While there have been advances in understanding post-traumatic stress disorder (PTSD) as a disorder and its biological features, unfortunately only one out of five traumatized persons with PTSD reach remission after cycling through evidence-based and/or FDA-approved medications. This is especially unfortunate given that people with PTSD are often from vulnerable populations, or those whose professions entail personal sacrifice. It is clear that new serotonergic antidepressants and atypical antipsychotics will not be sufficient to fix this gap, and new mechanisms of action need to be tested. In the current proposal, the investigators test the hypothesis that mixed amphetamine salts (brand name Adderall), FDA-approved for treating attention deficit hyperactivity disorder (ADHD), can improve PTSD outcomes.

Post-traumatic stress disorder is a debilitating neuropsychiatric condition triggered by exposure to a traumatic exposure. Approximately 8% of the US population will experience the condition in their lifetime. At-risk populations, such as those exposed to community violence or warfare, have nearly double the risk. Despite progress in recognizing that PTSD is a disorder of neural circuits that underlie how individuals learn from the world, available treatments, including two FDA-approved medications (serotonergic antidepressants) and gold-standard evidence-based psychotherapies, help only one in five individuals reach remission. One key aspect of PTSD is difficulty in engaging in social interactions. Based on surprising evidence published in peer-reviewed manuscripts from our research programs at The University of Chicago, medications used to treat ADHD have positive effects on social interaction. Combined with promising data from biological studies of PTSD, psychostimulants used to safely treat ADHD such as Adderall (generic: mixed amphetamine salts), can help people with PTSD re-engage in social relationships that are the key to their recovery. This study will test the hypothesis that mixed amphetamine salts will acutely increase social interaction in adults with PTSD compared to placebo in a novel laboratory-based social interaction task.

Inclusion Criteria:

• Age 18 - 65 years old
• BMI 19-30 kg/m2
• English fluency

Exclusion Criteria:

• Individuals with current moderate or severe substance use disorder, no past stimulant or cocaine use disorder
• Individuals with current acute or high risk of suicide or suicide attempt in past 6 months
• Individuals with current psychotic or bipolar disorder
• Individuals with past schizophrenia, schizoaffective disorder, psychotic bipolar disorder, stimulant or cocaine use disorder
• Individuals with chronic (non-PRN) treatment with antipsychotic drug (except PRN quetiapine 25mg PO qHS) or D2 antagonist
• Individuals with medications with significant PD or PK interactions
• Individuals with current treatment with a stimulant medication
• Individuals with court or legally mandated treatment
• Individuals with unstable or untreated medical disorder that would increase the risk of serious side effects of study drug (unstable hypertension, tachycardia, cardiac arrhythmia, recent MI or stroke, clinically significant neuropsychiatric or neurological disorder)
• Members of a vulnerable population
• High blood pressure (>140/90)
• Women who are pregnant, breastfeeding, or planning to become pregnant