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Psychosis can reshape your entire reality. Relationships feel strained, work becomes overwhelming, and distinguishing what's real from what isn't grows increasingly difficult.

If you're researching ketamine therapy for psychosis, you've likely heard about its success in treating depression and other mental health conditions. Ketamine can help treatment-resistant depression when nothing else works, but it isn't suitable for psychotic disorders— understanding why matters for your safety.

This guide explains what psychosis is, why ketamine poses specific risks for psychotic conditions despite helping other mental health disorders, and which evidence-based treatments can provide real relief when first-line options aren't enough.

Psychosis describes a collection of symptoms where someone becomes disconnected from reality. Schizophrenia, for example, the most well-known psychotic disorder, affects approximately 0.25-0.64% of the U.S. population. 

Globally, psychotic disorders impact 23 million people worldwide. Core symptoms fall into three categories:

Positive symptoms add experiences that weren't there before:

Hallucinations (seeing, hearing, or sensing things that aren't present)

Disorganized speech and unusual behaviors

Negative symptoms take away normal experiences:

Cognitive difficulties impact daily functioning:

Problems with reasoning and decision-making

Reduced ability to focus and process information

The most common psychotic disorders include schizophrenia, schizoaffective disorder (combining psychotic and mood symptoms), and brief psychotic disorder. These conditions rarely occur alone—half of individuals with schizophrenia also experience depression, and 45% have anxiety disorders.

Why Is Ketamine Therapy Not Recommended for Psychosis?

ketamine's mechanism of action directly conflicts with how psychotic disorders function in the brain. Ketamine works by blocking NMDA receptors. For depression, this promotes new neural connections and helps the brain form healthier pathways, but psychotic disorders are linked to NMDA receptor dysfunction. Blocking these receptors can intensify symptoms rather than relieve them.

Ketamine has been used as a model for schizophrenia since the 1960s because it reliably produces psychosis-like experiences in healthy volunteers. A JAMA Network Open review confirms that ketamine induces both positive and negative symptoms of schizophrenia—a key reason ketamine therapy for psychosis is not recommended.

The Ketamine Hydrochloride Monograph states clearly: Ketamine “may exacerbate schizophrenia; generally avoid use in patients with schizophrenia or active psychosis."

Why Is Psychosis a Contraindication for Ketamine?

Beyond the mechanism conflict, ketamine poses specific safety risks for people with psychotic disorders. Many clinical references and experts recommend avoiding ketamine in people with active psychosis or schizophrenia due to the risk of symptom exacerbation. 

The FDA issued a warning in October 2023 about compounded ketamine products, listing psychiatric events as a primary safety concern. Ketamine commonly causes dissociative states—feeling disconnected from yourself or your surroundings. If you already struggle with reality testing due to psychosis, these effects become indistinguishable from psychotic episodes. You can't tell if you're experiencing the effects of medication or a worsening of your condition.

Research also shows cognitive worsening rather than improvement in patients with schizophrenia following ketamine exposure.

Specifically, ketamine can cause or worsen symptoms, including:

Hallucinations: intensifying or new ones emerging

Increased disorganized thinking and speech

Social cognition problems affecting relationships

Ketamine is also a Schedule III controlled substance with documented abuse potential. People with psychotic disorders have elevated rates of substance use disorders (approximately 50% lifetime co-occurrence).

What Treatments Actually Work for Psychosis?

In accordance with the guidelines set out by the American Psychiatric Association, most people with psychosis begin treatment with second-generation antipsychotics. These medications block dopamine receptors, reducing hallucinations, delusions, and disorganized thinking.

However, 20-30% of people with schizophrenia don't respond adequately to first-line treatment. If that's you, evidence-based alternatives do exist.

Clozapine is specifically recommended for treatment-resistant schizophrenia by the American Psychiatric Association. While it requires regular blood monitoring, it helps many people who haven't responded to other medications.

Long-acting injectable antipsychotics improve medication consistency and significantly reduce relapse risk compared to daily pills.

Cognitive behavioral therapy for psychosis (CBTp) is strongly recommended by WHO and NICE guidelines for all adults with psychotic disorders, helping to manage symptoms, challenge distressing beliefs, and develop coping strategies.

Psychosocial services round out comprehensive care: case management, supported employment, social skills training, and family therapy all support long-term recovery.

What Conditions Can Ketamine Therapy Help With?

While ketamine isn't appropriate for psychotic disorders, it works remarkably well for other treatment-resistant mental health conditions.

Ketamine therapy has shown strong results for:

Treatment-resistant depression: Response rates exceed 50%, with effects beginning within hours rather than weeks

Anxiety disorders: Ketamine targets different brain pathways than traditional medications

PTSD: Helps process traumatic memories when other treatments haven't worked

Borderline personality disorder: Supports emotional regulation and stability

If you have one of these conditions and haven't found relief through standard care, ketamine therapy might offer the breakthrough you've been searching for. 

Learn more about whether ketamine therapy is right for you.

How Can Innerwell Support Your Mental Health Journey?

Innerwell provides at-home ketamine therapy for conditions where it's proven safe and effective, including treatment-resistant depression, anxiety disorders, and borderline personality disorder. Every potential patient undergoes a comprehensive psychiatric evaluation to ensure safety and appropriateness.

Innerwell's eligibility criteria explicitly exclude patients with psychosis or psychotic disorders from ketamine treatment. This isn't a limitation—it's a commitment to your safety.

If you have a psychotic disorder, Innerwell still offers traditional psychiatry and therapy services that include: 

Medication management with qualified psychiatric providers

Individual psychotherapy using evidence-based approaches

Ongoing clinical support through a secure patient portal 

These services provide comprehensive mental health support tailored to your condition.

Take our free assessment to connect with Innerwell's clinical team about the right treatment path for your condition.

Can ketamine ever be used safely with psychosis?

No. Medical guidelines and clinical research consistently show ketamine poses significant risks for people with psychotic disorders. Ketamine directly induces psychotic symptoms and has been used as a research model for schizophrenia. No clinical trial evidence supports its use for psychotic conditions.

Why does ketamine help depression but not psychosis?

Ketamine's NMDA receptor blocking mechanism helps depression by promoting new neural connections. However, psychotic disorders involve dysregulated NMDA function where blocking these receptors worsens rather than improves symptoms. The same mechanism that heals depression circuits triggers psychotic symptoms.

What should I try if standard antipsychotics aren't working?

Evidence-based alternatives include clozapine for treatment-resistant schizophrenia, cognitive behavioral therapy for psychosis (CBTp), long-acting injectable antipsychotics, and comprehensive psychosocial services including family therapy and case management. Innerwell's psychiatric team can help you explore which options fit your situation.

Are any psychedelic therapies being studied for psychosis?

Current psychedelic research focuses primarily on depression, PTSD, and anxiety disorders. Given that psychedelics can trigger psychotic episodes, research in psychotic disorders remains extremely limited with no large-scale trials establishing safety or efficacy.

 Ketamine therapy isn't suitable for psychosis. Learn why, what the risks are, and which evidence-based treatments actually work for psychotic disorders.

Ketamine Therapy for Psychosis: What You Need to Know | Innerwell

Introduction

What Is Psychosis?

Ketamine Therapy for Psychosis: What You Need to Know

When traditional treatments haven't worked, the search for relief becomes its own burden. About one-third of people with major depression don't respond to standard medications, which is why ketamine-based treatments have gained attention as a different path forward.

But there are two main options, and they're not the same. Racemic ketamine contains the complete molecule, and some research suggests it may offer advantages in speed or magnitude of response. Esketamine (Spravato) uses half the molecule and comes with access and logistical considerations.

This guide explains the differences and what they mean for your decision, including why ketamine therapy you can do at home, has become a compelling option for many.

Ketamine is a medication with over 50 years of clinical safety data, FDA-approved as an anesthetic since 1970. Doctors have used it off-label since the early 2000s for depression, anxiety, PTSD, trauma, chronic pain, and other conditions.

Unlike traditional psychiatric medications that adjust serotonin over four to six weeks, ketamine works through the glutamate system—your brain's primary excitatory neurotransmitter. This different pathway is why ketamine can produce noticeable effects within hours rather than weeks, making it particularly appealing for people who haven't responded to conventional treatments.

The effects of a single ketamine session typically last one to three weeks, which is why most treatment protocols involve multiple sessions. This isn't a one-and-done solution—but for many people, the relatively rapid relief provides a window to build momentum with therapy and other support.

Ketamine is a "racemic mixture," meaning it contains two mirror-image molecules: S-ketamine and R-ketamine. This distinction matters—and we'll explain why shortly. Ketamine can be administered via IV infusion, intramuscular injection, or sublingual tablets.

Esketamine uses only one half of the ketamine molecule—the S-ketamine portion, isolated and formulated as a nasal spray called Spravato. It received FDA approval in March 2019 for treatment-resistant depression and major depressive disorder with acute suicidal ideation.

The spray is self-administered under medical supervision at certified clinics. Because of risks including sedation and dissociation, the FDA requires a REMS program—staff monitor blood pressure and symptoms throughout a mandatory two-hour observation period before patients are cleared to leave.

Treatment typically starts with twice-weekly visits for the first month (eight sessions minimum), then tapers to weekly or biweekly depending on response.

What's the Difference Between S-Ketamine and R-Ketamine?

This distinction is central to understanding which treatment may work better.

Racemic ketamine contains both S-ketamine and R-ketamine working together. Esketamine contains only S-ketamine—the R-ketamine half is removed.

Why does this matter? Early research suggests that R-ketamine may have longer-lasting effects with fewer side effects than S-ketamine alone, though human evidence is still preliminary and largely based on limited trials. A clinical study of 153 patients found that IV racemic ketamine produced faster and greater improvement than intranasal esketamine. The delivery methods differed, and broader meta-analyses show mixed results—but the findings add to the case for exploring the complete molecule.

So what does this mean for you? Racemic ketamine gives you both components working together—which some studies suggest may offer advantages, though the evidence is still evolving. For people weighing their options, this research is one reason at-home racemic ketamine programs have drawn interest as an alternative to esketamine clinics.

How Do Ketamine and Esketamine Work in the Brain?

Both ketamine and esketamine block NMDA receptors, triggering changes in your brain's glutamate system. This rapidly increases Brain-Derived Neurotrophic Factor (BDNF)—a protein that helps brain cells grow and form new connections.

Mental health conditions appear to physically affect brain structures, weakening connections in areas that regulate mood and stress. According to research in Nature, ketamine helps rebuild these pathways by promoting synapse formation and enhancing neuroplasticity—your brain's ability to form new neural connections.

This is why many clinicians emphasize pairing ketamine with therapy. The medication opens a window of neuroplasticity; therapeutic support helps you make the most of it. Without that integration, the benefits may fade faster.

Racemic ketamine activates these processes through both enantiomers, while esketamine relies on only one.

Want to understand the mechanism more deeply? See our guide on the science behind ketamine.

Spravato vs Ketamine: How Do Access, Cost, and Risks Compare?

Understanding the practical differences between these treatments is just as important as understanding how they work. Here's how they stack up:

Esketamine requires in-person treatment at certified clinics—and access is limited. According to Medicare claims data, 24 states had zero clinic-billed esketamine use in 2023, meaning nearly half of U.S. states had no documented access through Medicare.

Ketamine is more widely available since it doesn't require REMS-certified facilities, but without federal standardization, the quality of treatment depends entirely on the provider you choose.

Esketamine is expensive. Preliminary cost analyses estimate expenses can reach $6,785 for the first month, plus facility and transportation fees. Insurance may help, but coverage varies widely.

Ketamine costs vary by provider and delivery method. At-home sublingual programs like Innerwell can bring costs significantly lower—as low as $54 per treatment with insurance partnerships in select states.

Esketamine comes with structured oversight through the REMS program: mandatory observation periods, blood pressure monitoring, and certified clinic requirements. However, this oversight focuses on safety monitoring—not therapeutic integration or mental health support.

Ketamine oversight depends entirely on the provider. The FDA has cautioned against compounded products distributed without proper safeguards. This makes choosing a provider with comprehensive screening, licensed clinicians, and built-in therapeutic support essential.

Both treatments carry similar side effect profiles: headache, dizziness, nausea, dissociation, and drowsiness are most common. These effects are generally short-lived, with over 90% of people ready to resume normal activities within 90 minutes.

The FDA has documented respiratory concerns with esketamine when combined with benzodiazepines, opioids, or alcohol. Esketamine may also not be appropriate for those with vascular abnormalities or history of brain hemorrhage.

Both medications are Schedule III controlled substances. Long-term use may cause bladder issues, so ongoing monitoring should include screening for urinary symptoms.

How Does Innerwell's At-Home Ketamine Therapy Work?

Innerwell was designed to address the limitations of both esketamine clinics and inconsistent ketamine providers. The program delivers racemic ketamine with built-in therapeutic support through four phases:

Evaluation: A comprehensive virtual psychiatric assessment determines whether ketamine is appropriate and builds your personalized protocol.

Delivery: Once cleared, you receive sublingual ketamine tablets shipped securely to your door with dosing instructions and direct clinician access.

Preparation and integration: Preparation sessions help you set intentions before treatment. Integration exercises help you process insights afterward. Experts warn that ketamine without mental health follow-up can be risky—Innerwell builds this support into every plan.

Ongoing monitoring: Your care team tracks progress and adjusts treatment as needed.

For details on the experience, see what to expect. Innerwell offers transparent pricing with insurance partnerships in select states bringing costs as low as $54 per treatment. Review ketamine laws to understand regulations in your area.

The right choice depends on your circumstances, and this is a decision worth discussing with a clinician who knows your history.

Esketamine may make sense if you have specific reasons to prefer FDA-approved treatment, have insurance that covers it well, and can commit to twice-weekly clinic visits with two-hour observation periods. Some patients—particularly those who benefit from structured clinical oversight—may be better served in a REMS clinic setting.

At-home ketamine may be a better fit if you need flexible scheduling, live in an area without esketamine access, want therapist support built into your plan, or find the emerging research on racemic formulations compelling.

Red flags to watch for: Any program that skips mental health follow-up, promises permanent cures, or lacks proper supervision isn't prioritizing your safety. Innerwell was built to address these gaps.

Both treatments require ongoing sessions—most people need multiple treatments for sustained benefit. If you’re still weighing your options, read our guide to find out if ketamine is right for you.

Ketamine and esketamine both offer a path forward when traditional treatments haven't worked—but the experience, accessibility, and support around each differ significantly. Innerwell also works with people navigating childhood trauma, veterans seeking support, and couples looking to deepen their connection.

With Innerwell, you get licensed clinicians guiding your treatment, therapists helping you prepare and integrate, and monitoring that evolves with your progress. Every step turns a window of neuroplasticity into lasting change.

If you've been searching for relief that fits your life, we're here to help.

Ready to learn more? Take our free assessment.

How Long Does It Take for Ketamine to Work?

Most people notice effects within two to four hours—a dramatic difference from traditional medications that take weeks. Lasting improvement typically builds over multiple sessions as your brain forms new pathways.

Single doses typically last about one week; repeated treatments can extend benefits to two to three weeks. Neither ketamine nor esketamine provides a permanent cure, which is why Innerwell builds maintenance planning into every care plan. Learn more about whether ketamine is permanent.

Esketamine may have better coverage due to FDA approval, but costs can still be substantial. Innerwell has insurance partnerships in California and New York—and transparent self-pay pricing for everyone else.

Standard employment panels don't include ketamine, but specialized tests can detect it. Read our guide on ketamine and drug tests.

You may experience dissociation—a floating sensation—along with perception changes. Effects typically peak around 40 minutes and resolve within two hours. Many find the experience meaningful with proper intention setting. For details, read about what ketamine feels like.

Compare ketamine vs esketamine for depression treatment. Learn about efficacy, cost, access, and why at-home sublingual ketamine may be the better choice.

Ketamine vs Esketamine: Key Differences Explained | Innerwell

What Is Ketamine?

What Is Esketamine (Spravato)?

Spravato vs Ketamine: How Do Access, Cost, and Risks Compare?

Is Ketamine or Esketamine Right for You?

Explore Your Options With Innerwell

Ketamine vs Esketamine: Key Differences Explained

Racemic ketamine. S-ketamine. Esketamine. R-ketamine. Ketamine therapy keeps coming up in mental health conversations, but so does confusing terminology. What do these terms actually mean, and which one might help you?

The short answer: Racemic ketamine is the original, complete form of ketamine — a half-and-half mixture of two mirror-image molecules that work together. With over 50 years of medical use, it's the most studied form for mental health treatment. 

This guide breaks down how racemic ketamine works, how it compares to esketamine (Spravato), and how it can be delivered in clinical settings or at home with telehealth oversight.

Racemic ketamine is ketamine's original formulation, containing equal parts of two mirror-image molecules called S-ketamine and R-ketamine. FDA-approved as an anesthetic in 1970, it has been used medically for over five decades. When people refer to "ketamine therapy" for mental health, they usually mean racemic ketamine.

Think of your left and right hands — mirror images with the same structure, but a left glove won't fit your right hand. S-ketamine and R-ketamine share this same relationship. "Racemic" is a chemistry term meaning equal parts of these mirror-image molecules, called enantiomers.

Here's what makes it different: Studies suggest racemic ketamine may provide broader therapeutic effects than isolated versions — potentially because each enantiomer contributes something different to the healing process.

How Does Racemic Ketamine Work in the Brain?

Traditional antidepressants slowly adjust neurotransmitter levels over weeks. Racemic ketamine works differently. It produces rapid changes in brain activity and synaptic function, with clinical effects often noticeable within 24 hours.

Depression doesn't just change how you feel. It changes how your brain cells communicate. Neural pathways that once fired easily become sluggish. Connections weaken. Racemic ketamine appears to reverse this through a four-stage cascade:

 Racemic ketamine combines two molecular forms for potentially greater antidepressant effects than esketamine alone. Learn how it works and who it helps.

Therapy

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