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One pill makes you larger
And one pill makes you small
And the ones that mother gives you
Don’t do anything at all…
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hat tip to Jamzo
I suppose this was inevitable, given the half century residue of the sixties drug scene and the increasing preoccupation of psychiatry with symptoms and symptomatic treatments. Even the accompanying slides of the little rat neurons growing pseudopods on Ketamine look a lot like the psychedelic art and tee-shirts from the age of bell-bottoms. The articles are full of testimonials, people depressed for years finally achieving relief. Such stories are hard to argue with. They are diagnosed as having Major Depressive Disorder or Bipolar Disorder based on their reports of being depressed for years. And those of us who work in Clinics can see in our minds a line of patients who have been depressed for years asking "Is Ketamine right for me?" And psychiatrists will be asking the question, "are we treating disease?" or "are we treating dis-ease?" "does it even matter which?" The articles make analogies to ECT – an empirically derived treatment that is both vilified and praised. "It damages the brain!" "It’s benign!" I suppose the difference is that there are no lines at ECT Clinics. It is usually used on recommendation of a physician rather than sought by clamoring patients, and for the most part is limited to use in refractory cases with fairly clear syndromatic diagnoses.
Having lived through the sixties as a person and the age of pharmacology as a psychiatrist, the things that bother me are the frenzy and the entrepreneurialism. This is touted to be a time when the pharmaceutical industry is abandoning CNS drug development, and yet these articles make it clear that there’s no shrinking from Ketamine or its derivatives. The drums are beating and it’s already on the market for the wealthy. One can even hear a fledgling ketaminergic hypothesis of depression being formulated as the new chemical imbalance.
Ever wonder how a neuron figures out how to connect to another neuron, or how many to connect to?
In neural networking software we have a math equation which is based on the activity (inputs and outputs) of the neuron. A neuron either fires or it doesn’t, then there’s frequency. This is how it is determined whether or not information processing is occuring properly. Connections are added or deleted as a feedback regulated mechanism. When you have groups of neurons doing this in the human brain, the process is continuous, this increase efficiency – finding the fewest neurons to complete a given task. It’s determined whether or not the task is completed properly by the same inputs and outputs, bascially the circuit feeds back on itself for ‘postive reenforcement’. Circuits are basically loops that branch out to other loops.
Since neurotransmitters are a component of neurons which regulate frequency and amplitude, psychotropic drugs get their effects from jumping in to this pathway and disrupting it. The frequency of neuronal firing is then altered. Guess what happens next? The neurons operate with altered activity, and they start making or deleting connections inappropriately. As the neurotransmitters themselves are also regulated by feedback, the degree of altered activity also changes with time.
So the neurons are bascially trying to push a ball up a ramp thats flopping around, and the balls keeps overshooting the hole at the top. The neurons make less and less efficient connections.. who knows what the subjective effects are.
Because everything is mediated by feedback, things should go back to normal when the drugs are stopped long enough, but the connections cannot. Altered synaptic connections remain until they are re-learned manually.
All psychotropic drugs make neurons grow or delete connections in disturbing ways.. but the more pathways that are affected, the worse this disturbance. Ketamine is one of the scarier drugs in that regard.
“Chronic ketamine exposure induces permanent impairment of brain functions in adolescent cynomolgus monkeys”
http://onlinelibrary.wiley.com/doi/10.1111/adb.12004/abstract
Scientific American put a quote under the picture: “Ketamine induces growth of tiny protuberances on a rat neuron (bottom) to allow it to better connect with neighbors.”
Those last 8 words, ha. The same way ecstasy helps you ‘better connect’ with complete strangers.
I laughed when i read the article though. All I could think about were the tie dye shirts and desert raves. Even the scientifc american article read “In the meantime, doctors and patients are increasingly adopting their own home-grown solutions.” lol. I can’t keep a straight face at how rediculous this is. My guess is drug addiction is equivalent to improvement.
It is scary. It’s for the lab neuroscientists right now – not the clinics. It reminds me of Freud’s early dabbling with psyhopharmacology in Über Coca, 1894.
While a great deal less complicated I have to wonder if this scenario is not playing out in this situation, and countless others in today’s medical office.
http://www.kevinmd.com/blog/2013/09/dissection-needless-hospitalization.html
A rushed doctor making an assumption before the patient has a chance to speak, this is repeated and eventually the patient ends up in the hospital in dire straits, only when a doctor sits down and listens to the patient do they realize a simple error has lead to this terrible situation.
Complicate this with a new drug, a drug company’s positive testing, and how many patients will end up in the hospital or damaged for life.
Steve Lucas
I’ve written about this issue, and quite frankly, it is just absurd to listen to those advocate loudly to legalize and legitimize drugs of frank risk for abuse and dependency just to benefit a very finite, and small minority who might actually have some efficacious response.
This medical marijuana tsunami is just ridiculous to watch. For every one patient who needs it and gains from it for psychological purposes, literally the next 4-5 don’t. What bothers me about the Ketamine debate is simply the short term impact it has, and the fact it is so expensive. I mean, really, we still know more about ECT, and what is the history of pharmacology, the 4 P’s: promise, panacea, placebo, and poison, in that order.
I guess when Ketamine’s poisons start to take on victims, the higher powers (pun not only intended but offered insultingly) may need to keep their eyes on the exit door right now!
But, where there is money to be made, sacrificial lambs need to be rounded up. And society certainly has too many lambs these days, eh?
That’s an interesting theory, TinCan. It comports with the theory that increased hippocampal volume is seen after SSRI use because of failure of normal neuronal pruning during sleep — SSRIs interfere with normal sleep patterns. The increased volume is not a good sign at all!
One might suppose that additional undeserving neurons are being retained because of artificially stimulated firing.
In addition, here’s a study suggesting that SSRI use interferes with learning from negative feedback: http://www.frontiersin.org/Integrative_Neuroscience/10.3389/fnint.2013.00067/abstract
Failure to prune?
@ Altostrata
I would say it’s safe bet! SSRI drug-induced connections are probably occuring, and would interfere with learning among other things.
“We recently found that repetitive administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine to naïve adult male rats induced an increase of mature, mushroom-type dendritic spines in several forebrain regions.”
http://www.ncbi.nlm.nih.gov/pubmed/23675317
I think the brain volume changes are mostly associated with grey matter (Glial cells). Those cells can pretty quickly replicate from stem cells to provide resources to neurons. They are regulated based on the degree of activity of the neurons. They remove themselves about as quickly too. However, I have read of white matter changes both ways though. Scary!
A neurologist also pointed out to me that increases in nervous tissue volume indicate damage to the tissue.
I’ve probably mentioned this before — I talked to a clinical psychiatrist who experimented with ketamine treatment. He told me miraculous recovery with one dose happens only occasionally and a repeated dose does nothing. He concluded the beneficial effect of ketamine was, as usual with psychiatric treatments, not predictable and probably not beyond placebo.
If ketamine has some merit as an emergency treatment to disrupt some individual’s terrible downward spiral, I can’t knock ’em for trying it. What scares me the most is the immediate, lockstep advocacy of “maintenance” ketamine treatment. Every article I have seen — and every enterprising clinic getting into the biz — is pushing this view, which has got to be terribly damaging. Come on! We have years of experience with this stuff as anesthesia … and what anesthesiologist in his or her right mind would consent to monthly anesthesia for life? They know better.
Unfortunately, this is now the party line on ECT as well which is really frightening …