® placebo solution (no CBD) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast).	First Methylphenidate and Placebo, Then Methylphenidate and CBD Subjects received a three day run in of 7.5 ml of Epidiolex® placebo solution (no CBD) orally twice daily. On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® placebo solution (no CBD) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast). After a minimum washout period of five days, subjects received a three day run in of CBD 750 mg orally twice daily (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]). On day four, all subjects returned to the clinical research center to receive one oral dose of CBD 750 mg orally (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast).
First Intervention (4 Days) Adverse Event	1	0
First Intervention (4 Days) Lost to Follow-up	1	0

Baseline Characteristics

Cannabidiol and CES1 Interactions in Healthy Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Study Subjects for Both Sequences n=14 Participants Sequence 1: Subjects received a three day run in of 7.5 mL of Epidiolex® solution \[100 mg/ml\]). On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® solution \[100 mg/ml\]) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast). After a minimum washout period of five days, subjects received a three day run in of 7.5 ml of Epidiolex® placebo solution orally twice daily. On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® placebo solution and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast). Sequence 2: Subjects received a three day run in of 7.5 ml of Epidiolex® placebo solution orally twice daily. On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® placebo solution and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast). After a minimum washout period of five days, Subjects received a three day run in of 7.5 mL of Epidiolex® solution \[100 mg/ml\]). On day four, all subjects returned to the clinical research center to receive one oral dose of Epidiolex® solution \[100 mg/ml\]) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast).
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	14 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	26.67 years STANDARD_DEVIATION 6.54 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	14 Participants n=5 Participants

PRIMARY outcome

Timeframe: 8 hours

Population: Each subject served as their own control, so since all 12 subjects that completed the study went through both arms, we were able to analyze the both arms for each subject. Hence, 12 subjects gave us 24 arms (2 arms/subject). The Cmax for each subject in the methylphenidate and CBD arm was directly compared to their methylphenidate and placebo arm, allowing us to determine the ratio of change in the presence of CBD.

Plasma methylphenidate (MPH) concentrations for both arms were determined by using a liquid-liquid extraction method and LC-MS/MS analysis. Peak concentration (Cmax) was reported as observed for each subject. The geometric mean ratios (GMR) of the Cmax for MPH were compared between the two exposure conditions, i.e., MPH with CBD versus MPH with placebo. In brief, if the 90% confidence interval (CI) of GMR for Cmax between the CBD group and placebo group extend beyond the FDA's established bioequivalent limits of 0.8-1.25, the result was interpreted to represent a DDI. In our case, a GMR greater than 1.25 would be indicative of a DDI, since CBD would impair CES1's ability to efficiently metabolize MPH, thus a higher ratio of Cmax's of MPH in our CBD group relative to our placebo group.

Outcome measures

Outcome measures
Measure	All Participants n=24 Participants Methylphenidate and CBD Arm Only Subjects received a three day run in of CBD 750 mg orally twice daily (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]). On day four, all subjects returned to the clinical research center to receive one oral dose of CBD 750 mg orally (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast). Methylphenidate and Placebo Arm Only Subjects received a three day run in of 7.5 ml of Epidiolex® placebo solution (no CBD) orally twice daily. On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® placebo solution (no CBD) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast). The subsequent analysis compared the geometric mean ratio of the Cmax for the methylphenidate and CBD arm to the methylphenidate and placebo arm of each subject.	Methylphenidate and Placebo Arm Only Subjects received a three day run in of 7.5 ml of Epidiolex® placebo solution (no CBD) orally twice daily. On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® placebo solution (no CBD) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast).
Differences in the Geometric Mean Ratio (GMR) of the Peak Concentration (Cmax) Will be Compared Between the Two Exposure Conditions; i.e. Methylphenidate + CBD vs Methylphenidate + Placebo.	1.08 Ratio Interval 0.85 to 1.37	—

PRIMARY outcome

Timeframe: 0-8 hours (determined), 8 hours-infinity (extrapolated)

Population: Each subject served as their own control, so since all 12 subjects that completed the study went through both arms, we were able to analyze the both arms for each subject. Hence, 12 subjects gave us 24 arms (2 arms/subject). The AUCinf for each subject in the methylphenidate and CBD arm was directly compared to their methylphenidate and placebo arm, allowing us to determine the ratio of change in the presence of CBD.

All methylphenidate plasma concentrations were quantified using liquid-liquid extraction method and LC-MS/MS analysis. The terminal elimination rate constant (λz) was estimated by linear least-squares regression of the terminal portion of the plasma concentration (on natural logarithmic scale)-time curve. The area under the plasma concentration-time curve of methylphenidate AUC 0-8h were calculated according to the linear trapezoidal rule. AUC8-inf was extrapolated by using the last observed concentration of MPH (Clast) and dividing it by λz. AUC0-8 was added to AUC8-inf to get AUCinf. The GMR of the AUCinf for MPH were compared between the two exposure conditions, i.e., MPH with CBD versus MPH with placebo. In brief, if the 90% confidence interval (CI) of GMR for Cmax between the CBD group and placebo group was beyond the FDA's established bioequivalent limits of 0.8-1.25, the result was interpreted to represent a DDI. A GMR greater than 1.25 would be indicative of a DDI.

Outcome measures

Outcome measures
Measure	All Participants n=24 Participants Methylphenidate and CBD Arm Only Subjects received a three day run in of CBD 750 mg orally twice daily (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]). On day four, all subjects returned to the clinical research center to receive one oral dose of CBD 750 mg orally (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast). Methylphenidate and Placebo Arm Only Subjects received a three day run in of 7.5 ml of Epidiolex® placebo solution (no CBD) orally twice daily. On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® placebo solution (no CBD) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast). The subsequent analysis compared the geometric mean ratio of the Cmax for the methylphenidate and CBD arm to the methylphenidate and placebo arm of each subject.	Methylphenidate and Placebo Arm Only Subjects received a three day run in of 7.5 ml of Epidiolex® placebo solution (no CBD) orally twice daily. On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® placebo solution (no CBD) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast).
Differences in the Geometric Mean Ratio (GMR) of the Area Under the Time Curve 0-infinity (AUCinf) for Methylphenidate Will be Compared Between the Two Exposure Conditions; i.e. Methylphenidate + CBD vs Methylphenidate + Placebo.	1.09 Ratio Interval 0.89 to 1.32	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 hours

Population: Each subject served as their own control, so since all 12 subjects that completed the study went through both arms, we were able to analyze the both arms for each subject. Hence, 12 subjects gave us 24 arms (2 arms/subject). The Cmax for each subject in the methylphenidate and CBD arm and the methylphenidate and placebo arm was directly reported/analyzed below.

Plasma methylphenidate (MPH) concentrations for both arms were determined by using a liquid-liquid extraction method and LC-MS/MS analysis. Peak concentration (Cmax) was reported as observed for each subject (highest observed plasma concentration of methylphenidate).

Outcome measures

Outcome measures
Measure	All Participants n=12 Participants Methylphenidate and CBD Arm Only Subjects received a three day run in of CBD 750 mg orally twice daily (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]). On day four, all subjects returned to the clinical research center to receive one oral dose of CBD 750 mg orally (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast). Methylphenidate and Placebo Arm Only Subjects received a three day run in of 7.5 ml of Epidiolex® placebo solution (no CBD) orally twice daily. On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® placebo solution (no CBD) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast). The subsequent analysis compared the geometric mean ratio of the Cmax for the methylphenidate and CBD arm to the methylphenidate and placebo arm of each subject.	Methylphenidate and Placebo Arm Only n=12 Participants Subjects received a three day run in of 7.5 ml of Epidiolex® placebo solution (no CBD) orally twice daily. On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® placebo solution (no CBD) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast).
Peak Methylphenidate Plasma Concentration (Cmax) for Methylphenidate and CBD Arms and Methylphenidate and Placebo Arms.	13.5 ng/mL Interval 6.9 to 26.5	12.2 ng/mL Interval 6.6 to 22.8

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 hours

Population: Each subject served as their own control, so since all 12 subjects that completed the study went through both arms, we were able to analyze the both arms for each subject. Hence, 12 subjects gave us 24 arms (2 arms/subject). The Tmax for each subject in the methylphenidate and CBD arm and the methylphenidate and placebo arm was directly reported/analyzed below.

Plasma methylphenidate (MPH) concentrations for both arms were determined by using a liquid-liquid extraction method and LC-MS/MS analysis. The time to peak plasma methylphenidate concentrations (Tmax) was reported as observed for each subject.

Outcome measures

Outcome measures
Measure	All Participants n=12 Participants Methylphenidate and CBD Arm Only Subjects received a three day run in of CBD 750 mg orally twice daily (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]). On day four, all subjects returned to the clinical research center to receive one oral dose of CBD 750 mg orally (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast). Methylphenidate and Placebo Arm Only Subjects received a three day run in of 7.5 ml of Epidiolex® placebo solution (no CBD) orally twice daily. On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® placebo solution (no CBD) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast). The subsequent analysis compared the geometric mean ratio of the Cmax for the methylphenidate and CBD arm to the methylphenidate and placebo arm of each subject.	Methylphenidate and Placebo Arm Only n=12 Participants Subjects received a three day run in of 7.5 ml of Epidiolex® placebo solution (no CBD) orally twice daily. On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® placebo solution (no CBD) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast).
Time to Peak Methylphenidate Plasma Concentration (Tmax) for Methylphenidate and CBD Arms and Methylphenidate and Placebo Arms.	1.25 hours (h) Interval 0.5 to 3.0	1.75 hours (h) Interval 0.5 to 3.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 hours

Population: Each subject served as their own control, so since all 12 subjects that completed the study went through both arms, we were able to analyze the both arms for each subject. Hence, 12 subjects gave us 24 arms (2 arms/subject).

All methylphenidate plasma concentrations were quantified using liquid-liquid extraction method and LC-MS/MS analysis. The area under the plasma concentration-time curve of methylphenidate AUC 0-8h was calculated according to the linear trapezoidal rule.

Outcome measures

Outcome measures
Measure	All Participants n=12 Participants Methylphenidate and CBD Arm Only Subjects received a three day run in of CBD 750 mg orally twice daily (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]). On day four, all subjects returned to the clinical research center to receive one oral dose of CBD 750 mg orally (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast). Methylphenidate and Placebo Arm Only Subjects received a three day run in of 7.5 ml of Epidiolex® placebo solution (no CBD) orally twice daily. On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® placebo solution (no CBD) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast). The subsequent analysis compared the geometric mean ratio of the Cmax for the methylphenidate and CBD arm to the methylphenidate and placebo arm of each subject.	Methylphenidate and Placebo Arm Only n=22 Participants Subjects received a three day run in of 7.5 ml of Epidiolex® placebo solution (no CBD) orally twice daily. On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® placebo solution (no CBD) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast).
Area Under the Time Curve 0-8hours (AUC0-8h) for Methylphenidate for the Two Exposure Conditions; Methylphenidate and CBD and Methylphenidate and Placebo.	55.7 ng/mL*h Interval 31.6 to 80.7	49.6 ng/mL*h Interval 30.7 to 74.3

OTHER_PRE_SPECIFIED outcome

Timeframe: 0-8 hours (determined), 8 hours-infinity (extrapolated)

Population: Each subject served as their own control, so since all 12 subjects that completed the study went through both arms, we were able to analyze the both arms for each subject. Hence, 12 subjects gave us 24 arms (2 arms/subject).

All methylphenidate plasma concentrations were quantified using liquid-liquid extraction method and LC-MS/MS analysis. The terminal elimination rate constant (λz) was estimated by linear least-squares regression of the terminal portion of the plasma concentration (on natural logarithmic scale)-time curve. The area under the plasma concentration-time curve of methylphenidate AUC 0-8h were calculated according to the linear trapezoidal rule. AUC8-inf was extrapolated by using the last observed concentration of MPH (Clast) and dividing it by λz. AUC0-8 was added to AUC8-inf to get AUCinf.

Outcome measures

Outcome measures
Measure	All Participants n=12 Participants Methylphenidate and CBD Arm Only Subjects received a three day run in of CBD 750 mg orally twice daily (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]). On day four, all subjects returned to the clinical research center to receive one oral dose of CBD 750 mg orally (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast). Methylphenidate and Placebo Arm Only Subjects received a three day run in of 7.5 ml of Epidiolex® placebo solution (no CBD) orally twice daily. On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® placebo solution (no CBD) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast). The subsequent analysis compared the geometric mean ratio of the Cmax for the methylphenidate and CBD arm to the methylphenidate and placebo arm of each subject.	Methylphenidate and Placebo Arm Only n=12 Participants Subjects received a three day run in of 7.5 ml of Epidiolex® placebo solution (no CBD) orally twice daily. On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® placebo solution (no CBD) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast).
Area Under the Time Curve 0-infinity (AUCinf) for Methylphenidate for the Two Exposure Conditions for Methylphenidate and CBD and Methylphenidate and Placebo.	70.7 ng/mL*h Interval 38.6 to 103.3	63.6 ng/mL*h Interval 42.6 to 98.6

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 hours

Population: Each subject served as their own control, so since all 12 subjects that completed the study went through both arms, we were able to analyze the both arms for each subject. Hence, 12 subjects gave us 24 arms (2 arms/subject).

All methylphenidate plasma concentrations were quantified using liquid-liquid extraction method and LC-MS/MS analysis. The terminal elimination rate constant (λz) was estimated by linear least-squares regression of the terminal portion of the plasma concentration (on natural logarithmic scale)-time curve. The elimination half-live (t1/2) was then calculated using the formula t1/2 = 0.693/λz.

Outcome measures

Outcome measures
Measure	All Participants n=12 Participants Methylphenidate and CBD Arm Only Subjects received a three day run in of CBD 750 mg orally twice daily (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]). On day four, all subjects returned to the clinical research center to receive one oral dose of CBD 750 mg orally (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast). Methylphenidate and Placebo Arm Only Subjects received a three day run in of 7.5 ml of Epidiolex® placebo solution (no CBD) orally twice daily. On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® placebo solution (no CBD) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast). The subsequent analysis compared the geometric mean ratio of the Cmax for the methylphenidate and CBD arm to the methylphenidate and placebo arm of each subject.	Methylphenidate and Placebo Arm Only n=12 Participants Subjects received a three day run in of 7.5 ml of Epidiolex® placebo solution (no CBD) orally twice daily. On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® placebo solution (no CBD) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast).
Half Life Determination (t1/2) for Methylphenidate for the Two Exposure Conditions for Methylphenidate and CBD and Methylphenidate and Placebo.	3.17 hours (h) Interval 2.24 to 4.52	3.12 hours (h) Interval 1.76 to 4.54

Adverse Events

Methylphenidate and CBD Arms Only

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Methylphenidate and Placebo Arms Only

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Methylphenidate and CBD Arms Only n=14 participants at risk Subjects received a three day run in of CBD 750 mg orally twice daily (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]). On day four, all subjects returned to the clinical research center to receive one oral dose of CBD 750 mg orally (administered as as 7.5 mL of Epidiolex® solution \[100 mg/ml\]) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast).	Methylphenidate and Placebo Arms Only n=12 participants at risk Subjects received a three day run in of 7.5 ml of Epidiolex® placebo solution (no CBD) orally twice daily. On day four, all subjects returned to the clinical research center to receive one oral dose of 7.5 mL of Epidiolex® placebo solution (no CBD) and one 10 mg tablet of dl-methylphenidate (Ritalin®) orally in a fed state (a 30 minute standardized breakfast).
Gastrointestinal disorders Nausea	7.1% 1/14 • Number of events 1 • Subjects participation lasted 45 days	0.00% 0/12 • Subjects participation lasted 45 days

Additional Information

John S. Markowitz, Pharm.D.

University of Florida

Phone: (352) 273-6262

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place