ANZCTR - Registration

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]

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

Psychosis

Cannabis use safety

Condition category

Condition code

Mental Health

Schizophrenia

Mental Health

Psychosis and personality disorders

Mental Health

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]

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]

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]

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]

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]

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]

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]

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]

This is a primary outcome. The effect of THC and CBD on the Spatial Span on the maximum span of digits achieved.

Timepoint [3]

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]

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]

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]

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]

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]

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]

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]

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]

This will be measured on all days of testing (placebo and drug days) 130 min after the first capsule is taken.

Secondary outcome [8]

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]

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]

This is a primary outcome. Heart rate by 3 repeats of a digital blood pressure machine

Timepoint [9]

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]

This is a primary outcome. Body temperature by 3 repeats of an infrared MediScan digital thermometer measuring supraorbital vein blood temperature

Timepoint [10]

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]

This is a primary outcome. Oxygen levels, measured in triplicate with an oximeter.

Timepoint [11]

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]

This is a primary outcome. The Amphetamine Mood Questionnaire (AMQ),

Timepoint [12]

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]

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]

This will be measured on all days of testing (placebo and drug days). 70 min after the first capsule is given.

Secondary outcome [14]

This is a primary outcome. Blood pressure by 3 repeats of a digital blood pressure machine.

Timepoint [14]

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]

This is a primary outcome. ARCI marijuana Scale (AMS)

Timepoint [15]

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]

This is a primary outcome. Marteau and Bekker Self-evaluation scale for anxiety (MBS)

Timepoint [16]

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]

This is a primary outcome. Metacognitions Questionnaire

Timepoint [17]

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]

This is a primary outcome. Dissociative Experience Scale

Timepoint [18]

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]

This is a primary outcome. Locus of Control Scale

Timepoint [19]

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]

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]

185 min after the second capsule is given.

Secondary outcome [21]

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]

185 min after the second capsule is given.

Secondary outcome [22]

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]

185 min after the second capsule is given.

Secondary outcome [23]

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]

~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

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]

6009 - Nedlands

Recruitment postcode(s) [2]

6009 - Crawley

Recruitment postcode(s) [3]

6009 - Broadway Nedlands

Funding & Sponsors

Funding source category [1]

University

Name [1]

University of Western Australia

Country [1]

Australia

Primary sponsor type

University

Name

University of Western Australia

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

The University of Western Australia Human Research Ethics Committee [EC00272]

Ethics committee address [1]

35 Stirling Highway, Crawley, WA 6009

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

06/02/2020

Approval date [1]

24/09/2020

Ethics approval number [1]

RA/4/20/5984

Summary

Brief summary

The hypothesis is that there are certain types of what are called schizotypy (schizophrenic-like) states or traits that can predict how a person may respond to THC and/or CBD: in a pro- or anti-psychotic manner, to guide potential medicinal use of cannabis in psychiatry.  The aim s to compare THC (the psychoactive component in cannabis) with CBD ("non-psychoactive" component in cannabis) on its effects on the multi-sensory perceptions in the healthy volunteers. We have previously shown that certain drugs can produce effects on the perception of illusions that are similar to differences in the perceptions of those illusions by people suffering from schizophrenia. Determining the effect of the cannabinoids on these differences in perceptions in healthy people, and the relationship of those effects with the effect on mild schizophrenic similar states and traits may allow us to determine which people will find THC or CBD to be medicinally helpful, and those that should avoid these drugs.

Trial website

Public notes

Contacts

Principal investigator

Name

Prof Mathew Martin-Iverson

Address

Pharmacology, School of Biomedical Sciences, University of Western Australia, M Block, QEII Medical Centre, Nedlands, WA 6009

Country

Australia

Phone

+61 8 6457 2982

Email

[email protected]

Contact person for public queries

Name

Mathew Martin-Iverson

Address

Pharmacology, School of Biomedical Sciences, University of Western Australia, Room 1.42B, M Block, Queen Elizabeth II Medical Centre, Nedlands, WA 6009

Country

Australia

Phone

+61 8 6457 2982

Email

[email protected]

Contact person for scientific queries

Name

Mathew Martin-Iverson

Address

Pharmacology, School of Biomedical Sciences, University of Western Australia, Room 1.42B, M Block, Queen Elizabeth II Medical Centre, Nedlands, WA 6009

Country

Australia

Phone

+61 8 6457 2982

Email

[email protected]

Trial Review

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