Why anxiety spikes happen, and why they aren't dangerous
Walking into a ketamine clinic for the first time is, for almost everyone, a little scary. The medication has a reputation. The setting is unfamiliar. If you came in for treatment-resistant depression, PTSD, or chronic pain, the conditions themselves often run on a baseline of vigilance. Anxiety in that situation is not a malfunction. It is the nervous system doing what it has been trained to do.
The good news is that the anxiety that shows up in a clinical IV session is bounded. The dose is fixed. The medication is short-acting. Vital signs are continuously monitored. Nothing about the experience escalates the way it can in uncontrolled recreational use. Knowing the ceiling exists tends, by itself, to lower the floor.
Ketamine itself is FDA-approved as an anesthetic; its use for depression, anxiety, PTSD, and pain is off-label. We mention that here because part of managing in-session anxiety is having an honest map of what is happening pharmacologically. You are not taking a drug designed to scare you. You are taking a drug whose full surgical-anesthesia version has been used safely for decades, at a much lower dose, in a setting designed for the experience to feel manageable.
Preparation: what to do in the days and hours before
The most reliable way to lower in-session anxiety is to handle what you can the day before. Eat normally up to the time we ask you to stop. Hydrate. Sleep as well as you can. Wear loose clothing you can settle into. Bring a list of questions; write down anything you want your CRNA to know, including new medications, supplements, or recent illness.
If this is your first time, reading what to expect at your first infusion and what a ketamine infusion actually feels like tends to take the edge off. Knowing the rough shape of the experience shrinks the unknown. Many of the patients who report the worst pre-session anxiety have built up a mental picture out of recreational-use horror stories or one viral first-person account. Reality is usually quieter and more workable.
On the morning of, the practical questions are around medications. Bring your full list. Some prescriptions, particularly benzodiazepines like alprazolam, lorazepam, or clonazepam, can blunt ketamine's effects on glutamate and may reduce antidepressant response. Whether to hold a dose is a clinical conversation. Never stop or change a prescription on your own; talk to your prescribing provider and let our team know what they advise.
The mechanism: glutamate, NMDA, and why anxiety often softens once the drip starts
Ketamine works primarily as an NMDA receptor antagonist. By temporarily blocking those receptors, it triggers a downstream surge in glutamate signaling, BDNF expression, and synaptic plasticity. That cascade is the basis for the antidepressant and anti-anxiety effects researchers have documented in the past two decades.
One practical implication: many patients notice that the racing, anticipatory anxiety they walked in with quiets down within the first five to ten minutes of the infusion. The medication does not numb feeling, but it does loosen the grip of the alarm circuits that have been holding tight. That is part of why ketamine is being studied for anxiety disorders in the first place. The dissociative quality of the experience is also part of how it works; some distance from the threat-monitoring self is actually the therapeutic mechanism, not a side effect to fight.
That said, dissociation is not always pleasant on the way in. The first minute or two, when the body and visual field start to feel different, can register as alarming. Knowing that this is the medicine doing its job, not a sign that something is wrong, is one of the most useful things to remember.
What the CADSS literature tells us about dissociative experiences
The Clinician-Administered Dissociative States Scale (CADSS) was developed by Bremner and colleagues in 1998 and published in the Journal of Traumatic Stress. It is the standard instrument researchers use to measure acute dissociative experiences during ketamine infusions and other interventions. It asks about altered perception of time, body, surroundings, and self. The scale matters here because it is what gives us actual numbers, rather than anecdotes, about what people experience.
An analysis published in 2018 in the Journal of Affective Disorders by van Schalkwyk and colleagues looked at CADSS scores across ketamine infusions for mood disorders. The study documented that dissociative and anxiety responses vary widely from patient to patient, and even from session to session in the same patient. Some sessions produce vivid altered states; others feel more like a deep, drifting calm. Most responses were transient and resolved within hours of the infusion ending.
A separate body of work, including a 2021 systematic review and meta-analysis by Bahji and colleagues in the Journal of Affective Disorders, looked at ketamine's antidepressant and anti-anxiety effects across multiple controlled trials and found consistent benefit, with side effects largely confined to the infusion window itself. In other words: research suggests that the strange parts pass quickly, and the durable effects lean toward less anxiety, not more.
Dissociative and anxiety responses to ketamine vary widely between patients, but most are transient and resolve within hours. The clinical task is to support the patient through the acute window so the underlying therapeutic effect can take hold. — Based on Bremner et al., Journal of Traumatic Stress, 1998; van Schalkwyk et al., Journal of Affective Disorders, 2018
In-session techniques: breath, grounding, eye mask, music
If anxiety does spike during a session, there are several straightforward tools that tend to help. None of them require you to be a meditator. They work because they give the nervous system something concrete to land on while the medication does its work.
- Slow exhale breathing. Inhale through your nose for a count of four. Exhale through your mouth for a count of six or eight. The longer exhale activates the parasympathetic nervous system. Three or four cycles is usually enough to shift the body's signal from alarm to settle.
- Body anchor. Notice where the recliner is touching your back, the blanket on your legs, the weight of your hands. Naming three points of contact silently to yourself pulls attention out of the swirl and back into the body.
- Eye mask on or off. Most patients find the eye mask deepens the experience and makes it easier to ride. If, instead, the dark feels overwhelming, you can slide it up. Either is fine. The room is dim and safe with or without it.
- Music. A curated playlist is part of the experience for a reason. If the track that is playing feels wrong, say so; we can change it. Some people prefer ambient instrumental, others prefer something with a clear melodic structure to follow. Music selection during ketamine is a meaningful tool, not background filler.
- Naming what is happening. Saying internally "this is the medicine, this will pass, my body is safe" sounds simple. Under altered states it is surprisingly effective, because it reminds the part of you that is monitoring for threat that the situation has a known shape and a known end.
It is also worth saying: crying during a session is not a problem. Tears, grief, and surfacing memories are often a sign that long-stuck material is finally moving. The clinical team is comfortable with strong emotion. You do not need to perform calm.
When and how to signal your CRNA
Music City Ketamine is CRNA-led. A Certified Registered Nurse Anesthetist is the clinician with the most relevant training for monitoring an IV anesthetic medication, and Marla Peterson, CRNA, oversees every infusion at our clinic with anesthesia-level monitoring. A CRNA is in the room or immediately available throughout the session, watching vitals and able to respond within seconds.
If anxiety becomes more than you can ride with the techniques above, the right move is to signal. You do not need to wait until things feel unmanageable. Options include:
- Speak. You can talk during a session. Your voice may sound a little strange to you, but it works. A simple "I'm getting anxious" is enough.
- Lift the eye mask and make eye contact. The clinical team is watching. A look usually gets a check-in immediately.
- Raise a hand. If words feel hard, a hand goes a long way. We agree on signaling at the start of the session for exactly this reason.
From there, the clinician will sit with you, lower the music, talk you through grounding, and check vitals. Your blood pressure and heart rate are already being tracked continuously, so we have an objective read alongside what you are reporting. Most spikes settle within a minute or two of contact and reassurance.
What we have available if anxiety becomes overwhelming
In the small percentage of sessions where grounding and conversation are not enough, there are more direct tools. The most common is a low dose of a benzodiazepine, typically midazolam, given intravenously. Onset is fast, usually under a minute. It softens anxiety and dissociation without ending the session abruptly. We use it sparingly because, as noted earlier, benzodiazepines can blunt ketamine's antidepressant signal, but in the moment, comfort takes priority.
The infusion itself can also be slowed or, if needed, paused. Ketamine has a short half-life, so reducing or stopping the drip leads to noticeable changes within minutes. This is one of the quiet advantages of IV over oral or intramuscular ketamine: the dose is titratable in real time.
Equally important, the clinical environment is set up so that nothing about anxiety becomes dangerous. Continuous pulse oximetry, blood pressure monitoring, and ECG are standard. The CRNA's training is precisely for situations where a patient's physiology needs attention. The product here is the clinical standard, not any one promise about how a session will feel.
Integration: turning a hard session into useful material
A session with anxiety, tears, or a difficult memory is not a failed session. In the framework Dore and colleagues describe in their 2019 paper in the Journal of Psychoactive Drugs, set, setting, preparation, and integration are the variables that determine whether a ketamine experience becomes durable change. The strange or hard parts often carry the most useful material.
Integration is the work of putting the session into language and into life. Talking it through with an integration therapist the next day helps. So does journaling within twenty-four hours, before the details soften. Many patients work with a therapist alongside their infusions, in a model called ketamine-assisted psychotherapy. If you do not yet have an integration therapist, our team can help with finding one in Tennessee. Understanding the broader process is also worth a few minutes; how our treatment program works outlines the full arc.
If you are early in the process and unsure what good integration looks like, the simplest version is this: write down what came up, talk to someone trained, and notice what is different in the days that follow. Sessions that include hard moments often produce the most growth, because the nervous system finally had room to surface what it had been holding.
Honest expectations
A few honest notes. No clinic can promise zero anxiety during a session. Some activation is part of how the medication works, and a small percentage of patients will have a session that feels harder than the rest. Research suggests these sessions are still often productive; data does not support the idea that a difficult session means treatment is failing.
Ketamine for psychiatric and pain conditions remains off-label, with the exception of Spravato (esketamine), which is FDA-approved for treatment-resistant depression and MDD with acute suicidal ideation. Sessions at Music City Ketamine are $475 each, and most insurance plans do not cover off-label IV ketamine.
The thing to remember: anxiety during a ketamine session is normal, expected, and well within the range the clinical team is trained to manage. Preparation, breath, grounding, and integration are the active ingredients that turn a single infusion into durable change.