Cannabidiol as an Add-on Treatment to substance abuse in juvenile patients with PSYchosis: a double-blind randomized placebo-controlled study.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Behavioral Disciplines and Activities [F04], Psychiatry and Psychology [F] - Behavior and Behavior Mechanisms [F01], Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

completed 6 Oct 2025

Decision date (initial)

2024-09-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

The primary objective is to demonstrate that CBD is a valid augmentation therapy to a long-acting/oral antipsychotic treatment in juvenile subjects who meet DSM-5 criteria for Cannabis Use Disorder and for Substance-Induced Psychotic Disorder in terms of: cannabis use relapse symptoms in CBD-group compared to placebo-group.
The incidence of cannabis abuse relapse symptoms will be assessed by a specific questionnaire, the Addiction Severity Index (ASI, no cut-off).
This scale will be administered to every enrolled subject by the same operator, every 28 days, for a total of 6 months, in order to favor a consistent approach. All the scores will be collected in a database and statistical analyses will be performed at the end of the treatment period. The score trend of the questionnaire will be analyzed for both the CBD-group and the placebo-group. Afterwards, we will perform a comparison of final scores between the two groups.

Secondary objectives 7

1. Assessing relapse symptoms with another scale, the Drug Abuse Screening Test (DAST, cut-off=1).
2. Assessing withdrawal symptoms with the Withdrawal Discomfort Score (AWDS, no cut-off: higher total scores reflect more severe withdrawal discomfort) and the Marijuana Withdrawal Symptom Checklist (MWSC, no cut-off: higher total scores reflect more severe withdrawal symptoms).
3. Assessing psychopathological symptoms with the Brief Psychiatric Rating Scale (BPRS, cut-off=18), the Hamilton Anxiety Scale (HAM-A, cut-off=18), the Beck Anxiety Inventory (BAI, cut-off=8), the Hamilton Rating Scale for Depression (HAM-D; cut-off=8), the Beck Depression Inventory (BDI, cut-off=11), the Beck Cognitive Insight Scale (BCIS, cut-off=5), the Insight Scale (IS,) and the Positive and Negative Syndrome Scale (PANSS, cut-off=50) in CBD group compared to placebo group.
4. Assessing the Efficacy Index of the treatment (risk/benefit) by the specific questionnaire Clinical Global Impression (CGI) in CBD-group compared to placebo-group.
5. Assessing the overall quality of life through specific questionnaires such as the Manchester Short Assessment of Quality of Life (MANSA), the Quality-of-Life Index (QL-index) and the Sheehan Disability Scale (SD) in CBD-group compared to placebo-group.
6. Assessing cognitive functions by specific tests such as the Brief assessment of cognition in Schizophrenia (BACS) in CBD-group compared to placebo-group. The BACS will be administered to every enrolled subject by the same operator at baseline and after 6 months.
7. Assessing social, occupational, and psychological functioning by specific scales such as the Short Form Health Survey (SF-36) and the Global Assessment of Functioning (GAF) in CBD-group compared to placebo-group.

Conditions and MedDRA coding

Substance-Induced Psychosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Signed informed consent by the subject or parent/legal guardian in case of a subject under the age of 18, indicating that the subject understands the purpose of and procedures required for the study before the initiation of any study specific procedures. Subjects who are unable to provide informed consent will not be included in the study.
2. Highly effective contraceptive measures under specific CTFG recommendations are required
3. Signed acknowledgment of responsibilities by an identified informant before the initiation of any activities required by the study for the designated informant.
4. Male or female subjects between the age of 15 and 25, inclusive.
5. Clinical diagnosis of Substance-Induced Psychosis according to DSM-5. This diagnosis can be established utilizing the SCID-I, direct clinical assessments, family, informants, and confirmation of diagnosis from clinical sources.
6. Clinical diagnosis of Cannabis Use Disorder according to DSM-5. This diagnosis can be established utilizing the SCID-I, direct clinical assessments, family, informants, and confirmation of diagnosis from clinical sources.
7. Heavy consumption at least in the previous six months before enrolment (presence of 6 or more symptoms of Cannabis Use Disorder DSM-5 Criteria).
8. Subjects must have been on treatment with oral aripiprazole for at least 2 weeks and a maximum duration of 6 months prior to enrolment to exclude the presence of side effects.
9. Onset of symptoms < 5 years.
10. Dosage of Beta-HCG in serum or urinary pregnancy test will be performed to every womaen of childbearing age before the treatment period and every 25+30 days to comply with the recommendations of the Clinical Trial Facilitation Group (CTFG) since CBD is potentially genotoxic. Also, since aripiprazole is potentially teratogenic, we acknowledge the importance of evaluating potential pregnancy through regular pregnancy tests and we will discuss with the patients regarding these theme (including evaluating with the patients’ planned pregnancy after the withdrawal of the drug etc). However, since all patients enrolled that present a good response to aripiprazole treatment in absence of relevant side effects, will continue with aripiprazole LAI after the end of this project and likely for a long time, all the good clinical practice actions required by the treatment with aripiprazole will be ensured even after the end of the trial. Regarding the pregnancy test, all the actions needed by the treatment with aripiprazole LAI will be performed even after the end of the study, since they represent good clinical practice.
11. Oral aripiprazole will then be switched to treatment with intramuscular injection of long-acting aripiprazole.

Exclusion criteria 12

1. Failure to perform screening or baseline examinations.
2. History of a hypersensitivity reaction to aripiprazole or cannabidiol (anaphylactic reaction, angioedema, laryngospasm, pruritus/urticaria, or oropharyngeal spasm).
3. History of hepatic impairment, renal impairment, cardiovascular disease such as history of myocardial infarction or ischemic heart disease, heart failure or conduction abnormalities, cerebrovascular disorder, conditions that may predispose to hypotension such as dehydration, hypovolemia and treatment with antihypertensive medicinal products or hypertension, including accelerated or malignancy, history of venous thromboembolism, prolongation of the QT interval, tardive dyskinesia, neuroleptic malignant syndrome (SNM), convulsions.
4. Any other Axis I psychiatric disorder according to DSM 5.
5. Any personality disorders according to DSM 5.
6. DSM 5 criteria for alcohol abuse.
7. History of traumatic head injury with loss of consciousness.
8. History of epilepsy or other neurological or medical diseases.
9. Mental retardation (assessed through the Wechsler Adult Intelligence Scale “WAIS”).
10. Previous hospitalization for psychiatric disorders.
11. Concomitant antipsychotic medication other than aripiprazole.
12. Subjects consume more than 2 unit of alcohol (each unit correspond to 12g of pure alcohol) per day.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. As primary endpoint, we expect a greater reduction of cannabis use relapse symptoms in the CBD-group compared to the placebo-group. Specifically, we expect a greater mean change on the ASI scores from baseline to follow-up (6 months) in the CBD group compared to the placebo group.

Secondary endpoints 2

1. We expect better scores, and therefore a reduction in clinical symptomatology and a better performance in cognitive tests, in the CBD-group compared to placebo-group in all the clinical and cognitive scales employed. Specifically, we expect a greater mean change on the above-mentioned scales scores from baseline to follow-up (6 months) in the CBD group compared to the placebo group.
2. Moreover, we expect to identify a more favorable brain connectivity and neuroplasticity profile the CBD-group vs placebo-group. Specifically, we expect a greater normalization of brain structural and functional alterations from baseline to follow-up (6 months) in the CBD group compared to the placebo group.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Sponsor organisation

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Address

Via Francesco Sforza 28

City

Milan

Postcode

20122

Country

Italy

Scientific contact point

Organisation

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Contact name

Paolo Brambilla

Public contact point

Organisation

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Contact name

Paolo Brambilla

Third parties 3

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Application history

1 submissions — initial application plus substantial / non-substantial modifications