rTMS Treatment for Cannabis Use Disorders in Psychosis

Evaluating Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Cannabis Dependence and Working Memory in Patients With Early Psychosis

Cannabis use during adolescence represents a significant risk factor for the development of psychosis including schizophrenia. Moreover, cannabis is the most commonly used drug among patients with an existing psychotic disorder. An estimated 25% of patients with psychosis reportedly meet the criteria of a cannabis use disorder particularly among younger patients experiencing their first episode. Cannabis use significantly exacerbates symptomatology resulting in an increased duration of the first hospitalization visit, number of hospital readmissions, and overall reduced functional outcome. Discovering novel strategies to treat the underlying pathophysiology of cannabis dependence early in the disorder may translate into improved functional outcome. Working memory deficits have been shown to predict relapse in the first-year of psychosis and is modulated with cannabis use. Repetitive transcranial magnetic stimulation (rTMS) targeted to the dorsolateral prefrontal cortex (DLPFC) has shown tremendous promise for the treatment of both tobacco dependence and working memory impairment in patients with psychosis possibly through the modulation of gamma (30-50 Hz) oscillations. The proposed study will therefore evaluate the effect of rTMS on abstinence, working memory performance, and gamma oscillations through a randomized, double-blind, placebo-controlled 28-day longitudinal abstinence study design in patients with early psychosis. It will further explore if baseline performance and gamma oscillations predict abstinence in response to rTMS. It is hypothesized that active compared to sham rTMS will improve abstinence rates and improve working memory performance through the modulation of gamma oscillations.

This a randomized, double-blind placebo-controlled, longitudinal 28-Day abstinence study design. Patients with psychosis will be randomized (1:1) to receive either active or sham stimulation that will be administered three times per week for 4 weeks (28 days) for a total of 12 treatments. Urine will be collected three times per week prior to the rTMS treatment. Cognition including the N-Back task and MATRICS cognitive battery will be administered on Day 0, Day 28, and Day 42 to determine the effect of rTMS on cognition compared to sham stimulation.

repetitive transcranial magnetic stimulation, working memory, gamma oscillations, dorsolateral prefrontal cortex

Repetitive transcranial magnetic stimulation (rTMS) will be administered bilaterally to the dorsolateral prefrontal cortex (DLPFC) at 20 Hz, 90% RMT in 25 trains.

Repetitive transcranial magnetic stimulation (rTMS) will be administered bilaterally to the dorsolateral prefrontal cortex (DLPFC) at 20 Hz, 90% RMT in 25 trains with a sham coil.

Gas chromatography/mass spectrometry (GC/MS) analysis to obtain quantitative THC-COOH and creatinine concentrations.

Inclusion Criteria: Age 16-35 Meet Diagnostic and Statistical Manual for Mental Disorders (DSM)-5 diagnostic criteria for a cannabis use disorder with physiological evidence of dependence; plus one of schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, bipolar I disorder, major depressive disorder with psychotic features, cannabis-induced psychosis, or psychosis not otherwise specified Full scale IQ ≥ 80 determined through the Wechler Test for Adult Reading (WTAR) Daily cigarette smoker of ≥ 5 cigarettes per day Exclusion Criteria: DSM-5 diagnoses of alcohol, substance or poly-use substance use disorder in the past 6 months (other than cannabis/caffeine or nicotine) Currently active suicidal ideation or self-harm (suicidal or non-suicidal) Head injury resulting in loss of consciousness and hospitalization Major neurological or medical illness including seizure disorder or syncope Metallic implants History of rTMS treatment Pregnancy

Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching hospital, fully affiliated with the University of Toronto, and a PAHO/WHO Collaborating CentreStudy Data/Documents: