The effects of medicinal cannabis products on eye movement behaviour during driving

Over the five-week experimental period, participants will receive all of the experimental doses. One dose (1mL of treatment) will be taken orally (by mouth) under supervised administration at each session [i.e. active treatment(s): 2 mg delta-9-tetrahydrocannabinol (THC) / 2 mg Cannabidiol (CBD) per 1mL; 5 mg THC / 5 mg CBD per 1mL; 2 mg THC / 32 mg CBD per 1mL; 5 mg THC / 80 mg CBD per 1mL; or placebo treatment, 1mL] and the order of dosing will be randomised. The active treatments are: 1. 2 mg THC / 2 mg CBD per 1mL (mixed with medium-chain triglyceride (MCT) oil) 2. 5 mg THC / 5 mg CBD per 1mL (mixed with MCT oil) 3. 2 mg THC / 32 mg CBD per 1mL (mixed with MCT oil) 4. 5 mg THC / 80 mg CBD per 1mL (mixed with MCT oil) The placebo treatments are: 1. Placebo oil, comprising medium-chain triglyceride (MCT) oil only (identical in taste, texture, weight and smell). A one-week washout period will occur between testing sessions. Prior to dosing at each testing visit (each at V1, V2, V3, V4 and V5), participants will provide one saliva sample to screen for evidence of recent use of drugs [amphetamine/d-methamphetamine, 3,4- methylenedioxymethamphetamine (MDMA), cocaine, cannabis (del ta-9-tetrahydrocannabinol) and opiates] using the Securetec DrugWipe 6s device. This screening assessment requires an absorbent pad to be placed over the tongue for approximately 20 seconds. 1ml of saliva will be taken per sample, therefore approximately 5ml in total over each of the four experimental sessions. A sample volume of less than 10 micro litres is sufficient for analysis. The device is wiped on the tongue, when the colour has changed from pink to yellow there is the required amount of saliva to obtain the results. A registered research nurse trained in venepuncture or a qualified venepuncture technician will collect three blood samples at each testing session (each at V1-V5), at 1, 3 and 4.5 hours post treatment administration. A research staff member will collect two oral fluid samples at each testing session (each at V1-V5), at 1 hour and 4.5 hours post treatment administration. The Cambridge Neuropsychological Test Automated Battery (CANTAB) will be used to assess the cognitive effects of the intervention. Four tasks will be used in this study to assess visual processing, processing speed and reaction/decision speed, specifically: Reaction Time, Paired Associates Learning, Spatial Working Memory and Rapid Visual Information Processing. Participants will be assessed at approximately 60 minutes post-dosing and at 3-hours post dosing. Driving performance with simultaneous eye movement monitoring will be assessed using the Forum 8 driving simulator, and driving performance will be assessed twice per study session, for a 20 minute duration. The simulator consists of a car unit with adjustable car seats and a dashboard and includes a steering wheel, turn sign indicators, gear lever, brake and accelerator pedals for vehicle control. The system generates realistic roadway scenery which is presented on three integrated TV screens 1.90 meters in front of the centre of the steering wheel. The speed and gear number are displayed on the dashboard and screen. Auditory feedback is provided by speakers and included the sound of the engine, braking, speeding in curves, and driving off-road. The simulation scenarios will incorporate features of a highway environment, comprising three in-built tasks to assess performance. The tasks include headway (distance to car in front), standard highway driving, and a response inhibition task. Driving assessment will take place at approximately 2 hours and 4-hours post dosing.