Precision Brain Stimulation to Reduce Cannabis Craving in Schizophrenia

NCT07196462 | Recruiting FDA Device

• 1 other identifier: 250955
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The central hypothesis is this: Brain circuits most relevant to cannabis use in schizophrenia are distinct from pathways identified in healthy controls who use cannabis. This study seeks to provide evidence that targeted stimulation of the DMN leads to both altered network activity and a concomitant behavioral change in cue-induced craving and cognitive performance in individuals with schizophrenia and schizoaffective disorder, while targeted stimulation of the L DLPFC leads to these changes in healthy controls who use cannabis. This study will test a model that integrates brain network pathophysiology and cognition to 1) explain the prevalence of cannabis use in schizophrenia and 2) identify a target for engagement in schizophrenia. This study seeks to establish a neuroscientific framework to guide future treatment-oriented studies aimed at reducing craving and improving cognitive performance in individuals with schizophrenia and schizoaffective disorder. This is a study of the effect of 2 rTMS interventions on functional connectivity and craving in individuals with schizophrenia or schizoaffective disorder and healthy controls who use cannabis. Aim 1: Target Engagement: Determine if rTMS manipulates functional connectivity of each target (DMN, L DLPFC) (n=100). Aim 2: Clinical Efficacy: Determine if rTMS affects cue-induced craving and if craving change correlates with change in functional connectivity (n=100). As an exploratory analysis, the factors that explain individual variance in rTMS-induced connectivity change will also be explored.

Conditions

Cannabis Use; SCHIZOPHRENIA; Psychosis; rTMS

Keywords

cannabis use; schizophrenia; rTMS; brain stimulation

Outcome Measures

Primary Outcomes (1)

• Clinical Efficacy: Determine if rTMS affects cue-induced craving and if craving change correlates with change in functional connectivity (n=100).

  Cue-induced craving will be measured using a 0-10 Visual Analog Scale (VAS) before, during, and after in-scanner presentation of visual cannabis cues. Whole DMN and L DLPFC-left insula connectivity will be calculated.

  Up to 12 weeks

Secondary Outcomes (1)

• 2. Resting-state functional connectivity

  Up to 12 weeks.

Study Arms (2)

Precision Brain Stimulation for Cannabis Users with Schizophrenia

EXPERIMENTAL

Participants with schizophrenia who use cannabis.

Device: 3 Minute iTBS to the L DLPFC; Device: One-Minute, Personalized, DMN Targeted CTBS

Precision Brain Stimulation for Cannabis Users with Healthy Controls

ACTIVE COMPARATOR

Healthy controls who use cannabis.

Device: 3 Minute iTBS to the L DLPFC; Device: One-Minute, Personalized, DMN Targeted CTBS

Interventions

3 Minute iTBS to the L DLPFC DEVICE

Five daily sessions of TMS (iTBS) to the L DLPFC target.

Precision Brain Stimulation for Cannabis Users with Healthy Controls; Precision Brain Stimulation for Cannabis Users with Schizophrenia

One-Minute, Personalized, DMN Targeted CTBS DEVICE

Personalized, DMN Targeted CTBS to the DMN for one minute, five daily sessions.

Precision Brain Stimulation for Cannabis Users with Healthy Controls; Precision Brain Stimulation for Cannabis Users with Schizophrenia

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18-65 years
• Diagnosis of a psychotic disorder according to DSM-5 criteria and confirmed by SCID
• Current cannabis use of at least 2/10 on a Visual Analog Scale
• Current cannabis use (confirmed by urine cannabis testing)
• Must be able to read, speak and understand English
• Must be judged by study staff to be capable of completing the study procedures
• Participants will be in stable outpatient psychiatric treatment and psychiatrically stable with no recent (within the past 30 days) psychiatric hospitalizations or changes in their psychiatric medication regimens.
• \- All of the above except for participants will not have a diagnosis of a psychotic disorder nor a first-degree relative with a psychotic disorder.

You may not qualify if:

• DSM-5 intellectual disability
• Substance use disorder (other than cannabis or nicotine) within the past three months
• Positive urine drug screen for illicit substance use that can increase seizure risk (cocaine, benzodiazepines, amphetamine, methamphetamine)
• Any history of a progressive or genetic neurologic disorder (e.g. Parkinson's disease, multiple sclerosis, tuberous sclerosis, Alzheimer's Disease) or acquired neurological disease (e.g. stroke, traumatic brain injury, tumor), including intracranial lesions
• History of head trauma resulting in any loss of consciousness (\>15 minutes) or neurological sequelae
• Current history of poorly controlled headaches including chronic medication for migraine prevention
• History of fainting spells of unknown or undetermined etiology that might constitute seizures
• History of seizures, diagnosis of epilepsy, or immediate (1st degree relative) family history epilepsy with the exception of a single seizure of benign etiology (e.g. febrile seizures) in the judgment of a board-certified neurologist
• Chronic (particularly) uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.)
• Any metal in the brain or skull (excluding dental fillings) or elsewhere in the body unless cleared by the responsible covering MD (e.g. MRI compatible joint replacement)
• Any devices such as pacemaker, medication pump, nerve stimulator, TENS unit, ventriculo-peritoneal shunt unless cleared by the responsible covering MD
• All female participants of child-bearing age will be required to have a pregnancy test; any participant who is pregnant or planning to become pregnant will not be enrolled in the study
• Any changes in medications or hospitalizations within the past 30 days.
• Participants who, in the investigator's opinion, might not be suitable for the study or would be unable to tolerate the study visit

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt Psychiatric Hospital

Nashville, Tennessee, 37212, United States

RECRUITING

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Central Study Contacts

Jillian G Connolly, B.S.

CONTACT

6154345891; jillian.connolly@vumc.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: September 13, 2025
• First Posted: September 29, 2025
• Study Start: January 15, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: June 2, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)