E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
'Moderate cannabis use disorder' as defined by the diagnostic criteria in DSM-5 (published in May 2013), similar to the previous term 'cannabis dependence' (DSM-4). |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007177 |
E.1.2 | Term | Cannabis dependence |
E.1.2 | System Organ Class | 100000004873 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
What is the most effective dose of cannabidiol for reducing cannabis use, and is this dose effective as a treatment for cannabis dependence? |
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E.2.2 | Secondary objectives of the trial |
Does cannabidiol improve cognitive function (e.g. memory), psychological wellbeing, and quality of life in depedendent cannabis users? Are these effects maintained up to 12 weeks after treatment ends and are they associated with biological changes that have been linked to heavy cannabis use? |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Age: between 16 and 26 years old 2.Gender: all 3.All will meet DSM-5 criteria for moderate cannabis use disorder (≥4 DSM-5 criteria). DSM refers to the Diagnostic and Statistical Manual for Mental Disorders, widely used to diagnose mental illness in psychiatry. Please note that the diagnostic criteria of 'cannabis dependence' in the previous edition (DSM-4) was replaced with 'cannabis use disorder' (DSM-5) in May 2013. 4.Express a desire to quit using cannabis within the next four weeks and report ≥1 previous failed quit attempt 5.Smoke tobacco with cannabis 6.Provide a urine sample positive for cannabis (qualitative urine screen) 7.Vital signs within healthy limits (blood pressure, heart rate, respiratory peak flow) 8.Capacity to give informed consent as defined by GCP guidelines 9.Females of childbearing potential and males must be willing to use an effective method of contraception including oral, injected or implanted hormonal methods of contraception; placement of an IUS (intrauterine system) or IUD (intrauterine device); barrier method of contraception (condom or occlusive cap with spermicidal foam/gel/film/cream/suppository; male sterilization); true abstinence of birth control; abstinence from the time consent is signed until 6 weeks after treatment discontinuation 10.Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for trial treatment. |
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E.4 | Principal exclusion criteria |
1.Females who are pregnant or breastfeeding 2.Allergies to IMP or placebo and its excipients 3.>twice/month use of other illicit drugs 4.Current prescribed psychotropic use 5.Outside normal Body Mass Index (<16 or >30) 6.Any physical health problem as deemed clinically significant by the investigator team 7.Non English speakers (because of verbal test assessments) |
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E.5 End points |
E.5.1 | Primary end point(s) |
For stage 1: Levels of cannabis use, as indexed by self report (number of days abstinent according to Time Line Follow Back interview) and objective assessment of cannabis use in urine (THC-COOH, corrected for creatinine) For state 2: Cannabis dependence as indexed by diagnosis using a DSM-5 questionnaire (less then 4 DSM-5 cannabis use disorder) criteria and cessation of cannabis use as evidenced by urinary THCCOOH (corrected for creatinine) below 50ng/ml. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepoints of evaluation will be made at week 4 (end of treatment)and at week 12. |
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E.5.2 | Secondary end point(s) |
The secondary endpoints are to determine whether MEDmg cannabidiol can significantly (a) reduce the number of participants meeting a cut-off of less than 4 days/week cannabis use (e.g. weekend only use); (b) alleviate withdrawal symptoms on the Cannabis Withdrawal Scale (total score) to baseline levels of withdrawal at study entry; (c) reduce adverse effects of cannabis use including cognition, psychological well-being, quality of life and nicotine dependence. Furthermore, we aim to investigate whether the efficacy of cannabidiol is maintained up to 12 weeks after treatment, and whether it is associated with changes in the endocannabinoid system (anandamide and 2-AG in plasma). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoints of evaluation will be made at week 4 (end of treatment)and at all follow up weeks (6,8,12,16,20 & 24) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 1 |