Ketamine for PTSD: What the Research Shows and Who May Benefit

Living with PTSD can be exhausting: flashbacks, hypervigilance, sleep disruption, and the weight of trauma make everyday life feel unsafe and draining. For people who try therapy, medications, or both and still struggle, that frustration is valid. Ketamine as a treatment for PTSD has generated excitement and confusion. Some studies report clinically meaningful benefits particularly for people who also have clinical depression, while others show more modest or mixed results for treating PTSD by itself. Below, we summarize the best-available evidence, what it suggests about who may benefit, and how Ember Health approaches this treatment in a safety-first, collaborative model.

It’s important to bear in mind that treatment outcomes vary across individuals, and not everyone responds the same way. Ember Health requires patients to work with a licensed mental-health provider, and we partner closely with each patient to provide individual-specific guidance on whether IV ketamine care may address mental health goals. The following information is educational and does not replace medical advice.

Understanding PTSD and Why Traditional Treatments Often Fall Short

PTSD results in more than intrusive memories. It also disrupts mood, cognition, sleep, and relationships. First-line care typically emphasizes trauma-focused psychotherapies such as prolonged exposure, cognitive processing therapy, and written exposure therapy, alongside medications. From a regulatory standpoint, only two medications, sertraline and paroxetine, are FDA-approved specifically for PTSD, and real-world remission rates are modest, around 20–30% (Brady et al., 2000; Marshall et al., 2001).

Engagement and retention in trauma-focused therapy are also challenging. Published programs report substantial dropout or nonresponse rates of 30–50%, often because exposure exercises can feel overwhelming or retraumatizing without adequate stabilization (Fremont et al., 2023).

When PTSD co-occurs with major depressive disorder (MDD) or bipolar depression, outcomes are frequently worse, and standard treatments may be insufficient for both conditions. This overlap is one reason clinicians are investigating the rapid-acting intervention of ketamine, aiming to reduce symptom burden quickly and make engagement in therapy more feasible (McInnes et al., 2025).

How Ketamine Works for PTSD: The Science of Memory Reconsolidation

Ketamine’s central pharmacology differs from conventional antidepressants. It is an NMDA receptor antagonist that triggers a glutamate surge and downstream signaling (including BDNF and mTOR cascades) that can rapidly promote synaptogenesis and strengthen new connections,  a neurobiological state often described as a “neuroplastic window.” These molecular and circuit changes can appear within hours and persist for days to weeks, creating a potentially advantageous period for learning and revisiting traumatic memories in therapy (Abdallah et al. 2016).

During the altered state experience when IV ketamine is being administered, patients often report profound and meaningful experiences. While it is impossible to perfectly predict each person’s unique experience, patients with trauma histories regularly report that they reflect on their traumatic events during the altered state. Some individuals experience these memories from a new perspective and are able to view them from a place of "emotional neutrality.” Other patients report psychological challenge of re-exposure to these memories. Ember’s 1:1 medical supervision is designed to keep the experience safe clinically and also psychologically, and clinicians often provide support to patients experiencing psychological distress or difficulty. Even patients who find the sessions uncomfortable, often report after the fact how helpful the experience was in surfacing important psychological content, and then work through it in a structured context with a supporting therapist. A 2023 open‑label trial, repeated, medically supervised ketamine infusions (0.5 mg/kg) combined with psychotherapy produced large and durable improvements in PTSD symptoms, providing real-world evidence that ketamine’s dissociative effects can be harnessed safely and therapeutically under close medical supervision (Krystal et al. 2023). 

Preclinical and human neuroimaging work supports that ketamine enhances neuroplasticity and can modify amygdala-prefrontal circuitry implicated in fear learning and recall (Aleksandrova & Phillips, 2021). Emerging evidence suggests that therapy delivered during the post-infusion neuroplastic period (hours to a few days after ketamine) produces consolidation of new, adaptive learning (Feder et al. 2025).  Through processes related to memory reconsolidation and extinction learning, ketamine may make traumatic memories more amenable to therapeutic modification, when paired with targeted trauma-focused interventions in the hours to days after an infusion. In practical terms, this means that patients with a trauma history have an opportunity for adaptive learning, to modify how prior memories and events impact them physically and psychologically, via therapy and self work in the days and weeks following ketamine treatment. 

Note: Ketamine is FDA-approved for anesthesia, and used off label for PTSD. Its use for PTSD should therefore be part of an informed consent conversation with a clinical team.

The Mixed Evidence: Why Ketamine Results Differ Between People Based On Their Background 

Ketamine shows promise for PTSD, particularly in people who also experience depression at the same time, a situation called comorbid depression. In plain terms, this means for someone who has PTSD and depressive symptoms simultaneously, IV ketamine treatment can be especially promising, especially since co-occurring conditions are harder to treat with standard approaches.

In people with PTSD without depression, the evidence is less consistent. While some studies report improvements in symptoms like intrusive memories, hyperarousal, or mood, other trials show smaller or more variable effects. This suggests that ketamine’s benefits may be strongest for those with overlapping depressive symptoms, which could amplify the impact of rapid-acting interventions and help patients engage more effectively in trauma-focused therapy.

Key points from higher-quality studies and reviews:

• PTSD with comorbid depression:  Several real-world and trial data suggest clinically meaningful improvement when ketamine is used in people who have both PTSD and depressive symptoms. A recent retrospective analysis of community-based ketamine infusion therapy (McInnes et al., 2025) reported reductions in both PTSD and depression symptoms. In other words, people with both conditions often feel relief in mood, energy, and PTSD-related distress after ketamine infusions, which can help them engage more fully in therapy.
• PTSD-only randomized trials: A landmark RCT of repeated IV ketamine versus an active control (midazolam) in chronic PTSD (Feder et al., 2021) found larger reductions in clinician-rated PTSD severity in the ketamine group at early timepoints (24 hours after the first infusion and across the 2-week course). Among responders, the median time to loss of response was about 27.5 days. Simply put, ketamine might be able to provide rapid symptom relief in PTSD even without depression, but as with ketamine for depression, patients need follow-up and maintenance treatments to maintain the benefits over time.
• Heterogeneity and negative/mixed trials: Other controlled trials and larger veteran-focused samples have reported more modest or dose-dependent effects, underscoring that not all PTSD samples respond equally. For example, some studies report rapid symptom reductions that attenuate over weeks, and other trials have failed to show a large, sustained effect across all participants. Meta-analyses and reviews therefore describe the evidence as promising but incomplete, and emphasize the need for larger, longer trials and clearer stratification by comorbidity (PTSD+depression vs PTSD only). (Fremont et al. 2023).
• Why comorbidity matters: When depression is present alongside PTSD, ketamine’s strong antidepressant effects may substantially reduce the depressive symptoms that interfere with engagement in trauma therapy and overall functioning. This often translates into clearer, larger clinical gains across both domains. Trials that enrich for comorbid depression tend to report more consistent improvements than trials of PTSD alone (McInnes et al. 2025).

Some studies enroll people with both PTSD and depression and report large improvements; others enroll PTSD without major depression and find smaller or less durable effects. Those population differences matter a lot when interpreting results (Fremont et al. 2023).

Ketamine Combined with Trauma-Focused Therapy: A Promising Approach

Combining ketamine with structured trauma therapy is an active and encouraging area of research. The rationale is straightforward: ketamine may temporarily enhance neuroplasticity, and trauma-focused therapies (prolonged exposure, written exposure therapy, cognitive processing) provide the behavioral learning to replace maladaptive fear responses with adaptive coping.

Recent early-phase studies illustrate this synergy:

• An open-label trial combining repeated ketamine infusions with Written Exposure Therapy (WET) reported substantial and sustained reductions in PTSD symptoms at follow-up, suggesting feasibility and promise for combination protocols. (Open-label work should be interpreted cautiously but is important for guiding larger RCTs.) (Feder et al. 2025).
  
  
• Multiple trials and pilot programs are now testing intensive schedules that pair brief, focused trauma therapy closely with ketamine dosing (for example, two infusions combined with a week of trauma-focused psychotherapy). Early clinical trials and registered studies (including ongoing RCTs) are designed to test whether pairing reduces relapse and increases durability (Yale Medicine, 2025)

Clinically, this pairing makes sense for two reasons: (1) Ketamine can reduce depressive symptoms that otherwise prevent patients from tolerating exposure-based therapy, and (2) the neuroplastic window after infusion may increase the likelihood that therapeutic learning “sticks.”  .That said, the evidence base is still emerging. Randomized, well-powered trials are needed to confirm optimal timing, dose, and therapy type (Almeida et al. 2024).

Ember Health encourages concurrent trauma-informed therapy and offers resources and training to collaborating therapists. 

What to Expect: The Treatment Experience at Ember Health and Timeline

At Ember Health, our approach is built on safety, transparency, and collaboration, ensuring that every patient feels supported and informed throughout their treatment journey.

Protocol
Many patients begin with a short course of ketamine infusions, typically 4–6 sessions over 1–2 weeks, depending on the individualized clinical plan. Each infusion lasts approximately 40 minutes, with the total visit taking about 90 minutes to allow for monitoring, onboarding, and recovery. All sessions include 1:1 supervision by emergency-medicine trained clinicians to ensure safety and immediate medical support if needed (Feder et al., 2021). Dosing and number of infusions are carefully tailored to each patient’s response and needs.

Dissociation and Ketamine
Patients often have questions about dissociation, a common effect of ketamine. It is important to distinguish between ketamine-induced dissociation and trauma-related dissociation:

• Trauma-related dissociation is a chronic psychological defense mechanism that helps the brain cope with overwhelming stress.
  
  
• Ketamine-induced dissociation is a transient, medication-related state, in which the brain temporarily separates body awareness from higher-level consciousness. This is the same mechanism by which high-dose ketamine functions as a surgical anesthetic.

At Ember Health, clinicians explain the sensations you might experience, such as floating, altered perception of time, memory recall, or mild detachment, and carefully modulate dose and environment (music, comfort measures, lighting) to minimize anxiety. This dissociation is short-lived and resolves within the session, and is closely monitored to maximize safety and comfort (Feder et al., 2021).

When Change Can Be Noticed
Some patients report improvements to depressive symptoms within 24 hours of their first infusion. Many experience meaningful symptom reduction within the first 1–2 weeks of a short course. Clinical trials indicate a median durability of response around 27–28 days among responders in repeated-dose studies, which is why individualized maintenance or “booster” infusions are often incorporated into ongoing care plans (Feder et al., 2021).

Ember works closely with each patient and their outside providers to design follow-up plans that balance benefit, safety, and patient goals, especially as evidence supports that structured therapy in the days and weeks following ketamine treatment can improve and elongate benefit. 

Who May Benefit from Ketamine for PTSD

IV ketamine care at Ember Health may be considered when:

• You have a formal diagnosis of PTSD from a licensed mental-health provider, and
• You have co-occurring depression (MDD or bipolar depressive episode) or significant depressive symptoms that limit your ability to engage in therapy, and
• Your mental health team is willing to partner with us at Ember in your collaborative mental healthcare.

Evidence is most consistent for people with PTSD and comorbid depression; for PTSD alone the evidence is promising but less certain. People with primary PTSD without depression should discuss the mixed evidence with their clinician. Ember requires patients to be actively engaged with a licensed mental-health provider and strongly recommends, but does not require, concurrent trauma-focused therapy to translate neurobiological changes into lasting psychological gains (McInnes et al. 2025).

Cost, Insurance, and Access Considerations

Because ketamine for depression and PTSD is administered off-label, insurance coverage is inconsistent. Coverage policies differ by insurer and by indication (some payers cover IV ketamine for treatment-resistant depression or suicidality but not for PTSD specifically). The VA has specific pathways for financial coverage, and covers treatment in at least 22 states. Ember provides transparent pricing, insurance navigation support, and guidance on potential reimbursement strategies, while helping patients weigh clinical benefit against out-of-pocket cost.

Ember Health’s Approach: When We Help Patients Consider Ketamine for PTSD

Ember’s primary focus remains evidence-driven treatment of depressive symptoms using IV ketamine, with special attention to safety and collaboration. For PTSD, we generally recommend ketamine when depressive symptoms are prominent or when rapid symptom reduction would enable meaningful engagement in trauma-focused therapy. We do not offer ketamine as a stand-alone replacement for trauma therapy. Rather, our model integrates medical infusions with strong coordination with therapists and psychiatrists to make therapy more accessible and effective during the post-infusion neuroplastic window. (Fremont et al. 2023).

Our primary focus is Depression with 84% success rate. PTSD comorbid depression often also responds (McInnes et al. 2025). Ember Health works and can make referrals to many trauma informed therapists. 

Frequently Asked Questions

Is ketamine FDA-approved for PTSD? No. Ketamine is FDA-approved as an anesthetic; its psychiatric uses (including for depression and PTSD) are off-label and supported by clinical research rather than an FDA indication. Ember will discuss risks, benefits, and alternatives during informed consent. 

Will ketamine worsen trauma-related dissociation? Not typically. Clinically supervised ketamine dissociation is distinct and temporary. That said, a prior history of dissociation or complex trauma requires careful assessment, and Ember coordinates with your therapist/psychiatrist to determine appropriateness. (Krystal et al. 2024).

Why do results differ for PTSD patients with vs. without depression? Evidence indicates ketamine’s strong antidepressant action can reduce depressive symptoms that otherwise limit therapy engagement; trials that include comorbid depression frequently report larger and more durable improvements across both symptom domains. Trials enrolling PTSD without depression have shown more variable outcomes (McInnes et al. 2025).

Can I do ketamine without therapy? Technically yes, but the strongest evidence for lasting benefit is when ketamine is combined with psychotherapy (especially trauma-focused approaches) or when it enables patients to engage in therapy they couldn’t before. (Feder et al. 2025). Ember requires patients to be working with a licensed mental-health provider.

What if I have a substance-use history? A history of substance use does not automatically disqualify you, but it requires careful risk assessment. Ember screens, monitors closely, and coordinates care with your treatment team to minimize risk.

Will I “dissociate” during the altered state? Ketamine-induced dissociation is a short, medically supervised, typically transient separation of sensory experience that resolves after the infusion. This is distinctive from trauma-driven dissociation, which is a chronic defensive response to overwhelming stress.

Disclaimer

This information is for educational purposes and does not replace medical advice. IV ketamine for depression and PTSD is an off-label use of an FDA-approved medication. Ember Health requires patients to work with a licensed mental health provider. Treatment outcomes vary by individual, and not everyone responds the same way. All treatments are administered in medically supervised settings with 1:1 patient-to-clinician ratios.