Cannabis Potency Effects on Brain White Matter in Early Phase Psychosis

NCT07001878 | Not Yet Recruiting Phase 4

• 1 other identifier: 73219
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

Canada reports some of the highest rates of cannabis use in our youth and young adult populations, among all the developed countries. Recent Health Canada surveys report that 27% of 16-19-year-olds and 32% of 20-24-year-olds have used cannabis in the past 30 days, with 16-24-year-olds showing the highest rates of daily or near-daily use. Unfortunately, cannabis use has also been found to be a risk factor for the development of a psychotic disorder in emerging adults, and in those who develop psychosis and continue cannabis use, there is a significant effect on long term outcomes. This includes the severity of symptoms, risks of relapse (being hospitalized) and not reaching a level of functioning that would be expected. Lifetime experience with cannabis is greater than 80% in young adults with early phase psychosis (EPP; the first 5 years of a psychosis illness) with up to 30% of Canadian EPP patients meeting criteria for a diagnosis of cannabis use disorder (CUD) at entry to care. A recent Canadian population-based study found that cannabis use disorder associated to psychosis has risen from 3.7% pre-2018 to 10.3% at present. There has been a significant increase in Δ9-tetrahydrocannabinol (THC) levels in cannabis products available globally over the years, with popular cannabis products available start as high as 18% THC in Canada. However high potency cannabis carries a more significant risk for psychosis development, as well as higher risk for cannabis dependence and other severe mental health issues. A major gap in the research is a specific focus on cannabis potency on brain white matter (WM) in youth and young adults, and if there are any potential treatment strategies that could be used to influence any of these cannabis WM effects. To address this, a medication called metformin, that is already used in psychosis to help with side effects of antipsychotic medications, will be used as it has also shown promise to influence WM changes in other illnesses. This project is thus focused on naturalistic cannabis potency effects on WM in emerging adults in EPP (divided into three groups; those using high potency cannabis, low potency cannabis, and minimal cannabis use) and treating them with metformin for 6 months and assessing effects on neuroimaging, cognitive and clinical variables. The purpose of this pilot feasibility study is to inform the development/refinement of an intervention protocol, and not to test potential effects or mechanisms as the sample size will have insufficient power to perform an in-depth analysis. The results of this work will inform our research strategy development and assess feasibility of our novel methodological approach. Participants will:

1. 1.Visit the clinic at baseline, 3 months (only Timeline Follow-Back Assessment administered), and 6 months post baseline to complete substance use and mental health questionnaires, and cognitive assessments
2. 2.Complete an MRI scan at baseline and 6 months
3. 3.Take Metformin every day for 6 months

Conditions

Psychosis; Cannabis Use

Keywords

cannabis; metformin; early phase psychosis; potency

Outcome Measures

Primary Outcomes (5)

• Change in cannabis use

  Cannabis Timeline Followback (TLFB) is a retrospective past 30 day calendar method used to collect detailed information about current cannabis use, which includes quantity, method of use (e.g. dried cannabis smoked, concentrate vaped, edibles, etc.), frequency, strain, and potency (e.g., THC %, THC/CBD).

  Baseline, 3 months, 6 months

• Treatment adherence

  The difference between the number of participants who completed 6 months of Metformin treatment compared to those who ceased using medication prior to study end at 6 months.

  Baseline to 6 months

• Change in white matter microstructure

  Changes from baseline to study end at 6 months in study completers using Orientation dispersion index values from Neurite orientation dispersion and density imaging (NODDI).

  Baseline to 6 Months

• Change in glial cell marker

  Measurement of glial cell marker neurochemical in the dorsomedial prefrontal region of brain Myo-inositol level changes from baseline to study end at 6 months for study completers using Magnetic resonance spectroscopy (MRS).

  Baseline to 6 months

• Recruitment success

  The difference between the number of patients approached about the opportunity to participate and the total number of participants enrolled in the study for each study cohort.

  Baseline

Secondary Outcomes (8)

• Change in white matter to grey matter ratio

  Baseline to 6 months

• Change in inflammatory neurochemicals

  Baseline to 6 months

• Change in overall substance use

  Baseline to 6 months

• Changes in problematic cannabis use

  Baseline to 6 months

• Change in severity of illness

  Baseline to 6 months

Study Arms (1)

Metformin

EXPERIMENTAL

All participants will receive 6 months of daily Metformin treatment and attend baseline, 3 months, and 6 months post baseline appointments.

Drug: Metformin

Interventions

Metformin DRUG

Metformin will be prescribed, reaching 1000mg/day (a standard dose). This will be done under the principal investigator's care and the patient's clinical team, including assessment of metformin adherence. Metformin will be prescribed for 6 months. Antipsychotic treatment will continue as per standard of care (metformin as adjunct therapy), as well as routine follow up.

Also known as: Glucophage, Metformin Hydrochloride

Metformin

Eligibility Criteria

• Age: 18 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• This study will enroll individuals 18-25 years of age from the Nova Scotia Early Psychosis Program

You may not qualify if:

• Current stimulant use disorder

Sponsors & Collaborators

• Nova Scotia Health Authority: lead
• Dalhousie University: collaborator

MeSH Terms

Conditions

Psychotic Disorders; Marijuana Abuse

Interventions

Metformin

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Philip G Tibbo, MD

  Nova Scotia Health Authority

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachel Church, MSc.OT

CONTACT

902-473-7474; rachel.church@nshealth.ca

Candice E Crocker, PhD

CONTACT

902-473-3755; candice.crocker@nshealth.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 7, 2025
• First Posted: June 3, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: June 3, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share