Among the recreational drugs currently entering the psychiatric mainstream (MDMA, LSD, etc.), ketamine is something of an outlier. Most people have a rough idea of what ‘sour’ or ‘molly’ should do, even if they’ve never tried it. Ketamine, meanwhile, remains – outside of a dedicated cult– a riddle. It does not matter popular recreational drugs. There is no standard Hollywood version of the ketamine trip. You hear talk about k-holes, and the occasional allusion to its use as a tranquilizer for horses, but little about its actual effects, and less about what it’s like to take it in a clinical setting, which is always more patients with depression and mood disorders will do soon. To correct the record for this week Giz asks we contacted a number of people who conducted clinical ketamine studies.
Mikael Tiger
Researcher, Clinical Neuroscience, Karolinska Institutet
In one of my studies, we treated thirty depressed patients with ketamine.
During treatment, most of the patients reported intense dissociation. They were disconnected from reality in different ways and saw things differently. One patient felt the radio playing in 3D, which she found deeply fascinating. When she returned to the same program afterwards, she realized that it was actually quite boring.
About 20% of the patients had hallucinations and the majority found the experience interesting; some compared it to being drunk. (Ketamine is addictive for this reason.) Two out of 30 thought it was a terrible experience, although as they responded to the treatment, they were willing to do it again. It was generally believed to be quite intense.
The drug was administered in a hospital setting and nurses were present for the duration of the experience. These were nurses who had 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 put the patient in what we call remission – to bring them back to their life before the onset of major depression. That differs from psilocybin therapy, for example, where the psychotherapy component is really important. Ketamine does not give people insights that they can integrate into their daily lives, such as with psychedelic therapy. They had a strange experience, but no insights.
After the treatment came the antidepressant effects. This is very new: most normal antidepressants take weeks to show an effect. 70% of the patients in our trial woke up the next morning feeling much better.
Michael Grunebaum
Associate Professor, Psychiatry, Columbia University
The vast majority of patients with mood disorders treated with ketamine infusions report feeling weird and / or limp. Some feel like they are floating. Some report that their arms or legs feel different in some way – bigger than normal, or numb, or harder to move. Some people develop a numbness around their face or mouth. Sometimes people are cold. A few experience mild hallucinations – shapes or colors on the walls or ceiling.
A small percentage of people may feel anxious when given ketamine, possibly because the sensations are not known; some people may find it more difficult to find the right words, which can cause anxiety. A small minority may also feel sad, come out in tears, or experience a wave of memories. Conversely, a small percentage of patients experience some type of euphoria. But more often, what is most experience is that madness / spaciousness. Usually all these effects disappear after about 15-30 minutes after the treatment.
Typically, the drug is administered intravenously, in a slow drop over forty minutes, but a nasal spray version has recently been approved. People may get two or three treatments a week for a few weeks, and then decrease in frequency. There is still a lot of research on the correct frequency for maintenance treatment, how long the treatment should last, how many are safe, etc. Studies on ketamine addiction show serious risks for long-term ketamine use, although therapeutic doses are much lower, maybe a tenth the size of typical street doses.
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Adam clutch
Clinical Director of the Psychiatric Esketamine Clinic and Assistant Professor of Psychiatry and Behavioral Sciences at Johns Hopkins University
One patient of ours turned off the lights every time and got into a dream-like state, flying 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. We had a patient for whom colors would vibrate outside the window – he described a green like he had never seen before. Another heard voices and saw spiders crawling on the door.
That is all to say that it has a wide range and depends on the patient for the most part. However, virtually no one we dosed said they didn’t want to continue. When ketamine works, it works dramatically – in the first or two doses, people get dramatically better; some even feel like they have returned to their old selves. To have this response in people with treatment-resistant depression, after just a few doses, is quite amazing.
The people most upset about it were people who had never experimented with drugs. One person we treated, a musician, had treated his body like a temple – no drugs or alcohol all his life. So for him, ketamine was a terrifying experience: he just didn’t know what was going to happen. But mostly people who have used drugs in the past think it’s a cool experience.
One thing that helped with the side effects – and I swear I’m not getting any money for this – was Enya. Enya invariably calmed our patients, even those who were hard rock partisans. It was Enya who really did it for them.
Rebecca Price
Associate Professor, Psychiatry and Psychology, University of Pittsburgh
During and immediately after a ketamine infusion, most patients feel numb, a little “high” or euphoric, and some feel distant or detached from what is going on around them. Some feel dizzy, nauseous or have a headache. Researchers don’t usually think there is anything special about the acute experience of receiving ketamine. When ketamine therapy is successful, the ‘special’ stuff comes downstream, in the form of an accumulating sense of relief from depression and other negative emotional symptoms, peaking about 24 hours after the infusion, which has been linked to neuroplasticity changes that occur later. Time points. In general, we think of the things that happen during and around the infusion as mostly bothersome side effects, rather than something particularly therapeutic. This makes ketamine very different from other drugs now being investigated as psychiatric treatments, such as psilocybin.
Joshua Berman
Associate Professor of Psychiatry and Clinical Direction of the Ketamine Program at Columbia University
Patients report a range of experiences while receiving ketamine therapy for depression, but in general, ketamine at a psychiatric dose is a ‘tamer’ than many might imagine. Most patients report feeling ‘spacious’ starting from 5-15 minutes after the first treatment, and that sensation disappears somewhere between 30-90 minutes. Some describe it as a high, and a small number of patients get a little dizzy. Some patients describe near-hallucinations, such as seeing patterns around them. While almost all describe a sense of dissociation, few really feel outside of their body and even fewer feel that they have lost touch with reality even for a short time. These feelings may increase with higher doses, and there is no universal agreement among ketamine physicians as to whether a high degree of dissociation is required to achieve the desired antidepressant effect.
Ketamine is administered by IV or through an intranasal inhaler in a medically 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 spatial, dissociated or high) disappear within one to two hours after administration, but any reduction in depressive symptoms can last for hours to days. Multiple treatments may be needed to consolidate an antidepressant and last longer. Once fully established, the antidepressant effect can be maintained with maintenance treatments that can be 2-4 weeks apart. In some patients long maintenance treatment is required, while in other patients there is remission after just 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 can work in minutes to hours. But for many, the first one or two (or even four) treatments produce a much more subtle feeling, with a variable improvement in the overall mood – it fluctuates at first, then consolidates. About one third of patients have no or no sustained response.
For most patients, the experience is either very pleasant or neutral, but occasionally patients may feel equally sad or tearful.
Ketamine treatment differs from psychedelic-guided therapies designed so that the altered states achieved yield therapeutic insights. The prevailing 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, a few patients describe having insight or a different perspective during ketamine treatments in ways that can contribute to their recovery from depression, and some therapists are exploring whether it can be used as an ‘ego-dissolving’ therapy enhancer , as better established with MDMA and psilocybin.
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