A Stabilized Intranasal Formulation of R-Ketamine and Delta-9-Tetrahydrocannabinol (THC) for the Treatment of Post-Traumatic Stress Disorder (PTSD) and Fear-Extinction Deficits

Post-traumatic stress disorder (PTSD) remains a debilitating condition with significant unmet clinical need; existing pharmacotherapies often provide incomplete symptom management and fail to target the underlying fear memory pathology. We describe a novel, stable intranasal formulation combining R-ketamine and Delta-9-tetrahydrocannabinol (THC) designed to target the neuroplasticity deficits inherent in the disorder. This approach leverages the distinct molecular mechanisms of R-ketamine (mTORC1 signaling, BDNF expression in the mPFC) with low-dose THC (CB1 receptor agonism in the BLA) to facilitate the "unlearning" of traumatic memories. The formulation uses advanced stabilization techniques, including micelle encapsulation and antioxidants, for optimal delivery via a calibrated mucosal atomization device (MAD). We outline a therapeutic strategy and clinical trial protocols designed to evaluate efficacy, safety, and durability of effect, specifically addressing the challenges of co-morbid substance use disorders. This work proposes a potent, non-invasive therapeutic agent to address the urgent need for effective PTSD interventions.