Through the k-hole

What do squat parties in Brixton, vetinarians in Buckinghamshire, and cereals in Budgens have in common?* The answer, of course, is Special K.**

Ketamine is a tranquillising agent that was widely used until patients began to complain of its hallucinogenic effects, which they experienced when coming out of sedation. Not too fun. Except, of course, for those who take it for pleasure – of whom, according to ongoing research by Mixmag magazine and the Institute of Psychiatry, there have been more than a fourfold increase between 1999 and 2003. Apart from this population, the drug is still administered as a tranquilliser for animals, and also young children for whom the trippy effects don’t seem to occur. Notably, after Putin banned the drug in Russia in 2003, Bridget Bardot campaigned for a reversal, on the basis that it would result in more suffering for animals; whether the implications for children were weighed is not on record, but in any case Russia reversed the ban in ’04. Notably, the drug is not illegal in the EU, and whilst a controlled substance is low down in priority, at least in the eyes of the law. But if you’re an ocassional taker, or curious about it, I suggest you read further, to get the skinny on the cognitive neuropsychopharmacology of ketamine.

My friend and colleague Celia Morgan has been doing her PhD on the cognitive effects of ketamine with Val Curran at UCL; Prof Curran gave a presentation about this last month; again, some findings described below may not yet be published.

To give the basic neurochemistry, ketamine is an nMDA antagonist – this means it acts on a specific type of neural receptor in the brain, the nMDA receptor, found throughout the brain but particularly in the cortex, and it act by suppressing its normal activity (whilst an agonist would boost it). This leads to an excessive release of the neurotransmitter glutamate. This lays a case for a possible harmful effect of ketamine: nMDA antagonists have been shown to disrupt long-term potentiation (the neural mechanism by which learning takes place in the brain). And the receptors are particularly heavily distributed in memory-critical areas such as the hippocampus and surrounding areas, which means adverse effects are likely to impact on memory.

Moreover, clinical reports document that being on ketamine produces symptoms very similar to those seen in schizophrenia. The similarities have been so striking as to contribute to a shift away from purely dopaminergic models of schizophrenia to nMDA hypofunction models, which suggest that glutamate as well as dopamine are responsible for the abnormal function of the schizotypic brain. (see e.g. Olney and Farber 1997).

Morgan and Curran have been investigating this using cognitive and neuropsychological testing, alongside clinical-style inventories of schizotypic symptoms and thoughts. One aspect of their research uses healthy people, dosed up with ketamine. Relative to doses of placebo, ketamine-addled subjects were impaired across a variety of tasks – short-term memory, attention, and problem solving. They also gave higher ratings when asked to score a number of schizophrenic-type experiences, such as such as ‘The world does not feel real to me’.

Anyone investigating specific populations (like patients, drug users or people with developmental disorders), rather than imposing different conditions on a generic population, will tell you nightmares of exclusion criteria, control group selection and so on. The difficulty with ketamine users is that they invariably take a lot more than ketamine – cocaine, weed, ecstacy and even more obscure drugs. Their solution was to accept poly-drug users in the ketamine group – and to match with a control group of poly-drug users, who had never done ketamine. In effect, this is a subtraction technique, similar to the kind that underlies many imaging studies (activation difference between complex and baseline tasks shows you the activation due to the processes unique to the complex task), and underlies much of the presuppositions of cognitive neuropsychology.

Compared to this control group, ketamine users were poorer on days following their drug intake, and still poorer three days afterward. As ketamine has a very short half-life, it seems fair evidence that this may represent neural degeneration (already established in laboratory work – Olney et al 1998), rather than active effects of the drug. (To make sure of this, they also compared subjects from their non-chronic use experiment after three days, and the placebo and ketamine group were not performing at different levels.) Their poorer performance was shown on tests of source memory, story recall, verbal fluency (being able to list words of a specific criteria rapidly) and speed of semantic processing (what things mean). They also, needless to say, showed higher ratings of schizotypic type symptoms. A follow-up study on a sample of former chronic users is also a window into how enduring these effects are; changes in certain measures were heavily correlated with changes in ketamine intake, but many others, including the schizotypic symptoms, continued to persevere. What is perhaps the most ominous of the findings is the apparent irreversability of the impairment produced in episodic memory (personal memories of events and instances), and possibly also attention.

Abstract of paper on healthy individuals link
Abstract of longitudinal paper in Addiction link
Drugscope Briefing paper, with some details of legal status, vulnerable groups, and usage rates link
Some older stories from the bbc on ketamine – link & link – clearly cocaine is far more newsworthy than club drugs these days…

*Non-UK readers, insert your own amusing locations (to wit: lively if rough urban area; rural dull spot; corner-store-cum-supermarket). Once you have done this, laugh appreciatively, and wonder at the marvel of international collaboration. Truly, is there nothing we cannot do?

** I hasten to add that Special K the cereal is not in any way hallucinogenic, unless you can hallucinate from eating damn fine flakes. Of maize!

5 Comments

  1. Vaughan
    Posted March 11, 2005 at 1:20 pm | Permalink

    According to an anaesthetist I met a while ago, ketamine is still used in adults during surgery in some cases.
    Largely, I was told, because it is one of the few analgesics that increases rather than decreases blood pressure, apparently because it has stimulant properties.
    This makes it quite useful for some patients with low blood pressure who would otherwise be at increased risk during surgery.
    Some info here:

    http://www.nda.ox.ac.uk/wfsa/html/u04/u04_010.htm

  2. erogul1
    Posted March 13, 2005 at 5:39 pm | Permalink

    This is news to me. I’m an emergency doctor in a hospital where we routinely use ketamine to sedate children for painful procedures. The drug is classified as a “dissociative anesthetic” and has certain favorable attributes including very powerful analgesia, or pain relief–many times more powerful than morphine. I wonder what the residual effect of single instance ketamine use is on these children.

  3. Posted March 13, 2005 at 5:58 pm | Permalink

    Well, from what I understand there is no evidence of malign effects for children, which is why it is still used. My recommendation would be to ‘watch this space’ – not this space here, necessarily (although I will post on the drug as and when I have something further to share), but the literature. I don’t know if this is an absence of evidence or evidence of absence situation – it may be that as children don’t report the overt effects, no-one has thought to look at the cognitive carryover. I did a quick search using Google Scholar, and although i found studies assessing the suitability of ketamine vis-a-vis side effects such as vomiting or bad dreams, couldn’t find anything that investigated cognitive effects.

  4. mayyo
    Posted July 29, 2006 at 8:55 pm | Permalink

    I was given ketamine during my cesarean section in 1999 in Canada. I had already received anathesia (morphine-based I think), but the surgery had started and I was very surprised to feel the pain of the scalpel. So the anathesiologist put ketamine in the IV, and the pain was instantly replaced by hallucinations, a sense of whirling rapidly through space, and disinhibition (I became very chatty and couldn’t stop myself, even though I felt I was embarassing myself). The ketamine was effective, but I’ve never felt so strange in my whole life. Once was enough, thank you! Vaughan mentions it could be helpful for patients with low blood pressure. I am an one of those, including during pregnancy. As for lingering effects, I am aware of none. It was my second cesarean section, and I was happy to get on with looking after two small children.

  5. Posted March 1, 2007 at 1:26 pm | Permalink

    One famous user of “Special K” was Canadian sex killer Karla Homolka, who later professed to have little or no memory of some of her horrific actions. Based on a cursory reading of Stephen Williams’ two books on her, I suspect Homolka and Bernardo were both being mind controlled, and did not act alone. It’s possible they were an “experiment” that went a little too far. Interestingly, before they began their killing spree, the newly wed couple visited Disney World, said by many to be a New World Order mind control programming site. Their intimate relationship was textbook BDSM based on “total power exchange.” Yet many people in Canada, including author Williams, were outraged when Homolka was declared to be suffering from battered woman syndrome. Many think she was the real, evil mastermind, manipulating media, courts and police to get herself a lighter sentence than her partner in these crimes.
    Behind all the publicity and angst over this case, I perceive the workings of a secret, shadowy cabal which truly DOES control the media. Homolka’s release in 1995 was interestingly timed to coincide with court rulings in two major Canadian abuse cases: one on HIV-tainted blood administered to thousands of hemophiliacs, and the other on abuse of aboriginal kids in residential schools. The week we should have been reading and hearing background on these two extremely important lawsuits, our media concentrated on Homolka’s release from prison. The circus lasted several days.
    Our media deliver “Special K” to the public every day in the form of mindless sensationalism and distortion of our reality.


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