Posting in Cancer
It's the pathway that matters, the idea that we can attack the chemical problems of depression in a new way.
It's not the kind of experiment you want to see people running on themselves, but it may lead to the most important breakthrough against depression in decades.
(This happy hippie was photographed at a Rainbow Gathering in Russia, in 2005. Picture from Wikipedia.)
Ketamine was developed in the 1960s as an anesthetic for animals. It was used on one of my cats, some years ago, when she got her teeth cleaned. The same shot relieved pain as it knocked out kitty, which made for a better recovery.
Then the druggies found that, by snorting it at low doses, they got high. As a street drug, called "Special-K" or "Kit-Kat," it could make you feel like you were floating out of your body.
Now pharmacologist (and LSD expert) George Aghajanian, along with former University of Texas Ph.D Ronald Duman at Yale, say they know how ketamine works, and they say this pathway can be used to develop an anti-depressant pill which delivers relief in just a few hours. Their research was published last week in Science.
Current anti-depressants, like Prozac and Zoloft, can take weeks to start working, and there is now some question as to whether they work at all. Talk therapy also takes a long time to have an effect. Meanwhile your life can spiral out of control. Suicide can be the result -- painless for you perhaps, painful for the rest of us.
Ketamine, the Yale researchers write, works on the pre-frontal cortex, the high-end brain, activating what is called the mammalian target of rapamycin (mTOR), a chemical pathway that is also being looked at by anti-cancer researchers.
Within the pre-frontal cortex, they write, it provides "rapid reversal of stress or depression-mediated deficits" by restoring connections between neurons damaged by stress. Therapists can use this quick relief to then probe into the cause of the stress or depression. When that's obvious or short-term, such a pill could provide a cure.
Now before you go running to your ketamine dealer, this has only been tried on rats, and the aim is to create another chemical using the same pathway that would not have ketamine's side effects. It's the pathway that matters, the idea that we can attack the chemical problems of depression in a new way.
Getting back to Dr. Aghajanian's original research target, Franz Vollenweider, a Swiss researcher, wrote last week in Nature Neuroscience that low doses of LSD or psilocybin may also be useful in the treatment of depression. Their proof comes from brain scans, not rat studies, and is a follow-up to a 2005 Canadian study, which also looked at ketamine.
Both LSD and psylocybin, however, are Schedule I drugs, meaning they are thought to have no medical use. This hampers research into them in the U.S.
Still, it will always bring to some minds the story of Cary Grant, who took LSD therapeutically in the 1950s but later became a foe of the counter-culture. Grant was experimenting to find relief, as the hippies were, but he was doing it with a doctor beside him.
Hippies, with their long hair and other accoutrement, as well as the uncontrolled nature of their experiments, put a stop to all that by scaring our parents to death. Now that the hippies are aging out maybe the labs can get back to work and deliver us from mental depression.
What do you think?
Aug 23, 2010
I think most researchers would admit that our knowledge of the brain is well behind that of the other organs. We're still wielding hammers in places where we should be using scalpels, but we have yet to develop all the scalpels we need.
@jeffpk I agree with almost everything you say. However, I would point out that the suicide rate of those who are on psycho-pharma (especially SSRIs) is higher than those who are not. You also advise not to listen to anyone with an agenda. Given where US MDs and psychiatrists get their money, their perks and their continuing "education", I believe your advice comes down to "don't listen to any US MD or psyciatrist". Your *good* psychiatrist would have to be one who is on the patient's side, bases their treatments on scientific evidence and is indepenedently-minded enough to resist the onslaught of drug company propaganda and bribery. If you know how to find such people in the US I would love you to share with me. Keith
I just wish that someone or some company would investigate the link between chronic, crippling insomnia->depression->suicide. Lose enough sleep and you will get to the point where you don't care about anything!!! else. Insomnia and depression feed off of each other and few, if any doctors take the problem seriously. The real problem here is that there is just too much money in selling the ?patch-it-up? drugs.
The phrase has been badly misused. What people who fought the "war on drugs" were on about was opposing the use of any drug that worked primarily on the mind. As though it were separate from the body. It's not. The broad brush approach to these questions was always institutionalized ignorance. It has led good people to paranoia, and bad people to wealth. If we could be more intelligent on what every chemical does to both mind and body, and have a meaningful dialog about it whenever and wherever the subject comes up, Mexico might be part of the First World instead of the next Afghanistan.
If you wait long enough, depression *always* goes away... its just that one way it does that is through suicide. People with an agenda, either pro OR anti drug, are dangerous. For some depressives where the causes truly are chemical in nature, chemicals are the right answer. For others where the real problems are behavioral, talk therapy may be right. For many patients, both are necessary for successful recovery. Anti-depressant however does NOT automatically mean Zoloft or Prozac, both of which are Lilly SSRIs. There are many other families of anti-depressants, including those that predate SSRIs such as the tryi-cyclics and the MOIs. SSRIs are not necessarily the best treatment, but they ARE by far the most prescribed thanks mostly to the marketing muscle Lilly has used to push them through MDs-- most of whom do not know a thing about proper psycho-pharmacological case management. This has led to many improperly supervised cases and the resulting problems, which those with a "no drugs" agenda capitalize on to scare people who really need them away from them. If you need help, don't listen to *anyone* with an agenda. Find a *good* psychiatrist and let them help you.
We used to keep this drug around for emergent C Sections. I was happy we rarely used it. When working for Friends of Animals long years ago I used Ketamine to induce the cats followed up by gas (Nitrous). Those cats woke up mean. Before their eyes were open they had the claws going. If you were reaching into a lower cage to check on a cat or dog post op, the cat on the top rack would be going for your head. Bare in mind the animal was still essentially unreactive. But somehow they could sense movement and they wanted to kill whatever was moving. I did not like the effect on cats and I am sure I don't want to try it on me. Of course, dosage can make or break any drug/medicine but still, it seemed to make the cats so frightened and thereby agressive that it just seems counterintiuitve to use it for depression. Unless the theory is that anger is better than depression.
Is there a drug which will induce depression so that an overdose of Ketamine, or something similar, can be reversed? We don't want our population to become TOO happy...
Before taking any drugs for depression or any other mental condition read Robert Whitaker's "Anatomy of an Epidemic". For 99% of people, the best way to deal with depression or similar conditions is to wait for them to go away. The second best method is meditation or talk therapy. Drugs come a distant third. If you insist on taking drugs, the evidence is that the illegal ones would be a better option than the ones your psyciatrist/doctor prescribes.
This is an obvious case of hair envy. Although the research is preliminary, the potential is great. As noted, the effectiveness, not to mention the long term side effects of many of our current choices are less than ideal. The broader issue of the criminalization of pharmacological agents handcuffing research and treatment in the USA, needs to be addressed. We have not educated the public not taken a pro-active approach to framing the debate in public policy forums. Until we do so, both research and treatment alternatives will be political footballs for the politician du jour.