Tuesday 6 June 2017

ketamine hollerin'

We used ketamine about the farm twice in the last 5 years: once to sedate a sheep, not very effectively, when the ewe needed to have a septic toe removed; and once to kill our dog Rashers, after she went into kidney-failure. That wasn't very effective either: she took a long time to die.

Ketamine surfaced a short while ago as some peculiar dissociative effects of the drug took hold on a middle aged chap getting his broken ankle set in hospital. It makes you wonder how that sort of thing a) gets filmed by the BBC and b) finishes up on youtube. There must be ethical, informed consent, issues and I guess / assume /hope the singer had final approval. Time to find out more, I said.

For once, I didn't have to go first to Wikipedia for this information because there is a neat 6 minute All you need to know about ketamine on youtube.  Ketamine was first synthesised in 1962 by Parke Davis [now a division of Pfizer]. 55 years on we're still finding out how it works, but one mode of action is as an NMDA receptor antagonist. NMDA is N-Methyl-D-aspartate and a wholly artificial analogue of glutamate which is a natural neurotransmitter. We name neuronal receptors after the drug which was first shown to affect them. Opioid receptors for example: we don't make opium or its derivatives in our brains but we do have receptors that are responsive to these alien chemicals. Muscarinic acetylcholine receptors, vital components of the parasympathetic nervous system, were discovered by injecting muscarine which is produced by certain mushrooms. Ketamine has two established uses
  • as an anesthetic, mainly in veterinary practice, which prevents the brain from experiencing pain. It is very effective at this and therefore appears on the list of about a dozen anesthetics put out by the WHO on their Model List of Essential Medicines (EML). otoh, maybe by altering the threshold of sensation, apart from causing euphoria, ketamine can drive some pretty peculiar effects including hallucination and out-of-body experience.
  • the hope of such a mind-bender has led to its adoption as a recreational drug called Special-K and a dozen other kode-words. If you snort the stuff, it works within minutes and the effects last about an hour, so you can trip out and be back at work after lunch.
It is long off-patent and retails at about 10-20c a dose if bought legally - by our veterinarian for example. I guess its street value is higher because it is illegal in many countries. It is illegal because it is potentially lethal. One of its early adopters / advocates D.M Turner gave himself an injeKtion in the bath and drowned giggling on or about New Year's Eve 1996: his body wasn't found until weeks later. Since then at least 90 people, mostly kids, have died under the influence.  If you don't die you are quite likely to fritz your urinary tract with ketamine-induced ulcerative cystitis. But this is really only manifest in those who do K every day and the symptoms dribble away if you can haul yourself off the drug.

What's the opposite of euphoria? Depression? Recent evidence is coming on stream that low-dose ketamine may be an effective anti-depressant, Polemical video with digest of evidence - 12 minutes. The usual treatment for depression is one or another SSRI - selective serotonin reuptake inhibitor. Serotonin is a neurotransmitter NT - it is secreted by one neuron into the synapse between that cell and the next neuron.  NTs need to be produced, act and then go away or you get persistent nervous stimulation as when sarin prevents the enzyme acetylcholinesterase degrading the NT acetylcholine. Another way of dealing with 'used' serotonin is for the upstream cell to suck it up again for recycling: serotonin reuptake. SSRIs force the serotonin to hang around stimulating the downstream neuron for a longer time and that works well for some sorts of clinical depression. The downside of SSRI treatment is that it may take 12 weeks [twelve weeks!] before the punter notes any effect and some depressions are resistant to SSRIs and get no benefit after that long period of anticipation. Ketamine otoh, as with its recreational use, is, compared to SSRIs, super-express acting. If you go to the doctor in Ireland it's costing you €50+ so you'll be at the end of your tether when you rock up in the GP surgery.  12 weeks of feeling grim with no certainty of symptom relief: is that the best you can hope for?  If we can free up ketamine for use in those circumstances, it might, just might, give sufficient relief to encourage the poor patient to keep on keeping on.

Here's Dr Dennis Chaney, from Mt Sinai, NYC, whose group carried out the original ketamine / depression studies:  ketamine helps with depression.  Depression? there is money to be made. Dr Steven Mendel runs the Ketamine Clinics of Los Angeles and claims an 83% success rate for SSRI- resistant depression. He charges $1500 for a 2x infusion course of treatment. My vet can buy the stuff for 20c / dose. If you're feeling low maybe you'd do better to call at the Los Angeles Small Animal Hospital with a dying pet and get an accidental needle-stick injury.  On a positive note here's another extraordinary ketamine-in-action short film: within an hour of a snort of K a clearly hurting person become human again.

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