Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000414415
Ethics application status
Approved
Date submitted
18/02/2016
Date registered
31/03/2016
Date last updated
10/07/2019
Date data sharing statement initially provided
10/07/2019
Date results information initially provided
10/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The effects of medicinal cannabinoids on driving
Scientific title
The effects of medicinal cannabinoids on driving in healthy adults with prior cannabis experience
Secondary ID [1] 288440 0
Nil known
Universal Trial Number (UTN)
U1111-1179-8392
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Driving ability under the influence of the cannabinoids tetrahydrocannabidiol (THC) and cannbidiol (CBD) 297463 0
Condition category
Condition code
Other 297652 297652 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study is a randomized, crossover, double blind trial comparing the effects of .125g inhaled vaporized cannabis containing various concentrations of tetrahydrocannabinol (THC) and cannabidiol (CBD) on driving performance. Participants will complete 3 sessions, seperated by a washout period of 7 days. Participants will receive one of three varieties of cannabis per session, in a randomised and counter-balanced order. Cannabis types will include cannabis containing either: (a) high THC/low CBD (11% THC / <1% CBD), (b) high THC/high CBD (11% THC / 11% CBD) or (c) placebo. Study medications will be administered using a Volcano Medic vaporiser under the supervision of study staff.. To assess driving ability, participants will complete a 45-minute advanced driving simulation, beginning 15 minutes after drug administration. Participants will additionally complete a series of cognitive tests designed to measure reaction time. attentional processing and executive function. Biological samples (urine, blood and saliva) will be taken before and at a series of time points following drug administration. These will later be analysed for THC, CBD and endocannabinoids.
Intervention code [1] 293766 0
Other interventions
Comparator / control treatment
The control arm of this study involves a placebo strain of cannabis that contains negligible amounts of THC and CBD. All participants will receive this placebo strain during one of the three sessions,
Control group
Placebo

Outcomes
Primary outcome [1] 297190 0
The primary outcome measure is Standard deviation of lateral position (SDLP), which is measured by Oktal SCANeR Studio driving simulation software.
Timepoint [1] 297190 0
The primary outcome is measured twice during two driving simulation tasks; the first occurs 30 minutes after drug administration, and the second ocurs 2 1/2 hours after drug administration.
Secondary outcome [1] 320280 0
Subjective measures of drug effects and driving ability, assessed by a VAS ranging from 0-100. These include:

1. Strength of drug effect (No effect – Very strong)
2. Liking of drug effect (Disliked very much – Liked very much
3. Sedation (Not sedated – Very sedated)
4. Confidence in ability to drive safely (Not confident – Very confident)

This is a composite secondary outcome.
Timepoint [1] 320280 0
+1, +2, + 3.25, +5hr post drug administration
Secondary outcome [2] 320281 0
Cognitive Performance.

This is comprised of test performance on the following cognitive tasks:
Flankers task (measure of choice reaction time)
Digit-Symbol Substitution Task (measure of speed of information processing)
Rapid Visual Information Processing task (measure of alertness under cognitive demand)
Stop Signal Task (measure of ability to stop a planned response)
N-Back (measure of verbal working memory)

This is a composite secondary outcome.
Timepoint [2] 320281 0
+1, +2, + 3.25, +5hr post drug administration
Secondary outcome [3] 320282 0
Plasma cannabinoid concentrations, including includes measures of THC, THC-COOH, 11-OH-THC, CBD, and endocannanoids including 2-AG and anandamide.

This is a composite secondary outcome.
Timepoint [3] 320282 0
+1, +2, + 3.25, +5hr post drug administration
Secondary outcome [4] 320283 0
Oral fluid cannabinoid concentrations, incuding oral fluid of measures THC, THC-COOH, 11-OH-THC, and CBD.

This is a composite secondary outcome.
Timepoint [4] 320283 0
+1, +2, + 3.25, +5hr post drug administration
Secondary outcome [5] 331358 0
Mean speed and standard deviation of speed
Timepoint [5] 331358 0
+30 minutes, + 150 minutes post drug administration
Secondary outcome [6] 331359 0
Number of lane crossings
Timepoint [6] 331359 0
+30 minutes, +150 minutes post drug administration

Eligibility
Key inclusion criteria
(a) At least 18 years of age, and no more than 50 years of age
(b) Prior experience with cannabis (>10 lifetime exposures, <2x/week in previous 2 months)
(c) In possession of full Australian drivers license for at least 1 year
(d) Proficiency in English, and willing and capable of providing informed consent to the study procedures
Minimum age
18 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
(a) Any clinically significant prior adverse response to cannabis, cannabinoid products or synthetic cannabinoids, as assessed by an Addiction Medicine specialist (e.g. panic or other anxiety attacks, arrhythmia, falls, seizures)
(b) Cannabis dependence (ICD-10 criteria)
(c) A desire to abstain from cannabis use
(d) Past year mood or anxiety disorder (DSM-V criteria)
(e) Lifetime manic episode or psychotic illness (DSM-V criteria), or suspected family history of schizophrenia
(f) Interest in treatment for cannabis use
(g) Hypertension, cardiovascular disease, chronic pulmonary disease or asthma
(h) Under 18 years of age or over 50 years of age
(i) Use of medications that may impact upon the metabolism and excretion of cannabinoids (e.g. CYP450 enyzme inducers/inhibitors), or may impact upon driving ability (e.g. mood stabilisers, sedatives); and
(j) Pregnancy (primary plasma hCG screen in women of child bearing potential, confirmed with blood test if urine test positive) and women of child bearing potential must agree to using a reliable form of contraception during and one month after completion of the project.
(k) Required to complete drug testing for cannabis (e.g. workplace testing; court order)

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/04/2017
Actual
2/10/2017
Date of last participant enrolment
Anticipated
Actual
2/04/2018
Date of last data collection
Anticipated
Actual
30/04/2018
Sample size
Target
21
Accrual to date
Final
14
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 5203 0
Royal Prince Alfred Hospital - Camperdown

Funding & Sponsors
Funding source category [1] 292788 0
University
Name [1] 292788 0
The Lambert Initiative for Cannabinoid Therapeutics at The University of Sydney
Country [1] 292788 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
The University of Sydney
NSW 2006
Country
Australia
Secondary sponsor category [1] 291522 0
None
Name [1] 291522 0
n/a
Address [1] 291522 0
n/a
Country [1] 291522 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294278 0
SLHD Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 294278 0
c/- Research Development Office
Royal Prince Alfred Hospital
Missenden Road
CAMPERDOWN NSW 2050
Ethics committee country [1] 294278 0
Australia
Date submitted for ethics approval [1] 294278 0
07/12/2015
Approval date [1] 294278 0
23/03/2016
Ethics approval number [1] 294278 0
HREC/15/RPAH/552

Summary
Brief summary
Following the recent decision made by the Australian Commonwealth government to enable the cultivation of cannabis crops for medicinal grade products, it is likely that medicinal cannabis products – plant matter or extracts – will become more available in Australia in the years to follow. Various states including NSW are also investing in clinical trials of cannabinoid medicines for a number of debilitating illnesses, including the use of vaporised leaf cannabis products containing THC (http://www.health.nsw.gov.au/cannabis/Pages/terminal-illness.aspx). In will therefore become increasingly relevant, from a road safety and medico-legal perspective, to better understand the effects of these medicines on driving.

The psychoactive constituent of cannabis, THC, is only one of over 100 phytocannabinoids present in the Cannabis Sativa plant that may be promising therapeutic targets in medicine. CBD, for example, is a non-psychoactive cannabinoid with anti-inflammatory, neuroprotective antioxidant, anticonvulsive and antipsychotic properties. Preliminary studies suggest that in animal models CBD also modulates the pharmacological action of THC, dampening its psychotomimetic properties. The presence of phytocannabinoids other than THC (such as CBD) in some medicinal grade cannabinoid products distinguishes them from Australian street grade illicit cannabis, which contains very little to nil CBD. The presence of CBD could have important implications for the effects of cannabis-based medicines on driving.

Although other medicines such as benzodiazepines, opioids, and some antidepressants have been shown to impair driving ability, NSW law permits a person who is taking these medicines to drive so long as the drivers’ mental or physical faculties are not affected [9]. The current legal framework for driving under the influence of cannabis (where it is a criminal offence to be driving if THC is detected in saliva – with no functional assessment) reflects the illegal status of cannabis and predates the emergence of medicinal cannabinoid preparations.

The premise of the current proposal is to test the effects of a variety of medicinal cannabinoid preparations that differ in their concentrations of the cannabinoids THC and CBD. It is hypothesised that the impairing effects of THC will be modulated and possibly negated by the presence of CBD in medical grade cannabis. This study also seeks to test the efficacy of roadside testing equipment in discerning impaired from non-impaired driving. To establish if there are methods other than saliva testing that can predict driving impairment, this study will utilise an eye-tracking task, subjective measures and cognitive testing procedures.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 63082 0
Prof Iain McGregor
Address 63082 0
School of Psychology
University of Sydney
Building A18
NSW 2006
Country 63082 0
Australia
Phone 63082 0
+61 2 9351 3571
Fax 63082 0
Email 63082 0
iain.mcgregor@sydney.edu.au
Contact person for public queries
Name 63083 0
Mr Thomas Arkell
Address 63083 0
Room 243
School of Psychology
University of Sydney
Building A18
NSW 2006
Country 63083 0
Australia
Phone 63083 0
+61 2 9351 3433
Fax 63083 0
Email 63083 0
thomas.arkell@sydney.edu.au
Contact person for scientific queries
Name 63084 0
Mr Thomas Arkell
Address 63084 0
Room 243
School of Psychology
University of Sydney
Building A18
NSW 2006
Country 63084 0
Australia
Phone 63084 0
+61 2 9351 3433
Fax 63084 0
Email 63084 0
thomas.arkell@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data of published results only.
When will data be available (start and end dates)?
Immediately following publication, no end date.
Available to whom?
Only researchers who provide a methodologically sound proposal.
Available for what types of analyses?
For meta-analyses.
How or where can data be obtained?
Please contact the principal investigator (iain.mcgregor@sydney.edu.au).


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseCannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition.2019https://dx.doi.org/10.1007/s00213-019-05246-8
N.B. These documents automatically identified may not have been verified by the study sponsor.