Cannabis Use Disorder, Cognition, Repetitive Transcranial Magnetic Stimulation (rTMS), Schizophrenia
Conditions
Keywords
Sham Repetitive Transcranial Magnetic Stimulation (rTMS), Schizophrenia, Cannabis Use Disorder, Cognitive Function
Brief summary
The high prevalence of cannabis and other substance use disorders are a major barrier to recovery in people with schizophrenia. Moreover, schizophrenia patients have significant deficits in cognitive function, which may be exacerbated by cannabis use. Complicating these problems is the lack of evidence-based treatments for co-morbid cannabis use disorders (CUDs) in schizophrenia; there are no established pharmacotherapies. Therefore, this study is investigating the effects of high-frequency (20Hz) repetitive transcranial magnetic stimulation (rTMS) on cannabis use disorder and cognitive function in patients with co-morbid schizophrenia/schizoaffective disorder. The proposed study would be the first randomized, double-blind, sham controlled trial of rTMS in patients with schizophrenia and co-morbid CUD. A total of N=40 schizophrenia smokers with co-morbid cannabis use disorder will be assigned to either active rTMS (N=20) or sham rTMS (N=20) as a treatment regimen of 5X/week treatment for four consecutive weeks. All participants will receive weekly behavioral therapy for 4 weeks. The investigators predict that active rTMS will be well-tolerated and superior to sham rTMS for the treatment of CUD in schizophrenia.
Interventions
DEVICERepetitive Transcranial Magnetic Stimulation (rTMS)
On Day 1, the resting motor threshold (RMT) will be determined according to previous published methods \[Cardenas-Morales et al. 2013\] and the rTMS will be delivered at an intensity of 90% of the participant's RMT. rTMS will be administered at 20 Hz (25 trains, 30 pulses per train, 30 second intertrain interval).
On Day 1, the resting motor threshold (RMT) will be determined according to previous published methods \[Cardenas-Morales et al. 2013\] and the Sham rTMS will be delivered at an intensity of 90% of the participant's RMT. rTMS will be administered at 20 Hz with the B65 placebo coil (25 trains, 30 pulses per train, 30 second intertrain interval).
BEHAVIORALWeekly Counselling Session
In order to support participants in their abstinence plan, individual weekly sessions of supportive counselling will be administered over the course of the study on 1 time per week over 4 weeks (28 days of abstinence).
Sponsors
Centre for Addiction and Mental Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The rTMS technicians, participants, research analysts and investigators involved in the study will be blind to the rTMS treatment assignment.
Intervention model description
Double-blind, placebo-controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Male (80%) or Female (20%); 2. Age 18-55; 3. Meet the Diagnostic and Statistical Manual of Mental Disorders version 5 (DSM-5) criteria for Schizophrenia (SZ) or schizoaffective disorder and cannabis use disorder with physiological dependence; 4. Full scale intelligence quotient (IQ) ≥ 80 determined through the Wechsler Test of Adult Reading (WTAR); 5. Non-smokers OR cigarette smokers as confirmed with Fragerstrom Test for Nicotine Dependence (FTND) score of 5 or higher, self reported smoking of at lest 5 cigarettes per day (measured by the Timeline Follow Back), and verified by a Smokerlyzer test, cut-off as 10 ppm.
Exclusion criteria
1. DSM-5 diagnoses of alcohol, substance or polyuse substance use disorder in the past 6 months (other than cannabis/caffeine or nicotine); 2. Currently active suicidal ideation or self-harm (suicidal or non-suicidal) as assessed by the Structured Clinical Interview for DSM-5 (SCID-5); 3. Head injury resulting in loss of consciousness (\>5 minutes) and hospitalization; 4. Major neurological or medical illness including seizure disorder or syncope; 5. Metallic implants; 6. History of rTMS treatment; 7. Pregnancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The effects of active versus sham rTMS directed to DLPFC on cannabis abstinence in cannabis-dependent patients with schizophrenia as assessed by urine screens for changes in Tetrahydrocannabinol (THC) content. | Weekly (Day 0, Day 7, Day 14, Day 21, Day 28) and at 8 weeks (Follow-up Day 56) | Urine samples will be collected weekly during the abstinence period and tested by study personnel using the Semi-Quantitative THC Pre-Dosage Test (NarcoCheck®, Villejuif, France). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The effects of active (20 Hz) versus sham rTMS on change in cognitive function in cannabis dependent patients with schizophrenia as assessed by a cognitive battery administered at Baseline and at Day 28. | Up to 4 weeks (Day 28) and 8 weeks (Follow-Up Day 56) | The cognitive battery (Day 28) will include the primary outcome of verbal memory (assessed by HVLT) and will be compared to baseline (Day 1) performance. Cortical inhibition will also be assessed and compared between Day 1 and Day 28 performance. |
Other
| Measure | Time frame | Description |
|---|---|---|
| The effects of active (20 Hz) versus sham rTMS on change in cannabis craving in cannabis-dependent patients with schizophrenia as assessed by the Marijuana Craving Questionnaire (MCQ). | Up to 4 weeks (Day 28) and 8 weeks (Follow-Up Day 56) | MCQ will be assessed over time, specifically at Day 1 compared to Day 28. |
| The effects of active (20 Hz) versus sham rTMS on change in cannabis withdrawal in cannabis-dependent patients with schizophrenia as assessed by the Marijuana Withdrawal Checklist (MWC). | Up to 4 weeks (Day 28) and 8 weeks (Follow-Up Day 56) | MWC will be assessed over time, specifically at Day 1 compared to Day 28. |
| The effects of active (20 Hz) versus sham rTMS on psychotic symptoms in cannabis-dependent patients with schizophrenia as assessed by the Calgary Depression Scale for Schizophrenia (CDSS). | Up to 4 weeks (Day 28) and 8 weeks (Follow-Up Day 56) | CDSS scores will be compared over time, specifically Day 1 compared to Day 28. The depressive subscales within the PANSS will also be compared with the CDSS final score. |
| The effects of active (20 Hz) versus sham rTMS on psychotic symptoms in cannabis-dependent patients with schizophrenia as assessed by the Positive and Negative Syndrome Scale (PANSS). | Up to 4 weeks (Day 28) and 8 weeks (Follow-Up Day 56) | PANSS will be compared over time, specifically Day 1 compared to Day 28. The depressive subscales within the PANSS will also be compared with the CDSS final score. |
Countries
Canada
Outcome results
None listed