club drug as antidepressant

Good morning. I would like to expose myself. No, wait, there's more!

I would like to expose myself as a person who knows and understands things scientific in a very limited and prejudicial manner. It's just the truth --my capacity is in the realm of the pseudo-, of pretense.

Of course, this being my blog, and this blog representing my real interests, when I present medical information pertaining to CRPS/RSD, I try to educate myself enough that I am not, at the least, being irresponsible.

Okay, okay, except perhaps as pertains to Jose Ochoa, who is clearly a turd but I don't see passing that fact on to my few readers as even remotely irresponsible. It's more like a Public Service Announcement.

I am trying to say that I am more humble than you might think when I set about to read and digest medical studies/announcements.

Even so, sometimes I just want to scream, and possibly shake someone silly.

On the off chance that some CRPS-related information is listed under the search term ketamine, one of my medical feeds checks for daily references to the drug. Most studies relate either to abuse of ketamine, its deleterious side effects, or to proposals of novel uses for the anesthetic.

Today? Well, there is something on the harmful effects of ketamine on the urinary tract ("a new radiological challenge"!), a bit about partial tripolar cochlear implant stimulation in ketamine/xylazine anesthetized guinea pigs, a veterinary medicine label update for KETAMINE HYDROCHLORIDE injection,/solution ("for Intramuscular Use in Cats and Subhuman Primates Only"!), and something about how ketamine can reverse "the expression of tolerance to the anticonvulsant effects of morphine."

Not stuff terribly applicable to CRPS;  Not stuff terribly accessible to a non-medico such as myself.

But then there was this -- An article in Nature, titled Neuroscience: Quick mood lift, with this come-hither statement serving as tantalizing abstract:  Patients taking traditional antidepressants have to wait several weeks for the drugs to kick in. However, a few severely depressed patients taking ketamine, an anaesthetic and recreational drug, have shown improvement within hours.

Okay, so I don't have a subscription to Nature... and cannot access the current edition without forking over $32.  By a search of the terms ketamine and antidepressants, limited to the past week, I feel pretty confident that I understand the claims of the Yale researchers.

A quick search of the journal finds this Nature article -- from 2006, about another study (at the National Institute of Mental Health) that revealed the exact same results and engendered the same excitement:

Club drug finds use as antidepressant:  Psychedelic ketamine hits the blues surprisingly fast

The 'club drug' ketamine may be the fastest-acting antidepressant ever tested, researchers report today.

A team based at the US National Institute of Mental Health (NIMH) in Bethesda, Maryland, studied ketamine in 17 people with major depression. All the subjects had failed to respond to treatment with standard antidepressant drugs or more drastic methods, such as electroshock therapy. But 71% felt better the day after taking ketamine, and 35% still felt better a week later. None improved when dosed with a placebo.

Most striking, the scientists say, was that some patients felt better less than 2 hours after taking ketamine. Currently approved drugs can take weeks to remedy depression. The work is published in the Archives of General Psychiatry.

"It's almost like there's a sound barrier for those us who do depression research, and we have not been able to break it," says Carlos Zarate, chief of the mood and anxiety disorders research unit at the NIMH, and first author of the study. "That's the exciting part of this — now there is evidence that we can."

Zarate and his colleagues are not advocating that doctors start giving depressed patients ketamine right away. Large doses of the drug can cause brain damage in rodents, and its long-term health effects have not been studied in people.

"We don't want to give anyone the message to run out on the street and use ketamine," says Nuri Farber, a psychiatrist at Washington University in St Louis, who was not involved with the work. "It makes you crazy — that's why it's a banned drug."

Scientists are currently testing a wide range of recreationally used-and-abused drugs, including ecstasy (MDMA; see 'The ups and downs of ecstasy') and psilocybin, the active ingredient of magic mushrooms, as potential therapeutics.

Ketamine, invented in 1962 as an anaesthetic, is chemically related to phencyclidine (PCP), also known as angel dust. Both induce hallucinations and out-of-body experiences, hence their use as illegal psychedelics.

Ketamine has milder psychotic effects than PCP and is therefore also used as a legal anesthetic and horse tranquillizer. Scientists are studying whether it can be used to treat alcoholism and chronic pain, as well as depression.

Ketamine targets a brain protein called the N-methyl-D-aspartate (NMDA) receptor. Existing antidepressants target brain chemicals such as serotonin, but there is growing evidence that these drugs eventually affect NMDA receptors. Ketamine may work so quickly because it takes a short-cut straight to this part of the brain.

The psychotic effects of ketamine, such as euphoria, wore off before the antidepressant effects kicked in, Zarate's team found, suggesting that the drug's psychotic and antidepressant effects are separate. One surprising aspect is that other drugs that induce euphoria, such as cocaine, usually lead to a depressive crash once the high wears off.

Zarate's group is looking for substances with some of the chemical properties of ketamine, such as the ability to target NMDA, without the psychedelic effects.

Oh, well, good.

Worried about, ummm, side effects?  No sweat!

Other scientists, including Farber, have developed drugs that can be taken with ketamine to damp its side effects. Giving these drugs together might help patients feel better without getting high.

Of course, in the same issue, there's an article about "what it means to be an ant."

"It's like a magic drug — one dose can work rapidly and last for seven to 10 days," said Dr. Ronald Duman, professor of psychiatry and pharmacology at Yale University, who led the study.

Oh, dear Lord.

One final admonition -- to myself. Keep an open mind. The Ketamine Coma protocol for intractable CRPS has actually allowed some people to mumble the C-word -- cure.

Remember, too, though, that there have been deaths and other bad outcomes in both the Mexican and German research sites.

That ought to attest to the horrors of this disease, that people are willing to be injected with ketamine in an amount sufficient to maintain a coma for 5-7 days, risking their lives to have a chance at lessening the pain of CRPS.

Hmmm.  Here's a thought:  Maybe I should try putting myself in the place of someone so depressed, clinically, that they, too, would choose ketamine...

But I would still find this research more bother than boon.

I still want to shake someone silly.