Computational Assessment of GABA Receptor Modulation in PTSD

Inclusion criteria

• 18-65 years of age, inclusive;
• Participants must be willing to abstain from alcohol 24 hours prior to and 24 hours after the testing session;
• Participants must be able to participate and willing to give written informed consent and to comply with the study restrictions; Additional Inclusion Criteria for PTSD Group: (a) Current diagnosis of PTSD based on CAPS-5.

Exclusion criteria

• Has uncontrolled, clinically significant neurologic (including seizure disorders), cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disorder, or other abnormality, which may impact the ability of the subject to participate or potentially confound the study results;
• Pregnancy (assessed by urine test at time of screening and prior to administration of study medication) or lactation;
• Lifetime history of a chronic psychotic disorder or bipolar disorder type I as assessed by MINI;
• Current moderate or severe substance use disorder as assessed by MINI;
• Positive urine toxicology (drugs of abuse as determined by a positive urine test) at screening and before drug administration. Subjects who screen positive for THC will be given an opportunity to be included in the event of a negative urine test 2 weeks later. THC is not infrequently used for medicinal purposes and, in California, is legal for recreational use. Subjects who are positive for THC will therefore not be excluded, but will be retested to ensure that THC is unlikely to be influencing results;
• Self-report or observable signs of drug or alcohol intoxication or withdrawal;
• Current benzodiazepine or opioid use; other psychotropic medications are allowed as long as they are at a stable dose for at least 2 weeks and do not exhibit an unsafe interaction with the study medication;
• Current or recent use of any medication deemed by the study physician (Dr. Howlett) to exhibit an unsafe interaction with lorazepam;
• Past intolerance (including allergic) to lorazepam or another benzodiazepine;
• Active suicidal ideation or otherwise considered at high suicidal risk by trained study staff using the C-SSRS;
• History of a traumatic brain injury (TBI) resulting in loss of consciousness for more than 30 minutes;
• Volunteers who do not have sufficient command of the English language, or who have any other impairment that would prevent them from reading and understanding the informed consent form(s) and completing the study procedures including clinical testing;
• Any other reason why, per study physician, the subject should not participate in this study, including concomitant disease or condition that could interfere with, or for which the study drug might interfere with, the conduct of the study, or that would, in the opinion of the study physician, pose an unacceptable risk to the subject in this study. Additional Exclusion Criteria for HC Group: (a) Axis I disorder as assessed by MINI. Additional Exclusion Criteria for fMRI Participants:
• Contraindication to magnetic resonance imaging.
• Not right-handed as assessed by Edinburgh Handedness Inventory.