Among the recreational drugs currently entering the psychiatric mainstream (MDMA, LSD, etc.), ketamine is something completely different. Most people have a rough idea of what “acid” or “molly” should do, even if they have never tried it. Meanwhile, ketamine remains – outside of an employed sect“An enigma.” It’s not very popular recreational drug. There is no standard Hollywood version of ketamine travel. 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’s like to take it in a clinical setting, which more and more patients with depression and mood disorders will do soon. To correct the record, for this week Giz asks I have contacted a number of people who have performed clinical trials with ketamine.
Michael Tiger
Researcher, Clinical Neuroscience, Karolinska Institute
In one of my studies, I treated thirty patients who were depressed with ketamine.
During treatment, most patients reported intense dissociation. They were disconnected from reality in different ways and perceived things differently. One patient felt that the radio was playing in 3D, which she found intensely absorbent. After that, returning to the same program, he realized that it was actually quite boring.
About 20% of patients had hallucinations, and most found the experience interesting; some likened him to drunkenness. (Ketamine is addictive for this reason.) Two out of thirty considered it a horrible experience, although since they responded to treatment, they were willing to do it again. It was generally thought to be quite intense.
The drug was administered in a hospital, and nurses were present during the experiment. These were nurses who worked intensively with patients with severe depression 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 bring the patient into what we call remission – to bring them back to life before severe depression occurs. This is distinct from, for example, psilocybin therapy, where the component of psychotherapy is really important. With ketamine, people do not receive information that they can integrate into their daily lives, as they could do with psychedelic therapy. They had a strange experience, but no perspective.
After treatment, antidepressant effects appeared. This is very new: most normal antidepressants take weeks before an effect is perceived. 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 are reported to feel strange and / or spacious. Some feel like they’re floating. Some register their arms or legs as feeling different in some way – larger than usual, or numb or harder to move. Some get a kind of numbness around the face or mouth. Sometimes people feel cold. A few rare ones experience mild hallucinations – shapes or colors on the walls or ceiling.
A small percentage of people may feel anxious when receiving ketamine, probably because the sensations are unfamiliar; Some people may find it harder to find the right words, which can cause anxiety. A small minority may also feel sad, teary, or experiencing a lot of memory. On the contrary, a small percentage of patients experience a kind of euphoria. But more often, what has the greatest experience is that strangeness / spatiality. Usually, all these effects disappear after about 15-30 minutes after treatment.
The drug is usually given intravenously, in slow drip for forty minutes, but a nasal spray version has recently been approved. People could receive two or three treatments a week for a few weeks and then reduce their frequency. There is still a lot of research on the right frequency for maintenance treatment, as well as how long the treatment should last, how many are safe, and so on. Studies of ketamine dependence demonstrate serious risks for long-term use of ketamine, although therapeutic doses are much lower, perhaps a tenth as high as typical street doses.
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Adam Coupling
Clinical Director of the Esketamine Psychiatric Clinic and Assistant Professor of Psychiatry and Behavioral Sciences at Johns Hopkins University
One of our patients, each time, turned off the lights and entered a dream state, during which she would fly over New York City, where she used to work. She was looking forward to it – her little trips to the city. Another woman swore we were hiding lemons in the room. I had a patient for whom the colors outside the window would vibrate – he described a green different from any green he had ever seen. Another heard voices and saw spiders crawling through the door.
Which means it runs a wide range and depends largely on the patient. However, virtually no one I dosed said they did not want to continue. When ketamine works, it works dramatically – in the first or two doses, people improve dramatically; some even feel that they have returned to their old selves. Having this response in people with treatment-resistant depression after just a few doses is kind of amazing.
The people who were most bothered by it were people who had never experienced drugs before. One person I treated, a musician, treated his body like a temple – without drugs or alcohol for the rest of his life. So for him, ketamine was a frightening experience: he just didn’t know what was going to happen. But usually people who have used drugs in the past think it’s a great experience.
One thing that helped with the side effects – and I swear I don’t get paid for it – was Enya. Invariably, Enya reassured our patients, even patients who were hard rock supporters. Enya really did it for them.
Rebecca Price
Associate Professor, Psychiatry and Psychology, University of Pittsburgh
During and immediately after the ketamine infusion, most patients feel sedated, a little “tall” or euphoric, and some feel distanced or a little detached from what is happening around them. Some feel dizzy, nauseous or have a headache. Researchers usually do not think that there is anything too special in the acute experience of receiving ketamine. When ketamine therapy is successful, “special” things come downstream, in the form of an accumulated feeling of relief from depression and other negative emotional symptoms, peaking at about 24 hours after the infusion, which has been linked to changes in neuroplasticity that time points appear later. In general, we believe that things that happen during and even around the infusion are more harmful side effects, rather than anything particularly therapeutic. This makes ketamine quite distinct from other drugs that are now being investigated 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 number of experiences while receiving ketamine therapy for depression, but in general, the psychiatric dose of ketamine is a “calmer” experience than many would imagine. Most patients describe that they feel “spacious”, starting from 5-15 minutes after the initial treatment, and that the sensation comes off anywhere between 30-90 minutes. Some describe it as high, and a small number of patients become slightly dizzy. Some patients almost describe hallucinations, such as observing patterns around them. While almost everyone describes a certain feeling of dissociation, very few really feel outside their body and fewer still feel that they have lost touch with reality even for a short time. These feelings may intensify if higher doses are used and there is no universal agreement among ketamine physicians on the need for a high degree of dissociation to achieve the desired antidepressant effect.
Ketamine is administered either by IV or by an intranasal inhaler in a medically controlled setting, where vital signs and the patient’s response can be monitored. Treatment sessions are usually two hours, after which the patient can go home.
Acute effects (feeling of space, dissociation or sea) disappear within one to two hours after administration, but any reduction in depressive symptoms may persist for hours. More treatments may be needed to strengthen the antidepressant effect and make it more lasting. Once fully established, the antidepressant effect may persist with maintenance treatments that may be 2-4 weeks apart. For some patients, a long period of maintenance treatment is required, while other patients have sustained remission after only a few months of maintenance.
Many patients report a rapid improvement in mood, anxiety and hedonic function, which 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 one or two (or even four) treatments produce a much more subtle sensation, with a variable improvement in general mood – it fluctuates at first, but then strengthens. About one-third of patients did not respond or did not respond strongly.
For most patients, the experience is either very pleasant or neutral, but sometimes patients may feel sad or in tears.
Ketamine treatment is different from guided psychedelic therapies that are designed so that the altered states achieved produce therapeutic perspectives. The predominant model for ketamine therapy is more like a physical treatment designed to enhance synaptic connections using mechanisms that work faster than those used by conventional antidepressants. That being said, some patients describe having perspectives or changes in perspective during ketamine treatments in ways that can help them recover from depression, and some therapists are exploring whether it can be used as a potentiator of “ego dissolution” therapy. as better established with MDMA and psilocybin.
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