Brain scans reveal how a calming drug affects emotion in psychosis
NCT ID NCT04004416
First seen Jun 27, 2026 · Last updated Jun 27, 2026
Summary
This study investigates how a medication called lorazepam, which boosts the calming brain chemical GABA, changes emotional brain activity in people with psychosis. Participants aged 16–60 with conditions like schizophrenia or bipolar disorder, along with healthy volunteers, will undergo brain scans after taking either lorazepam or a placebo. The goal is to better understand the role of GABA in emotional processing and mental illness.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- lorazepam
- What this could lead to
- If successful, this could reveal how brain chemistry differs in psychosis, pointing toward better-targeted treatments for emotional symptoms.
- What could go wrong
- This is an early-phase observational study, not a treatment trial. Lorazepam is used only as a probe, and results may not lead directly to new therapies.
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Study facts
What this study's own registry entry says, in plain language.
- Phase
-
Phase 4
Runs after approval, following long-term safety and how well the treatment works in everyday use.
- Participants
-
143 people
The number who actually took part.
- Started
-
Jan 2020
- Finished
-
Feb 2025
- Lead sponsor
-
Other sponsor
The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
-
16 to 60 years
- Sex
-
Anyone
- Healthy volunteers
-
Accepted
You do not need to have the condition being studied to take part.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
Early psychosis (EP) patients: Inclusion Criteria: * Ability and willingness to give informed consent to participate; * 16-35 years old * Meets DSM5 criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder, bipolar disorder type 1, with history of psychosis, major depressive disorder, with history of psychosis, brief psychotic disorder, or other specified/unspecified psychotic disorder; or, meets SIPS criteria for Presence of Psychotic Symptoms or Brief Intermittent Psychotic Syndrome (BIPS). * Positive symptom onset ≤ 2 years * No history of active substance use disorder in the past 2 months * Not currently on an involuntary treatment order * Not taking chronic narcotics, barbiturates, benzodiazepines * Absence of suicidal thoughts with plans or intentions, as assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) * No increases in psychotropic medication within the prior 4 weeks reflecting clinical instability and for half of the EP sample, not taking antipsychotic medication within the prior 4 weeks. Patients may take as needed doses of benzodiazepines as clinically prescribed, as long as those doses are not required within 5 half-lives of an fMRI session * Ability to tolerate small, enclosed spaces without anxiety * Vision equal to or better than 20/40 on a Snellen chart, with correction if necessary * No metals, implants or metallic substances within or on the body that might cause adverse effects to the subject in a strong magnetic field, or interfere with image acquisition, e. g. aneurysm clips, retained particles (metal workers excluded), neurostimulators, foil-backed transdermal patches, carotid or cerebral stents, cerebral spinal fluid (CSF) shunts; magnetic dental implants, ferromagnetic ocular implants, pacemakers, automatic implantable defibrillators * Size compatible with scanner gantry, e. g. men over 6 feet tall that weigh more than 250 pounds (lbs), men under 6 feet tall that weigh over 220 lbs, women over 5'11" tall that weigh more than 220 lbs, or women under 5'10" tall that weigh more than 200 lbs. Subjects of these weights or greater typically have difficulty fitting into the fMRI scanner properly. Exclusion Criteria: * If a woman of childbearing age, not pregnant or trying to become pregnant * History of serious neurological illness or current medical condition that could compromise brain function, such as liver failure * History of closed head injury, for example (e.g.) loss of consciousness \> \~5 min, hospitalization, neurological sequela * Hypersensitivity to benzodiazepines or to components of the formulation, per judgment of the principal investigator (PI) * Disorders affected by benzodiazepines, such as compromised respiratory function, e.g., chronic obstructive pulmonary disease, or acute, narrow angle glaucoma, per judgment of the principal investigator (PI) Schizophrenia/schizoaffective (SCZ) and bipolar affective disorder (BAD) patients: Inclusion Criteria: * Ability and willingness to give informed consent to participate; * 16- 60 years old * Meets DSM5 criteria for schizophrenia, schizoaffective disorder, other specified/unspecified psychotic disorder, or bipolar disorder type 1, with history of psychosis bipolar affective disorder * Duration of positive symptom onset \> 2 years * No history of active substance use disorder in the past 2 months * Not currently on an involuntary treatment order * Not taking chronic narcotics, barbiturates, benzodiazepines * Absence of suicidal thoughts with plans or intentions, as assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) * No increases in psychotropic medication within the prior 4 weeks reflecting clinical instability. Patients may take as needed doses of benzodiazepines as clinically prescribed, as long as those doses are not required within 5 half-lives of an fMRI session * Ability to tolerate small, enclosed spaces without anxiety * Vision equal to or better than 20/40 on a Snellen chart, with correction if necessary * No metals, implants or metallic substances within or on the body that might cause adverse effects to the subject in a strong magnetic field, or interfere with image acquisition, e. g. aneurysm clips, retained particles (metal workers excluded), neurostimulators, foil-backed transdermal patches, carotid or cerebral stents, cerebral spinal fluid (CSF) shunts; magnetic dental implants, ferromagnetic ocular implants, pacemakers, automatic implantable defibrillators * Size compatible with scanner gantry, e. g. men over 6 feet tall that weigh more than 250 pounds (lbs), men under 6 feet tall that weigh over 220 lbs, women over 5'11" tall that weigh more than 220 lbs, or women under 5'10" tall that weigh more than 200 lbs. Subjects of these weights or greater typically have difficulty fitting into the fMRI scanner properly. Exclusion Criteria: * If a woman of childbearing age, not pregnant or trying to become pregnant * History of serious neurological illness or current medical condition that could compromise brain function, such as liver failure * History of closed head injury, for example (e.g.) loss of consciousness \> \~5 min, hospitalization, neurological sequela * Hypersensitivity to benzodiazepines or to components of the formulation, per judgment of the principal investigator (PI) * Disorders affected by benzodiazepines, such as compromised respiratory function, e.g., chronic obstructive pulmonary disease, or acute, narrow angle glaucoma, per judgment of the principal investigator (PI) Healthy control subjects: Inclusion Criteria: * Ability and willingness to give informed consent to participate * 18- 60 years old * No history of (h/o) past or current mental illness (except for simple phobias), but prior h/o substance abuse okay if in remission for greater than 5 years * Not taking any medication, prescription or non-prescription, with psychotropic effects (birth control medications allowed) * No first-degree family members with a history of a psychotic disorder (including bipolar disorder) * Ability to tolerate small, enclosed spaces without anxiety * Vision equal to or better than 20/40 on a Snellen chart, with correction if necessary * No metals, implants or metallic substances within or on the body that might cause adverse effects to the subject in a strong magnetic field, or interfere with image acquisition, e. g. aneurysm clips, retained particles (metal workers excluded), neurostimulators, foil-backed transdermal patches, carotid or cerebral stents, cerebral spinal fluid (CSF) shunts; magnetic dental implants, ferromagnetic ocular implants, pacemakers, automatic implantable defibrillators * Size compatible with scanner gantry, e. g. men over 6 feet tall that weigh more than 250 pounds (lbs), men under 6 feet tall that weigh over 220 lbs, women over 5'11" tall that weigh more than 220 lbs, or women under 5'10" tall that weigh more than 200 lbs. Subjects of these weights or greater typically have difficulty fitting into the fMRI scanner properly. Exclusion Criteria: * If a woman of childbearing age, not pregnant or trying to become pregnant * History of serious neurological illness or current medical condition that could compromise brain function, such as liver failure * History of closed head injury, for example (e.g.) loss of consciousness \> \~5 min, hospitalization, neurological sequela * Hypersensitivity to benzodiazepines or to components of the formulation, per judgment of the principal investigator (PI) * Disorders affected by benzodiazepines, such as compromised respiratory function, e.g., chronic obstructive pulmonary disease, or acute, narrow angle glaucoma, per judgment of the principal investigator (PI)
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Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
Contacts and locations
Locations
-
University of Michigan
Ann Arbor, Michigan, 48109, United States
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