200mg ketamine trip

Mental Health

Mental health: why a ‘bad trip’ with ketamine treatment isn’t what you think it is.

Editor's Note

Any medical information included is based on a personal experience. For questions or concerns regarding health, please consult a doctor or medical professional.

Please see a doctor before starting or stopping a medication.

If you have experienced emotional abuse, the following post could be potentially triggering. You can contact the Crisis Text Line by texting “START” to 741741.

It was Wednesday and time for my ketamine treatment . There is a certain amount of routine to getting my treatments. When I started with ketamine I thought I would get the IV treatments once every three months or so. That’s what everything I had read said would happen. Maybe the “treatment-resistant” part of my bipolar disorder applies to ketamine too. I don’t know. In any case, we have determined that every other week works for me. By the beginning of the second week, I start to dip in mood. I can reach suicidal thinking by the time it’s time for the next infusion. We try not to let me get to that place.

The infusions are accompanied by psychedelic “trips.” That’s just part of ketamine. In the beginning, I believed that the trip didn’t matter — the drug got in me regardless of if the trip was “good” or “bad.” A lot of my trips are “bad.” I believe this is largely because of complex post-traumatic stress disorder ( C-PTSD ). I put bad in quotes because it’s not an accurate description. The trips can be scary. I see things and feel things that are frightening or unpleasant. I have been literally terrified several times. That doesn’t mean they’re bad, though.

The trip before last Wednesday’s infusion was terrifying. I screamed so hard that I lost my voice for almost a full week. I just screamed and screamed. I was certain that I was permanently trapped in this other world that I was hallucinating. The people in the room with me, the nurses and anesthetist, looked like stick figures. They were walking around and they were talking. I didn’t know what they were saying; I was too busy screaming, “Please, somebody, notice that I’m still trapped over here in this alternate universe. Let me out!” One of them was telling me I was OK. I was insisting, “I am not OK.” As the ketamine wore off, I returned to this world and realized everything was fine. Just like every other time.

When it was time for the next infusion two weeks later, the clinic director decided to have a nurse, Colleen, sit with me for the trip. The thinking was I would feel safer and stay calmer. Maybe not scream my head off. Colleen is special to me; she has been with me since my first infusion. She has held my hand many times when trips turned frightening, always reminding me “you are safe.” It was a logical and welcome decision to have Colleen sit with me.

Except in this trip, Colleen turned evil. The world was red and black, no other colors. The walls in the room looked like the walls in “The Matrix” with green code running down black walls. Except my “code” was red. Colleen was red and terrifying. She was saying terrible things. I was convinced that the clinic was a front for an evil organization trying to do mind control and keep me trapped in that cold, black-and-red world forever. I didn’t scream because Colleen was there. I was afraid of her. I was afraid of what might happen if I screamed. What would she do to me?

Coming out of that trip, I was convinced that it would be my last. I couldn’t keep doing this, I didn’t trust anyone; that’s part of C-PTSD after all. I sent the clinic director an email the next day and asked him if he could sedate me for my next trip. Sometimes when I get especially agitated during a trip, he will add in a little sedative toward the end. When he does that, I go home with little to no memory of anything that happened during the trip. He wisely answered that the trips were important; he wanted me to experience them.

And he’s right because here’s the thing. Those “bad” trips? They aren’t bad. They’re unpleasant. They’re scary. They’re challenging and very hard to go through. But they aren’t bad. Let me explain.

The day after the Red Colleen (sorry, Colleen) trip, I went to dinner with a friend. We talked about a lot of things. This was the first time we had gotten together since my suicide attempt two months earlier. I filled her in on what it was like when I made the attempt, the ambulance ride, the emergency room, the week spent on the medical floor of the hospital, and the week after that on the psychiatric floor. I walked her through all of it. On my drive home after dinner, I had to pull into a parking lot because I was so overcome with emotion that I couldn’t keep driving. I sat in the parking lot and sobbed, letting out all the emotion that had come up while talking to my friend. It was a good, cleansing cry. When I was composed enough to drive, I made my way home. Turned out, that cry was just the beginning.

Later that same night, after everyone had gone to bed, I was up by myself. I put YouTube on the television and played my favorite music video. I had discovered this video months earlier and it had become a constant as a self-care thing I did. This video could make me cry, it could make me laugh. Something about the music touched me deep in my soul; I physically felt the music. As it played this night, tears started to flow. And I let them.

That’s something my therapist has been working on with me for over a year: Feel the feelings. Don’t avoid them, don’t push them away. Stop the struggle. Feel them. As the song came to its end, I started to smile through my tears. This is an amazing piece of music. The next video started to play. I cried some more. For the next half hour, I cried as I listened to and felt the music. But I didn’t just cry. I was turned inside out. Something broke inside me. I sobbed. I laughed. I cried about the suicide attempt. I cried about the time in the hospital. I cried about how hard the past two years have been as I rapid-cycled through bipolar , up and down, going through six different medications on the way to being declared treatment-resistant and getting off all drugs. How much work I had done with my therapist, working through all the trauma of my childhood. And I kept crying.

Then I remembered my therapist had suggested the day before that I do a meditation we know called “Working with Difficulty.” It walks you through grounding like normal. But then the guide suggests that you take any negative emotion that is coming up and place it on the worktable of your mind. Find the physical sensations of it in your body. Where are you feeling this emotion?

The guide instructs that you don’t do anything to change your breathing, just notice it, focus on it. I was sobbing hysterically. And I kept sobbing. I was breathing; it was just sobs and hyperventilating, not the calm, controlled breathing I think of when I think of meditating. I let myself do it. I gave myself permission to feel this. To express it. As I worked through this 25-minute meditation, I let myself feel all of it. And as the crying continued, that traumatized little girl who had never been allowed to cry showed up. She started to cry. This is the miracle of ketamine: It allows your mind to do things it hasn’t been able to do before. That little girl had been shamed into never crying . It wasn’t allowed. And she desperately needed to cry. She was not going to be able to heal from the trauma until she could express all that she had stuffed so far down for so long. And I was able to give her permission. I encouraged her: yes, dear one, cry. Cry until you don’t have any tears left to cry.

And she did. She cried. She rocked back and forth. She hugged a pillow and sobbed into it. I don’t have words to describe what this experience was like. The intensity was beyond description. There was one point when I felt I was back in the psychedelic part of the ketamine trip. It’s like ketamine lets your mind open in places it hasn’t opened before. This gave me the space and the permission I needed to let this little girl cry her heart out.

This was such a healing episode. I’m not the same today. I’ve been used to learning coping skills in therapy. I assumed that was the best I could hope for — learning how to cope. But, no. This was healing. The pain that that little girl had held inside all these years was released. This isn’t the first time I’ve had such a physical reaction and release of repressed pain. And it is ketamine that allowed this — caused it.

As I said in the beginning, I believe there’s no such thing as a bad trip. Every trip I’ve had that was painful ended with something good. A new insight. An expression of long-buried pain. I feel it necessary to say that I have not arrived at these good results alone. I have needed the guidance of the people at the clinic. I have needed my therapist. I have needed my psychiatrist. I don’t know psychedelics. Had I done these trips on my own, I think I would have ended up further traumatized. These trips can get very difficult and very intense. But my subconscious has been hard at work during them. Things have bubbled to the surface — the conditioned emotional responses, the fight-or-flight triggers, the repressed memories, they have been in my mind all along. Ketamine, along with therapy, has allowed those things to surface and be dealt with. It’s a very powerful and healing combination.

For more on ketamine treatments for depression, bipolar disorder, trauma and other mental illnesses, see The Mighty Community’s posts here .

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Early childhood trauma and lifelong struggles with mental health led me to The Mighty. I've learned the power of sharing and not staying in this madness alone. Sometimes I can support, sometimes I need support.

Ketamine Dosage: How Much is OK and How Much is Too Much?

Ketamine dosage ranges depending on your consumption method. from intravenous to intramuscular to k-spray and more, here’s everything you should know..

Article by Jose Guzman & DoubleBlind Staff Medically Reviewed by: Dr. Michael Verbora Published on April 16, 2021 Updated February 23, 2024

We’ll start with the most important thing to know: Ketamine is powerful. The drug first appeared in clinical practice as an anesthetic in the 1960s. Doctors use ketamine in surgery to prevent people from feeling the pain of the operation. In veterinary science, ketamine tranquilizes large animals like horses. More recently, ketamine has a new purpose: treating depression and other mental health ailments. Ketamine is not considered a psychedelic in the usual sense—it’s a dissociative. But it can produce profound experiences comparable to classical psychedelics like LSD or psilocybin. Practitioners are leveraging these psychedelic properties to aid in the alleviation of mental health issues, particularly in the most complex and resistant cases. 

These same mind-altering properties also make ketamine a popular recreational drug: it’s a common find at music festivals and in the club scene. However, using ketamine outside of a medical provider’s care comes with a unique set of risks. Ketamine’s effects are dose-dependent, meaning that it can have drastically different effects depending on the dose. Further, different bodies respond differently to ketamine, meaning that the same dosage may affect every individual in unique ways. 

Taking too much ketamine can lead to a complete dissociation called a “K-hole,” making it risky to take alone. Many people find deep personal and spiritual meaning in their ketamine experiences—both in and outside of the clinic. However, having a skilled and trusted sitter or provider can be lifesaving. Ketamine can impact motor function after you cross a certain dosage threshold, making it difficult to move and easier to accidentally asphyxiate (suffocate) vomit. Mixing ketamine with other substances—particularly sedatives—can increase the likelihood of a deadly overdose. Those with pre-existing heart conditions and seizure disorders should be particularly mindful and seek medical supervision while using ketamine. 

Safety Note Ketamine overdose can be directly fatal in high doses and indirectly fatal even in lower doses due to severe injury and potential drowning.  It is not recommended to mix ketamine with other substances without medical supervision. It can be difficult to move your body after using this medicine, thus safety and surroundings should always be considered before use.  Always remain mindful and preference the lowest possible dose when engaging with ketamine outside of a provider’s care. It’s not recommended to use ketamine alone.

What is the ketamine experience like? 

Ketamine is a dissociative anesthetic with psychedelic properties. Dissociative drugs can cause both amnesia and pain relief, which is why they are commonly used in surgery. Overall, ketamine is a versatile molecule. It has a wide range of uses and effects. You can also take it in a variety of different ways—from nasal sprays to oral pills and powders. The drug has a short duration, around 45 minutes to 75 minutes, with an afterglow that can last a couple of hours. Generally speaking, low doses of ketamine will allow you to remain grounded in the “real world,” albeit in a dreamy floaty state where you can remain standing and—somewhat—interact with the people and things around you. People find that low doses cause increased sociability, mild inebriation, and a sense of seeing the world differently.

Higher doses can increase negative side effects like nausea and confusion. Increasingly higher doses will make physical movement hard or impossible, culminating in a K-hole. The K-hole experience can be risky and challenging, affecting both mental and physical safety. During a k-hole, your ability to move is decreased substantially. This means that it will be very difficult to move your body away from danger or help yourself if you begin to vomit while lying on your back. For this reason, it’s not recommended to use ketamine alone. The safest way to consume ketamine is under the guidance of professional care, someone who can address medical emergencies if they arise. 

During a k-hole or therapeutic ketamine experience, a person may undergo a partial or complete dissociation. This experience can be intensely visionary in the appropriate supportive circumstances. You may feel that your mind leaves your body and journeys into other realms. Your sense of self may disappear. Ego death is possible. But, while this experience can be fascinating and healing, it can also be disturbing and scary if not well supported or later integrated. Ketamine dosages used in surgery and anesthesiology go beyond these visionary doses, requiring continuous medical monitoring for heart rate and other complications. 

Read: There are 3 Types of Ketamine—Which One Works Best?

Deeper Learning Did you know that many psychonauts enjoy working with a trip sitter? A trip sitter is a trusted person who agrees to stay with you during your trips. Learn more about what makes a good trip sitter here .

So, is there a “safe” ketamine dosage?

Ketamine is a legal substance with ample medical use. So, precise dosage is generally calculated easily in medical centers. It is manufactured industrially in liquid form. In underground markets, liquid ketamine is often dried into a powder and sold in this crystalline form. Calculating doses is much easier with measurement devices.  Doctors and medical practitioners calculate ketamine dosage in milligrams per unit of body weight (kilos or pounds). The same should be done in non-medical settings to reduce accidental overdosing. You can always take more, but never less. 60 milligrams is a starting dose for intramuscular (IM) and intravenous (IV) treatments in clinics that use ketamine to treat mental health ailments. But, in an underground setting, it’s imperative to keep in mind that this amount can do little to a seasoned ketamine user, but it can send a first-timer directly into a K-hole. This is a very powerful medicine, and caution is always advised.

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The website Erowid is one of the most popular online resources to find information on all kinds of mind-altering substances and plants that aren’t often talked about in mainstream media, with abundant information and practical advice. The guidelines in this article should be taken as an orientation and not as medical advice, and as Erowid reminds us: “Every individual reacts differently to every chemical. Know your body, know your mind, know your substance, know your source…Individuals can respond differently to the same dosage. What is safe for one, can be deadly for another. Start low with new substances. Have a trusted companion/guide/sitter/friend present and/or available.”

Intranasal Ketamine Dosage

Powdered ketamine is the most usual route of administration (ROA) for people who use it outside of medical settings. It’s usually diverted from medical sources to the underground market, where it’s manufactured in liquid form and then dried up into a white powder. As a form of harm reduction, it’s a good idea to grind it well to reduce abrasion in the nasal mucosa. According to Erowid : 

• A threshold dose is 0.1mg/lb, approximately 10 to 15 milligrams. 
• A light dose is 0.15mg/lb, approximately 15 to 30 milligrams, enough for a beginner to experiment it’s effects. 
• A common dose is 0.3mg/lb, approximately 30 to 75 milligrams. 
• A strong dose is 0.5 to 0.75 mg/lb, approximately 60 to 125 milligrams. The K-hole can be reached with 1 mg/lb, approximately 100-250 milligrams.

Tolerance is a very important concept to take into consideration with ketamine. Heavy users take larger quantities to achieve desired effects, and reports of people snorting very large quantities of ketamine at once, sometimes 500 milligrams or more, are not unheard of—and also not recommended. Regardless of tolerance, the same harm reduction practices apply: Even experienced consumers can risk their physical safety by assuming they need a higher dose and falling into an unexpected K-hole at the wrong place at the wrong time. New users need much less ketamine. The onset of insufflated (snorted) ketamine takes about 10 to 15 minutes. It is always smart to weigh doses, at least at the beginning, when unfamiliar with the substance, one can be surprised at how many milligrams fit on the tip of a key or miniature spoon, a common method to insufflate small doses or ‘bumps’ of ketamine. The bioavailability of intranasal ketamine is considered low compared to IV and IM administration. Bioavailability refers to the amount of the substance that enters circulation through your body via different administration routes. According to most sources, insufflated ketamine has an availability of between 25 to 50 percent. Snorting ketamine is likely to be one of the greatest risks of developing ketamine abuse and dependence/addiction. While addiction and dependence are rare, most people addicted to ketamine today are using this medicine via snorting from street dealers. Testing underground ketamine with an at-home drug-checking kit is also extremely important: Underground powders and tablets can contain adulterants. Testing is the only way to make sure you’re getting what you expect.

Ketamine Dosage: Intranasal Spray

While this ROA is the same as insufflated, the method of delivery is different. An intranasal ketamine spray is a device designed to deliver a predetermined dose through the nasal mucosa, with the substance dissolved in a saline water solution at different concentrations. K-sprays make ketamine consumption less messy than snorting and also offer the advantage of knowing that each hit is the same dose. It is also more readily absorbable by the mucosa as it is in liquid form. Some users may opt to obtain or prepare their own makeshift sprays, but they are also made to order in pharmacies with a doctor’s prescription with a predetermined dose.

In 2019, the FDA approved Spravato, a ketamine nasal spray manufactured by the pharmaceutical Jansen, containing a filtered version of the medicine, esketamine. Esketamine is supposed to be more effective for treatment-resistant depression, although there is an ongoing debate around this aspect. Esketamine is the s-enantiomer of ketamine. Ketamine is a mixture of two enantiomers (mirror image molecules, like your hands): S-ketamine and R-ketamine (more on that here ). Spravato comes in prefixed single-use dose units of 56 and 84 milligrams, meant to be taken only in a physician’s office for treatment-resistant depression.

Intramuscular (IM) Ketamine Dosage

This ROA is used by therapists and psychiatrists in their practices who offer ketamine-assisted psychotherapy to treat depression and other mental health conditions. Therapists , treating conditions like depression, utilize a standardized dosage of 1 milligram per kilo of body weight with the goal of providing a “powerful interruption of the ordinary mind,” according to ketamine therapist Lauren Taus LCSW. Naturally, the dose is adjusted at the discretion of the therapist, starting lower or increasing it, depending on multiple factors. The onset of the medicine is around three minutes, and its bioavailability is almost total, at 93 percent.

The threshold for IM ketamine is at 0.1 milligram per pound; a light dose at 0.15 milligrams/lb; common is 0.2 mg/lb; strong is 0.5 mg/lb; the K-hole can be reached at 0.75 mg/lb and anesthetic doses at 1mg/lb. It’s not recommended to self-inject outside of a provider’s care; it’s not necessary, and it poses risks that other forms don’t while producing a similar experience. 

John Lilly MD (1915-2001) was a key figure in the history of ketamine. A neuroscientist, inventor, and writer, he explored human consciousness, dolphin communication, and described his experiments with high doses of ketamine. He mapped the inner realms of the ketamine experience and explained it in his book The Scientist: A Metaphysical Autobiography . Using IM ketamine injections, he established the areas reached with a graph of increasing dosages: At 30 milligrams, the “I” or Internal Reality was reached; at 75 milligrams, the “They” or Extraterrestrial Reality; at 150 milligrams, the “We” or Network of Creation; and at 300 milligrams the “Unknown” could be reached. But, these dosages are best saved for the guidance and supervision of a trained practitioner. It’s dangerous to self-experiment with high dosages, especially for people unfamiliar with ketamine. High dosages can severely limit your ability to move your body and make you more likely to overdose, which can be fatal.

Intravenous (IV) Ketamine Dosage

The intravenous route is mainly used by clinicians offering ketamine treatment for depression. It is done in a medical setting with a dripper and a needle inserted in the patient’s arm, wrist, or hand. The infusion is slowly paced in a period of time, usually around an hour. Most reports indicate a standardized dosage of 0.5 milligrams per kilo of body weight, but again, with this method being the domain of licensed medical practitioners, doctors may adjust the dose anywhere from 0.1 to 0.75 milligrams per kilo of weight at their discretion, taking multiple factors into consideration. The bioavailability of this delivery method is the highest at 100 percent.

Oral Ketamine Dosage

Swallowing ketamine is the least efficient method to take ketamine, as its bioavailability is the lowest among all the ROA at around 17 percent. The onset comes slowly, depending on stomach contents.The duration is longer, but the peak is not as high. It is considered by many to be a waste of medicine, as you are only effectively using a small percentage of it. Dosage ranges from 0.3 milligrams per pound for a threshold dose (40-50 milligrams); 0.6mg/lb for a light dose; 0.75-2mg/lb for a common dose; 1.5-2.5mg/lb for a strong dose; and 3-4 mg/lb to reach the k-hole.

Another method is to use ketamine troches or lozenges, meant to be swooshed in the mouth until complete dissolution and absorbed by the mouth’s mucosa. This method offers a bioavailability of around 25 to 30 percent, rendering a slower onset than IM, IV, or intranasal methods. As ketamine’s taste is pretty unpleasant, it is usually masked with some fruity flavoring. Troches and lozenges are compounded by specialized pharmacies with a doctor’s prescription, establishing the desired dosage, which can be anywhere from 100 mg to 1 gr troches, again at the discretion of a licensed medical practitioner.

Rectal Ketamine Dosage

Rectal administration of drugs is common for medical treatments, and people have used recreational drugs like amphetamines, MDMA , or cocaine with this method (called plugging or boofing in non-medical jargon). Ketamine is no different. The bioavailability is at 25 percent. The threshold starts at 0.3 mg/lb; a light dose 0.6mg/lb; a common dose 0.75-2mg/lb; a strong dose at 1.5-2.5 mg/lb; and the k-hole at 3-4 mg/lb. The onset is slow from five to 20 minutes, and the duration is longer, lasting one to two hours. Being the availability on the low side and a rather complex operation, it is not a common ROA for recreational users of ketamine. Rectal administration can also be quite dangerous as it more easily leads to overdose. Most patients who use this as such may have localized chronic pain to the rectum or pelvic region. 

Ketamine Dosage for Anesthesia

While this is the domain of anesthesiologists, it is interesting to note dosage values for anesthesia, compared to recreational dosages or for the treatment of mental health issues. The usual dose to induce anesthesia for surgery is at 1-4.5 mg/kg IV, repeated as needed to maintain this state. IM dosages are 6.5-13mg/kg for surgical anesthesia, repeated as needed to maintain it. This is how they started using ketamine for soldiers wounded in Vietnam in the Seventies, where respiratory monitoring was not available. Ketamine is widely used in veterinary medicine, hence the horse-tranquilizer stigma. Your cat or dog have probably taken more ketamine at once for surgery when spayed or neutered than many people. Dosages of this level require medical supervision. In summary, ketamine is a very versatile medicine and recreational substance. It can be delivered in many different forms to target pain, prepare for surgery, or alleviate mental pain and suffering. Many self-medicate with ketamine and may choose more riskier methods of consumption (snorting). It is prudent to always speak to a medical provider before engaging in the use of any substances. Ketamine addiction, while rare, can be extremely destabilizing and harmful.

Was this article helpful? Deepen your learning here.

Ketamine dependence is a real thing. Dr. Wesley Ryan talks to DoubleBlind about the dissociative drug. Learn more about ketamine dependence from Jose Guzman . 

Drugs acquired in underground settings can be contaminated. Testing before use is always advisable .

High doses of ketamine can cause a “k-hole,” a period of complete dissociation that can also cause temporary paralysis , which can be distressing and unsafe, particularly in the wrong set and setting . We asked the experts how to navigate the abyss.

In the event of an emergency, please dial local emergency services. For mental health assistance in the US, dial 988. For substance abuse help in the US, please dial the Substance Abuse and Mental Health Services Administration National Helpline at +1 (800) 662-4357.

This article is intended for educational and harm reduction purposes and should not be used in place of medical advice or treatment. DoubleBlind does not advocate participating in illicit activities. Always consult your local drug laws before engaging with illicit substances. Those who consume ketamine outside of medical supervision do so at their own risk.

DoubleBlind is a trusted resource for news, evidence-based education, and reporting on psychedelics. We work with leading medical professionals, scientific researchers, journalists, mycologists, indigenous stewards, and cultural pioneers. Read about our editorial policy and fact-checking process here.

DoubleBlind Magazine does not encourage or condone any illegal activities, including but not limited to the use of illegal substances. We do not provide mental health, clinical, or medical services. We are not a substitute for medical, psychological, or psychiatric diagnosis, treatment, or advice. If you are in a crisis or if you or any other person may be in danger or experiencing a mental health emergency, immediately call 911 or your local emergency resources. If you are considering suicide, please call 988 to connect with the National Suicide Prevention Lifeline.

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What to Know About Ketamine for Psychiatric Use

Its history and current use to treat depression and other disorders..

Updated April 26, 2024 | Reviewed by Michelle Quirk

• What Is Ketamine?
• Find a therapist to overcome depression
• Ketamine, initially devised as a surgical anesthetic, is now gaining in popularity as a psychiatric drug.
• Different forms of ketamine exist, but only the nasal spray "Spravato" is FDA-approved for psychiatric use.
• Ketamine induces feelings of relaxation and dissociation that can assist psychotherapy in different ways.

This post is Part 1 of a series.

Ketamine is a surgical anesthetic and analgesic drug that was first synthesized in 1962 and gained US Food and Drug Administration (FDA) approval in 1970 (Scarepace, Baresi & Morley, 1988) but more recently has been gaining traction for psychiatric treatment. At present, ketamine is now seen as a go-to drug, under controlled conditions, for those with treatment-resistant forms of depression , posttraumatic stress disorder ( PTSD ), and other psychological diagnoses.

Ketamine: A Brief History

Ketamine gained popularity during the Vietnam War for surgical use because of its safety profile, relative to phencyclidine (PCP); however, for various reasons, its use at high doses declined over time for surgical purposes (Carillo et al., 2022; Sachdeval et al., 2023). The years following the Vietnam War saw increasing reports—both published and unpublished—of ketamine being used off-label to treat numerous psychiatric conditions, especially depression (Dore et al., 2019).

Then, in the 1990s, dissatisfaction with existing antidepressants that modulate norepinephrine and serotonin (i.e., tricyclic antidepressants and selective serotonin reuptake inhibitors, or SSRIs) led researchers to explore drugs that affected glutamate—and specifically within the N-methyl-D-aspartate (NMDA) receptor class—with ketamine being a prime focus (Berman et al., 2000). Though at the time the serotonin hypothesis of depression appeared to have considerable scientific support, decades later we'd learn that many of the studies validating this hypothesis (and SSRI use for depression) were either faulty or their treatment effects were misrepresented ( Moncrief et al., 2023 ).

Though ketamine's exact mechanisms of action are not completely understood, as it has both direct and indirect effects involving multiple neurotransmitters and brain regions, it's believed that ketamine’s psychotropic effects come, in part, from its antagonism of NMDA glutamate receptors (Bahji et al., 2021) and subsequent suppression of glutamatergic input onto GABA-ergic interneurons. Interestingly, ketamine's novelty as an antidepressant isn't just because it works on different neurotransmitters than existing drugs; findings from animal studies suggest that ketamine’s psychological/psychotherapeutic benefits may be related to its potential for neuroplastic and neurogenic responses (Bahji et al., 2021), as well as synaptogenesis and synaptic potentiation (Abdallah et al., 2015; Drodz et al., 2022; Zanos et al., 2018).

Ketamine also has applications in veterinary medicine as both an anesthetic and analgesic; however, it's important to note that in addition to its medical uses, ketamine has a dark history as an illicit street drug (under the name "Special K") used for getting high.

Ketamine's Different Forms and Their Legal Status

The original form of ketamine, formally known as "racemic" ketamine, is composed of two mirror-image molecules or enantiomers, known as S(+)-ketamine and R(–)-ketamine. S(+) and R(–) forms of ketamine can be isolated and compounded independently, and, theoretically, all three forms can be used pharmaceutically (Bahji et al., 2021; Scarepace, Baresi, & Morley, 1988), though typically only the racemic and S(+) forms are used.

At present, racemic ketamine is not FDA-approved for psychiatric treatment; however, it's been used off-label for decades for psychiatric treatment, and it's currently one of the two forms commonly used today in this capacity. However, in 2019, the S(+) form of ketamine (generic name " esketamine "; trade name “Spravato”) attained limited FDA approval as a nasal spray for adults with treatment-resistant depression (TRD) , and then in 2020 approval was extended to those with major depressive disorder with suicidal thoughts or behavior (Mischel & Balon, 2021). In both cases, approval limited use to the Risk Evaluation and Mitigation Strategy (REMS) safety program . Under the REMS program, Spravato must be administered in certified, medically supervised health care settings where patients are closely monitored (Cottone, 2023).

Though esketamine/Spravato is offered exclusively as a nasal spray, racemic ketamine can be administered in several ways, including noninvasively through oral and nasal routes, as well as by injection (i.e., subcutaneous, intramuscular, or intravenous), with each route of administration having advantages and disadvantages. In general, administration routes that are less invasive (e.g., oral and nasal) have lower bioavailability and absorption rates and, thus, require higher doses (with greater side effects) than injection routes (e.g., IV).

As noted above, ketamine dosing depends on which form (racemic vs. esketamine) and which administration route (e.g., oral, nasal, IV) is used. The esketamine/Spravato nasal spray , which at present is the only FDA-approved form of ketamine, is dispensed in spray bottles that have two sprays of the drug in each device, with each spray being 14 mg (and each bottle having 28 mg). Officially, Janssen (the manufacturer of Spravato) recommends dosages up to 84 mg (i.e., six sprays or three spray bottles); however, unofficially, I've worked with patients taking Spravato who have had off-label doses higher than this.

Racemic ketamine can be administered, off-label, in several forms. As a nasal spray, racemic ketamine is often compounded in bottles with higher volumes than Spravato bottles, where each spray is 10 mg, and typical doses are between 100 and 200 mg (i.e., 10 to 20 sprays). When administered intravenously, dosages (which are typically smaller than the nasal sprays) can be fine-tuned more easily to a patient’s optimal level, and it works faster than other routes (Tully et al., 2022). Fava and colleagues (2018) demonstrated that both standard IV doses (0.5 mg/kg) and high IV doses (1.0 mg/kg) are superior to placebo ; however, interestingly, standard IV doses (0.5 mg/kg) showed greater and longer-lasting effects than high IV doses (1.0 mg/kg). To put these doses into context, a 200-pound man has a mass of 91 kg, and so a standard IV dose of 0.5 mg/kg equates to 45.5 mg while a high IV dose equates to 91 mg.

Oral forms of racemic ketamine (e.g., tablets, lozenges, and sublingual wafers) have lower bioavailability (20-25 percent) than intravenous (almost 100 percent) or intranasal esketamine (50 percent), and they're non-FDA-approved as well (Sobule & Ithman, 2023). Higher doses of oral ketamine (e.g., 150–250 mg, sublingually) are typically required due to their lower bioavailability, thus increasing the likelihood of adverse side effects.

What Does Ketamine Feel Like?

During an active treatment, which ranges from 30 to 90 minutes, individuals taking ketamine commonly report feeling relaxation, dissociation, being in a "trance-like state," relief of physical pain, floating, having an out-of-body experience , synesthesia , and subjective distortions of time (e.g., an hour feels like five minutes). On an anecdotal level, one patient recently told me that she often feels "the cord is cut" between her thoughts and her emotions during a ketamine session. Another patient frequently tells me that during each session he feels "the deck is cleared" in his mind of any psychological or emotional obstacles bringing him down or holding him back.

It's because of the emotional freedom referenced above that some of the best psychotherapy sessions may be possible when patients are having a ketamine session. Apropos of this, I recently published an account of one of the many impactful ketamine-assisted psychotherapy (KAP) sessions that I've had with my patients. During this session, ketamine allowed one of my patients to achieve significant separation between the memories of her past traumas and her emotional reactivity to them. As a result, she was able to consider ideas, perspectives, and interventions that, previously, her defense mechanisms would have rejected, and this spurred considerable progress in therapy in the weeks that followed (Cottone, 2023).

Depending on the dose, some patients can talk during a ketamine treatment while others can not. When doing a KAP with one of my patients and their psychiatrist, we often use a lower dosage so that they can communicate with me during their ketamine session.

Ketamine Side Effects

At the low doses of ketamine used for psychiatric treatment, most side effects are transient and usually resolve in an hour, with the most common being sleepiness, dizziness, blurred vision, nausea, and dry mouth. Other temporary, cardiovascular side effects include palpitations, elevated blood pressure, and increased heart rate, and, for this reason, ketamine treatment is often contraindicated for individuals with serious cardiovascular conditions. Furthermore, ketamine treatment is not recommended for anyone who has, or is at risk for, a psychotic disorder, as ketamine can induce psychotic-like symptoms in these individuals.

It's also possible that an individual having a ketamine treatment may experience a "bad trip," colloquially known as "falling into a k-hole." A k-hole is an acute, dissociative state that results from ketamine intoxication. It can sometimes be accompanied by physical immobilization, an inability to speak, and anxiety symptoms. K-hole experiences are more common when ketamine is used illicitly, outside of a medical context, but can sometimes occur during a formal treatment session. In my experience, k-holes are more common when an individual has not eaten all day before a session, is sleep-deprived, or is sick.

In Part 2 of this series, a summary and case report of ketamine-assisted psychotherapy (KAP) is presented.

Abdallah, C.G., Sanacora, G., Duman, R.S., & Krystal, J.H. (2015). Ketamine and rapid-acting antidepressants: A window into a new neurobiology for mood disorder therapeutics. Annual Review of Medicine 66(1), 509–523. doi: 10.1146/annurev-med-053013-062946

Bahji, A., Vazquez, G.H., Zarate Jr., C.A. (2021). Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis. Journal of Affective Disorders , 278:542–555. doi: 10.1016/j.jad.2020.09.071

Berman R.M., Cappiello A., Anand A., Oren, D.A., Heninger, G.R., Charney, D.S., & Krystal, J.H. (2000). Antidepressant effects of ketamine in depressed patients. Biological Psychiatry . 47(4), 351–354. doi : 10.1016/s0006-3223(99)00230-9 .

Carrillo, R. L., Garcia, K., Yalcin, N., Shah, M. (2022). Ketamine and its emergence in the field of neurology. Cureus 14(7). doi: 10.7759/cureus.27389

Cottone JG. Ketamine-Assisted Psychodynamic Psychotherapy. Psychodyn Psychiatry. 2023 Dec;51(4):467–478. doi: 10.1521/pdps.2023.51.4.467. PMID: 38047669.

Dore, J., Tunipseed, B., Dwyer, S., Turnipseed, A., Andries, J., Ascani, G., Monnette, C., Huidekoper, A., Strauss, N. & Wolfson, P. (2019). Ketamine assisted psychotherapy (KAP): Patient demographics, clinical data and outcomes in three large practices administering ketamine with psychotherapy. Journal of Psychoactive Drugs , 51(2), 189–198. https://doi.org/10.1080/02791072.2019.1587556

Moncrieff, J., Cooper, R.E., Stockmann, T. et al. The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry 28, 3243–3256 (2023). https://doi.org/10.1038/s41380-022-01661-0

Mischel, N.A. & Balon, R. (2021). J Clin Psychopharmacol. 2021 May-Jun; 41(3): 233–235. Published online 2021 Apr 23. doi: 10.1097/JCP.0000000000001395

Sachdeva, B., Sachdeva, P., Ghosh, S., Ahmad, F., Sinha, J.K. (2023). Ketamine as a therapeutic agent in major depressive disorder and posttraumatic stress disorder: Potential medicinal and deleterious effects. Ibrain, 9(1), 90–101. https://doi.org/10.1002/ibra.12094

Scarpace PJ, Baresi LA, Morley JE. (1988). Glucocorticoids modulate beta‐adrenoceptor subtypes and adenylate cyclase in brown fat. American Journal of Physiology: Endocrinology and Metabolism, 255(2):E153–E158. doi: 10.1152/ajpendo.1988.255.2.E153.

Sobule R, Ithman M. Ketamine: Studies Show Benefit. Mo Med. 2023 Jan-Feb;120(1):29–30. PMID: 36860608; PMCID: PMC9970333.

Tully, J. L., Dahlén, A. D., Haggarty, C. J., Schiöth, H. B., & Brooks, S. (2022). Ketamine treatment for refractory anxiety: A systematic review. British Journal of Clinical Pharmacology, 88(10), 4412–4426.

John G. Cottone, Ph.D., is a psychologist in private practice, a clinical assistant professor of psychiatry at the Renaissance School of Medicine at Stony Brook University, and the author of Who Are You?

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At any moment, someone’s aggravating behavior or our own bad luck can set us off on an emotional spiral that threatens to derail our entire day. Here’s how we can face our triggers with less reactivity so that we can get on with our lives.

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Ketamine trips are uncannily like near-death experiences

Photo by JR Korpa/Unsplash

by Christian Jarrett   + BIO

First-hand accounts of what it is like to come close to death often contain the same recurring themes, such as the sense of leaving the body, a review of one’s life, tunnelled vision and a magical sense of reality. Mystics, optimists and people of religious faith interpret this as evidence of an afterlife. Skeptically minded neuroscientists and psychologists think that there might be a more terrestrial, neurochemical explanation – that the profound and magical near-death experience (NDE) is caused by the natural release of brain chemicals at or near the end of life.

Supporting this, observers have noted the striking similarities between first-hand accounts of NDEs and the psychedelic experiences described by people who have taken mind-altering drugs.

Perhaps, near death, the brain naturally releases the same psychoactive substances as used by drug-takers, or substances that act on the same brain receptors as the drugs. It’s also notable that psychedelic drugs have been taken by the shamans of traditional far-flung cultures through history as a way to, as they see it, visit the afterworld or speak to the dead.

To date, however, much of the evidence comparing NDEs and psychedelic trips has been anecdotal or based on questionnaire measures that arguably struggle to capture the complexity of these life-changing experiences. Pursuing this line of enquiry with a new approach, an international team of researchers led by Charlotte Martial at the University Hospital of Liège in Belgium has conducted a deep lexical analysis , comparing 625 written narrative accounts of NDEs with more than 15,000 written narrative accounts of experiences taking psychoactive drugs ( sourced from the Erowid Experience Vaults, a US-based non-profit that documents psychoactives), including 165 different substances in 10 drug classes.

The analysis, published online in Consciousness and Cognition in February 2019, uncovered remarkable similarities between the psychological effects of certain drugs – most of all ketamine, but also notably the serotonergic psychedelic drugs such as LSD – and NDEs. Indeed, the five most common category terms in the narrative accounts of people who’d taken ketamine were the same as the five most common in the accounts of NDEs, suggesting ‘shared phenomenological features associated with an altered state of perception of the self and the environment, and a departure from the everyday contents of conscious mentation’.

From category to category, the semantic similarity is profound. When referring to perceptions, both groups used the words ‘face’ and ‘vision’. The emotional word most commonly used by both was ‘fear’. In the category of consciousness and cognition, drug-takers and participants who’d been close to death most often referred to words such as ‘reality’, ‘moment’, ‘universe’, and ‘learn’. The setting was often described as ‘door’ and ‘floor’. A negative tone emphasising unpleasant bodily sensations was a shared common theme, as well.

T he findings back up the observations of some of the most famous 20th-century explorers of the psychedelic world – the American psychologist Timothy Leary described trips as ‘experiments in voluntary death’, and the British-born writer and philosopher Gerald Heard said of the psychedelic experience: ‘That’s what death is going to be like. And, oh, what fun it will be!’ But claims about the similarities go beyond these famous reports. The new research legitimises the long-standing analogy between the experience of dying and the acute effects of certain psychoactive drugs. Links between dying, death, a potential existence of afterlife and certain hallucinogenic plants and fungi emerged independently across different societies, and are also ubiquitous in contemporary psychedelic culture. However, empirical research has been scarce, until now.

To an extent, the results also support neurochemical accounts of NDEs, and especially the controversial proposal that such experiences are caused by the natural release of an as-yet-to-be-discovered ketamine-like drug in the brain (adding plausibility to this account, ketamine is known to act on neural receptors that, when activated, help to prevent cell death and offer protection from lack of oxygen).

‘This body of empirical evidence supports that near-death is by itself an altered state of consciousness that can be investigated using quantitative psychometric scales,’ the researchers say. That in itself is quite a realisation. As they note wryly, ‘Unlike other human experiences, dying is difficult to study under controlled laboratory conditions by means of repeated measurements,’ making it a challenge to investigate NDEs experimentally. Although the new research lacks laboratory control, on the plus side, the lexical comparison that Martial’s team conducted is ‘massive both in terms of the investigated drugs and the number of associated reports’.

The limitations of the current approach, including a reliance on retrospective reports, often decades-old, means, as the researchers put it, that they cannot validate nor refute the neurochemical models of NDEs. ‘However,’ they add, ‘our results do provide evidence that ketamine, as well as other psychoactive substances, result in a state phenomenologically similar to that of “dying” (understood as the content of NDE narratives). This could have important implications for the pharmacological induction of NDE-like states for scientific purposes, as well as for therapeutic uses in the terminally ill as means to alleviate death anxiety. We believe that the development of evidence-based treatments for such anxiety is a cornerstone of a more compassionate approach towards the universal experience of transitioning between life and death.’

They also warn experimenters to be prepared and beware. ‘The intensity of the experience elicited by [ketamine] relative to cannabis may represent a shock to unsuspecting users, who could retrospectively report the belief of being close to death,’ the researchers say. Pot-smokers, you’ve been warned. As one of the most intense and life-changing altered states known, an NDE is no toke on a pipe after class or work.

This is an adaptation of an article originally published by The British Psychological Society’s Research Digest.

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Ketamine for Depression, 4: In What Dose, at What Rate, by What Route, for How Long, and at What Frequency?

Affiliation.

• 1 Department of Psychopharmacology, National Institute of Mental Health and Neurosciences, Bangalore, India. [email protected].
• PMID: 28749092
• DOI: 10.4088/JCP.17f11738

Background: Ketamine, administered in subanesthetic doses, is an effective off-label treatment for severe and even treatment-refractory depression; however, despite dozens of studies across nearly 2 decades of research, there is no definitive guidance on matters related to core practice issues.

Methods: This article presents a qualitative review and summary about what is known about ketamine dosing, rate of administration, route of administration, duration of treatment, and frequency of sessions.

Results: Ketamine is most commonly administered in the dose of 0.5 mg/kg, but some patients may respond to doses as low as 0.1 mg/kg, and others may require up to 0.75 mg/kg. The ketamine dose is conventionally administered across 40 minutes; however, safety and efficacy have been demonstrated in sessions ranging between 2 and 100 minutes in duration. Bolus administration is safe and effective when the drug is administered intramuscularly or subcutaneously. Whereas the intravenous route is the most commonly employed, safety and efficacy have been described with other routes of administration, as well; these include oral, sublingual, transmucosal, intranasal, intramuscular, and subcutaneous routes. Patients may receive a single session of treatment or a course of treatment during the acute phase, and treatment may rarely be continued for weeks to years to extend and maintain treatment gains in refractory cases. When so extended, the ideal frequency is perhaps best individualized wherein ketamine is dosed a little before the effect of the previous session is expected to wear off.

Conclusions: There is likely to be a complex interaction between ketamine dose, session duration, route of administration, frequency of administration, and related practice. Until definitive studies comparing different doses, rates of administration, routes of administration, and other considerations are conducted, firm recommendations are not possible. From the point of view of clinical practicability, subcutaneous, intranasal, and oral ketamine warrant further study. If domiciliary treatment is considered, the risk of abuse must be kept in mind.

© Copyright 2017 Physicians Postgraduate Press, Inc.

Publication types

• Comparative Study
• Antidepressive Agents / administration & dosage*
• Antidepressive Agents / adverse effects
• Depressive Disorder, Major / drug therapy*
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Infusions, Intravenous
• Injections, Intramuscular
• Injections, Subcutaneous
• Ketamine / administration & dosage*
• Ketamine / adverse effects
• Treatment Outcome
• Antidepressive Agents

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Safety, effectiveness and tolerability of sublingual ketamine in depression and anxiety: A retrospective study of off-label, at-home use

Kazi hassan.

1 Nue Life Health, Miami, FL, United States

William M. Struthers

2 Psychology Department, Wheaton College, Wheaton, IL, United States

Aditya Sankarabhotla

Patrick davis.

3 Children's Hospital, Boston, MA, United States

Associated Data

The datasets presented in this article are not readily available because this data is a retrospective chart study of patient data from a private healthcare provider. Requests to access the datasets should be directed to efil.eun@hk .

Intravenous and intranasal ketamine have been shown to be effective therapeutic options in patients suffering from treatment-resistant depression (TRD). The use of sublingual (SL), rapid dissolve ketamine tablets (RDT) offers a novel approach for delivery for mental health indications. This study assessed the effectiveness and safety of self-administration of off-label, SL, rapid dissolve ketamine tablets (RDT) at-home for depression and anxiety. Intake scores on the Generalized Anxiety Disorder Screener (GAD-7) and Patient Health Questionnaire (PHQ-9) were compared to scores after treatments of three doses of ketamine RDT, and after six doses of ketamine RDT. After three doses of SL ketamine, 47.6% of patients showed a significant decrease in PHQ-9 scores, and 47.6% of patients showed a significant reduction in GAD-7 scores. Reduction rates were higher in those patients who completed a clinically recommended six doses of RDT ketamine. This study demonstrates that SL ketamine is a novel, safe, and effective treatment for TRD and treatment-resistant anxiety. SL ketamine offers an alternative therapeutic approach to IV ketamine when treating those with TRD.

Introduction

Major Depressive disorder (MDD) is a common and debilitating psychiatric condition that affects nearly 350 million people globally ( 1 ). Approximately 8.1% of Americans aged 20 and over reported depression symptoms in a given 2-weeks period ( 2 ). First-line treatment of MDD utilizes antidepressants that prove to be effective in alleviating symptoms in approximately 50% of patients ( 3 ). It is estimated 30% of MDD patients fail to respond to at least two antidepressants resulting in treatment-resistant depression (TRD). Suicide risk for TRD patients is higher than that of non-TRD patients diagnosed ( 4 ). Range of symptom severity, sequelae, and clinical comorbidity continue to be an area of interest when determining best course of treatment for MDD.

Clinicians have also long recognized that treatment of depression may be unsuccessful if accompanying anxiety disorders are not recognized and addressed ( 5 ). Of note, generalized anxiety disorder (GAD) is known to have a high comorbidity rate in patients with TRD ( 6 , 7 ). Benzodiazepines are commonly utilized in the treatment of depression with anxiety and offer a different pharmacodynamic profile when compared to antidepressants ( 8 ), it has been reported that IV ketamine antidepressant effects are interfered with in those concurrently using benzodiazepines ( 9 ). The use of benzodiazepines complicates the use of ketamine since anxiety and depression co-occur frequently, and either's symptoms may present as the primary diagnosis. The National Comorbidity Survey demonstrated that an anxiety disorder was comorbid in 58% of the patients diagnosed with MDD at some point in their lifetime ( 10 ). These comorbid anxiety symptoms (and potential comorbidity) can complicate the treatment of depression and comorbid anxiety is associated with a greater severity of depressive symptoms and an increased time to recovery. Comorbid anxiety is also associated with a resistance to pharmacological treatment for depression (i.e., TRD), increased incidence of relapse, and suicidal ideation ( 11 ). A balanced assessment and approach to TRD also requires an examination of comorbidity issues which may mediate response to treatment.

In recent years there has been increased attention paid to alternative pharmacological interventions for patients with TRD ( 12 ). One of these drugs is the anesthetic ketamine ( 12 – 16 ). Ketamine's pharmacodynamic profile is that of a dissociative anesthetic and N-methyl-d-aspartate receptor (NMDA) receptor antagonist ( 17 – 19 ). Berman et al. was the first study to reveal that a single intravenous (IV) dose of ketamine as effective in treating MDD ( 20 ). Their randomized, doubl- blind study on a small group of subjects with MDD using IV ketamine hydrochloride (0.5 mg/kg) or saline over 2 days resulted in a significant reduction of depression symptoms as measured by a reduction in Hamilton Depression Rating Scale after ketamine treatment when compared to saline. Reports examining the effectiveness of ketamine in randomized, double-blind controlled trials in the past decade has seen an increase in clinical interest ( 21 , 22 ). A review of the literature reveals intravenous (IV) infusions of ketamine tend to be the preferred route of administration ( 23 ). A systematic review of 288 published studies on IV ketamine's side effects and safety profile reported that acute side-effects were commonly associated with single-dose use ketamine for TRD, though they are generally transient and spontaneously resolve and are relatively understudied ( 24 ). A limitation of IV ketamine infusions is that they require a medicalized setting and incur considerable resources and cost. There is sufficient evidence of effectiveness to warrant inclusion as a treatment option with intranasal (IN) esketamine approved by the FDA in 2019 for TRD. Several randomized control trials of racemic ketamine have been published since IN esketamine's approval demonstrating its effectiveness as a tool in treating MDD or TRD ( 25 – 36 ). Studies on transmucosal and sublingual (SL) ketamine provide another alternative to oral ketamine use in the treatment of depression ( 37 – 41 ). Oral ketamine, while less commonly used compared to the gold standard of IV ketamine, has been tested extensively from a pharmacodynamic and pharmacokinetic perspective. Specifically, oral ketamine has been shown to undergo extensive first-pass metabolism and consequently has approximately 10–20% bioavailability, while SL ketamine has a bioavailability of approximately 30% ( 42 , 43 ), a fact which must be taken into account when designing outpatient oral or SL ketamine treatment regimens. A recently published manuscript has reported similar effectiveness and safety of at-home SL ketamine using a prospective study design ( 44 ). The authors found that SL ketamine (three treatments with doses ranging 300–450 mg/kg) in combination with telehealth produced approximately 60% reduction in PHQ-9 and GAD scores at the 4-weeks timepoint compared to baseline scores, roughly comparable with our study. Further work, which we are currently engaged in, will be needed to delineate not only the most effective dosing regimen, but also to identify likely responders based on patient characteristics.

The present study is a retrospective review of patients who had received off-label ketamine using a rapid dissolve tablet for SL delivery treatment at-home for their TRD. The present study examined the effectiveness and safety of the clinical use of at-home, self-administered SL ketamine (300/450 mg) on depression and anxiety symptoms in treatment-resistant patients. This data is related to patients who were treated at home, a model that was created in response to COVID-19 restrictions and using off-label prescription of SL ketamine rapid dissolve tablets, and extends on previous research in that it is the first of its kind examining at-home use of SL ketamine within a clinical context.

Ethics approval

The protocol for this retrospective study was reviewed by the Wheaton College (Wheaton, IL) Institutional Review Board (Protocol #1828103-1; Exempt Category 4.iii) which follows the ethical principles outlined in 45 CFR 46.104(d). The protocol was approved on 11/15/2021.

Dataset and chart review process

An overview of the dataset analysis and process by which the data was obtained is shown in Figure 1 . Data was obtained from a telemedicine practice that offered ketamine treatment that specializes in at-home, SL ketamine use. Between 12/1/2020-9/30/2021, 1101 individuals experiencing treatment-resistant anxiety or depression sought treatment from the telemedicine practice My Ketamine Home. A new patient registration form including a detailed health history and demographic information was completed, and a telemedicine intake consult was then performed. Relevant medical history was evaluated by Psychiatric Mental Health Nurse Practitioners to diagnose MDD and Generalized anxiety on DSM-5 criteria. This intake also included: (1) any current or presenting medical illnesses or previous psychiatric diagnosis, (2) information about previous failed pharmacological treatments for any depression or anxiety, and (3) other comorbid symptoms. Additionally, respondents were given the Patient Health Questionnaire (PHQ-9) to establish an intake baseline for their depressive symptoms, and the Generalized Anxiety Disorder Screener (GAD-7) to determine baseline anxiety symptoms. Based on this information, an evaluation for the clinical appropriateness of ketamine treatment for depression or anxiety was made by the practice. Exclusion criteria for ketamine consisted of indications of any of the following conditions/symptoms: (1) active suicidal ideation, (2) uncontrolled hypertension (HTN), (3) liver disease, or (4) schizophrenia, active substance use disorder, or other primary psychotic disorder. Uncontrolled HTN was defined as systolic blood pressure ≥140 mmHg or an average diastolic blood pressure ≥90 mmHg and patients were excluded based on self-reported BP screening. Absence of liver disease was excluded on the basis of available normal liver function test report information and self-reported past medical history. Potential for diversion for abuse was evaluated by psychiatric mental health nurse practitioners by querying state prescription monitoring databases as part of the medical consultation. Patients who were not excluded were provided with information about the ketamine treatment. Terms and conditions for use of data use were addressed during the onboarding process. Patients then signed a detailed informed consent form.

Dataset and process flowchart.

After obtaining informed consent, an express-mailed package containing a 300 mg rapid dissolve tablet (RDT) of ketamine for SL administration with instructions was shipped to the patient. The basis for a treatment course of 6 treatments was based on the extensive evidence showing effectiveness of 6 IV ketamine infusions and to mirror prior treatment schedules as closely as possible in order to minimize unforeseen variables ( 45 ). In line with this, a first shipment contained an RDT tab and additional information providing comprehensive instructions on how to safely to self-administer the ketamine RDT. These instructions included careful preparation and creation of an optimal set and setting (i.e. quiet comfortable environment with dedicated time before and after to meditate and/or reflect), safety instructions including fall risk precautions and avoidance of any sharp or dangerous objects or operation of heavy machinery including cars was explicitly prohibited as was the combination of any other psychotropic substance including alcohol or marijuana. Patients on benzodiazepines were instructed to hold this medication on the day of ketamine therapy due to evidence that it may reduce antidepressant effectiveness ( 46 ). This guidance instructed patients to consume the RDT in the presence of a sitter who would provide support as needed. This sitter was also provided ketamine safety education by the medical provider which included information about fall risk and the avoidance of drugs or alcohol. After ketamine use, patients were instructed to recline with an eye-covering (i.e., a sleep mask) in a quiet location. Patients were instructed to listen to provider-prepared music using headphones to minimize distraction and support the ketamine experience.

Upon completion of this initial ketamine administration, patients were asked to complete an online experience report for this first ketamine dose for clinical review by the provider. The decision to use ketamine at 300 mg was determined by providers with experiential CME training in ketamine therapy. This training provided the guidance for determination of the clinically recommended course of ketamine treatment ( 12 ). Patients were instructed to self-administer their doses twice a week and complete the online experience survey within 2 days of their final dose from the shipment. The duration of therapy ranged from 2–3 weeks to complete the number of doses prescribed. Decisions to increase doses to 450 mg were made collaboratively between the patient and providers. Based on data from the patient's experience report, a clinical judgment was then made by the provider to maintain or increase (up to 450 mg) the dosage of a second shipment containing two additional ketamine RDT.

A second shipment contained either two 300 mg RDT or two 450 mg RDT, and was also express-mailed to patients. Patients repeated the self-administration procedure for the two additional RDT treatments on separate days, bringing their ketamine treatment to three doses (3-RDT). Upon completion, patients were again asked to complete the online experience report which included the PHQ-9 and GAD-7 measures for clinical review, and rank experiences (None, Mild, Moderate, Severe) of several potential side effects. These included: Anxiety, Blurred Vision, Difficulty Speaking, Difficulty Thinking, Dizziness, Loss of Balance, Memory Issues, Nausea, Pain with Urination, Palpitations, and Pelvic Pain.

After a review of the patient report, a clinical determination for a final shipment of 3 additional ketamine RDT (300 mg or 450 mg) was made, and a third shipment was sent. Patients were again instructed to use the three additional doses as directed and then complete another experience report with PHQ-9, GAD-7, and side effect measures after taking their sixth ketamine RDT (6-RDT) within 2 days of their final dose from the shipment. In summary, data from all patients who had contacted the practice and then completed the follow up surveys after at least 3-RDT ketamine were analyzed. Analysis of the data revealed a subgroup of patients that had received an additional three RDT ketamine (raising their total to six; 6-RDT) that had completed follow up surveys was also conducted.

Statistical analysis

SPSS (v28) software was used for frequencies and descriptive measures, and to perform inferential analyses of changes in GAD-7 and PHQ-9 scores between intake levels and post-treatment scores. Wilcoxon Matched Pairs analysis were performed for GAD-7 and PHQ-9 scores for both patients at three-, and six-ketamine RDT treatment times as available. Reductions of ≥ 50% of raw score reductions and from intake are also reported, as well % reductions and clinically significant reductions in those patients whose intake GAD-7 and/or PHQ-9 scores placed them in the Moderate to Severe ranges at intake.

Sample characteristics

A total of 4,404 people were assessed for eligibility out of which 1,101 patients were enrolled. A review of their clinical data revealed that 669 patients had completed a course of treatment including at least three SL ketamine RDT (3-RDT) and completed the post-treatment experience report. Of these, 5 patients contained missing or corrupted data and were excluded when analyzing GAD-7 and PHQ-9 measures, however their reports of side effects are included in Table 1 . Of the remaining 664 patients remaining for GAD-7 and PHQ-9 data analysis 210 patients had received a third shipment with three additional ketamine RDT. These patients completed an additional post-treatment experience report after completing a clinically recommended six ketamine RDT treatment course (6-RDT, n=210). Based on this process we analyzed a group of patients actively involved in ongoing treatment at the time of data collection who had finished 3-RDT of SL ketamine ( n = 464), and a second group of patients who had completed a 6-RDT course of SL ketamine. Demographic characteristics are shown in Table 2 .

Ketamine side effect incidence and severity after 3- or 6-RDT.

Percentage of all subjects who reported None, Mild, Moderate, or Severe after their 3 rd or 6 th RDT of Ketamine.

Demographic characteristics and GAD-7 and PHQ-9 scores.

The asterisk (*) indicates statistical significance as cited in the text ( p < 0.001).

A review of systems and follow up visits systematically screened for major adverse events (symptoms requiring medical care including hospitalizations as part of structured clinical interview in follow-up). Minor adverse events and side effects including nausea, dizziness, headache, loss of balance, were assessed on self-report questionnaires for each set of experiences. Side effects of ketamine RDT that were reported as part of the experience report are shown in Table 1 . These effects were self-limited and resolved without any further medical intervention.

Impact of three RDT ketamine-induced impact on depression and anxiety

Wilcoxon Matched Pairs analysis of all patients after 3-RDT ( n = 654) indicated a statistically significant decrease from GAD-7 intake after three ketamine RDT treatment ( z = −18.52, p < 0.001). Average raw GAD-7 score reduction was−4.86, with 47.6% of patients ( n = 316) having experienced a reduction of 50% or more when compared to their intake GAD-7 score (see Figure 2 ). As indicated in Table 2 , 47.6% ( n = 199) of patients whose intake GAD-7 scores placed them in the Moderate to Severe range (GAD-7 ≥ 10; n = 418) reported reductions to at least half of their intake scores. Of these same Moderate to Severe patients, 63% reported clinically significant drops in GAD-7 scores resulting in either None (0–4) or Mild (5–9) anxiety categorization. The remaining 36.4% ( n = 152) of Moderate to Severe patients at intake did not experience a clinical reduction in anxiety scores after three ketamine RDT treatment.

Mean GAD-7 and PHQ-9 scores at baseline, after 3-RTD, and 6-RDT ketamine treatments.

Analysis of changes in PHQ-9 depression scores revealed statistically significant reductions after three RDT ketamine treatment (z = −19.71, p < 0.001) when compared to intake scores ( Table 2 ). There was an overall reduction of 47.59% from intake to post-ketamine treatment PHQ-9 scores. In patients whose intake PHQ-9 scores placed them in the Moderate to Severe range ( n = 463), three RDT ketamine treatment resulted in PHQ-9 scores dropping to at least half of intake scores in 49.5% of patients ( n = 229). Of these same Moderate to Severe PHQ-9 intake patients, 59% ( n = 273) reported clinically significant drops that placed them in the None (0–4) to Mild (5–9) depression categories. The remaining 41% ( n = 190) did not experience a clinical reduction in depression scores after three ketamine RDT.

Impact of six RDT ketamine-induced impact on depression and anxiety

Wilcoxon Matched Pairs analysis of patients who completed a clinically recommended six dose course of RDT ketamine treatment ( n = 210) revealed a statistically significant decrease in final reported GAD-7 scores when compared to intake after 3-RDT ( z = −10.12, p < 0.001) that was comparable to those reported in the previous group of ongoing patients (see the above 3-RDT). Upon completion of three additional ketamine treatments there was an additional decrease in GAD-7 rank scores (z = −4.62, p < 0.001; see Figure 2 ).

As shown in Table 2 , average raw GAD-7 score was reduced by 5.88, and 72.4% of those receiving 6 ketamine RDT ( n = 152) experienced a reduction of 50% or more from their intake GAD-7 score. For patients whose intake GAD-7 scores placed them in the Moderate to Severe range (see Table 2 ; n = 133), six ketamine RDT treatment resulted in GAD-7 scores dropping to at least half of intake GAD-7 scores in 60.2% ( n = 80). For these same patients with Moderate to Severe intake GAD-7 scores ( n = 133; Table 2 ), 69.2% ( n = 92) reported clinically significant reductions resulting in None (0–4) or Mild (5–9) post-treatment anxiety categorization. The remaining 30.8% ( n = 41) of intake Moderate to Severe patients did not experience a clinical reduction in anxiety after six ketamine RDT treatment.

Similarly, Wilcoxon Matched Pairs analysis of PHQ-9 scores revealed a significant reduction in PHQ-9 scores after three RDT ketamine doses ( z = 10.96, p < 0.001) and then after 6-RDT ( z = 4.45, p < 0.001). Of patients whose intake PHQ-9 scores placed them in the Moderate to Severe range ( n = 156), six ketamine RDT treatment resulted in PHQ-9 scores dropping to at least half of intake scores in 65.4% of patients ( n = 102). Of these same Moderate to Severe PHQ-9 intake patients, 71.2% ( n = 111) reported clinically significant drops that placed them in the None (0–4) to Mild (5–9) depression categories. A comparison of 3-RDT only ( n = 454) and 6-RDT ( n = 210) GAD-7 and PHQ-9 mean scores from Baseline, 3- and 6-RDT are shown in Figure 2 .

Previous studies have indicated that IV ketamine infusions can serve as an effective course of treatment for patients with TRD ( 23 , 24 ). This study aimed to examine the safety and effectiveness of at-home use of SL ketamine for TRD and treatment-resistant anxiety. This study has shown that in as few as three doses of ketamine therapy nearly 50% of patients with moderate to severe depression saw an improvement of reducing their PHQ-9 and GAD-7 scores to half of their intake scores. This reduction rate improved to 60% in patients who completed a clinically recommended six ketamine RDT course of treatment. Of note, for patients with moderate to severe intake GAD-7 scores there was a clinical effect with ketamine therapy of reducing anxiety categorization in as few as three doses, and of those who were with moderate to severe intake GAD-7 scores who completed six ketamine RDT 65.4%, saw their GAD-7 scores reduced to 50% or more of their intake scores. Reductions in scores for those who had only received 3-RDT matched those who had completed 6-RDT (see Figure 2 ), and it is reasonable to speculate that there would be maintenance of improvement with three additional RDT ketamine treatments.

Our findings indicate that SL ketamine is clinically effective in reducing depression and anxiety in an at-home setting. The use of SL ketamine at home presents a promising approach in the treatment of TRD where treatment resistance may be the result of prior treatment approaches being mismatched with underlying neurobiological etiology. Since most antidepressants target monoaminergic mechanisms, the effectiveness of ketamine's pharmacological profile suggests an underlying role for glutamate in some individuals who experience TRD ( 47 ).

Limitations of the study were that it was a retrospective review of chart data from a self-selecting convenience sample. Measures of depression and anxiety relied extensively on self-report, though there was considerable provider care given. There was no placebo/control group, and given the dissociative effects of ketamine, a strong placebo effect is possible. Caution should be exercised whenever treating patients with depression and anxiety, especially those with complicating presenting symptoms (i.e., suicidality) or health problems (i.e., hypertension, substance abuse). While the majority of patients respond after 3 doses, we did not determine whether there are differences in the durability of response based on the number of treatments,; this an active area of investigation. Further work, which we are currently engaged in, will be needed to delineate not only the most effective dosing regimen, but also to identify likely responders based on patient characteristics and maintain continued analysis of patient data. The researchers also acknowledge the need for continued analysis of patient data. Nonetheless, we argue that SL ketamine offers a safe and effective tool in the treatment of anxiety and depression. This study represents a step toward consideration of at-home, SL ketamine for treatment-resistant depression and treatment-resistant anxiety.

In conclusion, this study adds to a growing literature on the effectiveness of ketamine treatment for TRD ( 22 , 48 ). The improvements in depression and anxiety symptomology demonstrated in those who received as few as three at-home ketamine RDT present a safe, effective, and reasonable alternative to inpatient IV infusions of ketamine. These improvements in symptoms are further improved with completion of a clinically recommended course of six ketamine RDT. In addition to providing an effective treatment for those with TRD and comorbid anxiety, it also suggests alternative neurobiological modes for understanding MDD and anxiety symptoms. Additional studies including randomized trials, long-term impact on remission rates, combinations with additional psychosocial interventions, other functional outcomes, and cost-effectiveness analysis are needed.

Data availability statement

Ethics statement.

The studies involving human participants were reviewed and approved by Wheaton College, Wheaton, IL. The patients/participants provided their written informed consent to participate in this study.

Author contributions

KH: project administration and writing—review and editing. WS: writing—review and editing and formal/statistical analysis. AS: data curation, review, and editing. PD: writing—review and editing. All authors contributed to the article and approved the submitted version.

Conflict of interest

Authors KH, AS, and PD hold restricted shares of Nue Life Health, P.B.C. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher's note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Ketamine Dosage

Medically reviewed by Drugs.com. Last updated on Aug 16, 2023.

Applies to the following strengths: 100 mg/mL; 50 mg/mL; 10 mg/mL; 10 mg/mL-NaCl 0.9%; 1 mg/mL-NaCl 0.9%; 50 mg/5 mL; 100 mg/10 mL; 50 mg/5 mL-NaCl 0.9%; 100 mg/10 mL-NaCl 0.9%; 10 mg/mL-NaCl 0.69%; 10 mg/mL-NaCl 0.65%

Usual Adult Dose for:

Usual pediatric dose for:, additional dosage information:, renal dose adjustments, liver dose adjustments, dose adjustments, precautions, other comments, usual adult dose for anesthesia.

• Induction: 1 to 4.5 mg/kg IV; alternatively, 1 to 2 mg/kg IV at a rate of 0.5 mg/kg/min; (2 mg/kg dose provides 5 to 10 minutes of surgical anesthesia within 30 seconds)
• Maintenance: The maintenance dose should be adjusted according to the patient's anesthetic needs and whether an additional anesthetic is employed. Increments of one-half to the full induction dose may be repeated as needed for maintenance of anesthesia.
• Induction: 6.5 to 13 mg/kg IM; (9 to 13 mg/kg IM provides 12 to 25 minutes of surgical anesthesia)
• This drug should be administered slowly over a period of 60 seconds (more rapid administration may result in respiratory depression and enhanced pressor response).
• The larger the total dose, the longer will be complete recovery.
• Because of rapid induction following the initial IV injection, the patient should be in a supported position during administration.

Usual Pediatric Dose for Anesthesia

16 years and older: See adult dosing

Data not available

• The individual response is somewhat varied depending on the dose, route of administration, and age of patient, so that the dosage recommendation cannot be absolutely fixed. The drug should be titrated against the patient's requirements.
• Diazepam (2 to 5 mg over 60 seconds), administered in a separate syringe, may be used along with ketamine IV infusion for induction or maintenance of anesthesia. In most cases, 15 mg of IV diazepam or less will suffice.
• Adult patients induced with ketamine augmented with IV diazepam may be maintained on ketamine given by slow microdrip infusion technique at a dose of 0.1 to 0.5 mg/min, augmented with diazepam 2 to 5 mg administered IV as needed. In many cases, 20 mg or less of IV diazepam total for combined induction and maintenance will suffice. However, slightly more diazepam may be required depending on the nature and duration of the operation, physical status of the patient, and other factors. The incidence of psychological manifestations during emergence, particularly dream-like observations and emergence delirium, may be reduced by this maintenance dosage program.

Safety and efficacy have not been established in patients younger than 16 years. Consult WARNINGS section for additional precautions.

Administration advice:

• This drug should be administered slowly (over a period of 60 seconds). More rapid administration may result in respiratory depression and enhanced pressor response.
• Since aspiration may occur and since protective reflexes may also be diminished by supplementary anesthetics and muscle relaxants, the possibility of aspiration should be considered.
• This drug is recommended for use in the patient whose stomach is not empty when, in the judgment of the practitioner, the benefits of the drug outweigh the possible risks.
• Atropine, scopolamine, or another drying agent should be given at an appropriate interval prior to induction.
• Purposeless and tonic-clonic movements of extremities may occur during the course of anesthesia. These movements do not imply a light plane and are not indicative of the need for additional doses.
• This drug has a wide margin of safety; several instances of unintentional administration of overdoses of up to 10 times that usually required have been followed by prolonged but complete recovery.
• The larger the total dose administered, the longer will be the time to complete recovery.
• This drug is compatible with commonly used general and local anesthetic agents when an adequate respiratory exchange is maintained.
• The regimen of a reduced dose of this drug, supplemented with diazepam can be used to produce balanced anesthesia by combination with other agents such as nitrous oxide and oxygen.
• Elevation of blood pressure begins shortly after injection, reaches a maximum within a few minutes and usually returns to preanesthetic values within 15 minutes after injection. In the majority of cases, the systolic and diastolic blood pressure peaks from 10% to 50 % above preanesthetic levels shortly after induction of anesthesia, but the elevation can be higher or longer in individual cases.
• The 100 mg/mL concentration should not be injected IV without proper dilution. It is recommended the drug be diluted with an equal volume of either Sterile Water for injection, USP, Normal Saline, or 5% Dextrose in Water.

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