Among recreational drugs currently entering the mainstream of psychiatry (MDMA, LSD, etc.), ketamine is a kind of outlier. Most people have a rough idea of what “acid” or “molly” should do, even if they have never tried it. Ketamine, however, remains – outside a compromised sect“An enigma. It is not much popular recreational drug. There is no standard Hollywood version of the ketamine journey. You hear about k-holes and the occasional allusion to its use as a tranquilizer for horses, but little about its real effects, and less about what it is like to take it in a clinical setting, which increasingly makes patients with depression and mood disorders soon will be doing. To correct the registration, for the Chalk Question we came in contact with several people who underwent clinical tests with ketamine.
Mikael Tiger
Researcher, Clinical Neuroscience, Karolinska Institutet
In one of my studies, we treated thirty depressed patients with ketamine.
During treatment, most patients reported intense dissociation. They were disconnected from reality in many ways and perceived things differently. A patient felt that the radio was playing in 3D, which she found extremely absorbing. Then, returning to the same program, she realized that it was actually quite boring.
About 20% of patients had hallucinations, and most found the experience interesting; some compared him to being drunk. (Ketamine is addictive for that reason.) Two out of thirty thought it was a horrible experience, even though, as they responded to treatment, they were willing to repeat it. Overall, it was considered quite intense.
The medication was administered in a hospital environment and nurses were present throughout the experience. They were nurses who worked extensively with severely depressed patients and helped administer ECT, which as a treatment is (in a sense) closer to ketamine therapy than LSD or psilocybin therapy. With ECT, as with ketamine, the goal is to take the patient to what we call remission – to bring him back to life before the onset of severe depression. This is different, for example, from psilocybin therapy, in which the psychotherapeutic component is really important. With ketamine, people do not get insights that they can integrate into their daily lives, as they would with psychedelic therapy. They had a strange experience, but no perception.
After treatment, antidepressant effects came. This is very new: most normal antidepressants take weeks before an effect is noticed. 70% of the patients in our study woke up the next morning feeling much better.
Michael Grunebaum
Associate Professor, Psychiatry, Columbia University
The vast majority of patients with mood disorders who are treated with ketamine infusions report feeling weird and / or stunned. Some seem to be floating. Some register their arms or legs as if they were different in some way – bigger than normal, or numb, or more difficult to move. Some have a kind of numbness around their face or mouth. Sometimes, people feel cold. Some rare ones have mild hallucinations – shapes or colors on the walls or ceiling.
A small percentage of people may be anxious when receiving ketamine, possibly because the sensations are unfamiliar; some people may find it more difficult to find the right words, which can cause anxiety. A small minority may also be sad, cry or have a fast memory. On the other hand, a small percentage of patients experience a kind of euphoria. But more often, what we experience most is this strangeness / spacing. Usually, all of these effects disappear after about 15-30 minutes after treatment.
Usually, the drug is administered intravenously, in a slow drip for more than forty minutes, but a nasal spray version has recently been approved. People can receive two or three treatments a week for a few weeks and then decrease the frequency. There is still a lot of research on what is the right frequency for maintenance treatment, as well as how long the treatment should last, how many are safe, etc. Studies on ketamine addiction demonstrate serious risks for long-term ketamine use, although therapeutic doses are much lower, perhaps one-tenth of normal street doses.
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Adam Kaplin
Clinical Director of Esketamine Psychiatric Clinic and Assistant Professor of Psychiatry and Behavioral Sciences at Johns Hopkins University
A patient of ours turned off the lights each time and entered a dream state, during which she flew over New York City, where she used to work. She longed for it – her little trips to the city. Another woman swore that we were hiding lemons in the room. We had a patient for whom the colors outside the window would vibrate – he described a green unlike any green he had seen before. Another heard voices and saw spiders crawling at the door.
Which means that there is a wide range and depends largely on the patient. Virtually no one we dosed, however, said that he didn’t want to continue. When ketamine works, it works dramatically – in the first few doses or two, people improve dramatically; some even feel that they are back to what they were. Having that response in people with treatment-resistant depression after just a few doses is incredible.
The people who were most distressed by this were people who had never tried drugs before. One person we treated, a musician, treated his body like a temple – no drugs or alcohol for life. So for him, ketamine was a scary experience: he just didn’t know what was going to happen. But usually, people who have used drugs in the past think it is a legal experience.
One thing that helped with the side effects – and I swear I won’t get any money for it – was Enya. Invariably, Enya calmed our patients, even patients who were supporters of heavy rock. It was Enya who actually did this for them.
Rebecca Price
Associate Professor, Psychiatry and Psychology, University of Pittsburgh
During and immediately after a ketamine infusion, most patients feel sedated, a little “high” or euphoric, and some feel distant or a little disconnected from what is happening around them. Some experience dizziness, nausea or headache. Researchers usually don’t think there is anything very special about the acute experience of receiving ketamine. When ketamine therapy is successful, the “special” material comes downstream, in the form of an increased sense of relief from depression and other negative emotional symptoms, peaking about 24 hours after the infusion, which has been associated neuroplasticity changes that occur later. Time points. We usually think of the things that happen during and immediately around the infusion as mostly annoying side effects, rather than something particularly therapeutic. This makes ketamine quite distinct from other drugs now under investigation as psychiatric treatments, such as psilocybin.
Joshua Berman
Assistant professor of psychiatry and clinical leader of the ketamine program at Columbia University
Patients report a series of experiences when receiving ketamine therapy for depression, but in general, the psychiatric dose of ketamine is a “tighter” experience than many could imagine. Most patients describe the feeling of “dizziness”, starting 5 to 15 minutes after the initial treatment, and this sensation subsides anywhere from 30 to 90 minutes. Some describe it as a feeling of euphoria, and a small number of patients become slightly dizzy. Some patients describe almost hallucinations, like seeing patterns around them. Although almost everyone describes some sense of dissociation, very few feel truly out of their bodies and even less feel that they have lost touch with reality for a short period of time. These feelings can intensify if higher doses are used, and there is no universal agreement among ketamine doctors about the need for a high degree of dissociation to achieve the desired antidepressant effect.
Ketamine is administered intravenously or via an intranasal inhaler in a clinically controlled environment, where vital signs and the patient’s response can be monitored. Treatment sessions usually last two hours, after which the patient can go home.
The acute effects (feeling of disorientation, dissociation or discharge) disappear within one to two hours after administration, but any reduction in depressive symptoms can persist for hours to days. Various treatments may be necessary for an antidepressant effect to consolidate and become more lasting. Once fully established, the antidepressant effect can be made to persist with maintenance treatments that can last 2 to 4 weeks. For some patients, a long period of maintenance treatment is necessary, while other patients experience remission after only a few months of maintenance.
Many patients report rapid improvement in mood, anxiety and hedonic function, which is what initially attracted the psychiatric profession to the use of ketamine. It is the first treatment for depression that has the potential to work in minutes to hours. But for many, the first or two (or even four) treatments produce a much more subtle sensation, with variable improvement in general mood – it fluctuates at first, but then it consolidates. About a third of patients have no response or no sustained response.
For most patients, the experience is very pleasant or neutral, but sometimes patients may feel sad or tearful for a moment.
Ketamine treatment is different from guided psychedelic therapies, which are designed in such a way that the altered states achieved produce therapeutic perceptions. The predominant model for ketamine therapy is more like a physical treatment designed to improve synaptic connections using mechanisms that work faster than those used by conventional antidepressants. That said, some patients describe having insights or changing perspectives during ketamine treatments in ways that can contribute to recovery from depression, and some therapists are exploring whether this can be used as an intensifier of “ego dissolution” therapy, as it was best established with MDMA and psilocybin.
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