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Trial registered on ANZCTR


Registration number
ACTRN12621000469819
Ethics application status
Approved
Date submitted
19/01/2021
Date registered
21/04/2021
Date last updated
21/04/2021
Date data sharing statement initially provided
21/04/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Delta-9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) effects on perception of illusions, schizotypy and cognition in healthy volunteers
Scientific title
Delta-9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) effects on perception of illusions, schizotypy and cognition in healthy volunteers
Secondary ID [1] 302663 0
TGA CT-2020-CTN-04520-1 v1
Universal Trial Number (UTN)
U1111-1262-6903
Trial acronym
CATE (Cannabidiol and THC Effects)
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Schizophrenia 320004 0
Psychosis 320008 0
Cannabis use safety 320778 0
Condition category
Condition code
Mental Health 317932 317932 0 0
Schizophrenia
Mental Health 317933 317933 0 0
Psychosis and personality disorders
Mental Health 317934 317934 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The participants receive each of oral THC 5 mg (twice a day, 2.5 hours apart, one day only ), oral CBD 500 mg (twice a day, 2.5 hours apart, one day only), and placebo (same excipient as in THC and CBD, twice a day, 2.5 hours apart, one day only) each being at least one week apart. Participants will be given 2 oil capsules on all three testing days, one day receiving placebo (capsule of olive oil), THC (capsule of THC in olive oil ), and CBD (capsule of olive oil) so that the duration of the study is one day a week for 3 weeks (~14 days)
Intervention code [1] 319252 0
Treatment: Drugs
Comparator / control treatment
The placebo (olive oil capsule) treatment is the control and CBD is the comparator
Control group
Placebo

Outcomes
Primary outcome [1] 325940 0
Experience of the rubber hand illusion with varying temporal and spatial interstimulus intervals assessed as the change in a self-report subjective experience scale (scores after the illusion - scores before the illusion)
Timepoint [1] 325940 0
These will be measured on all days of testing (placebo and drug days). The rubber hand illusion is measured ~255 min after the second capsule. This is the last test of the day for each day.
Secondary outcome [1] 389613 0
This is a primary outcome. Effect of THC and CBD on the Visual Induced Flash illusions with varying temporal and spatial interstimulus intervals. The illusion is assessed by recording the number of flashes the participant sees.
Timepoint [1] 389613 0
This will be measured on all days of testing (placebo and drug days). The Visual Induced Flash Illusion will be tested ~160 min after the second capsule is taken.
Secondary outcome [2] 389615 0
This is a primary outcome. The effect of THC and CBD on the Rey Auditory Verbal Learning Test (RAVLT), with the outcome being how many words can be recalled over a period of time, short or long term.
Timepoint [2] 389615 0
This will be measured 3 times on all days of testing (placebo and drug days). Will be done firstly at ~65 min (Short-Term Memory), secondly ~99 min (Long-Term Memory) and lastly ~179 min (Long-Term Memory) after the first capsule. The last point of each day is 179 min after first capsule.
Secondary outcome [3] 389617 0
This is a primary outcome. The effect of THC and CBD on the Spatial Span on the maximum span of digits achieved.
Timepoint [3] 389617 0
These will be measured on all days of testing (placebo and drug days). This will be performed ~70 min after the first capsule was given.
Secondary outcome [4] 389619 0
This is the primary outcome. The effect of THC and CBD on the recognition of facial emotions. The participants choice of facial expression anger, fear, happiness, sadness, and neutral. Participants report which emotion from the list best describes the image of that emotion as fast as possible. The outcome being a compound of which emotion was chosen and the time taken to choose the emotion.
Timepoint [4] 389619 0
These will be measured on all days of testing (placebo and drug days). This will be performed ~170 min after the first capsule.
Secondary outcome [5] 389620 0
This is the primary outcome. The effect of THC and CBD on the Modified Concept Set-shifting Task (mCST) where the outcome will be judged on the compound of the time to complete the trials and accuracy of performance in crossing out the correct number or letter.
Timepoint [5] 389620 0
These will be measured on all days of testing (placebo and drug days). This will be performed ~215 min after the second capsule.
Secondary outcome [6] 389621 0
This is a primary outcome. The effect of THC and CBD on the Continuous Performance Test - Identical Pairs (CPT-IP) where the outcome is based on false alarm errors and catch trail errors made throughout the task, how well participants can continuously perform throughout the trial and match correct trials
Timepoint [6] 389621 0
These will be measured on all days of testing (placebo and drug days). This will be performed 45 min after the second capsule.
Secondary outcome [7] 389622 0
This is a primary outcome. The effect of THC and CBD on the Effort Expenditure for Reward Task, the outcome is based on how the participants choose to respond to the task based on the probability of winning, the difficulty of the task, and the size of the reward of the task to elucidate participants judgment of effort expenditure for reward.
Timepoint [7] 389622 0
This will be measured on all days of testing (placebo and drug days) 130 min after the first capsule is taken.
Secondary outcome [8] 389623 0
This is a primary outcome. Schizotypy, measured by a composite z-score derived from the Launey-Slade Hallucination scale (LSH), the Magical Ideation Scale (MIS), the Perceptual Aberration Scale (PAS), the Brief Psychiatric Rating Scale (BPRS) and selected items from the Scale for the Assessment of Positive symptoms (SAPS, Items 15-48). Positive and Negative and negative syndrome scale (PANSS).
Timepoint [8] 389623 0
This will be measured on twice on all 3 days of testing (placebo and drug days), ~100 min after capsule 1, and ~95 min after capsule 2 taken. The results of the two tests under each drug condition will be averaged.
Secondary outcome [9] 389624 0
This is a primary outcome. Heart rate by 3 repeats of a digital blood pressure machine
Timepoint [9] 389624 0
This will be measured on all days of testing (placebo and drug days). Repeated 5 times along with physiological measures: immediately after first capsule taken,
and then ~100 and ~195 min after first capsule taken, and ~30 and ~195 min after second capsule taken.
Secondary outcome [10] 389625 0
This is a primary outcome. Body temperature by 3 repeats of an infrared MediScan digital thermometer measuring supraorbital vein blood temperature
Timepoint [10] 389625 0
This will be measured on all days of testing (placebo and drug days). Repeated 5 times along with drug effect and anxiety measures: immediately after first capsule taken,
and then ~100 and ~195 min after first capsule taken, and ~30 and ~195 min after second capsule taken.
Secondary outcome [11] 389626 0
This is a primary outcome. Oxygen levels, measured in triplicate with an oximeter.
Timepoint [11] 389626 0
This will be measured on all days of testing (placebo and drug days). Repeated 5 times along with drug effect, blood pressure and anxiety measures: immediately after first capsule taken,
and then ~100 and ~195 min after first capsule taken, and ~30 and ~195 min after second capsule taken.
Secondary outcome [12] 390752 0
This is a primary outcome. The Amphetamine Mood Questionnaire (AMQ),
Timepoint [12] 390752 0
This will be measured on all days of testing (placebo and drug days). Repeated 5 times along with physiological measures: immediately after first capsule taken,
and then ~100 and ~195 min after first capsule taken, and ~30 and ~195 min after second capsule taken.
Secondary outcome [13] 391875 0
This is a primary outcome. Spatial Span tests spatial working memory. The researcher taps a sequence of cubes in front of the participant, who is then asked to repeat the sequence back. Conditions are the same as Digit Span.
Timepoint [13] 391875 0
This will be measured on all days of testing (placebo and drug days). 70 min after the first capsule is given.
Secondary outcome [14] 391878 0
This is a primary outcome. Blood pressure by 3 repeats of a digital blood pressure machine.
Timepoint [14] 391878 0
This will be measured on all days of testing (placebo and drug days). Repeated 5 times along with physiological measures: immediately after first capsule taken,
and then ~100 and ~195 min after first capsule taken, and ~30 and ~195 min after second capsule taken.
Secondary outcome [15] 391879 0
This is a primary outcome. ARCI marijuana Scale (AMS)
Timepoint [15] 391879 0
This will be measured on all days of testing (placebo and drug days). Repeated 5 times along with physiological measures: immediately after first capsule taken,
and then ~100 and ~195 min after first capsule taken, and ~30 and ~195 min after second capsule taken.
Secondary outcome [16] 391880 0
This is a primary outcome. Marteau and Bekker Self-evaluation scale for anxiety (MBS)
Timepoint [16] 391880 0
This will be measured on all days of testing (placebo and drug days). Repeated 5 times along with physiological measures: immediately after first capsule taken,
and then ~100 and ~195 min after first capsule taken, and ~30 and ~195 min after second capsule taken.
.
Secondary outcome [17] 391889 0
This is a primary outcome. Metacognitions Questionnaire
Timepoint [17] 391889 0
This will be measured on all days of testing (placebo and drug days). Repeated 5 times along with physiological measures: immediately after first capsule taken,
and then ~100 and ~195 min after first capsule taken, and ~30 and ~195 min after second capsule taken.
Secondary outcome [18] 391890 0
This is a primary outcome. Dissociative Experience Scale
Timepoint [18] 391890 0
This will be measured on all days of testing (placebo and drug days). Repeated 5 times along with physiological measures: immediately after first capsule taken,
and then ~100 and ~195 min after first capsule taken, and ~30 and ~195 min after second capsule taken.
Secondary outcome [19] 391891 0
This is a primary outcome. Locus of Control Scale
Timepoint [19] 391891 0
This will be measured on all days of testing (placebo and drug days). Repeated 5 times along with physiological measures: immediately after first capsule taken,
and then ~100 and ~195 min after first capsule taken, and ~30 and ~195 min after second capsule taken.
Secondary outcome [20] 391893 0
Duration Discrimination task where participants discriminate if a test tone is longer or shorter then a standard tone. The outcome being the decision about tone length.
Timepoint [20] 391893 0
185 min after the second capsule is given.
Secondary outcome [21] 391894 0
Prospective time estimation task where participants are presented with a start point (green dot) and then after a period of time 1 second to 3 minutes and a completion point (red dot) after which they are asked to estimate the time of the interval on a slider.
Timepoint [21] 391894 0
185 min after the second capsule is given.
Secondary outcome [22] 391895 0
Temporal time reproduction task asks participants to listen to a length of the sound and then replicate the same length of sound by holding down a key. The outcome being the accuracy in replicating the length of the tone.
Timepoint [22] 391895 0
185 min after the second capsule is given.
Secondary outcome [23] 391896 0
Auditory Selective Attention Task two independent auditory stimuli (target phrase vs. distractor phrase) are simultaneously presented through headphones either monaurally or binaurally consisting of a call sign. Participants are asked to only attend to the target phrase and then select the phrase they heard. The outcome being compound the percentage of correct responses and mean response reaction times for dichotic and monaural listening are recorded.
Timepoint [23] 391896 0
~150 min after the first capsule is given.

Eligibility
Key inclusion criteria
Inclusion Criteria:
1. They are between 18 and 59 years of age.
2. They are healthy (have no ongoing medical, including psychiatric, condition, other than acne.
Minimum age
18 Years
Maximum age
59 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion Criteria:
1. Any current medical (including psychiatric) condition other than acne.
2. Women that are pregnant or breast-feeding.
3. Women that fertile, sexually active, and not using a contraceptive.
4. Using current prescription medications other than contraceptives or acne medications.
5. A family history of a psychotic illness (E.g., schizophrenia or bipolar disorder) in their first-degree relatives.
6. Use of any drugs other than contraceptives or acne medications 48 hours before the testing days. These include prescription medications, over-the-counter medications or “naturopathy” medications such as St John’s Wort (that can interfere with drug metabolism), but do not include nicotine if the person is nicotine-dependent as withdrawal from nicotine produces an unusual physiological state.
7. History of a major brain or head injury.
8. Need for a hearing aid.
9. Poor eyesight when wearing glasses.

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)
Allocation concealment does not apply as this is within-subject cross-over treatment (AB) where the order of treatment is a permuted block randomisation, As it is a cross-over study, each participant experiences all three conditions, but none of the psychiatrists who conduct the medical and psychiatric exam to determine eligibility, testers or the participant knows on which day they receive drug or placebo. Which day is which is concealed by using the same kind of capsules for both drugs and placebo. Allocation of treatment is concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation with a block size of 6 (two sets of the 3 different drugs).
The maximum limit of the same type of capsule given in sequence is therefore 4 (last two of one block and first two of the second block). This ensures that every sequence of 6 participants is balanced for drug order. Randomisation is used by a computer random number selection of the list of 6 treatments without replacement.
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
Intervention assignment
Crossover
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
We will use Analysis of Variance with multiple pairwise comparisons using the exact Bonferroni correction to analyse parametric data. Where there are more than two levels of an independent variable (e.g., interstimulus time or distance interval), a linear or nonlinear regression modelling approach will be taken as required. Physiological data with multiple time-points will be analysed with linear regression modelling. Nonparametric data will be analysed using kernel density analysis of the difference from placebo scores for each drug with permutation tests, also using the exact Bonferroni correction. All analyses will be performed with R Statistics and R Studio with the ‘ez’ or 'lm' and ‘sm’ packages for parametric and nonparametric tests respectively.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/05/2021
Actual
Date of last participant enrolment
Anticipated
22/12/2023
Actual
Date of last data collection
Anticipated
22/12/2023
Actual
Sample size
Target
36
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment postcode(s) [1] 32579 0
6009 - Nedlands
Recruitment postcode(s) [2] 32594 0
6009 - Crawley
Recruitment postcode(s) [3] 32595 0
6009 - Broadway Nedlands

Funding & Sponsors
Funding source category [1] 307103 0
University
Name [1] 307103 0
University of Western Australia
Country [1] 307103 0
Australia
Primary sponsor type
University
Name
University of Western Australia
Address
35 Stirling Highway, Crawley, WA 6009
Country
Australia
Secondary sponsor category [1] 308073 0
None
Name [1] 308073 0
Address [1] 308073 0
Country [1] 308073 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307217 0
The University of Western Australia Human Research Ethics Committee [EC00272]
Ethics committee address [1] 307217 0
Ethics committee country [1] 307217 0
Australia
Date submitted for ethics approval [1] 307217 0
06/02/2020
Approval date [1] 307217 0
24/09/2020
Ethics approval number [1] 307217 0
RA/4/20/5984

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

Contacts
Principal investigator
Name 106442 0
Prof Mathew Martin-Iverson
Address 106442 0
Pharmacology, School of Biomedical Sciences, University of Western Australia, M Block, QEII Medical Centre, Nedlands, WA 6009
Country 106442 0
Australia
Phone 106442 0
+61 8 6457 2982
Fax 106442 0
Email 106442 0
[email protected]
Contact person for public queries
Name 106443 0
Mathew Martin-Iverson
Address 106443 0
Pharmacology, School of Biomedical Sciences, University of Western Australia, Room 1.42B, M Block, Queen Elizabeth II Medical Centre, Nedlands, WA 6009
Country 106443 0
Australia
Phone 106443 0
+61 8 6457 2982
Fax 106443 0
Email 106443 0
[email protected]
Contact person for scientific queries
Name 106444 0
Mathew Martin-Iverson
Address 106444 0
Pharmacology, School of Biomedical Sciences, University of Western Australia, Room 1.42B, M Block, Queen Elizabeth II Medical Centre, Nedlands, WA 6009
Country 106444 0
Australia
Phone 106444 0
+61 8 6457 2982
Fax 106444 0
Email 106444 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


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.