Please note the ANZCTR will be unattended from Friday 24 December 2021 for the holidays. The Registry will re-open on Monday 17 January 2022. Submissions and updates will not be processed during that time.

For new and updated trial submissions, we are processing trials as quickly as possible and appreciate your patience. We recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12616001001482p
Ethics application status
Not yet submitted
Date submitted
25/07/2016
Date registered
28/07/2016
Date last updated
28/07/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Cannabidiol (CBD) for Cannabis and Mood Disorders in Adolescence (CCAMDA)
Scientific title
Cannabidiol (CBD) for Cannabis and Mood Disorders in Adolescence (CCAMDA)
Secondary ID [1] 289754 0
Nil
Universal Trial Number (UTN)
Trial acronym
CCAMDA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mood disorders 299605 0
Cannabis use 299606 0
Condition category
Condition code
Mental Health 299572 299572 0 0
Depression
Mental Health 299573 299573 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a double blind placebo controlled RCT consisting of two groups. An intervention and a control group.
The intervention group will receive 800mg of CBD will be administered in 100mg capsules. Participants will be required to take 400mg (i.e. 4 capsules) of CBD twice a day (morning and night) approximately 12 hours apart for a 12 week treatment period. The active ingredient is fully synthetic (99.6% Cannabidiol powder dissolved in corn oil encapsulated in gelatine). It is the equivalent isomer of naturally occurring Cannabidiol. The active ingredient is produced at BioSynthesis Pharma Group FDA and MHRA approved facility in the UK.
The matching placebo will be administered in capsules with same appearance and taste and participants will be required to take of the same number of capsules twice daily as participants in the active arm.
All medications received and dispensed as part of this trial will be inventoried and accounted for throughout the trial on the Investigation Agent Accountability Record (study medication log) by the clinical trials pharmacists. The medication will be dispensed weekly for the first month, and then monthly after that. Patient compliance will be assessed through pill counts when participants return to receive their next lot of medication, as well as through self-report measures and the level of CBD in blood and urine from samples collected at baseline, week 2, week 6 and week 12. At the completion of each participant’s treatment period, any unused medications will be returned to the trial pharmacist, documented, and then subsequently destroyed.
All participants will be provided with five 50 minute sessions of cognitive behavioural therapy (CBT), which are offered as part of the study by a trial therapist in the form of cognitive behavioural case management (CBCM), during the 12-week intervention period (approximately fortnightly). Depending on the participant’s needs, additional sessions may be provided. After the 12 week intervention period (or if any participant meets exit or withdrawal criteria), treatment as usual will be provided by Headspace clinicians. For the purposes of the study analyses, ‘entry’ will be considered to be the date the participant commences the study medication.
Participants will also be directed to the ‘Reduce your use’ website as an adjunct to treatment, which contains six core modules, informed by the principles of cognitive behavioural therapy and motivational enhancement therapy. These are: 1) Feedback and Building Motivation; 2) Managing Smoking Urges and Withdrawal; 3) Changing Your Thinking; 4) Coping Strategies and Skill Enhancement; 5) Activities and Interpersonal Skills; and 6) Relapse Prevention and Lifestyle Changes.
Intervention code [1] 295402 0
Treatment: Drugs
Intervention code [2] 295435 0
Behaviour
Intervention code [3] 295436 0
Treatment: Other
Comparator / control treatment
The matching placebo will be administered in capsules with the same appearance and taste as active participants (400 mg of glucose i.e. 4 capsules twice a day (800mg in total) approximately 12 hours apart for a 12 week treatment period) will be required to take of the same number of capsules twice daily as participants in the active arm.
Control participants will be treated exactly as active participants and will also receive CBCM and reduce your use.
Control group
Placebo

Outcomes
Primary outcome [1] 299049 0
Depressive symptoms from baseline to 12 weeks, assessed with the Quick Inventory of Depression Symptomology, Adolescent Version (QIDS-A17-C). The QIDS-A17-C has been shown to be a reliable tool for assessing adolescent depression.
Timepoint [1] 299049 0
baseline to 12 weeks
Primary outcome [2] 299050 0
Self-reported measures of cannabis use (quantity and frequency) with total days cannabis used (levels of cannabis use, and cannabis related problems at follow up). Cannabis use will be assessed at baseline (cannabis use during preceding 30 days) and at each month during treatment and at follow-up (6 months). The Timeline Followback Method (TLFB) will be used.
Self-reported cannabis use will be corroborated with serial urinalysis of carboxy-CBD: creatinine ratio using Gas Chromatography/Mass Spectrometry (GC/MS) at baseline and each follow-up point.
Timepoint [2] 299050 0
Monthly for 3 months and then at 6 month follow-up
Primary outcome [3] 299051 0
Treatment completion, defined as completing 12 weeks of treatment with CBD under protocol conditions.
This outcome is assessed by whether or not the patient has finished the full 12 week treatment period. Any exit before this time will be considered as incomplete treatment.
Timepoint [3] 299051 0
12 week end of treatment
Secondary outcome [1] 326008 0
At treatment entry, urine profiles of cannabinoid metabolites (THC and its primary metabolite (THC-COOH) and CBD and its primary metabolite (CBD-7-oic acid)) from prior illicit cannabis use (measured at baseline) will be collected. The same measures will be repeated after CBD has been administered to participants (taken on week 1, 2, 6 and 12).
Timepoint [1] 326008 0
Weeks 1, 2, 6 and 12
Secondary outcome [2] 326009 0
To determine whether there is evidence of an interaction with the efficacy of CBD and mental health outcomes at end of treatment. This is a composite secondary outcome which will be assessed through;; CPQ, Kessler Psychological Distress Scale, Self-Efficacy for Quitting Cannabis Questionnaire, Overall Anxiety Severity and Impairment Scale, Generalised Anxiety Disorder Assessment, Alcohol Smoking and Substance Involvement Screening Test, Dietary Questionnaire for Epidemiological Studies (Version 2), Altman self-report mania screen, Structural Clinical Interview for Diagnostic and Statistical Manual of Mental disorders, Fifth Edition (DSM-V) Axis I Disorders, patient version, Montgomery-Asberg Depression Rating Scale, Columbia Suicide Severity Rating Scale (C-SSRS; baseline and since last visit), Comprehensive Assessment of At-Risk Mental State (CAARMS), Young Mania Rating Scale, Social and Occupational Functioning Scale, Clinical Global Impressions Scale.
Timepoint [2] 326009 0
12 week end of treatment
Secondary outcome [3] 326049 0
Adverse events during the treatment period. This will be assessed by a self-report Adverse Events Checklist administered by a clinician during assessment.
An adverse event is any untoward event that may inconvenience a study participant, staff member or other individual. The event may or may not be related to the treatment received within the framework of the study. This includes the onset of new illnesses and the exacerbation of pre-existing conditions. Additionally, any event that is associated with or observed in conjunction with a product overdose (whether accidental or intentional) or a product abuse and/or withdrawal is also considered an adverse event.
Timepoint [3] 326049 0
12 week end of treatment

Eligibility
Key inclusion criteria
1. At least 16 years of age & less than 26 years of age at presentation.
2. Male
3. Cannabis use on average 3 days per week (over last 30 days)
4. Help seeking for psychological distress
5. Moderate to severe depression, indicated by a score between 11 and 20 on the QIDS-A17-C64 at first contact with the service, and again after approximately 1 week
6. A diagnosis of a mood disorder with or without psychotic features at baseline using a structured clinical interview
7. Fluency in English
8. Ability to give informed consent (for individuals under 18, written informed consent of at least one parent or guardian is required.)
9. Agree to participate in all scans and tests
10. Prepared to take trial medications as requested
11. Agreement to be available for follow-up interview at 6 months
Minimum age
16 Years
Maximum age
26 Years
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. More than weekly use of an illicit drug in the last 30 days (other than cannabis)
2. Female
3. Dependence on a substance other than cannabis and tobacco
4. Specialist substance use treatment in the last 30 days;
5. Acute suicidal behaviour or aggressive behaviour (indicated by a CAARMS49 score of 6 on relevant items)
6. Evidence of severe medical (including chronic pain, severe hepatic and or renal impairment or cardiovascular disease).
7. People with current prescriptions (within past month) for antipsychotic, mood stabilising medications (e.g. Lithium) or antidepressants.
8. Known or suspected allergy to cannabinoids, propylene glycol, ethanol or peppermint oil;
9. Males who are planning on trying for a baby in the following 3 months.

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 to treatment will be concealed and carried out by a senior researcher uninvolved with the conduct of the intervention or participant assessment. Participants will be randomized to one of two possible treatment groups. The participants, treating clinicians, and research personnel (including research assistants, investigators and project manager) will remain blinded to treatment allocation until database lock.
The Headspace access team will assist in identifying potential participants. Individuals will be assessed for eligibility at initial contact with Headspace by a clinician as part of routine clinical assessment. Once a participant is randomized, their treatment group allocation will be sent by the senior researcher via a previously prepared email to the trial pharmacist. Access to un-blinding will be available through the senior researcher and available and validated for emergency situations.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised 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
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Primary analyses will be undertaken on an intention to treat basis, including all participants as randomized, regardless of treatment actually received. Effectiveness of CBD will be established using a planned contrast of change from baseline to week 12 end point in the active compared with placebo condition on the QIDS-A17-C within a mixed model repeated measure analysis. Stratification variables will be evaluated and retained in analyses where they are significant or quasi significant. Other relevant covariates may be included in the model to adjust for baseline and subsequent group differences. An unconstrained variance-covariance matrix will model within individual dependencies. Transformation of scores, including categorization, may be undertaken in order to meet distributional assumptions and accommodate outliers. Contrasts comparing change on the QIDS-A17-C from baseline to other time points will be undertaken as secondary analysis. Should the number of participants meeting exit/transition criteria be non-eligible (defined as greater than 5% in either treatment arm), transition rates and time to transition will be considered as secondary outcome and be subject to analysis using survival methods. Under these circumstances, analyses of continuous measures that treat exit as a competing outcome will be explored.
Because this is a small Phase II drug trial, a small sample is needed in order to replicate the initial efficacy of the drug and confirm the absence of adverse drug effects. This study will then form the basis of a further large scale RCT study into the efficacy of CBD for the management of mood disorders in cannabis smokers.
Models for binary outcomes analogous to the primary analysis approach will be used to compare the remission rates (MDD status) and other dichotomous outcomes between the two treatment arms at endpoint and other occasions of measurement. Safety data will be compared between treatment arms – in particular the rates of harm and suicide related adverse events – using Fisher’s exact test. All tests will be conducted using a two sided alpha level of 0.05 and 95% confidence intervals.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 294138 0
Government body
Name [1] 294138 0
National Cannabis Prevention and Information Centre
Address [1] 294138 0
22-32 King Street Randwick NSW 2031
Country [1] 294138 0
Australia
Primary sponsor type
University
Name
University of New South Wales
Address
22-32 King Street Randwick NSW 2031
Country
Australia
Secondary sponsor category [1] 292967 0
None
Name [1] 292967 0
Address [1] 292967 0
Country [1] 292967 0
Other collaborator category [1] 279097 0
University
Name [1] 279097 0
Brain and Mind Centre, University of Sydney
Address [1] 279097 0
94 Mallett St, Camperdown NSW 2050
Country [1] 279097 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 295550 0
UNSW Australia Human Research Ethics Advisory Panel
Ethics committee address [1] 295550 0
UNSW, Sydney, NSW, 2052,
Ethics committee country [1] 295550 0
Australia
Date submitted for ethics approval [1] 295550 0
28/07/2016
Approval date [1] 295550 0
Ethics approval number [1] 295550 0

Summary
Brief summary
The primary objectives of the study is to examine the safety and efficacy of cannabidiol (CBD) in the management of mood disorders in adolescent/young adult males with concurrent cannabis use, in a randomized controlled study. Specifically, the study will assess the impact of CBD on mood treatment outcomes and retention rates, the quantity and frequency of cannabis use, and the impact of CBD on patient mental health outcomes and well-being. The study will also explore the cognitive and neurobiological markers associated with CBD response.
Current treatments for anxiety and depression are of limited efficacy in a considerable proportion of patients (30% of depressed patients are pharmacoresistant) and are associated with troublesome side effects that reduce compliance; the development of novel, improved therapeutic treatments would fill a considerable unmet medical need. CBD has emerged as one of the most promising candidates in treating psychiatric disorders. Research suggests that greater rates of mental health problems in cannabis users are related to increased use of high THC/low CBD varieties of cannabis. In various animal and human laboratory and clinical studies, CBD has been found to reduce the intoxicating and psychotomimetic effects of THC, while CBD given alone has also been found to relieve anxiety and nausea and to have anti-inflammatory and antipsychotic effects.

All young males presenting to participating headspace centres will be screened for eligibility. Twenty participants will be recruited over a period of 6 months. Participants will complete an initial assessment with headspace staff as per normal clinical practice. Eligible participants will be contacted to attend a baseline assessment and consent at the Brain and Mind Centre. Participants will undergo a clinical assessment, provide blood and urine samples, and undergo an MRI. They will be randomized into either a CBD or placebo treatment group for a period of 12 weeks, with a 6 month follow-up. All participants will receive at least cognitive behavioural case management (CBCM) which includes 5 sessions of CBT with a therapist during the 12 week study period. More sessions are available if requested by the participant. All participants will also have access to and be encouraged to use reduce which is an automated website based on Cognitive Behavioural Therapy (CBT) and Motivational Interviewing (MI) principles that teach cannabis users the skills and techniques to assist them to cut back or cease their cannabis intake. Built into the program are additional skill building resources and quick assist links that allow participants to access additional information quickly.your use, both based on cognitive behavioural therapy (CBT) and motivational interviewing (MI). Participants will be assessed on symptoms of their mood disorders, retention in treatment and their cannabis use.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 67682 0
Prof Jan Copeland
Address 67682 0
UNSW NCPIC 22-32 King Street Randwick NSW 2031
Country 67682 0
Australia
Phone 67682 0
+61 2 93850231
Fax 67682 0
Email 67682 0
j.copeland@unsw.edu.au
Contact person for public queries
Name 67683 0
Ms Izabella Pokorski
Address 67683 0
UNSW NCPIC 22-32 King Street Randwick NSW 2031
Country 67683 0
Australia
Phone 67683 0
+61 2 89361139
Fax 67683 0
Email 67683 0
i.pokorski@unsw.edu.au
Contact person for scientific queries
Name 67684 0
Ms Izabella Pokorski
Address 67684 0
UNSW NCPIC 22-32 King Street Randwick NSW 2031
Country 67684 0
Australia
Phone 67684 0
+61 2 89361139
Fax 67684 0
Email 67684 0
i.pokorski@unsw.edu.au

No information has been provided regarding IPD availability
Summary results
No Results