Cannabis Potency Effects on Brain White Matter in Early Phase Psychosis
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18-25
SponsorNova Scotia Health Authority
About this trial
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. 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. Complete an MRI scan at baseline and 6 months 3. Take Metformin every day for 6 months
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
This study will enroll individuals 18-25 years of age from the Nova Scotia Early Psychosis Program
Disqualifiers
Current stimulant use disorder
Trial design
Design model
Single group
Treatments tested in this trial
Metformin
DrugMetformin 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.
Treatment groups
24 Participants
are divided into 1 treatment groupGroup A: MetforminExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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).
Time frame
Baseline, 3 months, 6 months2
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.
Time frame
Baseline to 6 months3
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).
Time frame
Baseline to 6 Months4
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).
Time frame
Baseline to 6 monthsSecondary outcomes
1
Change in white matter to grey matter ratio
Changes from baseline in percent whole brain gray and white matter at 6 months assessed with MPRAGE imaging.
Time frame
Baseline to 6 months2
Change in inflammatory neurochemicals
Measurement of inflammatory neurochemical changes in the dorsomedial prefrontal region of brain by measurement of total choline level changes in dorsomedial prefrontal region of the brain from baseline to 6 months using Magnetic resonance spectroscopy (MRS).
Time frame
Baseline to 6 months3
Change in overall substance use
The WHO Alcohol, Smoking, and Substance Involvement Screening Test (WHO-ASSIST) will measure substance use risk scores to account for problematic use other than cannabis use from baseline to 6 months. Scores range from 0-39 for each substance with higher scores indicating more severe risk associated with use.
Time frame
Baseline to 6 months4
Changes in problematic cannabis use
Cannabis Use Disorder Identification Test - Revised (CUDIT-R) will be used to measure problematic cannabis use scores from baseline to 6 months on a scale of 0-32 with higher scores indicating more problematic use.
Time frame
Baseline to 6 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Nova Scotia Health Authority
Lead sponsor
Dalhousie University
Collaborator
Source ClinicalTrials.gov