Combined Alcohol and Cannabis Effects on Skills of Young Drivers

Study Overview
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Brief Summary
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Alcohol and cannabis are the two most widely used substances of abuse in the world and are the psychoactive substances most often found in seriously and fatally injured drivers. In a recent study, it was observed that individuals who reported both driving under the influence of alcohol (DUIA) and the influence of cannabis (DUIC) experienced collision risk that was nearly 4 times that of individuals who reported driving after using only one of these drugs. Recent research in the United States and Canada indicates that the prevalence of DUIC among young drivers of high school and university age, and young adults is similar to, or higher than, the prevalence of DUIA. This is a serious public health issue, since motor vehicle collisions are the leading cause of death in this age group. Given the frequency with which alcohol and cannabis are consumed together, it is important to understand their combined effects on driver behaviour. The current study will examine the acute effects of a moderate dose of cannabis (12.5% THC) combined with an intoxicating amount of alcohol (BAC=0.08) on driving simulator performance of young drivers. Following an eligibility screening and practice session, a total of 70 participants aged 19 to 29 years will each complete 4 experimental sessions. During each session, participants will drink alcohol or placebo alcohol and smoke an active or placebo cannabis cigarette. The effects of alcohol and cannabis on the performance of driving-related skills will be assessed using a high-fidelity driving simulator. Cognitive, psychomotor, and mood effects will also be assessed.

Detailed Description
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The proposed study will pursue the following primary aims: Aim 1: Examine the acute effects of a moderate dose of cannabis (12.5% THC) combined with an intoxicating amount of alcohol (BAC=0.08) on driving simulator performance of young drivers. Simulated driving performance, tests of cognition, verbal memory, and mood will be measured concurrently with BAC and levels of cannabinoids in biological fluids before and after acute drug exposure in male and female drivers aged 19 to 29. BAC and biological fluids will be measured up to 5 hours following drug exposure. Aim 2: Explore the effects of driving history, driving attitudes, and individual difference measures (e.g., demographics, drug and alcohol use, etc.) on the acute effects of alcohol and cannabis on driving simulator performance of young drivers. Exploratory analyses will be undertaken to determine if the acute effects of cannabis plus alcohol on the driving simulator task are influenced by these measures. Study Design and Duration This study will be a within-subjects, double-blind, double-dummy, placebo-controlled, counterbalanced, randomized clinical trial assessing the impact of alcohol and cannabis combined on driver behaviour. Although a placebo condition is part of the study, this is not a treatment study. Initial contact with potential participants will be made via telephone, and study personnel will conduct a telephone screen for eligibility. Upon eligibility confirmation by telephone, participants will be asked to attend CAMH for an eligibility assessment. Participants will attend CAMH for a total of 6 study sessions (an eligibility assessment, a practice day, and 4 test sessions). At each of four test sessions, participants will undergo one of these alcohol and cannabis exposure conditions: 1) placebo alcohol and placebo cannabis; 2) intoxicating dose of alcohol and placebo cannabis; 3) placebo alcohol and active cannabis, and; 4) intoxicating dose of alcohol and active cannabis. The order of these conditions will be randomly assigned. Participants will complete the alcohol manipulation followed by the cannabis manipulation. The alcohol and cannabis exposure sessions will be separated by at least 72 hours. Participants will be asked not to use cannabis for 72 hours and alcohol for 48 hours prior to attending CAMH. In certain instances, the Qualified Investigator may ask a participant to return for re-screening, e.g. repeat of urine test or other assessments performed for eligibility assessment. Also, in case of unforeseen delays in scheduling study participation, the Qualified Investigator will determine if there is a need to ask a participant to repeat some assessments, e.g., physical examination.

Official Title
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Effects of Combined Alcohol and Cannabis on Young Drivers' Simulated Driving

Conditions
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Psychomotor Impairment

Intervention / Treatment
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* Drug: delta 9 tetrahydrocannabinol
* Drug: placebo delta 9 tetrahydrocannabinol
* Drug: Alcohol
* Drug: Placebo alcohol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Use of cannabis at least once a week confirmed by urine point-of-care testing; Males who report consuming at least 5 drinks and females who report consuming at least 4 drinks in about 2 hours in the past 6 months and at least one episode of rapid alcohol consumption in the past 6 months (3 or more drinks over a span of one hour) 19-29 years of age; Holds a class G or G2 Ontario driver's licence (or equivalent from another jurisdiction) for at least 12 months; Willing to abstain from using alcohol for 48 hours and cannabis for 72 hours prior to Practice and Test Sessions. Willing to abstain from all other drugs not prescribed for medical purposes for the duration of the study; Provides written and informed consent. Exclusion Criteria: Urine toxicology screens negative for cannabis upon eligibility assessment; Diagnosis of severe medical or psychiatric conditions; Females: Pregnancy or breastfeeding; Meets criteria for Alcohol or Substance Dependence (current or lifetime) (DSM-IV); Is a regular user of medications that affect brain function (i.e., antidepressants, benzodiazepines, stimulants); Taking medications or have any medical condition for which alcohol is contraindicated; First-degree relative diagnosed with schizophrenia; Severe allergy to citrus (lemon-lime).

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 29 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Alcohol/Placebo Cannabis<br>Participant will drink an alcoholic beverage to obtain a target blood alcohol content of 0.08mg% and will smoke a placebo delta 9 tetrahydrocannabinol (< 0.03%) cigarette. | Drug: placebo delta 9 tetrahydrocannabinol<br>* A single placebo cannabis cigarette (<0.03% delta 9 tetrahydrocannabinol) will be given to participants to smoke over a 10 minute period, ad libitum. If the placebo cannabis cigarette is not smoked in its entirety, the remainder will be weighed to estimate dose (as this is a double-blind study).<br>* Other names: marijuana;Drug: Alcohol<br>* A single oral administration of an alcoholic beverage mixed in a 1:3 ratio of alcohol to tonic water to obtain a target blood alcohol content of 0.08mg%.<br>* Other names: ethanol;|
| Active Comparator: Placebo Alcohol/Cannabis<br>Participant will drink tonic water (capped with a minimal amount of alcohol to enhance alcohol cues) and will smoke a delta 9 tetrahydrocannabinol (potency 12.5%) cigarette. | Drug: delta 9 tetrahydrocannabinol<br>* A single cannabis cigarette (potency 12.5% delta 9 tetrahydrocannabinol) will be given to participants to smoke over a 10 minute period, ad libitum. If the cannabis cigarette is not smoked in its entirety, the remainder will be weighed to estimate dose.<br>* Other names: marijuana;Drug: Placebo alcohol<br>* A single oral administration of a beverage containing tonic water of the same volume as the alcoholic beverage.<br>* Other names: Tonic water;|
| Active Comparator: Alcohol/Cannabis<br>Participant will drink an alcoholic beverage to obtain a target blood alcohol content of 0.08mg% and will smoke a delta 9 tetrahydrocannabinol (potency 12.5%) cigarette. | Drug: delta 9 tetrahydrocannabinol<br>* A single cannabis cigarette (potency 12.5% delta 9 tetrahydrocannabinol) will be given to participants to smoke over a 10 minute period, ad libitum. If the cannabis cigarette is not smoked in its entirety, the remainder will be weighed to estimate dose.<br>* Other names: marijuana;Drug: Alcohol<br>* A single oral administration of an alcoholic beverage mixed in a 1:3 ratio of alcohol to tonic water to obtain a target blood alcohol content of 0.08mg%.<br>* Other names: ethanol;|
| Placebo Comparator: Placebo Alcohol/Placebo Cannabis<br>Participant will drink tonic water (capped with a minimal amount of alcohol to enhance alcohol cues) and will smoke a placebo delta 9 tetrahydrocannabinol (< 0.03%) cigarette. | Drug: placebo delta 9 tetrahydrocannabinol<br>* A single placebo cannabis cigarette (<0.03% delta 9 tetrahydrocannabinol) will be given to participants to smoke over a 10 minute period, ad libitum. If the placebo cannabis cigarette is not smoked in its entirety, the remainder will be weighed to estimate dose (as this is a double-blind study).<br>* Other names: marijuana;Drug: Placebo alcohol<br>* A single oral administration of a beverage containing tonic water of the same volume as the alcoholic beverage.<br>* Other names: Tonic water;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psychomotor impairment: Standard deviation of lateral position | The driving simulator will objectively measure changes in driving behavior after alcohol and/or cannabis exposure. | Alcohol exposure is Time 0. Cannabis exposure follows 15 minutes after Time 0. Driving simulation tests occur within 2 hours before and approximately 45 minutes after Time 0. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psychomotor impairment: Mean speed, standard deviation of speed, and maximum speed | The driving simulator will objectively measure changes in driving behavior after alcohol and/or cannabis exposure. | Alcohol exposure is Time 0. Cannabis exposure follows 15 minutes after Time 0. Driving simulation tests occur within 2 hours before and approximately 45 minutes after Time 0. | 
| Psychomotor impairment: Minimum time to collision and brake latency | The driving simulator will objectively measure changes in driving behavior after alcohol and/or cannabis exposure. | Alcohol exposure is Time 0. Cannabis exposure follows 15 minutes after Time 0. Driving simulation tests occur within 2 hours before and approximately 45 minutes after Time 0. | 
| Psychomotor impairment: Number of collisions | The driving simulator will objectively measure changes in driving behavior after alcohol and/or cannabis exposure. | Alcohol exposure is Time 0. Cannabis exposure follows 15 minutes after Time 0. Driving simulation tests occur within 2 hours before and approximately 45 minutes after Time 0. | 
| Subjective alcohol and cannabis effects | Visual analogue scale measures how participants feel before and after alcohol and/or cannabis exposure. | Alcohol exposure is Time 0. Cannabis exposure follows 15 minutes after Time 0. Visual analogue scales are administered within 2 hours before as well as approximately 15, 30, 45, and 75 minutes and 2, 3, 4, and 5 hours after Time 0. | 
| Cognitive testing | Measures changes in performance related to attention, memory, field of view, and dexterity before and after alcohol and/or cannabis exposure. | Alcohol exposure is Time 0. Cannabis exposure follows 15 minutes after Time 0. Cognitive testing is administered within 2 hours before Time 0 as well as approximately 75 minutes after Time 0. | 
| Breath alcohol content | Changes in BAC after drinking alcohol. | Alcohol exposure is Time 0. Cannabis exposure follows 15 minutes after Time 0. Breath alcohol content is measured within 2 hours before Time 0 as well as approximately 15, 30, 45, and 75 minutes and 2, 3, 4, and 5 hours after Time 0. | 
| Blood concentration for delta 9 tetrahydrocannabinol, carboxy-tetrahydrocannabinol, and 11 hydroxy tetrahydrocannabinol. | Changes in concentration of delta 9 tetrahydrocannabinol (THC) , carboxy-tetrahydrocannabinol (THC-COOH), and 11 hydroxy tetrahydrocannabinol (11-OH-THC) in blood. | Alcohol exposure is Time 0. Cannabis exposure follows 15 minutes after Time 0. Blood concentration for THC, THC-COOH, and 11-OH-THC is assessed within 2 hours before Time 0 as well approximately 45 minutes after Time 0. | 
| Urine cannabinoids corrected for creatinine | Determination of the ratio of excreted THC metabolite carboxy-THC to creatinine will determine whether participants have used cannabis between testing days, and hence will be excluded from further participation. | Alcohol exposure is Time 0. Cannabis exposure follows 15 minutes after Time 0. Ratio of excreted THC metabolite carboxy-THC to creatinine is assessed within 2 hours before Time 0 as well as approximately 5 hours after Time 0. | 
| Vital signs: blood pressure | Changes in blood pressure (systolic/diastolic) | Alcohol exposure is Time 0. Cannabis exposure follows 15 minutes after Time 0. Vital signs are assessed within 2 hours before as well as approximately 15, 30, 45, and 75 minutes and 2, 3, 4, and 5 hours after Time 0. | 
| Vital signs: pulse | Changes in pulse | Alcohol exposure is Time 0. Cannabis exposure follows 15 minutes after Time 0. Vital signs are assessed within 2 hours before as well as approximately 15, 30, 45, and 75 minutes and 2, 3, 4, and 5 hours after Time 0. | 
| Vital signs: temperature | Changes in temperature | Alcohol exposure is Time 0. Cannabis exposure follows 15 minutes after Time 0. Vital signs are assessed within 2 hours before as well as approximately 15, 30, 45, and 75 minutes and 2, 3, 4, and 5 hours after Time 0. | 
| Vital signs: respiration | Changes in respiration | Alcohol exposure is Time 0. Cannabis exposure follows 15 minutes after Time 0. Vital signs are assessed within 2 hours before as well as approximately 15, 30, 45, and 75 minutes and 2, 3, 4, and 5 hours after Time 0. |