Effects of Inhaled Cannabis on Driving Performance | NCT01620177

NCT01620177

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
National Highway Traffic Safety Administration (NHTSA)	FED
National Institute on Drug Abuse (NIDA)	NIH

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
0% THC with 0.065 g/dL BAC	Experimental	Drug: Alcohol(oral) and placebo Drug: Cannabis(THC)(Inhaled) and Placebo
2.5-3.5% THC with 0.065 g/dL BAC	Experimental	Drug: Alcohol(oral) and placebo Drug: Cannabis(THC)(Inhaled) and Placebo
6.0-7.5% THC and 0.065 g/dL BAC	Experimental	Drug: Alcohol(oral) and placebo Drug: Cannabis(THC)(Inhaled) and Placebo
2.5-3.5% THC with 0 g/dL BAC	Experimental	Drug: Alcohol(oral) and placebo Drug: Cannabis(THC)(Inhaled) and Placebo
6.0-7.5% THC with 0 g/dL BAC	Experimental	Drug: Alcohol(oral) and placebo Drug: Cannabis(THC)(Inhaled) and Placebo
0% THC with 0 g/dL BAC	Experimental	Drug: Alcohol(oral) and placebo Drug: Cannabis(THC)(Inhaled) and Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Alcohol(oral) and placebo	Drug	Subjects will be dosed to an approximate peak BAC of 0.065%. Subjects will be tested on the decline such that subjects will be at or above the goal BAC (0.05%) throughout the drive

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Driving Performance	Measured by standard deviation of lane position. Metrics of driving performance were modeled using the SAS GLM Select function to identify changes in driver performance. Numbers represents coefficients on the regression equation such that this increase would be expected for every unit increase. A unit for THC is 1 ng/ml and a unit for BAC is 0.01% BAC. In understanding the regression coefficients, for THC the units for the coefficient would be expressed as cm per (ng/ml of THC), and for BrAC the units for the coefficient would be expressed as cm per (0.01% BrAC). The overall regression equation would be represented as SDLP = Intercept + Cthc x THC + Cbrac x BrAC. The coefficients indicate the strength of the effect on driving performance with higher coefficients indicating larger effects relative to the concentrations. Coefficients of zero indicate no effect or interactive effect.	Through entire drive, 0.5-1.3 hr post cannabis administration.

Secondary Outcomes

Measure	Description	Time Frame
THC Concentration in Plasma Sample	Measurement of THC concentration levels in plasma over the course of each visit compared to that of the other visits.	-0.7 hr, 0.25hr, 1.1 hr, 2 hr, 3 hr, 4.5 hr, 6 hr, 8 hr post cannabis administration
THC Concentration Levels in Whole Blood

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Healthy adult (age 21-55) men and women, based on medical and psychological evaluation
Currently valid unrestricted (except for vision correction) US driver's license
Licensed driver for at least the past two years
Drove at least 1300 miles in the past year, by self-report
Live within an 80 mile radius of NADS
Available for an overnight stay followed by a full-day study session for six sessions
Must be considered a light or moderate drinker according to Quantity-Frequency-Variability Scale (QFV)
Cannabis use with a minimum frequency averaging at least one day per quarter and no more than three days a week during the three months prior to study entry
Peripheral veins suitable for repeated venipuncture and/or placement of an intravenous catheter
Systolic blood pressure within a clinically normal range (120 ± 30 mmHg) and -diastolic blood pressure of 80 ± 20 mmHg..
Good command of written and spoken English
Female subjects with reproductive potential must agree to use (and/or have their partner use) one (1) acceptable method of birth control beginning at the screening visit throughout the study (including intervals between treatment periods/panels) and until 2 weeks after the last dose of study drug in the last treatment period. Acceptable methods of birth control include the following: intrauterine device (IUD-with or without local hormone release), diaphragm, spermicides, cervical cap, contraceptive sponge, oral contraceptives or condoms. Abstinence is an alternative lifestyle and subjects practicing abstinence may be included in the study.

Exclusion Criteria:

Presence of any clinically significant illness, as detected by history, physical examination, and/or laboratory tests, that might influence driving performance (e.g., seizures, sleep apnea, narcolepsy, vertigo, chronic fatigue syndrome) or put the subject at increased risk of adverse events (e.g., cardiac arrhythmia, hypertension)
History of a clinically significant adverse event associated with cannabis or alcohol intoxication
Donation of more than 450 mL of blood within 14 days of study drug administration
If female, pregnant or nursing
Currently interested in or participating in drug abuse treatment, or participated in drug abuse treatment within 60 days preceding study enrollment
Currently taking drugs that are contraindicated for use with study drugs
Requires any special equipment to aid in driving (ex. pedal extensions, hand brake or throttle, spinner wheel knobs or other non-standard equipment)
Significant history of motion sickness or demonstrates significant simulator sickness during practice drives at screening (SSQ). Subjects must have scores below the following values on the SSQ: Nausea < 21, Oculomotor <32, Disorientation < 15, and Total Score < 32.
Current alcohol or cannabis use disorder, as identified by the Alcohol Use Disorders Identification Test for alcohol or Cannabis Use Disorders Identification Test for cannabis.
History of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the subject from study participation
Prior participation in a driver impairment or distraction-related research study conducted at NADS that uses the same base drive.

Name	Affiliation	Role
Gary G Gaffney, M.D.	National Advanced Driving Simulator	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
National Advanced Driving Simulator		Iowa City	Iowa	52242	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
26144593	Result	Hartman RL, Brown TL, Milavetz G, Spurgin A, Pierce RS, Gorelick DA, Gaffney G, Huestis MA. Cannabis effects on driving lateral control with and without alcohol. Drug Alcohol Depend. 2015 Sep 1;154:25-37. doi: 10.1016/j.drugalcdep.2015.06.015. Epub 2015 Jun 23.
26019183	Result	Hartman RL, Brown TL, Milavetz G, Spurgin A, Gorelick DA, Gaffney G, Huestis MA. Controlled Cannabis Vaporizer Administration: Blood and Plasma Cannabinoids with and without Alcohol. Clin Chem. 2015 Jun;61(6):850-69. doi: 10.1373/clinchem.2015.238287. Epub 2015 May 27.

Arm/Group Information

ID	Title	Description
FG000	Overall Study	Individuals who completed the study completed all six arms of the study and the data is aggregated. Non-completers may have completed some arms and not others and their data is aggregated. There will be six study visits where the subject will arrive at the Clinical Research Unit(University of Iowa Hospitals & Clinics) the night before dosing. At each visit subjects will be receive one of the following six dosing regimens: placebo alcohol with placebo cannabis; placebo alcohol with low-dose cannabis, placebo alcohol with higher-dose of cannabis, low dose alcohol with placebo cannabis; low dose alcohol with low dose cannabis, low dose alcohol with higher-dose of cannabis.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Overall Study	Individuals who completed the study completed all six arms of the study and the data is aggregated. Non-completers may have completed some arms and not others and their data is aggregated.

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Driving Performance

Measured by standard deviation of lane position. Metrics of driving performance were modeled using the SAS GLM Select function to identify changes in driver performance. Numbers represents coefficients on the regression equation such that this increase would be expected for every unit increase. A unit for THC is 1 ng/ml and a unit for BAC is 0.01% BAC. In understanding the regression coefficients, for THC the units for the coefficient would be expressed as cm per (ng/ml of THC), and for BrAC the units for the coefficient would be expressed as cm per (0.01% BrAC). The overall regression equation would be represented as SDLP = Intercept + Cthc x THC + Cbrac x BrAC. The coefficients indicate the strength of the effect on driving performance with higher coefficients indicating larger effects relative to the concentrations. Coefficients of zero indicate no effect or interactive effect.

One subject who was an extreme outlier across driving performance measures was excluded. Due to the variability in THC and BrAC levels across subjects and conditions, a regression model was used which combined all of the data.

Posted

Number

Through entire drive, 0.5-1.3 hr post cannabis administration.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	0% THC With 0.065 g/dL BAC	Alcohol(oral) and placebo: Subjects will be dosed to an approximate peak BAC of 0.065%. Subjects will be tested on the decline such that subjects will be at or above the goal BAC (0.05%) throughout the drive Cannabis(THC)(Inhaled) and Placebo: Cannabis vapor is produced from 500 mg either placebo (0% THC), approximately 2.5-3.5% THC (low dose), or approximately 6.0-7.5% THC (high dose) bulk cannabis plant material to yield doses of approximately 0, 12.5-17.5, or 30-37.5 mg THC

ID	Term
D000428	Alcohol Drinking
D002189	Marijuana Abuse

ID	Term
D004327	Drinking Behavior
D001519	Behavior
D019966	Substance-Related Disorders
D064419	Chemically-Induced Disorders

ID	Term
D000431	Ethanol
C587251	nabiximols

ID	Term
D000438	Alcohols
D009930	Organic Chemicals

OG000	Cannabis - THC	Data from all dosing conditions combined to estimate the effect of THC concentrations using a regression equation.
OG001	Alcohol - BrAC (Breath Alcohol Concentration)	Data from all dosing conditions combined to estimate the effect of BrACconcentrations using a regression equation.
OG002	THC x BrAC	Data from all dosing conditions combined to estimate the interactive effect of THC and BrAC concentrations using a regression equation.