Alcohol Drinking, Cannabis
Conditions
Keywords
Cannabis, Marijuana, Marihuana, Alcohol, Driving
Brief summary
The purpose of this study is to expand understanding of the effects of cannabis on driving performance with and without the presence of low levels of alcohol. This project will involve the development a of a protocol and driving environment that is sensitive to the effects of cannabis on driving performance by building on prior driving situations used previously for testing the effects of alcohol on driving.
Detailed description
Individuals will be recruited who are currently users of cannabis and alcohol to participate in this study. They will undergo a physical exam at screening. 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. After dosing, participants will have provide saliva samples and blood drawn periodically to check cannabis levels and will complete a driving simulation. After completing the drive, additional saliva samples and blood draws will occur and participants will be monitored until it is safe to transport home.
Interventions
DRUGAlcohol(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
DRUGCannabis(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
Sponsors
National Highway Traffic Safety Administration (NHTSA)
National Institute on Drug Abuse (NIDA)
Gary R Gaffney
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Driving Performance | Through entire drive, 0.5-1.3 hr post cannabis administration. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| THC Concentration in Plasma Sample | -0.7 hr, 0.25hr, 1.1 hr, 2 hr, 3 hr, 4.5 hr, 6 hr, 8 hr post cannabis administration | Measurement of THC concentration levels in plasma over the course of each visit compared to that of the other visits. |
| THC Concentration Levels in Whole Blood | -0.7 hr, 0.25hr, 1.1 hr, 2 hr, 3 hr, 4.5 hr, 6 hr, 8 hr post cannabis | Measurement of THC concentration levels in whole blood over the course of each visit compared to that of the other visits. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 98 |
| Total | 98 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Failure at Screening Visit | 43 |
| Overall Study | Lost to Follow-up | 7 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Randomized, Not Active due to Scheduling | 1 |
| Overall Study | Withdrawal by Subject | 26 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 98 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 89 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 84 Participants |
| Region of Enrollment United States | 98 participants |
| Sex: Female, Male Female | 39 Participants |
| Sex: Female, Male Male | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 29 | 4 / 27 | 6 / 24 | 0 / 26 | 3 / 31 | 0 / 27 |
| serious Total, serious adverse events | 0 / 29 | 0 / 27 | 0 / 24 | 0 / 26 | 0 / 31 | 0 / 27 |
Outcome results
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.
Time frame: Through entire drive, 0.5-1.3 hr post cannabis administration.
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cannabis - THC | Driving Performance | 0.26 cm |
| Alcohol - BrAC (Breath Alcohol Concentration) | Driving Performance | 0.42 cm |
| THC x BrAC | Driving Performance | 0 cm |
Secondary
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.
Time frame: -0.7 hr, 0.25hr, 1.1 hr, 2 hr, 3 hr, 4.5 hr, 6 hr, 8 hr post cannabis administration
Population: We performed noncompartmental analyses with Phoenix WinNonLin® 6.3 for Windows (Pharsight) for maximum concentration (Cmax) of 11-OH-THC (LOQ 1 μg/L).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cannabis - THC | THC Concentration in Plasma Sample | 0 ng/ml |
| Alcohol - BrAC (Breath Alcohol Concentration) | THC Concentration in Plasma Sample | 4.8 ng/ml |
| THC x BrAC | THC Concentration in Plasma Sample | 7.5 ng/ml |
| 2.5-3.5% THC With 0 g/dL BAC | THC Concentration in Plasma Sample | 4.1 ng/ml |
| 6.0-7.5% THC With 0 g/dL BAC | THC Concentration in Plasma Sample | 7 ng/ml |
| 0% THC With 0 g/dL BAC | THC Concentration in Plasma Sample | 0 ng/ml |
Secondary
THC Concentration Levels in Whole Blood
Measurement of THC concentration levels in whole blood over the course of each visit compared to that of the other visits.
Time frame: -0.7 hr, 0.25hr, 1.1 hr, 2 hr, 3 hr, 4.5 hr, 6 hr, 8 hr post cannabis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cannabis - THC | THC Concentration Levels in Whole Blood | 0 ng/ml |
| Alcohol - BrAC (Breath Alcohol Concentration) | THC Concentration Levels in Whole Blood | 3.7 ng/ml |
| THC x BrAC | THC Concentration Levels in Whole Blood | 6.0 ng/ml |
| 2.5-3.5% THC With 0 g/dL BAC | THC Concentration Levels in Whole Blood | 2.8 ng/ml |
| 6.0-7.5% THC With 0 g/dL BAC | THC Concentration Levels in Whole Blood | 5.0 ng/ml |
| 0% THC With 0 g/dL BAC | THC Concentration Levels in Whole Blood | 0 ng/ml |