This research responds to NHTSA's request with a proposal to increase our understanding of smoked cannabis' (CNB's) acute effects on driving-relevant cognition and simulated driving performance, the persistence of these deficits over the hours after use, and the influence of prior experience with CNB on these effects. This extension study will aim to further investigate marijuana impaired behavior, using a similar design to our previous NHTSA Examine the Feasibility of a Standardized Field Test for Marijuana Impairment and the prior NIDA Neuroscience of Marijuana-Impaired Driving award, that used similar techniques and measures to quantify marijuana impaired automobile driving. We will be utilizing tasks and assessments that were shown to be strong indicators for cognitive and driving impairment in our NHTSA study.

The proposed study was based upon a careful and thorough review of the scientific literature describing CNB effects on cognitive test performance and driving, as well as current state-of-knowledge on the sensitivity of biological assays for identifying recent CNB use. The study will carefully characterize the persistence of CNB's acute effects on cognitive test performance and driving over a several-hour time span. This will allow us to identify the point at which any effects of CNB intoxication driving-related cognitive tests, and driving performance cannot be distinguished from normal, i.e., the first step towards establishing standards for legal and social policy. The data obtained from simulated driving, cognitive tests, and biological assays of THC will be used in analyses aimed at identifying what tests or combination of tests predict both recent use and driving impairment risk.

This study will consist of 2 days (screening visit and dose visit). In a non-randomized, single blinded study, we will dose participants with placebo and high THC marijuana, about an hour apart, using paced inhalation through a vaporizer, an efficient means of delivering a standard THC dose. Participants will be told that the order they receive the doses will be random but they will always receive the placebo first, followed by the high dose. This will allow for standardization across all subjects and comparative values between placebo and drug. After inhaling the placebo dose, participants will be asked to complete one round of cognitive testing and a shortened version of the driving simulator (10 mins vs 30 mins). Approximately one hour post placebo dose, subjects will be administered high THC marijuana. Following this dosing, we will assess impairment through cognitive testing as well as a simulated driving test and neuropsychological tests. Samples of blood will also be collected at multiple time points throughout the study visits to be measured for THC concentration and its metabolites. This allows clarification between the relationship of impairment, as well as subjective and objective intoxication, and levels of THC and it's metabolites in the users system.

Inclusion Criteria:

• 18-55 yrs/ old
• Current driver's license and history of repeated highway vehicle driving experience (at least 2 years)
• Recent, recurrent CNB use and felt high when used
• Able to read, speak, and understand English
• Able and willing to provide written informed consent, and willing to commit to the study protocol

Exclusion Criteria:

• Current marijuana tolerance, desire to cut down, or cravings to use during periods of abstinence
• New CNB users who have not used at least once during their lifetime.
• Positive screen for drug and alcohol (except THC) on test day will result in rescheduling the appointment
• Former CNB users who are abstaining
• Pregnancy, breastfeeding, and ineffective birth control methods.
• History of adverse psychological or medical effects following cannabis use
• serious medical, neuro-ophthalmological, or neurological illness (i.e. cancer, seizure disorders, encephalopathy)
• History of head trauma with loss of consciousness > 30 minutes or concussion lasting 30 days.
• IQ <80 on the Wechsler Abbreviated Scale of Intelligence
• Inability to comprehend written instructions using the WRAT 4 reading achievement test
• Any medical/neurological condition that could compromise neurocognitive performance (i.e. epilepsy, multiple sclerosis, fetal alcohol syndrome)
• Uncontrolled, persistent high blood pressure
• Anyone deemed unsafe to study personnel for any reason