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Sunday, August 2, 2009

I'm On K, You're On K

According to CNN, the kids in Hong Kong are all taking ketamine ("the horse tranquilizer") nowadays - although we're not given much in the way of statistics.

Ketamine is a fascinating molecule. On the street, it's a drug, naturally. High doses produce a state of dissociative unconciousness affectionately called the "K-hole", while lower doses have a sedative and mild hallucinogenic effect which goes well with dancing, allegedly. It's also used medically as an anaesthetic.

In psychiatry, ketamine is three things: a drug of abuse, an antidepressant, and a way to mimic schizophrenia. Or rather, there are people who think of ketamine as each of these things. It seems somewhat unlikely that it could be all three at once. You don't treat depression by causing schizophrenia, and people don't deliberately give themselves psychosis, even temporarily.

Yet a journal could publish a paper about using ketamine as a model of schizophrenia, and another paper about its supposed antidepressant effects a few pages later, and few people would bat an eyelid. This is because most researchers interested in schizophrenia wouldn't read the depression paper, and vice versa.

Partly this is because, like all scientists today, psychopharmacologists tend to stick to their own research niches. But it's also a symptom of the fact that no-one's job is to study ketamine, as such. We study diseases, rather than drugs, which can lead to theories which fly in the face of half of the evidence. (See this post for another example.)

The evidence that ketamine can treat depression essentially consists of one study from 2006 (ref) and a pilot study from the same group (ref), plus a handful of case reports. Zarate et al reported that a single injection with a moderate dose of ketamine (0.5mg/kg) had a dramatic antidepressant effect in a large proportion of depressed patients, and that this lasted at least a week in some cases.

This paper sparked a flurry of interest into ketamine and depression, with animal studies and brain scans galore trying to explain how it might work. Maybe ketamine does have an antidepressant effect. But if it does, it's a miracle drug, acting much faster than any other. You need to take Prozac for several days or weeks before feeling any benefit. A single injection does diddly-squat.

The dramatic benefits seen in this study may have been simply placebo effects: the patients expected to feel much better after taking this exciting new drug, so they said they did. The study was placebo controlled, true. When people got injections of salt water, they didn't report any benefit. In theory, it was double blind - neither the patients nor the doctors knew whether they were getting ketamine or water. But you'll know when you've been injected with 0.5mg/kg ketamine. You get high. That's why people take it. The study can't really be called double blind.

To their credit, Zarate et al did acknowledge this, and suggested that in future ketamine could be compared to another drug which produces noticeable effects. But they really should have done that to begin with. This is not a criticism of these researchers - what they did was par for the course in psychopharmacology. Unfortunately.

The idea that ketamine intoxication mimics schizophrenia (ref) is an interesting one, and it may well be a model of some of the symptoms. My only ketamine experience doesn't really fit with either the schizophrenia or the antidepressant theory, however. I was slightly depressed before I took it, and it made me feel much worse. I didn't hear any voices, though. On the other hand, a good friend became addicted to the stuff for several months, and still craves it. To each his own...

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