Mental IllnessIMAGINENCT03601026
Genetic Counselling in the Prevention of Mental Health Consequences of Cannabis Use
A study testing Genetic counselling in people with Mental Illness and Schizophrenia, run by Nova Scotia Health Authority at 1 site in Canada.
Trial summary
Severe mental illness (SMI) refers to the most burdensome psychiatric conditions. The need to pre-empt the onset of SMI is pressing because once SMI develops, quality of life is poor and available treatments have limited efficacy. Read more about this study
- Who is it for?
- Ages 12 to 21 years
- Conditions the study is for
- Mental Illness, Schizophrenia, Bipolar Disorder
- What is being tested?
- Genetic counselling
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteCanada
- Study dates
- 1 Nov 2019to 1 Sep 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 12 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Enrolment in the Families Overcoming Risks and Building Opportunities for Well-being (FORBOW) study.
- Age between 12 and 21 years.
- Knowledge of English sufficient to benefit from the intervention.
- Capacity to provide informed consent at most recent FORBOW assessment.
- Provision of consent to be contacted about future studies at most recent FORBOW assessment.
Who cannot join
- A diagnosis of severe mental illness (psychotic disorder, bipolar disorder, severe/recurrent depression) at baseline
- Autism or intellectual disability of a degree that interferes with assessment (IQ < 70)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Nova Scotia Health Authority
Halifax, Nova Scotia, B3H 2E2
Rudolf Uher, MD PhD, uher@dal.ca
Jill Cumby, RN, jill.cumby@nshealth.ca
About this study
Official title: Interdisciplinary Approach to Maximize Adolescent Potential: Genetic Counselling Interventions to Reduce Negative Environmental Effects
Severe mental illness (SMI) refers to the most burdensome psychiatric conditions. The need to pre-empt the onset of SMI is pressing because once SMI develops, quality of life is poor and available treatments have limited efficacy. Most risk factors for SMI are either unchangeable (e.g., genetics) or difficult to alter (e.g., low socio-economic status). In contrast, cannabis use is one specific risk factor that could be avoided. Certain individuals are more vulnerable to the harmful effects of cannabis. Genetic factors can help us identify these high-risk individuals. One in three individuals are carriers of a higher-risk genetic variant, and cannabis users with this genotype are at up to 7-fold increased risk of developing schizophrenia. In our study, genetic counselling will be provided to participants by a board-certified genetic counsellor. During the genetic counselling session, participants will have the option to receive their genotype. Participants will be counselled regarding their individualized risk of developing and of not developing SMI based on family history, whether or not they choose to use cannabis, and genotype (if the participants accept the genetic test results). The investigators hypothesize that this intervention will reduce exposure to cannabis compared to the youth who are not offered the intervention.
Read the detailed description
Severe mental illness (SMI) refers to the most burdensome forms of psychiatric disorder, including schizophrenia, bipolar disorder, and severe depression. These illnesses typically emerge in adolescence or young adulthood and are associated with substantial impairment in functioning. A significant proportion (~30%) of individuals with SMI remain resistant to any form of available pharmacotherapy. The combination of early onset, poor response to treatment and persistent disability makes SMI the most problematic group of illnesses to individuals and society. The need for early interventions to pre-empt the onset of SMI is pressing because once SMI develops, quality of life is poor for patients and their families. There is substantial overlap in the genetic and environmental risk factors for individual forms of SMI, and predictors of SMI are not specific to any one disorder. It is therefore necessary to conceptualize SMI as transdiagnostic and include diagnoses of schizophrenia, bipolar disorder, and depression, rather than focusing on single illnesses when developing preventative interventions. Prevention of SMI is currently hindered by the inability to identify those at risk early enough to normalize their developmental trajectory. Recent advances in genomics and the understanding of important gene-environment interactions may help overcome this challenge and enable effective and targeted prevention of SMI. Cannabis exposure during critical periods of brain maturation is an avoidable environmental risk factor for SMI. A replicated gene-cannabis interaction shows that carriers of a common genetic variant (C alleles at rs2494732 in the AKT1 gene) are at up to 7-fold increased risk of developing psychosis if they use cannabis. Genetic counselling provides a powerful tool to communicate genetic information to youth in a way that empowers and enhances health. The present project involves the delivery of a genetic counselling intervention to inform youth of their personalized risk of developing SMI based on genotype, family history, and whether or not they choose to use cannabis. This project will be the first application of molecular genetic information and genetic counselling to prevent SMI.
Aim: To test if genetic counselling regarding personalized risk information based on a replicated gene-cannabis interaction reduces cannabis use in youth at high risk of developing severe mental illness.
Hypotheses:
- A genetic counselling intervention will be acceptable to youth at high familial risk of SMI.
- A genetic counselling intervention with personalized feedback of AKT1 genotype will reduce cannabis use among vulnerable youth.
- The effect of the intervention will be moderated by AKT1 genotype, with greater reduction of cannabis use among carriers of the sensitive C alleles.
Method: A cohort of over 450 youth (aged 3-29) has been enrolled as part of the Families Overcoming Risks and Building Opportunities for Well-being (FORBOW) study. The investigators have obtained biological samples for measurement of genetic variation and the investigators will obtain biological samples to measure cannabis exposure. The investigators will randomly select one in every two eligible youth (aged 12-21) to be offered genetic counselling during which the participants will be provided with personalized genetic information and they will be counselled regarding risk of developing SMI based on genotype, family history, and whether or not they choose to use cannabis. The investigators will follow the participants through the developmental period with the highest risk of cannabis use initiation and the investigators will assess cannabis use and psychopathology annually. The primary outcome will be abstinence from cannabis reported by participants in confidential interviews and confirmed by measurement of the primary metabolites of psychoactive Δ9-tetrahydrocannabinol in blood and urine samples.
Significance: This project will realize the first translational application of a gene-environment interaction to improve mental health and test an intervention with potential public health benefits.
- Conditions
- Mental Illness, Schizophrenia, Bipolar Disorder, Major Depressive Disorder, Cannabis Use, Psychosis
- Being tested
- Genetic counselling
- Keywords
- Severe mental illness, Developmental psychopathology, Trial-within-cohort, Genetic counselling, Cannabis use, Prevention
- Medical subject headings
- Mental Disorders, Schizophrenia, Bipolar Disorder, Depressive Disorder, Major, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genetic counsellingBehavioural
Participants will receive information on risk/protective factors and causes of mental illness. Participants are not required to receive numeric/genetic risk information. Participants who choose to receive genetic and/or numeric risk information will be counselled on their risk of NOT developing and of developing SMI based on their genetic test results and/or family history information they provide. Risk estimates will be derived by genetic counsellors, according to standard practice guidelines. Participants who receive genetic information will be counselled on the possible influence of cannabis use on risk of mental illness based on their genotype. Participants who choose to not receive genetic information will be counselled on the influence of cannabis on mental health.
| Study group | Role | What they receive |
|---|---|---|
| Genetic counselling | Experimental | Eligible participants who are randomized will be contacted and offered an invitation to attend the intervention. Genetic counselling will be provided to participants who accept the intervention as a single 1-2 hour session by a board-certified genetic counsellor. During the genetic counselling session, participants will have the option to receive their genotype at rs2494732. Participants will be counselled regarding their individualized risk of developing and of NOT developing SMI based on family history, whether or not they choose to use cannabis, and genotype (if they accept the genetic test results). Approximately 1 month after the intervention, participants will receive a follow-up interview. Receives: Behavioral: Genetic counselling |
| Control group | No intervention | Eligible participants who are not randomized to be offered the intervention will continue with their annual assessments as part of the parent study. These participants will receive the current standard of care (no intervention), and will not be offered or informed of the intervention. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Self-reported cannabis use
Self-reported cannabis use on a questionnaire.
Measured: 1 month
Secondary outcomes (2)
The proportion of participants who complete the intervention after receiving an offer to participate (intervention acceptability)
Acceptability will be established as the proportion of individuals accepting the offer of intervention.
Measured: Completion of study (2 years).
Presence of cannabinoids in urine
Urine will be screened for the presence/absence of cannabinoids.
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2018
- Study start1 Nov 2019
- Primary completion1 Sep 2026 (estimated)
- Study completion1 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mental IllnessStudies of the same condition, open and under way.
- More trials run by Nova Scotia Health AuthorityThe 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Trial-within-cohort
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nova Scotia Health Authority
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rudolf Uher, MD, PhD, Principal investigator, Nova Scotia Health Authority, Dalhousie University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03601026
- Sponsor's protocol ID
- IMGN18
- Acronym
- IMAGINE
- Status last verified
- May 2025
- First submitted
- 5 Jul 2018
- Last updated
- 14 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zwicker A, LeBlanc MA, Pavlova B, Alda M, Denovan-Wright EM, Uher R, Austin JC. Genetic counselling for the prevention of mental health consequences of cannabis use: A randomized controlled trial-within-cohort. Early Interv Psychiatry. 2021 Oct;15(5):1306-1314. doi: 10.1111/eip.13082. Epub 2020 Nov 26.
PubMed 33242924
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interdisciplinary Approach to Maximize Adolescent Potential: Genetic Counselling Interventions to Reduce Negative Environmental Effects
- ClinicalTrials.gov ID
- NCT03601026
- Acronym / sponsor ID
- IMAGINE / IMGN18
- Conditions
- Mental Illness, Schizophrenia, Bipolar Disorder, Major Depressive Disorder, Cannabis Use, Psychosis
- Keywords
- Severe mental illness, Developmental psychopathology, Trial-within-cohort, Genetic counselling, Cannabis use, Prevention
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Nova Scotia Health AuthorityUniversity, hospital or other
- Study start
- 1 Nov 2019 (actual)
- Primary completion
- 1 Sep 2026 (estimated)
- Study completion
- 1 Sep 2027 (estimated)
- First posted
- 26 Jul 2018 (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.
Severe mental illness (SMI) refers to the most burdensome psychiatric conditions. The need to pre-empt the onset of SMI is pressing because once SMI develops, quality of life is poor and available treatments have limited efficacy. Most risk factors for SMI are either unchangeable (e.g., genetics) or difficult to alter (e.g., low socio-economic status). In contrast, cannabis use is one specific risk factor that could be avoided. Certain individuals are more vulnerable to the harmful effects of cannabis. Genetic factors can help us identify these high-risk individuals. One in three individuals are carriers of a higher-risk genetic variant, and cannabis users with this genotype are at up to 7-fold increased risk of developing schizophrenia. In our study, genetic counselling will be provided to participants by a board-certified genetic counsellor. During the genetic counselling session, participants will have the option to receive their genotype. Participants will be counselled regarding their individualized risk of developing and of not developing SMI based on family history, whether or not they choose to use cannabis, and genotype (if the participants accept the genetic test results). The investigators hypothesize that this intervention will reduce exposure to cannabis compared to the youth who are not offered the intervention.
Detailed description
Severe mental illness (SMI) refers to the most burdensome forms of psychiatric disorder, including schizophrenia, bipolar disorder, and severe depression. These illnesses typically emerge in adolescence or young adulthood and are associated with substantial impairment in functioning. A significant proportion (~30%) of individuals with SMI remain resistant to any form of available pharmacotherapy. The combination of early onset, poor response to treatment and persistent disability makes SMI the most problematic group of illnesses to individuals and society. The need for early interventions to pre-empt the onset of SMI is pressing because once SMI develops, quality of life is poor for patients and their families. There is substantial overlap in the genetic and environmental risk factors for individual forms of SMI, and predictors of SMI are not specific to any one disorder. It is therefore necessary to conceptualize SMI as transdiagnostic and include diagnoses of schizophrenia, bipolar disorder, and depression, rather than focusing on single illnesses when developing preventative interventions. Prevention of SMI is currently hindered by the inability to identify those at risk early enough to normalize their developmental trajectory. Recent advances in genomics and the understanding of important gene-environment interactions may help overcome this challenge and enable effective and targeted prevention of SMI. Cannabis exposure during critical periods of brain maturation is an avoidable environmental risk factor for SMI. A replicated gene-cannabis interaction shows that carriers of a common genetic variant (C alleles at rs2494732 in the AKT1 gene) are at up to 7-fold increased risk of developing psychosis if they use cannabis. Genetic counselling provides a powerful tool to communicate genetic information to youth in a way that empowers and enhances health. The present project involves the delivery of a genetic counselling intervention to inform youth of their personalized risk of developing SMI based on genotype, family history, and whether or not they choose to use cannabis. This project will be the first application of molecular genetic information and genetic counselling to prevent SMI.
Aim: To test if genetic counselling regarding personalized risk information based on a replicated gene-cannabis interaction reduces cannabis use in youth at high risk of developing severe mental illness.
Hypotheses:
- A genetic counselling intervention will be acceptable to youth at high familial risk of SMI.
- A genetic counselling intervention with personalized feedback of AKT1 genotype will reduce cannabis use among vulnerable youth.
- The effect of the intervention will be moderated by AKT1 genotype, with greater reduction of cannabis use among carriers of the sensitive C alleles.
Method: A cohort of over 450 youth (aged 3-29) has been enrolled as part of the Families Overcoming Risks and Building Opportunities for Well-being (FORBOW) study. The investigators have obtained biological samples for measurement of genetic variation and the investigators will obtain biological samples to measure cannabis exposure. The investigators will randomly select one in every two eligible youth (aged 12-21) to be offered genetic counselling during which the participants will be provided with personalized genetic information and they will be counselled regarding risk of developing SMI based on genotype, family history, and whether or not they choose to use cannabis. The investigators will follow the participants through the developmental period with the highest risk of cannabis use initiation and the investigators will assess cannabis use and psychopathology annually. The primary outcome will be abstinence from cannabis reported by participants in confidential interviews and confirmed by measurement of the primary metabolites of psychoactive Δ9-tetrahydrocannabinol in blood and urine samples.
Significance: This project will realize the first translational application of a gene-environment interaction to improve mental health and test an intervention with potential public health benefits.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Trial-within-cohort
| Arm | Type | Receives |
|---|---|---|
| Genetic counselling | Experimental | Behavioral: Genetic counsellingEligible participants who are randomized will be contacted and offered an invitation to attend the intervention. Genetic counselling will be provided to participants who accept the intervention as a single 1-2 hour session by a board-certified genetic counsellor. During the genetic counselling session, participants will have the option to receive their genotype at rs2494732. Participants will be counselled regarding their individualized risk of developing and of NOT developing SMI based on family history, whether or not they choose to use cannabis, and genotype (if they accept the genetic test results). Approximately 1 month after the intervention, participants will receive a follow-up interview. |
| Control group | No intervention | –Eligible participants who are not randomized to be offered the intervention will continue with their annual assessments as part of the parent study. These participants will receive the current standard of care (no intervention), and will not be offered or informed of the intervention. |
Who may qualify
- Ages
- 12 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Enrolment in the Families Overcoming Risks and Building Opportunities for Well-being (FORBOW) study.
- Age between 12 and 21 years.
- Knowledge of English sufficient to benefit from the intervention.
- Capacity to provide informed consent at most recent FORBOW assessment.
- Provision of consent to be contacted about future studies at most recent FORBOW assessment.
Key exclusion criteria (2 listed)
- A diagnosis of severe mental illness (psychotic disorder, bipolar disorder, severe/recurrent depression) at baseline
- Autism or intellectual disability of a degree that interferes with assessment (IQ < 70)
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 |
|---|---|---|
| Genetic counsellingParticipants will receive information on risk/protective factors and causes of mental illness. Participants are not required to receive numeric/genetic risk information. Participants who choose to receive genetic and/or numeric risk information will be counselled on their risk of NOT developing and of developing SMI based on their genetic test results and/or family history information they provide. Risk estimates will be derived by genetic counsellors, according to standard practice guidelines. Participants who receive genetic information will be counselled on the possible influence of cannabis use on risk of mental illness based on their genotype. Participants who choose to not receive genetic information will be counselled on the influence of cannabis on mental health. | Behavioural | Genetic counselling |
Primary outcome
Self-reported cannabis use
Time frame: 1 month
Self-reported cannabis use on a questionnaire.
2 secondary outcomes
The proportion of participants who complete the intervention after receiving an offer to participate (intervention acceptability)
Time frame: Completion of study (2 years).
Presence of cannabinoids in urine
Time frame: 1 month
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2025.
- Derived from this study: PubMed 33242924Zwicker A, LeBlanc MA, Pavlova B, Alda M, Denovan-Wright EM, Uher R, Austin JC. Genetic counselling for the prevention of mental health consequences of cannabis use: A randomized controlled trial-within-cohort. Early Interv Psychiatry. 2021 Oct;15(5):1306-1314. doi: 10.1111/eip.13082. Epub 2020 Nov 26.
- FORBOW study website.Link provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Mental Illness
Not yet recruiting
Effect of Stress Ball Use During Femoral Arterial Sheath Removal After Coronary Angiography
Femoral Arterial Sheath Removal, Stress Ball
RecruitingPhase 2
Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin
Alzheimer's Disease
Enrolling by invitationPhase 3
An Open-Label Study to Assess the Long-Term Safety of Solriamfetol in Children and Adolescents With ADHD
ADHD
Recruiting
Unified Protocol in Penitentiary Facilities
Depression Disorders, Anxiety
Recruiting
Safety and Performance of UCon Patch Electrode
Urinary Incontinence, Urinary Incontinence, Urge
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.
Rudolf Uher, MD, PhD principal investigator
Nova Scotia Health Authority, Dalhousie University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Genetic counselling in people with Mental Illness and Schizophrenia, run by Nova Scotia Health Authority at 1 site in Canada.
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 5 inclusion and 2 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: looking for participants now, as of the sponsor's last update on 14 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rudolf Uher, MD, PhD (902-473-7209, uher@dal.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Self-reported cannabis use (time frame: 1 month). 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 NCT03601026, which also lists 1 linked publication.
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 14 May 2025.