Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001539729
Ethics application status
Approved
Date submitted
29/11/2022
Date registered
13/12/2022
Date last updated
24/03/2024
Date data sharing statement initially provided
13/12/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
The effects of medicinal cannabis products on eye movement behaviour during driving
Scientific title
A 5-week randomised, placebo-controlled crossover trial comparing the effects of medicinal cannabis products on ocular parameters during driving in healthy volunteers (MEDICO)
Secondary ID [1] 308514 0
Nil
Universal Trial Number (UTN)
U1111-1285-5138
Trial acronym
MEDICO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neurological 328336 0
Condition category
Condition code
Neurological 325375 325375 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 324951 0
Treatment: Drugs
Comparator / control treatment
Placebo oil (identical in taste, texture, weight and smell). Medium-chain triglyceride (MCT) oil
Control group
Placebo

Outcomes
Primary outcome [1] 333231 0
Associations between acute dose of combination of CBD and THC (2 mg THC/ 2 mg 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) and eye movement behaviour during driving.
Timepoint [1] 333231 0
After administration of treatment. Specifically, this will occur at ~2 hours and ~4 hours post dosing. This will be assessed using the PC-DMS eye monitoring system during the driving task using the Forum 8 driving simulator. Gaze behaviour, expressed as gaze transition entropy will be assessed.
Primary outcome [2] 333232 0
Associations between acute dose of combination of CBD and THC (2 mg THC/ 2 mg 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) and driving performance will be assessed.
Timepoint [2] 333232 0
After administration of treatment. Specifically, this will occur at ~2 hours and ~4 hours post dosing. This will be assessed using the Forum 8 driving simulator. Weaving of the car, expressed as standard deviation of the lateral position (SDLP), will be assessed.
Primary outcome [3] 333233 0
Associations between acute dose of combination of CBD and THC (2 mg THC/ 2 mg 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) and eye movement behaviour during driving
Timepoint [3] 333233 0
After administration of treatment. Specifically, this will occur at ~2 hours and ~4 hours post dosing. This will be assessed using the PC-DMS eye monitoring system during the driving task using the Forum 8 driving simulator. Gaze behaviour, expressed as saccade (duration, amplitude), will be assessed.
Secondary outcome [1] 416256 0
Associations between acute dose of combination of CBD and THC (2 mg THC/ 2 mg 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) and eye movement behaviour during Visuospatial Working Memory (VSWM) task
Timepoint [1] 416256 0
After administration of treatment. Specifically, this will occur at ~1.5 hours and ~3.5 hours post dosing. This will be assessed using the EyeLink eye monitoring system during the VSWM task. Eye movement behaviour, expressed as saccades (amplitude, velocity, duration) will be assessed.
Secondary outcome [2] 416257 0
Associations between acute dose of combination of CBD and THC (2 mg THC/ 2 mg 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) and cognitive performance (reaction and movement time)
Timepoint [2] 416257 0
After administration of treatment. Specifically, this will occur at ~2 hours and ~3 hours post dosing. This will be assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) online test battery.
Secondary outcome [3] 416258 0
Associations between acute dose of combination of CBD and THC (2 mg THC/ 2 mg 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) and cognitive performance (memory score)
Timepoint [3] 416258 0
After administration of treatment. Specifically, this will occur at ~2 hours and ~3 hours post dosing. This will be assessed using the CANTAB online test battery.
Secondary outcome [4] 416259 0
Associations between acute dose of combination of CBD and THC (2 mg THC/ 2 mg 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) and cognitive performance (% correct - Paired Associates Learning, PAL)
Timepoint [4] 416259 0
After administration of treatment. Specifically, this will occur at ~2 hours and ~3 hours post dosing. This will be assessed using the CANTAB online test battery.
Secondary outcome [5] 416260 0
Associations between acute dose of combination of CBD and THC (2 mg THC/ 2 mg 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) and cognitive performance (stages completed - PAL)
Timepoint [5] 416260 0
After administration of treatment. Specifically, this will occur at ~2 hours and ~3 hours post dosing. This will be assessed using the CANTAB online test battery.
Secondary outcome [6] 416261 0
Associations between acute dose of combination of CBD and THC (2 mg THC/ 2 mg 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) and cognitive performance (errors - Spatial Working Memory, SWM)
Timepoint [6] 416261 0
After administration of treatment. Specifically, this will occur at ~2 hours and ~3 hours post dosing. This will be assessed using the CANTAB online test battery.
Secondary outcome [7] 416262 0
Associations between acute dose of combination of CBD and THC (2 mg THC/ 2 mg 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) and cognitive performance (strategy score - SWM)
Timepoint [7] 416262 0
After administration of treatment. Specifically, this will occur at ~2 hours and ~3 hours post dosing. This will be assessed using the CANTAB online test battery.
Secondary outcome [8] 416263 0
Associations between acute dose of combination of CBD and THC (2 mg THC/ 2 mg 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) and cognitive performance (prime score - Rapid Visual Processing, RVP)
Timepoint [8] 416263 0
After administration of treatment. Specifically, this will occur at ~2 hours and ~3 hours post dosing. This will be assessed using the CANTAB online test battery.
Secondary outcome [9] 416264 0
Associations between acute dose of combination of CBD and THC (2 mg THC/ 2 mg 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) and cognitive performance (overall task score - Driving Under the Influence of Drugs, DRUIDApp)
Timepoint [9] 416264 0
After administration of treatment. Specifically, this will occur at ~1.5 hours and ~4 hours post dosing. This will be assessed using the DRUID test battery.
Secondary outcome [10] 416265 0
Associations between acute dose of combination of CBD and THC ( 2 mg THC/ 2 mg 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) and eye movement behaviour during driving (PRIMARY OUTCOME)
Timepoint [10] 416265 0
After administration of treatment. Specifically, this will occur at ~2 hours and ~4 hours post dosing. This will be assessed using the PC-DMS eye monitoring system during the driving task using the Forum 8 driving simulator. Eye movement behaviour, expressed as fixation, will be assessed.
Secondary outcome [11] 416266 0
Associations between acute dose of combination of CBD and THC (2 mg THC/ 2 mg 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) and eye movement behaviour during driving (PRIMARY OUTCOME)
Timepoint [11] 416266 0
After administration of treatment. Specifically, this will occur at ~2 hours and ~4 hours post dosing. This will be assessed using the PC-DMS eye monitoring system during the driving task using the Forum 8 driving simulator. Eye movement behaviour, expressed as blink (amplitude, velocity, duration) will be assessed.
Secondary outcome [12] 416267 0
Associations between acute dose of combination of CBD and THC (2 mg THC/ 2 mg 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) and driving performance (PRIMARY OUTCOME)
Timepoint [12] 416267 0
After administration of treatment. Specifically, this will occur at ~2 hours and ~4 hours post dosing. This will be assessed using the Forum 8 driving simulator. Headway, expressed as distance to front vehicle will be assessed
Secondary outcome [13] 416268 0
Associations between acute dose of combination of CBD and THC (2 mg THC/ 2 mg 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) and driving performance (PRIMARY OUTCOME)
Timepoint [13] 416268 0
After administration of treatment. Specifically, this will occur at ~2 hours and ~4 hours post dosing. This will be assessed using the Forum 8 driving simulator. Reaction time, expressed as time to react to front vehicle, will be assessed
Secondary outcome [14] 416269 0
Associations between acute dose of combination of CBD and THC (2 mg THC/ 2 mg 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) and driving performance (PRIMARY OUTCOME)
Timepoint [14] 416269 0
After administration of treatment. Specifically, this will occur at ~2 hours and ~4 hours post dosing. This will be assessed using the Forum 8 driving simulator. Reaction time, expressed as time to respond during the go-no-go task, will be assessed
Secondary outcome [15] 416271 0
To identify the effect of combination of CBD and THC (2 mg THC/ 2 mg 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) on objective sleep parameters. The outcome to be assessed is: sleep duration (total sleep time, hours)
Timepoint [15] 416271 0
On conclusion of the testing session and for the one-week wash-out period between sessions using a wrist-mounted actigraphy device
Secondary outcome [16] 416272 0
To identify the effect of combination of CBD and THC (2 mg THC/ 2 mg 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) on objective sleep parameters. The outcome to be assessed is: sleep latency (time to get to sleep)
Timepoint [16] 416272 0
On conclusion of the testing session and for the one-week wash-out period between sessions using a wrist-mounted actigraphy device
Secondary outcome [17] 416273 0
To identify the effect of combination of CBD and THC (2 mg THC/ 2 mg 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) on objective sleep parameters. The outcome to be assessed is: number of awakenings
Timepoint [17] 416273 0
On conclusion of the testing session and for the one-week wash-out period between sessions using a wrist-mounted actigraphy device
Secondary outcome [18] 416274 0
To identify the effect of combination of CBD and THC (2 mg THC/ 2 mg 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) on subjective drug effects
Timepoint [18] 416274 0
After administration of treatment. Specifically, this will occur at approximately 40 minutes, 135 minutes and 4.5 hours post dosing using a subjective questionnaire. The question is a 100-mm VAS anchored by “not at all” and variants of “extremely” (e.g., “very strong,” “very much”) to capture the post-drug experience. The drug type of interest will be sedative, and composite score of sedative items will be used.
Secondary outcome [19] 416275 0
To identify the effect of combination of CBD and THC (2 mg THC/ 2 mg 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) on subjective sleepiness effects
Timepoint [19] 416275 0
After administration of treatment. Specifically, this will occur at approximately 40 minutes, 135 minutes and 4.5 hours post dosing using a subjective questionnaire. Participants be asked to rate their levels of sleepiness using the Karolinska Sleepiness Scale. Participants are to indicate which response best reflects their psycho-physical state in the last 10 minutes. There are 9 levels of response, ranging from 1 (extremely alert) to 9 (very sleepy, great effort to keep awake, fighting sleep).
Secondary outcome [20] 416276 0
o identify the effect of combination of CBD and THC (2 mg THC/ 2 mg 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) on subjective driving ability
Timepoint [20] 416276 0
After administration of treatment. Specifically, this will occur at approximately 135 minutes and 4.5 hours post dosing using a subjective questionnaire. Participants be asked to rate the perceived quality of their driving performance on the Perceived Driving Quality Scale; a visual analogue scale that ranges from 0 (I drove exceptionally poorly) to 20 (I drove exceptionally well) around a midpoint of I drove normally.
Secondary outcome [21] 416277 0
To identify the effect of combination of CBD and THC (2 mg THC/ 2 mg 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) on mental load
Timepoint [21] 416277 0
After administration of treatment. Specifically, this will occur at approximately 135 minutes and 4.5 hours post dosing using a subjective questionnaire. Participants be asked to rate the perceived quality of effort using the NASA Task Load Index (TLX). Increments of high, medium, and low estimates for each point result in 21 gradations on the scales:
- Mental Demand
- Physical Demand
- Temporal Demand
- Performance
- Effort
- Frustration
Secondary outcome [22] 416278 0
To identify the effect of combination of CBD and THC (2 mg THC/ 2 mg 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) on state anxiety
Timepoint [22] 416278 0
After administration of treatment. Specifically, this will occur at approximately 135 minutes and 4.5 hours post dosing using a subjective questionnaire. Participants be asked to rate the perceived anxiety levels on the State-Trait Anxiety Inventory (STAI). There are 20 items for assessing trait anxiety and 20 for state anxiety. State anxiety items include: “I am tense; I am worried” and “I feel calm; I feel secure.” Trait anxiety items include: “I worry too much over something that really doesn’t matter” and “I am content; I am a steady person.” All items are rated on a 4-point scale (e.g., from “Almost Never” to “Almost Always”).
Secondary outcome [23] 416279 0
To identify the effect of combination of CBD and THC (2 mg THC/ 2 mg 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) on aggression
Timepoint [23] 416279 0
After administration of treatment. Specifically, this will occur at approximately 135 minutes and 4.5 hours post dosing using a subjective questionnaire. Participants be asked to rate the perceived anxiety levels on the State-Trait Anger Expression Inventory–2 (STAXI-2). The STAXI-2 consists of 2 sub-scales (State and Trait Aggression), and an Anger Expression Index that provides an overall measure of total anger expression
Secondary outcome [24] 416616 0
Associations between acute dose of combination of CBD and THC (2 mg THC/ 2 mg 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) and eye movement behaviour during driving (PRIMARY OUTCOME)
Timepoint [24] 416616 0
After administration of treatment. Specifically, this will occur at ~2 hours and ~4 hours post dosing. This will be assessed using the PC-DMS eye monitoring system during the driving task using the Forum 8 driving simulator. Gaze behaviour, expressed as stationary gaze entropy, will be assessed.
Secondary outcome [25] 416617 0
Associations between acute dose of combination of CBD and THC (2 mg THC/ 2 mg 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) and driving performance (PRIMARY OUTCOME)
Timepoint [25] 416617 0
After administration of treatment. Specifically, this will occur at ~2 hours and ~4 hours post dosing. This will be assessed using the Forum 8 driving simulator. Headway, expressed as distance to front vehicle will be assessed
Secondary outcome [26] 416618 0
Associations between acute dose of combination of CBD and THC (2 mg THC/ 2 mg 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) and driving performance (PRIMARY OUTCOME)
Timepoint [26] 416618 0
After administration of treatment. Specifically, this will occur at ~2 hours and ~4 hours post dosing. This will be assessed using the Forum 8 driving simulator. Psychomotor speed, expressed as reaction time (ms) will be assessed
Secondary outcome [27] 416619 0
Associations between acute dose of combination of CBD and THC (2 mg THC/ 2 mg 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) and eye movement behaviour during Visuospatial Working Memory (VSWM) task
Timepoint [27] 416619 0
After administration of treatment. Specifically, this will occur at ~1.5 hours and ~3.5 hours post dosing. This will be assessed using the EyeLink eye monitoring system during the VSWM task. Eye movement behaviour, expressed as saccades (amplitude, velocity, duration) will be assessed.
Secondary outcome [28] 416620 0
Associations between acute dose of combination of CBD and THC (2 mg THC/ 2 mg 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) and eye movement behaviour during Visuospatial Working Memory (VSWM) task
Timepoint [28] 416620 0
After administration of treatment. Specifically, this will occur at ~1.5 hours and ~3.5 hours post dosing. This will be assessed using the EyeLink eye monitoring system during the VSWM task. Eye movement behaviour, expressed as blink activity (amplitude, velocity, duration) will be assessed.
Secondary outcome [29] 416621 0
Associations between acute dose of combination of CBD and THC (2 mg THC/ 2 mg 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) and eye movement behaviour during Visuospatial Working Memory (VSWM) task
Timepoint [29] 416621 0
After administration of treatment. Specifically, this will occur at ~1.5 hours and ~3.5 hours post dosing. This will be assessed using the EyeLink eye monitoring system during the VSWM task. Eye movement behaviour, expressed as fixations (duration, number) will be assessed
Secondary outcome [30] 416622 0
Identify associations between plasma blood concentrations of cannabidiol (CBD) and tetrahydrocannabinol (THC) on stationary gaze entropy during driving.
Timepoint [30] 416622 0
After administration of treatment using cannulation procedure. Specifically, this will occur at approximately 1 hour, 3 hours and 4.5 hours post-dosing and over the duration of the driving task as function of treatment.
Secondary outcome [31] 416625 0
Identify associations between plasma blood concentrations of cannabidiol (CBD) and tetrahydrocannabinol (THC) on gaze transition entropy during driving eye movement, cognitive, driving, subjective, aggression and sleep outcomes.
Timepoint [31] 416625 0
After administration of treatment using cannulation procedure. Specifically, this will occur at approximately 1 hour, 3 hours and 4.5 hours post-dosing and over the duration of the driving task as function of treatment
Secondary outcome [32] 416626 0
Identify associations between plasma blood concentrations of cannabidiol (CBD) and tetrahydrocannabinol (THC) on blink (duration, frequency) during driving
Timepoint [32] 416626 0
After administration of treatment using cannulation procedure. Specifically, this will occur at approximately 1 hour, 3 hours and 4.5 hours post-dosing and over the duration of the driving task as function of treatment
Secondary outcome [33] 416627 0
Identify associations between plasma blood concentrations of cannabidiol (CBD) and tetrahydrocannabinol (THC) on saccadic eye movement (duration, amplitude) during driving
Timepoint [33] 416627 0
After administration of treatment using cannulation procedure. Specifically, this will occur at approximately 1 hour, 3 hours and 4.5 hours post-dosing and over the duration of the driving task as function of treatment
Secondary outcome [34] 416628 0
Identify associations between plasma blood concentrations of cannabidiol (CBD) and tetrahydrocannabinol (THC) and cognitive performance (% correct - PAL)
Timepoint [34] 416628 0
After administration of treatment. Specifically, this will occur at approximately 1 hour, 3 hours and 4.5 hours post-dosing and at ~2 hours and ~3 hours post dosing. This will be assessed using the CANTAB online test battery.
Secondary outcome [35] 416629 0
Identify associations between plasma blood concentrations of cannabidiol (CBD) and tetrahydrocannabinol (THC) and cognitive performance (stages completed - PAL)
Timepoint [35] 416629 0
After administration of treatment. Specifically, this will occur at approximately 1 hour, 3 hours and 4.5 hours post-dosing and at ~2 hours and ~3 hours post dosing. This will be assessed using the CANTAB online test battery.
Secondary outcome [36] 416630 0
Identify associations between plasma blood concentrations of cannabidiol (CBD) and tetrahydrocannabinol (THC) and cognitive performance (errors - SWM)
Timepoint [36] 416630 0
After administration of treatment. Specifically, this will occur at approximately 1 hour, 3 hours and 4.5 hours post-dosing and at ~2 hours and ~3 hours post dosing. This will be assessed using the CANTAB online test battery.
Secondary outcome [37] 416631 0
Identify associations between plasma blood concentrations of cannabidiol (CBD) and tetrahydrocannabinol (THC) and cognitive performance (strategy score - SWM)
Timepoint [37] 416631 0
After administration of treatment. Specifically, this will occur at approximately 1 hour, 3 hours and 4.5 hours post-dosing and at ~2 hours and ~3 hours post dosing. This will be assessed using the CANTAB online test battery.
Secondary outcome [38] 416632 0
Identify associations between plasma blood concentrations of cannabidiol (CBD) and tetrahydrocannabinol (THC) and cognitive performance (prime score - RVP)
Timepoint [38] 416632 0
After administration of treatment. Specifically, this will occur at approximately 1 hour, 3 hours and 4.5 hours post-dosing and at ~2 hours and ~3 hours post dosing. This will be assessed using the CANTAB online test battery.
Secondary outcome [39] 416633 0
Identify associations between plasma blood concentrations of cannabidiol (CBD) and tetrahydrocannabinol (THC) and total anger expression
Timepoint [39] 416633 0
After administration of treatment. Specifically, this will occur at approximately 1 hour, 3 hours and 4.5 hours post-dosing and at approximately 135 minutes and 4.5 hours post dosing
Secondary outcome [40] 416634 0
Identify associations between plasma blood concentrations of cannabidiol (CBD) and tetrahydrocannabinol (THC) and sleep latency
Timepoint [40] 416634 0
At conclusion of the testing session and for the one-week wash-out period between sessions using a wrist-mounted actigraphy device

Eligibility
Key inclusion criteria
Male or female, aged 21 to 55 years
• Willing and able to provide written informed consent
• Understands and is willing and able to comply with all study procedures
• Fluent in written and spoken English
• Previous (lifetime) history of cannabis use, with no known adverse reactions
• Must have normal or corrected-to-normal vision
• Is a regular driver (> 4,000 km/year) with three years of driving with a full driver’s licence (no ‘P-Plate’ drivers).
• BMI is within the normal range (18.5-30.0) [due to expected absorption rate of THC and THC/CBD combined products when given at static doses]
• Willing to abstain from the following prior to their scheduled visit:
o No food or drinks (except water) within 2 hours prior to testing
o No caffeine-containing products within 12 hours prior to testing
o No alcohol within 12 hours prior to testing
o No medication for at least 1 week prior to testing (except for prophylactic antibiotics, contraceptive pill or other routine medications to treat benign conditions, such as antibiotics to treat acne)
o No illicit substance use for one week prior to, and for the duration of the trial.
o No driving or riding a bicycle or motorbike from the testing site
o No driving, riding, operating heavy machinery for 12 hours after leaving the site
o No alcohol, illicit drugs, or medication (unless consulted with doctor) for 12 hours after leaving the site.
Minimum age
21 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Unable to understand or comply with testing procedures
• Inability to speak or read English
• History of drug abuse or dependence or current illicit drug abuse
• Current neurological, psychiatric, cardiac, endocrine, gastrointestinal, or bleeding disorders
• Pregnant or lactating
• Taking any form of medication within one week of admission (except for prophylactic antibiotics, contraceptive pill or other routine medications to treat benign conditions, such as antibiotics to treat acne) and agree not to take any medication throughout the study
• Unable to participate in scheduled visit, treatment plan, tests and other study procedures according to the protocol
• BMI less than 18.5 or over 30.0
• Moderate-severe current depression (BDI score of greater than or equal to 20)
• Severe current anxiety (BAI score greater than or equal to 16)
• Current participation in any other studies involving investigational or marketed products within 30 days prior to the screening visit;
• Currently under administrative or legal supervision.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Blinding will be achieved by enlisting a disinterested third-party to code the treatments, and maintain the key to this code until data collection is completed.
The study treatment bottles will be delivered to the Principal Investigator, labelled with the name of the drug in capital letters and the letter “A” to “E” to signify the blinded drug randomisation group.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation of the order of treatment visits will be determined by random allocation by a disinterested third party. All consenting participants will be assigned a participant number. The randomisation order that has been placed next to the participants’ number will be the allocated treatment order for that individual using publicly available randomisation software (Research Randomiser Software Version 4.0).

Randomisation codes will be kept in a sealed envelope in a locked filing cabinet. Although study investigators will know the location of, and have access to, the sealed envelope, they will not access it during data collection and data screening procedures. Access will only occur in the case of an emergency when the participant’s allocated treatment needs to be known. If this occurs, the ethics committee will be informed.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Demographic data will be presented with summary statistics (number of participants, mean, standard deviation, median and range for variables) for each study. A fixed-effect Linear Mixed Model will be used to assess differences in neurocognitive and driving performance variables between the treatments (THC:CBD combinations vs placebo) and across time (drive duration) examined in 10-minute bins) for each condition. Post hoc comparisons will be undertaken where significant condition or interaction effects are observed to determine the significance of differences as a function of time and treatment.
Correlations between biological sample data (oral fluid, blood concentrations of THC:CBD), subjective measures, cognitive outcomes, and performance on the driving simulator across time points as function of treatment will be conducted using Pearson product moment coefficient r. The predictive ability of performance on cognitive outcome to performance on the driving simulator task will be assessed using linear regression models.
Performance measures in the driving simulator will be modelled as dependent variables using generalized linear mixed effect models. Outcomes that are counts will be modelled by a Poisson-distribution. The main effects will be time, age, sex, blood THC, change in THC, THC/CBD metabolite ratios, amount ingested and two-way interactions with time and condition. Other covariates, including but not limited to, milligrams of THC consumed and driving experience, will be measured, and examined in regression models. All statistical analyses will be conducted with the use of SPSS 26.0 (SPSS Inc., USA), and tests are two-tailed with a conventional level of significance of p < 0.05

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
20/03/2023
Actual
3/05/2023
Date of last participant enrolment
Anticipated
1/11/2024
Actual
Date of last data collection
Anticipated
29/11/2024
Actual
Sample size
Target
31
Accrual to date
7
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 312754 0
Government body
Name [1] 312754 0
Office of Road Safety, Department of Infrastructure, Australian Federal Government
Country [1] 312754 0
Australia
Funding source category [2] 313120 0
Commercial sector/Industry
Name [2] 313120 0
Seeing Machines
Country [2] 313120 0
Australia
Primary sponsor type
University
Name
Swinburne University of Technology
Address
427-451 Burwood Road
Hawthorn, Victoria, 3122
Country
Australia
Secondary sponsor category [1] 314386 0
None
Name [1] 314386 0
Address [1] 314386 0
Country [1] 314386 0
Other collaborator category [1] 282542 0
Commercial sector/Industry
Name [1] 282542 0
Seeing Machines
Address [1] 282542 0
80 Mildura St. Fyshwick,
Australian Capital Territory 2609, AU
Country [1] 282542 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312056 0
Swinburne University Human Research Ethics
Ethics committee address [1] 312056 0
Ethics committee country [1] 312056 0
Australia
Date submitted for ethics approval [1] 312056 0
24/11/2022
Approval date [1] 312056 0
22/12/2022
Ethics approval number [1] 312056 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 123302 0
Dr Amie Hayley
Address 123302 0
Swinburne University of Technology,
School of Health Sciences
Centre for Human Psychopharmacology
Mail H24
PO Box 218
Hawthorn, Victoria, 3122
Country 123302 0
Australia
Phone 123302 0
+61 03 9214 5585
Fax 123302 0
Email 123302 0
[email protected]
Contact person for public queries
Name 123303 0
Amie Hayley
Address 123303 0
Swinburne University of Technology,
School of Health Sciences
Centre for Human Psychopharmacology
Mail H24
PO Box 218
Hawthorn, Victoria, 3122
Country 123303 0
Australia
Phone 123303 0
+61 03 9214 5585
Fax 123303 0
Email 123303 0
[email protected]
Contact person for scientific queries
Name 123304 0
Amie Hayley
Address 123304 0
Swinburne University of Technology,
School of Health Sciences
Centre for Human Psychopharmacology
Mail H24
PO Box 218
Hawthorn, Victoria, 3122
Country 123304 0
Australia
Phone 123304 0
+61 03 9214 5585
Fax 123304 0
Email 123304 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Due to the sensitive nature of the data collected, we will not be making IPD available.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.