Research & Outcomes
Brief history of psychedelic-assisted therapy in medicine
Sanacora G, Frye MA, McDonald W, et al. A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders. JAMA Psychiatry. 2017.
This APA task force statement acknowledged that ketamine produces rapid and robust antidepressant effects in patients with treatment-resistant mood disorders, while cautioning that sample sizes in existing trials were small and long-term safety data were limited. It provided clinical guidance on patient selection and safety considerations to help practitioners use ketamine responsibly in an off-label context.
Andrade C. Ketamine for Depression: Clinical Summary of Efficacy and Adverse Effects. J Clin Psychiatry. 2017.
This clinical summary outlined that ketamine, given as a slow IV infusion at subanesthetic doses, produces rapid and marked reduction in depressive symptoms — including in treatment-resistant patients — with benefits appearing within hours, peaking around day one, and fading within 3–12 days. It also reviewed adverse effects and proposed mechanisms of action to help clinicians contextualize ketamine's unique profile compared to conventional antidepressants.
Naughton M, Clarke G, O'Leary OF, Cryan JF, Dinan TG. A Review of Ketamine in Affective Disorders. J Affect Disord. 2014.
This review examined both clinical evidence of ketamine's efficacy in unipolar and bipolar depression and preclinical data on proposed mechanisms, including its enhancement of neuroplasticity in the amygdala and hippocampus. It also addressed limitations of existing evidence and safety/tolerability concerns including cardiovascular risks and psychotomimetic side effects.
Marwaha S, Palmer E, Suppes T, et al. Novel and Emerging Treatments for Major Depression. The Lancet. 2023.
This review assessed novel and emerging biological treatments for major depressive disorder, evaluated their putative brain and body mechanisms, and highlighted the unmet need for faster-acting options given that conventional antidepressants can take up to 6 weeks to work and often require multiple treatment trials. Ketamine/esketamine, psychedelics, neuromodulation, and neuroinflammation-targeting therapies were among the interventions covered.
Johnston JN, Kadriu B, Kraus C, et al. Ketamine in Neuropsychiatric Disorders: An Update. Neuropsychopharmacology. 2023.
This update reviewed the pharmacology and hypothesized mechanisms of subanesthetic ketamine and presented evidence supporting its use across multiple neuropsychiatric conditions — including depression, bipolar disorder, anxiety disorders, substance use disorders, and eating disorders — as well as chronic pain. The authors noted that while ketamine's therapeutic mechanisms remain incompletely understood, ongoing research into other targeted interventions is helping clarify how its NMDA antagonism and AMPA modulation contribute to symptom improvement across disorders.
Wilkinson ST, Rhee TG, Joormann J, et al. Cognitive-Behavioral Therapy Following Ketamine. Am J Psychiatry. 2017.
This open-label trial investigated whether CBT could sustain ketamine's short-lived antidepressant effects in treatment-resistant depression, motivated by concerns about neurobiological risks from long-term ketamine exposure. Of patients who responded to four ketamine infusions, 87.5% achieved remission, supporting the concept of pairing ketamine's rapid neurobiological window with structured psychotherapy to extend durability.
Kwan ATH, Lakhani M, Singh G, et al. Ketamine for the Treatment of Psychiatric Disorders: A Systematic Review and Meta-Analysis. CNS Spectrums. 2024.
This systematic review and meta-analysis examined the therapeutic applications of ketamine across multiple psychiatric disorders beyond mood disorders, in the context of high rates of inadequate response to first- and second-line treatments. It found evidence supporting ketamine's off-label use across several conditions, though heterogeneity in clinical practice was identified as a barrier to consistent quality of care.
Marchi M, Magarini FM, Galli G, et al. Effects of Ketamine on Anxiety and Cognition. Front Neurosci. 2022.
Noting that most prior ketamine research focused on depression and suicidality, this systematic review specifically investigated its effects on cognition, anxiety, quality of life, and social functioning in adults with psychiatric disorders. Results suggested meaningful anxiety reduction, with approximately 1 in 5 patients achieving at least 50% improvement in anxiety, though the authors called for future trials at lower doses and in less medically complex populations.
Quintero JM, Bustos RH, Lechtig-Wassermann S, et al. Ketamine in Clinical Practice. CNS Spectrums. 2025.
This 2025 review traced ketamine's evolution from anesthetic agent to psychiatric therapeutic, highlighting its rapid and sustained antidepressant effects in treatment-resistant depression via a novel mechanism — NMDA receptor antagonism and AMPA potentiation — distinct from traditional antidepressants. It also covered its broader clinical utility in pain management and emerging evidence for anti-inflammatory and neuroprotective properties.