Aims: Both substance use and mental illness commonly onset during adolescence or young adulthood, and rates of substance use in young people with mental illness are disproportionately high. This baseline data paper from a clinical trial testing an integrated early intervention for substance use and mental health problems aims to 1) describe the characteristics of participants enrolled; and 2) compare young people with a current and without a lifetime diagnosis of Substance Use Disorder (SUD) in terms of psychiatric symptoms, functioning, and substance use. Methods: Seventy-nine participants aged 12-25 years with high prevalence mental illness (e.g., depression, anxiety) and substance use seeking mental healthcare were recruited from headspace primary mental health centres in North-Western Melbourne. At baseline, they completed self-report and interview measures of psychiatric diagnoses and symptoms, functioning, and substance use. We compared those with a current (n=51) and without a lifetime (n=21) SUD on these measures. Results: Youth with an SUD endorsed more severe depressive and anxiety symptoms, and lower quality of life and role functioning than those who used substances without a lifetime SUD. They also had more alcohol-related problems and higher frequency cannabis use, and higher risk scores for alcohol, tobacco, cannabis, cocaine, amphetamine-type stimulants, and hallucinogen use. There were no group differences in social and occupational functioning or subjectively-rated sleep quality. Conclusions: Findings highlight the need for early identification and integrated care models within youth mental health services to address the high prevalence and impact of problematic substance use, potentially reducing adverse effects of co-occurring SUD and mental illness on youth development and functioning.

Aim: Cannabis use disorder (CUD) typically onsets before age 22 and accounts for the majority of substance use treatment presentations by Australian youth. There are no established pharmacotherapies for CUD. Guanfacine extended-release (XR) is an alpha 2a adrenergic receptor agonist that is approved for attention deficit hyperactivity disorder in children and adolescents. Immediate-release guanfacine alleviates some cannabis withdrawal symptoms in adults. The XR formulation can be taken once daily, is well-characterised in children and adolescents, and reduces impulsivity in those with ADHD. The GRACE study – embedded within youth substance use treatment services in Victoria, Australia – will assess whether guanfacine XR added to treatment as usual (TAU) reduces the frequency of cannabis use following monitored abstinence in youth with CUD. Methods: GRACE is a pragmatic Phase 2b, double-blind, parallel-group superiority randomised controlled trial of guanfacine XR for youth aged 12-25 years seeking treatment for CUD (mild-severe). Participants (N=100) are randomly assigned in a 1:1 ratio to receive guanfacine XR (target dose 4 mg/day) or placebo plus TAU, including residential admission for supervised withdrawal for up to 14 days. The primary endpoint is efficacy, indexed by change from baseline in frequency of cannabis use (days/week) during 4-weeks in the community following discharge from residential withdrawal, measured weekly with the Timeline Follow Back. Results. GRACE commenced recruitment in August 2023; data collection is ongoing. Conclusions. The GRACE trial will investigate the efficacy of guanfacine XR – a promising candidate for CUD – in young people presenting for CUD treatment.