Exploring the Therapeutic Potential of Ketamine and Psilocybin in Comparison to Current Treatment Regimens for Treatment-Resistant Depression, Mood Disorders, and Post-traumatic Stress Disorder in the Pediatric Population: A Narrative Review.
Brett Hughes, Soz Mirza, Manasi Ponamala, James Sagaser, Riley Paredes, Naomi Hematillake, Chandni Tailor, Rahim Khan, Sudhakar Pemminati
Cureus August 1, 2025 DOI: 10.7759/cureus.90425 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Narrative review Peer reviewed |
|---|---|
| Population | Children and adolescents with non-psychotic disorders (treatment-resistant depression, mood disorders, PTSD) |
| Interventions | Ketamine Psilocybin Ketamine-assisted psychotherapy |
| Topics | Depression Ketamine Psilocybin Esketamine PTSD |
| Keywords | Mood disorders |
| Key findings | Ketamine and psilocybin show promise as rapid-onset therapies for pediatric treatment-resistant depression, mood disorders, and PTSD, with ketamine providing rapid relief for depression and psilocybin decreasing symptoms in refractory depression and aiding emotional processing. |
Abstract
The stresses of the Coronavirus Disease of 2019 (COVID-19) pandemic highlighted the burden of psychiatric disorders within the pediatric population, revealing a pre-existing need for rapid-onset therapies that have since driven efforts to expand effective therapeutic interventions. In this narrative review, we utilized the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines to direct our report and study selection. We explored the current-state efficacy and therapeutic potential of ketamine and psilocybin in comparison to current treatment regimens for pediatric non-psychotic disorders, including Treatment-Resistant Depression (TRD), mood disorders like anxiety and bipolar disorder, and Post-Traumatic Stress Disorder (PTSD). We chose these pediatric disorders to eliminate concerns regarding reality orientation and the use of dissociative and/or psychedelic medicines in patients who are experiencing symptoms of psychosis. Also, we briefly discuss ketamine's more widely accepted utilization by medical providers as a pediatric anesthetic, and how this gives credence to further evaluation of ketamine's multifaceted indications in pediatric psychiatry. Recent studies have shed light on the involvement of glutamate pathways in the pathophysiology of TRD, mood disorders, and PTSD, and both ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, and psilocybin, a 5-hydroxytryptamine receptor 2A (5-HT2A) agonist, have emerged as promising options due to their ability to augment glutamate release. Ketamine's use for pediatric TRD demonstrated rapid-onset relief for signs and symptoms of depression in children and adolescents, and psilocybin also decreased symptoms in patients with longstanding or refractory depression. Ketamine has been well tolerated and exhibited symptom improvements for youth with mood disorders such as anxiety and bipolar depression, while psilocybin showed promise in fostering emotional processing. In youth suffering from PTSD, ketamine-assisted psychotherapy (KAP) brought about decreases in PTSD symptom severity, though outcomes varied across populations. Psilocybin enhanced neural plasticity, allowing patients to revisit and reframe memories under therapeutic guidance, especially for those with complex or treatment-resistant PTSD. Ethical considerations are involved in the use of dissociative and hallucinogenic therapies like ketamine and psilocybin in the pediatric population, and we explore some ethical issues regarding their use. Further research exploring specific brain locations and mechanisms of action underlying glutamate modulation by ketamine and psilocybin, and the subsequent rapid-acting relief of psychiatric symptoms offered by these substances, could pave the way for innovative treatments targeting pediatric mental health disorders.
Comparable studies
Other narrative reviews on psilocybin for PTSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Novel psychopharmacological therapies for psychiatric disorders: psilocybin and MDMA. | 2016 | Review | |
| Registered clinical studies investigating psychedelic drugs for psychiatric disorders. Registered clinical trials on clinicaltrials.gov evaluating psychedelics for... | 2021 | Review | n = 70 |
| The Psychedelic Future of Post-Traumatic Stress Disorder Treatment | 2024 | Comprehensive review | |
| Diverse therapeutic developments for post-traumatic stress disorder (PTSD) indicate common mechanisms of memory modulation. | 2022 | Review | |
| Is it now time to prepare psychiatry for a psychedelic future? | 2024 | Review |