Investigational drugs in PTSD.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology June 1, 2026 Ted Obi, Kerry J Ressler
PTSD remains difficult to treat; only two medications are FDA-approved and have modest efficacy, and even first-line psychotherapies leave up to half of patients with persistent symptoms. Advances in neurobiology now frame PTSD as a disorder of maladaptive stress circuitry, neuroplasticity, and memory reconsolidation, opening new therapeutic possibilities. This review examines current pharmacotherapy, emerging targets, and 45 actively enrolling clinical trials. Rapid-acting interventions such as ketamine (producing symptom reductions within hours) and MDMA-assisted psychotherapy (demonstrating Phase 3 efficacy) represent major advances, though questions remain about durability, dosing, and safety. Many mechanistically plausible candidates have failed in late-stage trials due to high placebo responses, patient heterogeneity, and translational gaps.