Comment from Shaare Nefesh

Title: Beyond Symptom-Suppression: Establishing a Regulatory Pathway for Ketamine as a Psychotherapeutic Catalyst Submitted by: Sinai Oren, MD, Director of Sha'arei Nefesh Clinic Date: June 24, 2026 1. Executive Summary This submission advocates for a regulatory shift in the repurposing of ketamine from a purely symptom-based pharmaceutical intervention to a "Psychotherapeutic Catalyst" model. Based on clinical experience treating hundreds of patients with ketamine-assisted psychotherapy, we propose that the FDA recognizes the value of ketamine as a tool to enhance the psychotherapeutic process itself, leveraging its capacity to induce neuroplasticity and witness consciousness. This approach addresses a critical unmet need: the stagnation of long-term psychotherapy in treatment-resistant cases, while providing a cost-effective and accessible solution for broader patient populations. 2. Clinical Rationale and Methodology In my clinical practice as a psychiatrist and Director of the Sha'arei Nefesh clinic, I have utilized ketamine-assisted psychotherapy to successfully treat hundreds of patients. My experience consistently demonstrates that ketamine functions most effectively not as a monotherapy for specific DSM-5 diagnoses, but as a catalyst that bridges the gap between biological intervention and psychological integration. Furthermore, I advocate for the prioritized use of generic ketamine over other derivatives. Ketamine’s unique pharmacological profile creates an optimal "neuroplastic window" while remaining significantly more cost-effective, ensuring that this life-changing intervention remains accessible to a wide range of patients, rather than being restricted by the prohibitive costs of proprietary derivatives. 3. The "Catalyst" Model: Process-Based Enhancement We propose defining a new clinical category: Psychotherapeutic Catalyst. This model focuses on the following mechanisms: Cognitive Reframing: Ketamine induces a state of "witness consciousness," allowing patients to observe entrenched cognitive patterns with reduced emotional reactivity, facilitating the integration of new perspectives within the therapeutic session. Neuroplasticity Induction: The transient window of synaptic plasticity induced by ketamine serves as the biological substrate that, when coupled with concurrent, licensed psychotherapy, allows for the permanent dissolution of maladaptive cognitive loops. 4. Proposed Regulatory Approach To address safety and efficacy, we propose the following regulatory framework: Indication: Adjunct to licensed psychotherapy for the facilitation of cognitive reframing in treatment-resistant cases. Mandatory Integration: The drug should not be authorized for monotherapy. The prescription must be contingent upon a verified, licensed psychotherapeutic protocol to ensure the neuroplastic window is utilized for cognitive integration. Outcome Metrics: Future clinical evaluations should move beyond symptom-reduction scales (e.g., MADRS) to "functional progression metrics" that measure the rate of cognitive reframing and long-term behavioral change. 5. Conclusion Repurposing ketamine as a Psychotherapeutic Catalyst is a high-impact, cost-effective solution to the systemic inefficiencies in mental health care. By shifting the regulatory focus from symptom suppression to process enhancement, the FDA can enable a scientifically integrated approach that values the interaction between biology and human psychology.