Genetic Counseling for Mental Health Risks Associated with Cannabis Use

(IMAGINE Trial)

Overseen By Rudolf Uher, MD, PhD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Nova Scotia Health Authority

Disqualifiers: Psychotic disorder, Bipolar, Severe depression, Autism, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

Is genetic counseling safe for humans?

Genetic counseling is generally considered safe for humans as it involves discussing genetic risks and providing support without any physical interventions. ^{1 2 3 4 5}

How is genetic counseling for mental health risks associated with cannabis use different from other treatments?

Genetic counseling for mental health risks associated with cannabis use is unique because it focuses on understanding the genetic and environmental factors that contribute to mental health issues, helping individuals explore their beliefs and fears, and providing support for decision-making, rather than prescribing medication or other traditional therapies. ^{1 2 3 6 7}

What data supports the effectiveness of genetic counseling as a treatment for mental health risks associated with cannabis use?

Research suggests that genetic counseling can help people with mental health conditions by reducing fear, stigma, and misconceptions about their illness, and improving their adherence to treatment. This approach has shown benefits in psychiatric disorders like schizophrenia and depression, which may indicate its potential usefulness for mental health risks related to cannabis use. ^{1 2 6 7 8}

Who Is on the Research Team?

Rudolf Uher, MD

Principal Investigator

Nova Scotia Health Authority, Dalhousie University

Are You a Good Fit for This Trial?

This trial is for English-speaking individuals aged 12-21 who are part of the FORBOW study, can consent to future contact, and have the capacity to give informed consent. It excludes those with severe mental illness, autism, or intellectual disability (IQ < 70).

Inclusion Criteria

Knowledge of English sufficient to benefit from the intervention.

I was able to understand and agree to the study's requirements recently.

Enrolment in the Families Overcoming Risks and Building Opportunities for Well-being (FORBOW) study.

Exclusion Criteria

Your intellectual disability is severe enough that it affects your ability to be assessed (IQ score below 70).

I have been diagnosed with a severe mental illness.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Genetic Counselling Intervention

Participants receive genetic counselling regarding their personalized risk of developing SMI based on genotype, family history, and cannabis use. They have the option to receive their genotype.

1-2 hours

1 visit (in-person)

Follow-up

Participants are monitored for changes in cannabis use and psychopathology, with assessments conducted annually.

2 years

Annual assessments

Post-Intervention Follow-up

Approximately 1 month after the intervention, participants receive a follow-up interview to assess cannabis use and intervention impact.

1 month

1 follow-up interview

What Are the Treatments Tested in This Trial?

Interventions

• Genetic counselling

Trial Overview The trial tests if genetic counselling can help young people understand their personal risk of developing severe mental illness due to cannabis use. Participants may learn about their own genetic predisposition towards such risks.

How Is the Trial Designed?

Group I: Genetic counselling Experimental Treatment 1 Intervention

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.

Group II: Control group Active Control 1 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 Is Running the Clinical Trial?

Nova Scotia Health Authority

Lead Sponsor

Trials

302

Recruited

95,300+

Published Research Related to This Trial

Psychiatric genetic counseling can empower individuals with psychiatric disorders and their families by providing valuable insights into the genetic factors influencing these conditions, despite the lack of clinical guidelines for genetic testing in this area.

Currently, psychiatric genetic counseling is not widely available, highlighting a significant gap in mental health care that could improve patient outcomes and understanding of psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence-Based Genetic Counseling for Psychiatric Disorders: A Road Map. Austin, JC.[2022]

Genetic counseling, while commonly offered for genetic disorders, is not yet standard for individuals with serious mental illnesses, but it could help reduce stigma and fear associated with these conditions.

A multidisciplinary approach involving both psychiatrists and genetic counselors may enhance the effectiveness of genetic counseling, leading to better understanding and management of mental illnesses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The genomic era and serious mental illness: a potential application for psychiatric genetic counseling. Austin, JC., Honer, WG.[2007]

Genetic counselling for psychiatric disorders, such as affective disorders and schizophrenia, relies on empirical risk figures, while molecular genetic methods can be applied to conditions like Huntington's disease and Alzheimer's, highlighting the varying levels of genetic understanding across these disorders.

The review emphasizes the importance of addressing presymptomatic testing challenges and the teratogenic risks associated with psychopharmacological treatments during pregnancy, which are critical considerations in genetic counselling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Genetic counseling in psychiatric diseases]. Körner, J., Rietschel, M., Nöthen, MM., et al.[2006]

Genetic counselling is essential for individuals at risk of hereditary disorders, as it provides crucial information about the disorder's implications, risk of transmission, and potential preventive measures.

It is particularly important for asymptomatic individuals at risk for late-onset genetic disorders to receive counselling before undergoing predictive genetic testing, ensuring they understand the broader personal and familial consequences of their test results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Genetic counselling]. Rehder, H.[2019]

Genetic counselling plays a crucial role in helping individuals with psychiatric illnesses, such as schizophrenia, by providing information on inheritance patterns and recurrence risks, which can alleviate concerns for patients and their families.

The review highlights the importance of making genetic counselling accessible to all individuals with schizophrenia, as new genetic findings can significantly impact clinical management and support for patients and their families.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic counselling for schizophrenia in the era of molecular genetics. Hodgkinson, KA., Murphy, J., O'Neill, S., et al.[2020]

In a study of 766 patients at increased risk of hereditary cancer, the General Health Questionnaire (GHQ-28) effectively identified psychiatric morbidity, with 27.9% of participants showing signs of psychological distress.

Key predictors of psychiatric morbidity included being female, aged 41-59, having a personal or family history of cancer, and not having received previous psychiatric treatment, highlighting the importance of considering these factors in mental health screenings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychiatric symptoms in a Spanish sample with hereditary cancer risk. Costa-Requena, G., Garcia-Garijo, M., Richart-Aznar, P., et al.[2022]

Genetic factors play a significant role in the vulnerability to psychiatric illnesses, with evidence supporting gene-environment interactions particularly in schizophrenia and affective disorders, as shown through family, twin, and adoption studies.

Genetic counseling can provide empirical risk estimates for individuals based on family history, but it requires a collaborative approach among psychiatrists, geneticists, and social workers to ensure accurate diagnosis and understanding of the information provided.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic counselling: its need in psychiatry and the directions it gives for future research. Stancer, HC., Wagener, DK.[2019]

Genetic counseling for psychiatric disorders is complex due to the interplay of genetic and environmental factors, and current risk assessments primarily rely on medical history rather than genetic testing.

Emerging tools like polygenic risk scores may enhance the ability to assess and communicate risks for conditions such as schizophrenia, offering new opportunities for diagnosis and management in genetic counseling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic Risk Assessment in Psychiatry. Peay, HL.[2022]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Evidence-Based Genetic Counseling for Psychiatric Disorders: A Road Map. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

The genomic era and serious mental illness: a potential application for psychiatric genetic counseling. [2007]

3. Germany pubmed.ncbi.nlm.nih.gov

[Genetic counseling in psychiatric diseases]. [2006]

4. Austria pubmed.ncbi.nlm.nih.gov

[Genetic counselling]. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Genetic counselling for schizophrenia in the era of molecular genetics. [2020]

6. Germany pubmed.ncbi.nlm.nih.gov

Psychiatric symptoms in a Spanish sample with hereditary cancer risk. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Genetic counselling: its need in psychiatry and the directions it gives for future research. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Genetic Risk Assessment in Psychiatry. [2022]