Intravenous Alcohol and THC Effects on Simulated Driving and Related Cognition



 DESCRIPTION (provided by applicant): Motor vehicle accidents (MVAs) are among the top 10 leading causes of morbidity and mortality worldwide (1). In 2012, within the United States (US) there were about 30,000 MVAs that resulted in 33,561 fatalities, in addition to 1,634,000 reported MVAs that caused injury (2). Alcohol and cannabis are very important contributors to both impaired driving and MVA's (3). While the effects of alcohol on driving are well- known and have been widely studied (4), the effects of cannabis or its constituent cannabinoids on driving are less clear (5), and there is even less known about the effects of the combination of alcohol and cannabinoids on driving. With the growing legalization of both recreational and "medical" use of cannabis, the growing perception, especially among young adults, that cannabis is safe (6), and the paucity of experimental data to inform public health policy regarding driving under the influence of both substances, there is a need to study the combined effects of cannabinoids and alcohol on driving. Hypothesis: The combination of modest recreational doses of THC and ethanol, will impair simulated driving, event related potentials (ERPs) relevant to driving, and driving related cognitive function to a greater extent than either drug individually. Methods: In a randomized, double-blind, placebo-controlled, crossover (2x2), counterbalanced laboratory study, healthy subjects (n=25) will simultaneously receive through separate intravenous (IV) lines 1) IV ethanol or placebo (saline) to reach a BrAC of 0.04% (equivalent to ~2 drinks over 1 hour) within 20 minutes and remain clamped at this level for an additional 60 minutes using a computer-assisted alcohol infusion system, and 2) IV THC (0.015 mg/kg = 1/4 - 1/2 cannabis joint) or placebo (saline) over 20 minutes. Subjects will complete 1) a day and night driving course on a driving simulator, while EEG is recorded to obtain the driving error related ERPs - ERN and Pe; 2) an EEG P300 novelty task, and 3) a battery (CogState) of cognitive tests relevant to driving. Supporting feasibility data: We have the experience and expertise, to administer IV ethanol (n>20) and THC (n>400), in addition to having the regulatory approvals (IND, Schedule 1 license) necessary to administer IV THC. We have demonstrated that IV ethanol increases SDLP on a simulated driving task, and have also shown the separate effects of both IV ethanol and IV THC on reducing amplitude of the P3a.