Intellectual DisabilityPhase 2NCT04821856
Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
A Phase 2 study testing Cannabidiol Oil in people with Intellectual Disability and Child Behavior Problem, run by Murdoch Childrens Research Institute at 3 sites in Australia.
Trial summary
This is a multi-site, double-blind, parallel group, randomized, placebo-controlled study of 140 participants comparing oral purified cannabidiol isolate (CBD) with placebo in reducing Severe Behavioral Problems (SBP) at 8 weeks in children aged 6 - 18 years with Intellectual Disability (ID). Read more about this study
- Who is it for?
- Ages 6 to 18 years
- Conditions the study is for
- Intellectual Disability, Child Behavior Problem
- What is being tested?
- Cannabidiol Oil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 132 participants
- Where
- 3 sitesAustralia
- Study dates
- 11 May 2021to 19 Aug 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Males and females aged 6 - 18 years of age;
- DSM-5 diagnosis of intellectual disability (ID):
- Full scale IQ < 70 on standardized cognitive assessment. Testing results must be sighted by the investigators and performed within two years of enrollment. In the event that records of prior testing are unavailable or the assessment was more than 2 years prior, IQ will be estimated using the Wechsler Abbreviated Scale of Intelligence-II.
- Deficit in adaptive function (basis for severity rating of ID in DSM-5) in at least one activity of life on the Vineland Adaptive Behavior Scales (derives scores in Communication, Daily Living Skills and Socialization domains, and a Global Adaptive score). If records of prior testing are unavailable or the assessment was more than 2 years prior, this will be completed by the parent or guardian.
- SBP: Defined as scores of:
- 18 or higher on the Aberrant Behavior Checklist-Irritability subscale (ABC-I), and
Show all 10Show fewer
- moderate or higher on the Clinical Global Impressions-Severity scale;
- No changes in either medication or other interventions in the 4 weeks prior to randomization, and intention to remain on same dose for the duration of the study;
- Written informed consent from parent or legal guardian;
- Participant and family have the ability to comply with the protocol requirements, in the opinion of the investigator.
Who cannot join
- Non-English speaking parents;
- Psychosis;
- Taking clobazam, mTOR inhibitors (e.g sirolimus, tacrolimus), anti-cancer agents, citalopram >20mg/day, escitalopram >10mg/day.;
- Abnormal liver function tests: defined as ALT > twice ULN;
- Abnormal renal function tests: defined as creatinine > ULN
- Current use of medicinal cannabis, or use in the 4 weeks prior to screening;
- Pregnant or intending to become pregnant during the study, or breastfeeding;
- Known allergy to cannabidiol or cannabis products
Trial locations and contacts
3 sites in 1 country.
Australia3 sites
Monash Children's Hospital
Clayton, Victoria, 3168
Royal Children's Hospital / Murdoch Children's Research Institute
Parkville, Victoria, 3052
The Children's Hospital at Westmead
Westmead, New South Wales, 2145
About this study
Official title: A Randomized Placebo-controlled Trial of Cannabidiol to Treat Severe Behavioral Problems in Children and Adolescents With Intellectual Disability
This is a multi-site, double-blind, parallel group, randomized, placebo-controlled study of 140 participants comparing oral purified cannabidiol isolate (CBD) with placebo in reducing Severe Behavioral Problems (SBP) at 8 weeks in children aged 6 - 18 years with Intellectual Disability (ID). Eligible participants will be randomized 1:1 to receive either CBD or placebo.
- Conditions
- Intellectual Disability, Child Behavior Problem
- Being tested
- Cannabidiol Oil, Placebo
- Keywords
- pediatric, intellectual disability, severe behavior problems
- Medical subject headings
- Intellectual Disability, Mental Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cannabidiol OilDrug
Cannabidiol (CBD) isolate 100mg/ml in MCT oil oral solution, manufactured by THC Pharma
PlaceboDrug
MCT oil and flavoring solution, also manufactured by THC Pharma
| Study group | Role | What they receive |
|---|---|---|
| Cannabidiol 100mg/ml | Experimental | The starting dose of cannabidiol (CBD) will be 5 mg/kg/day and will be administered orally twice daily in doses of 2.5 mg/kg (up titration phase from day 1 to 7). After one week, the dose of CBD will be increased to 10 mg/kg/day in two daily doses of 5mg/kg (8-week maintenance phase from day 8 to 63). On completion of the maintenance phase the dose of CBD will be decreased to 5mg/kg/day for one week (day 64 to 70), after which the CBD administration will cease.
A ceiling dose of 1000mg/day will be administered to all participants weighing 100kg or greater. These participants will receive a dose of 500mg/day during up- and down-titration.
Doses will be rounded to the nearest 10mg (0.1mL). Receives: Drug: Cannabidiol Oil |
| Placebo | Placebo comparator | The control group will receive placebo medium-chain triglyceride (MCT) oil which is indistinguishable from the active medication in appearance, smell and taste.
Dose will be matched for volume to the cannabidiol arm, and administered twice daily for 10 weeks (including up- and down-titration). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean difference between the cannabidiol 100mg/ml and placebo arms on the Aberrant Behavior Checklist-Irritability (ABC-I) subscale total score at day 64
This is a 15 item parent-rated questionnaire, used to measure Severe Behavioral Problems in children
Measured: At day 64 (end of maintenance treatment period)
Secondary outcomes (11)
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total scores of the four remaining subscales of the Aberrant Behavior Checklist (ABC) at day 64
43 parent-rated items assessing: Social withdrawal, Stereotypic behavior, Hyperactivity/Noncompliance and Inappropriate Speech
Measured: At day 64 (end of maintenance treatment period)
Comparison between the cannabidiol 100mg/ml and placebo arms of clinician ratings on the Clinical Global Impressions-Improvement at day 64. Data will be presented as the proportion of participants in each arm with a rating suggesting improvement
This is a single item clinician-rated summary measure of improvement
Measured: At day 64 (end of maintenance treatment period)
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Parent Rated Anxiety Scale-ASD at day 64
This is a 25 item parent-rated measure of anxiety in youth with ASD
Measured: At day 64 (end of maintenance treatment period)
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Child & Adolescent Scale of Participation at day 64
This is a 20 item parent-rated questionnaire that includes sub-scales for participation in home, school, and community activities
Measured: At day 64 (end of maintenance treatment period)
Mean difference between the cannabidiol 100mg/ml and placebo arms on the weighted total score of the Child Health Utility 9D (CHU-9D) at day 64
This is a 9 item parent-rated, preference-weighted measure used to calculate quality adjusted life years for children
Measured: At day 64 (end of maintenance treatment period)
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Sleep Disturbance Scale for Children at day 64
This is a 26 item parent-rated questionnaire assessing sleep difficulties in children
Measured: At day 64 (end of maintenance treatment period)
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Assessment of Quality of Life 4D (AQOL-4D) at day 64
This is a 12 item self-report health-related instrument used to calculate quality adjusted life years for parents
Measured: At day 64 (end of maintenance treatment period)
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Beach Center Family Quality of Life at day 64
This is a 25 item parent report measure that includes subscales assessing family interaction, parenting, emotional and material wellbeing, and disability-related support.
Measured: At day 64 (end of maintenance treatment period)
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Depression Anxiety Stress Scale-21 at day 64
This is a 21 item self-rated assessment of parent mental health, including symptoms of depression, anxiety and stress
Measured: At day 64 (end of maintenance treatment period)
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Autism Parenting Stress Index at day 64
This is a 13 item self-rated measure of 3 categories of stress drivers in parents: core social disability, difficult behavior, physical issues
Measured: At day 64 (end of maintenance treatment period)
The frequency of adverse events as reported on the modified version of the Liverpool Adverse Event Profile (LAEP) at day 64 will be summarised across the cannabidiol 100mg/ml and placebo arms
Completed by the parent or guardian, the LAEP was designed to capture known side-effects of anti-epileptic medication. The modified version includes additional items to ascertain other known side-effects of CBD. This measure includes 34 items.
Measured: At day 64 (end of maintenance treatment period)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2021
- Study start11 May 2021
- Primary completion9 Jul 2025
- Study completion19 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Intellectual DisabilityStudies of the same condition, open and under way.
- More trials run by Murdoch Childrens Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 132 participants (actual)
Sponsor and investigators
- Lead sponsor
- Murdoch Childrens Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Monash University, University of Sydney, Deakin University
- Responsible party
- Sponsor
- Investigators
- Daryl Efron, Study director, Murdoch Childrens Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04821856
- Sponsor's protocol ID
- RCH HREC 70053
- Status last verified
- Aug 2025
- First submitted
- 25 Mar 2021
- Last updated
- 3 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The de-identified data set collected for this analysis of the RCT of CBD in children and adolescents with ID will be available six months after publication of the primary outcome. The study protocol and analysis plan will also be available. The data must be obtained from the Murdoch Children's Research Institute. Prior to releasing any data the following are required: a data access agreement must be signed between relevant parties, the 'RCT of CBD in children and adolescents with ID' Trial Steering Committee must see and approve the data analysis plan describing how the data will be analysed, there must be an agreement around appropriate acknowledgment and any additional costs involved must be covered. Should the Trial Steering Committee be unavailable, this role is delegated to the Murdoch Children's Research Institute. Data will only be shared with a recognized research organisation which has approved the proposed analysis plan.
Publications
Efron D, Taylor K, Payne JM, Freeman JL, Cranswick N, Mulraney M, Prakash C, Lee KJ, Williams K. Does cannabidiol reduce severe behavioural problems in children with intellectual disability? Study protocol for a pilot single-site phase I/II randomised placebo controlled trial. BMJ Open. 2020 Mar 8;10(3):e034362. doi: 10.1136/bmjopen-2019-034362.
PubMed 32152170Efron D, Freeman JL, Cranswick N, Payne JM, Mulraney M, Prakash C, Lee KJ, Taylor K, Williams K. A pilot randomised placebo-controlled trial of cannabidiol to reduce severe behavioural problems in children and adolescents with intellectual disability. Br J Clin Pharmacol. 2021 Feb;87(2):436-446. doi: 10.1111/bcp.14399. Epub 2020 Jul 1.
PubMed 32478863
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Placebo-controlled Trial of Cannabidiol to Treat Severe Behavioral Problems in Children and Adolescents With Intellectual Disability
- ClinicalTrials.gov ID
- NCT04821856
- Acronym / sponsor ID
- RCH HREC 70053
- Conditions
- Intellectual Disability, Child Behavior Problem
- Keywords
- pediatric, intellectual disability, severe behavior problems
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 132 participants (actual)
- Lead sponsor
- Murdoch Childrens Research InstituteUniversity, hospital or other
- Collaborators
- Monash University, University of Sydney, Deakin University
- Study start
- 11 May 2021 (actual)
- Primary completion
- 9 Jul 2025 (actual)
- Study completion
- 19 Aug 2025 (actual)
- First posted
- 30 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multi-site, double-blind, parallel group, randomized, placebo-controlled study of 140 participants comparing oral purified cannabidiol isolate (CBD) with placebo in reducing Severe Behavioral Problems (SBP) at 8 weeks in children aged 6 - 18 years with Intellectual Disability (ID). Eligible participants will be randomized 1:1 to receive either CBD or placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cannabidiol 100mg/ml | Experimental | Drug: Cannabidiol OilThe starting dose of cannabidiol (CBD) will be 5 mg/kg/day and will be administered orally twice daily in doses of 2.5 mg/kg (up titration phase from day 1 to 7). After one week, the dose of CBD will be increased to 10 mg/kg/day in two daily doses of 5mg/kg (8-week maintenance phase from day 8 to 63). On completion of the maintenance phase the dose of CBD will be decreased to 5mg/kg/day for one week (day 64 to 70), after which the CBD administration will cease. A ceiling dose of 1000mg/day will be administered to all participants weighing 100kg or greater. These participants will receive a dose of 500mg/day during up- and down-titration. Doses will be rounded to the nearest 10mg (0.1mL). |
| Placebo | Placebo comparator | Drug: PlaceboThe control group will receive placebo medium-chain triglyceride (MCT) oil which is indistinguishable from the active medication in appearance, smell and taste. Dose will be matched for volume to the cannabidiol arm, and administered twice daily for 10 weeks (including up- and down-titration). |
Who may qualify
- Ages
- 6 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- Males and females aged 6 - 18 years of age;
- DSM-5 diagnosis of intellectual disability (ID):
- SBP: Defined as scores of:
- No changes in either medication or other interventions in the 4 weeks prior to randomization, and intention to remain on same dose for the duration of the study;
- Written informed consent from parent or legal guardian;
Key exclusion criteria (8 listed)
- Non-English speaking parents;
- Psychosis;
- Taking clobazam, mTOR inhibitors (e.g sirolimus, tacrolimus), anti-cancer agents, citalopram >20mg/day, escitalopram >10mg/day.;
- Abnormal liver function tests: defined as ALT > twice ULN;
- Abnormal renal function tests: defined as creatinine > ULN
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cannabidiol OilCannabidiol (CBD) isolate 100mg/ml in MCT oil oral solution, manufactured by THC Pharma | Drug | Cannabidiol 100mg/ml |
| PlaceboMCT oil and flavoring solution, also manufactured by THC Pharma | Drug | Placebo |
Primary outcome
Mean difference between the cannabidiol 100mg/ml and placebo arms on the Aberrant Behavior Checklist-Irritability (ABC-I) subscale total score at day 64
Time frame: At day 64 (end of maintenance treatment period)
This is a 15 item parent-rated questionnaire, used to measure Severe Behavioral Problems in children
11 secondary outcomes
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total scores of the four remaining subscales of the Aberrant Behavior Checklist (ABC) at day 64
Time frame: At day 64 (end of maintenance treatment period)
Comparison between the cannabidiol 100mg/ml and placebo arms of clinician ratings on the Clinical Global Impressions-Improvement at day 64. Data will be presented as the proportion of participants in each arm with a rating suggesting improvement
Time frame: At day 64 (end of maintenance treatment period)
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Parent Rated Anxiety Scale-ASD at day 64
Time frame: At day 64 (end of maintenance treatment period)
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Child & Adolescent Scale of Participation at day 64
Time frame: At day 64 (end of maintenance treatment period)
Mean difference between the cannabidiol 100mg/ml and placebo arms on the weighted total score of the Child Health Utility 9D (CHU-9D) at day 64
Time frame: At day 64 (end of maintenance treatment period)
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Sleep Disturbance Scale for Children at day 64
Time frame: At day 64 (end of maintenance treatment period)
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Assessment of Quality of Life 4D (AQOL-4D) at day 64
Time frame: At day 64 (end of maintenance treatment period)
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Beach Center Family Quality of Life at day 64
Time frame: At day 64 (end of maintenance treatment period)
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Depression Anxiety Stress Scale-21 at day 64
Time frame: At day 64 (end of maintenance treatment period)
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Autism Parenting Stress Index at day 64
Time frame: At day 64 (end of maintenance treatment period)
The frequency of adverse events as reported on the modified version of the Liverpool Adverse Event Profile (LAEP) at day 64 will be summarised across the cannabidiol 100mg/ml and placebo arms
Time frame: At day 64 (end of maintenance treatment period)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2025.
- Background: PubMed 32152170Efron D, Taylor K, Payne JM, Freeman JL, Cranswick N, Mulraney M, Prakash C, Lee KJ, Williams K. Does cannabidiol reduce severe behavioural problems in children with intellectual disability? Study protocol for a pilot single-site phase I/II randomised placebo controlled trial. BMJ Open. 2020 Mar 8;10(3):e034362. doi: 10.1136/bmjopen-2019-034362.
- Background: PubMed 32478863Efron D, Freeman JL, Cranswick N, Payne JM, Mulraney M, Prakash C, Lee KJ, Taylor K, Williams K. A pilot randomised placebo-controlled trial of cannabidiol to reduce severe behavioural problems in children and adolescents with intellectual disability. Br J Clin Pharmacol. 2021 Feb;87(2):436-446. doi: 10.1111/bcp.14399. Epub 2020 Jul 1.
- Individual participant dataSharing planned: Yes. The de-identified data set collected for this analysis of the RCT of CBD in children and adolescents with ID will be available six months after publication of the primary outcome. The study protocol and analysis plan will also be available. The data must be obtained from the Murdoch Children's Research Institute. Prior to releasing any data the following are required: a data access agreement must be signed between relevant parties, the 'RCT of CBD in children and adolescents with ID' Trial Steering Committee must see and approve the data analysis plan describing how the data will be analysed, there must be an agreement around appropriate acknowledgment and any additional costs involved must be covered. Should the Trial Steering Committee be unavailable, this role is delegated to the Murdoch Children's Research Institute. Data will only be shared with a recognized research organisation which has approved the proposed analysis plan.
Related trials for Intellectual Disability
RecruitingObservational study
Longitudinal Study of Ultra-rare Inherited Metabolic and Degenerative Neurological Diseases.
Inherited Disease, Rare Diseases
Not yet recruiting
Advancing Cardiovascular Health Among Adolescents With Intellectual Disabilities: Co-Development of Technology Interventions to Enhance Physical Activity
Physical Activity, Intellectual Disabilities
RecruitingObservational study
Clinical and Basic Investigations Into Known and Suspected Congenital Disorders of Glycosylation
Congenital Disorders of Glycosylation
RecruitingObservational study
Genome Medical Sequencing for Gene Discovery
Intellectual Disabilities, Congenital Anomaly
RecruitingObservational study
Adrenal Diseases in the Population of Modena: A Clinical-Epidemiological Database of Patients Referred to the Adrenal Disorders Outpatient Clinic of the Clinical Unit of Endocrinology at the Modena University Hospital (AOU Modena)
Cushing s Syndrome, Cushing Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daryl Efron study director
Murdoch Childrens Research Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cannabidiol Oil in people with Intellectual Disability and Child Behavior Problem, run by Murdoch Childrens Research Institute at 3 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean difference between the cannabidiol 100mg/ml and placebo arms on the Aberrant Behavior Checklist-Irritability (ABC-I) subscale total score at day 64 (time frame: At day 64 (end of maintenance treatment period)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04821856, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2025.