PSYCHEDELIC RESPONSE?: The anesthetic ketamine has several notable side effects, including hallucinations and, according to new research, strengthening synapses. The top synapse pictured here is untreated whereas the more connected synapse below shows regeneration in a rat receiving ketamine.
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The Wisdom of Psychopaths
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Ketamine—a powerful anesthetic for humans and animals that lists hallucinations among its side effects and therefore is often abused under the name Special K—delivers rapid relief to chronically depressed patients, and researchers may now have discovered why. In fact, the latest evidence reinforces the idea that the psychedelic drug could be the first new drug in decades to lift the fog of depression.
"We were trying to figure out what ketamine was doing to produce this rapid response," which can take as little as two hours to begin to act, says neuroscientist Ron Duman of the Yale University School of Medicine. So Duman and his colleagues gave a small amount of ketamine (10 milligrams per kilogram of body weight) to rats and watched the drug literally transform the animals' brains. "Ketamine… can induce a rapid increase in connections in the brain, the synapses by which neurons interact and communicate with each other, " Duman says. "You can visually see this response that occurs in response to ketamine."
More specifically, as the researchers report in the August 20 issue of Science, ketamine seems to stimulate a biochemical pathway in the brain (known as mTOR) to strengthen synapses in a rat's prefrontal cortex—the region of the brain associated with thinking and personality in humans. And the ketamine helped rats cope with the depression analog experience brought on by forcing the rodents to swim or exposing them to inescapable stress. "Preclinical and clinical studies show that repeated stress or depression can cause a decrease in connections and an atrophy of connections in the same region of the brain," Duman explains, noting that magnetic resonance imaging shows that some depressed patients have a smaller prefrontal cortex as a result. "Ketamine has the opposite effect and can oppose or reverse the effects of depression" for roughly seven days per dose.
Rats and humans have similar biochemical pathways. "There's a fair amount of similarity between the neurotransmitter systems and the way drugs act in the brains of rodents and humans. Biochemically, there is good correlation," Duman notes. "Behaviorally, it's much more difficult to know whether an animal is depressed and the drug is making it less depressed."
But ketamine is not alone among psychedelics in having potentially therapeutic effects. A review, published August 18 in Nature Reviews Neuroscience, of research on this grouping of drugs generally—ranging from dissociative anesthetics such as ketamine to naturally occurring hallucinogenic compounds such as the psilocybin in "magic mushrooms"— shows their efficacy at treating obsessive-compulsive disorders and addiction as well as depression and anxiety, among other disorders. (Scientific American is part of the Nature Publishing Group.)
In fact, ketamine has shown promise at reducing the risk of suicide and is currently being tested in humans for effectiveness in treating bipolar disorder and addiction. Psilocybin can decrease obsessive-compulsive behaviors, or even eliminate them entirely, for as long as a full day after treatment and is being tested to reduce anxiety and depression in terminal cancer patients. And even LSD—lysergic acid diethylamide-25—can combat inflammation, among other potential therapeutic uses. "The potency is about 300 times more potent than steroidal anti-inflammatories," says pharmacologist Charles Nichols of the Louisiana State University Health Sciences Center, who is working with the drug. "My lab is currently studying the ability of it to block or prevent inflammation in models of human inflammatory disorders, and the results are very promising so far."
The August 18 review, by psychiatrist Franz Vollenweider and neuropsychologist Michael Kometer of the University Hospital of Psychiatry in Zurich, proposes that various psychedelics' interaction with the receptors for the neurotransmitter serotonin may prove key to understanding their beneficial—and mind-bending—effects. "Psychedelics activate neuronal networks and the glutamate system that are implicated in the regulation of emotion," Vollenweider says, noting that their hallucinogenic effects can be impeded by blocking specific serotonin receptors in the brain (known as 5-HT2A). Psychedelics typically boost serotonin and may also boost the release of glutamate, according to the review authors, another neurotransmitter that has been linked to short-term but long-lasting brain functions such as learning and memory. More glutamate also has an impact on synapses. "This might result in an increased number and function of spine synapses in the prefrontal cortex," Vollenweider says.
That's exactly what Yale's Duman and his colleagues have now found, at least in the case of ketamine, though Duman is skeptical of a shared mechanism, given that ketamine and other hallucinogens affect different biochemical pathways. "There is evidence that the psychedelic agents enhance glutamate," he says. "I don't think the evidence is all that strong."
Regardless, it is unlikely that ketamine, psilocybin or any of these psychedelics would be used directly, because of their hallucinogenic and other side effects. According to Duman, several pharmaceutical companies have already begun the search for alternative compounds that target the same biochemistry or brain function, including some that his lab is testing. "We are testing other targets that we identified that we now know are potentially related and could impact pathways we have found to try to come up with novel targets and treatments that produce a ketamine-like effect with a better safety profile." In other words, a drug that treats depression the same basic way as a psychedelic but without any of the hallucinations and other mind-bending effects.
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31 Comments
Add CommentThe article ends by " try to come up with a drug that treats depression the same basic way as a psychedelic but without any of the hallucinations and other mind-bending effects."
Reply | Report Abuse | Link to thisFunnily enough is the mind bending effects that treats depression... keep searching...
A psychedelic treated ex-patient
Aren't ALL psychotherapeutic DRUGS "mind bending" by definition?
Reply | Report Abuse | Link to this(sorry typo...)
This drug boosts brain connections. Would it also be useful in repairing brain connections, such as in ageing related diseases?
Reply | Report Abuse | Link to thisI am not going to vilify Timothy Leary but he probably did more to hurt the "cause" than help in the long run.
Reply | Report Abuse | Link to thisSalvia, In my opinion, is the strongest hallucinogen I have ever taken by far and it is legal and lasts only a few minutes. Im curious as to why this drug is not mentioned r being used.
Reply | Report Abuse | Link to thisa comment from left field : actually the soon to be verified spiritual field : transcendental meditation(TM) reliefs depression [ ditto ADHD ditto PTSD and anxiety...] . Dr Norman Rosenthal is writing a definitive book about the benefits of TM and 340 peer reviewed articles about the research with TM
Reply | Report Abuse | Link to thisthe reason i say left field is to call attention to the unconscious assumption that any condition needs a manmade chemical substance a drug to remedy it
firstly nature has provided herbs and spices with medicinal properties and all knowledge traditions have practiced meditation of some type in order to reduce entropy in the system
and first recourse is allways consciousness of healthier habits rather than monkeying around with symptoms of entropy
entropy is insoluble complexity unless a effective meditation practice is learned by doctors and patients
NHS in england now pays for instruction in Maharishi's TM
what is lacking is equality of funding for research about alternative medicine ; in other words the majority among doctors had badly discriminated against the minority
Just give it to the patients if it works, the hallucination is an added bonus.
Reply | Report Abuse | Link to thisGroovy man...
Reply | Report Abuse | Link to thisBasic research on Psycadellics have shown promising results for decade but are too controversial to get to any real answers,glad to know they're gaining momentum in this area;)
Reply | Report Abuse | Link to thisI am also surprised they do not mention DMT or ayahuasca. This is probably the strongest hallucinogen around. However, this being beside the point, if you read testimonials of people who have experienced the ayahuasca journey (especially guided by a local shaman in Peru or some such rainforest filled country) almost all of them are very positive in nature. Granted it is always a possibility one can experience a terrible trip regardless of the hallucinogen. There are absolutely tons of reports of people being cured of mental illnesses including depression and bi-polar disorder. Many of the reports even go so far as to claim that long lasting pains (like intense back / leg pains that have plagued the person for years or even decades) miraculously disappeared after the experience.
Reply | Report Abuse | Link to thisAs one who practices TM and has tried all sorts of alternatives therapies...I have still experienced episodic deep depression for thirty years, still get suicidal at times and would rather stay alive and live a good life--even if it involves taking "Special K."
Reply | Report Abuse | Link to thisCan't produce any more side effects than Cymbalta. Might even work better. Most anti-depressive drugs on the market do about the same thing...........nothing! Keep searching, we need it!
Reply | Report Abuse | Link to thisHarmaline, the active principle in Peganum harmala, probably the Soma plant of ancient Vedic literature, whose juice changed men into gods, is identical to the psychoactive ingredient in Ayahuasca, Banisteriopsis caapi, used by native southamericans, and has a MAOI (mono-amine oxidase inhibitor) power. MAOIs are a class of very powerful antidepressants, that also stimulate activity. They have not a widespread use within the medical community because the older members of this class had dangerous interactions with other drugs and with some foods, an untoward effect present in a lesser degree in more recent compounds. If you look at the web, it seems that there are sellers of Harmaline by pounds, but can't imagine what is it for
Reply | Report Abuse | Link to thisI would like to be included in your study,please contact me jozo150@yahoo.com. Thank you.
Reply | Report Abuse | Link to thisIn Saskatchewan Mental Hospital, in both North Battleford and Weyburn, Saskatchewan, Canada, LSD and other hallucinogenics were given to patients and staff in the 60's to test their effects on human brain chemistry. I don't know what happened to the research papers from those old studies 50 years ago. Seems researchers are on the same trail again. Perhaps some chemical can be synthesized from these drugs to help people, but I hope the side effects are small. I myself took effexor for one year for depression. I managed to wean myself off it, although withdrawal was a nightmare, and I still have after effects from the drug. For the first time in my life, I have hypertension, caused by effexor, and in the six months I've been off the drug, it still hasn't gone away. My friend William nearly had a stroke and was taken by ambulance to hospital because of his taking effexor. It's great to cook things up in test tubes that help mental illness, but until all the side effects are known, they shouldn't be given to humans.
Reply | Report Abuse | Link to thisIn the two Saskatchewan Mental Hospitals, in North Battleford and Weyburn, Saskatchewan, Canada, LSD and other hallucinogenics were given to patients and staff in the 50's and 60's to test their effects on human brain chemistry. I don't know what happened to the research papers from those old studies 50 years ago. Seems researchers are on the same trail again. Perhaps some chemical can be synthesized from these drugs to help people, but I hope the side effects are small. I myself took effexor for one year for depression. I managed to wean myself off it, although withdrawal was a nightmare, and I still have after effects from the drug. For the first time in my life, I have hypertension, caused by effexor, and in the six months I've been off the drug, it still hasn't gone away. My friend William nearly had a stroke and was taken by ambulance to hospital because of his taking effexor. It's great to cook things up in test tubes that help mental illness, but until all the side effects are known, they shouldn't be given to humans.
Reply | Report Abuse | Link to thisThe new cure for depression is finally coming your way.
Reply | Report Abuse | Link to thisThe only question now, is how long will it take before it all becomes legal?
http://scallywagandvagabond.com/2010/08/its-confirmed-special-k-mushrooms-and-lsd-are-good-for-you/
The new cure for depression is finally coming your way.
Reply | Report Abuse | Link to thisThe only question now, is how long will it take before it all becomes legal?
http://scallywagandvagabond.com/2010/08/its-confirmed-special-k-mushrooms-and-lsd-are-good-for-you/
From my own experience (which is considerable and has included many of the side effect riddled FDA approved drugs) with my ailments I can say absolutely, positively and without a doubt that mushrooms were the most and only effective treatment. It's a pity I can't legally continue what worked. I'm afraid I'll be dead and gone before psilocybin is recognized and available without the threat of incarceration.
Reply | Report Abuse | Link to thisSalvia divinorum works differently than either the dissociatives, such as ketamine and dextromethorphan (NMDA), or the hallucinogenics, such as LSD or psylocibin (seratonin). S. divinorum works on k-opiate receptors (if I remember correctly), and has been considered as an agent to block cravings for methamphetamine.
Reply | Report Abuse | Link to thisIf you make a man-made chemical pharmaceutical, doesn't it them became somewhat similar to a 'foreign-object' in the body? Then it would not be recognised by the body, due to lack of evolutionary exposure, and cause unwanted ''side'' effects?
Reply | Report Abuse | Link to thisWhy not trial starting with low doses of mushrooms and then build up to the clinical required level gradually, and see if the unwanted(!?) hallucinogenic "side" effects are reduced through habituation.
This phenomenon has been observed in peer-accompanied field trials ;)
It's time this country advanced its approach to drugs by ending the doomed War on Drugs and rescheduling them. Marijuana is still Federally schedule I, which is supposed to be where the drugs go that don't have medical uses.
Reply | Report Abuse | Link to thisThe current scheduling system does nothing more than assure pharmaceutical companies have a lock on certain medicines while turning people into criminals who are simply doing what is right for them. I mean, can it really be that people on the street who use certain drugs might actually be doing what they can to help themselves overcome diseases like major depression?
We need a realistic approach to drugs. Painting them as sheer evil only evidences the lies and cover-ups once people discover they have beneficial values. "Just say no" only works so long as nobody at all does any research.
People being able to grow their own medicine does not bode well for the pharmaceutical industry who used to have a lock on medical marijuana. The federal government is however still fighting tooth and nail to prevent the industry from losing its lock.
If the public's health and safety was really the purpose, drug laws would be vastly different. The use of drugs is in human nature. Use cannot be stopped, so the issue should concern safety. With drug safety as the priority instead of 'just say no hide our heads in the sand', lives might actually be saved.
War is not the answer.
If these drugs are helpful it is horrendous that they will not use them until they don't make you high. Why don't they ask people if they are distressed at the idea of hallucinating. Let them wait for the right wingers to give their blessing. How dare they make people suffer this crippling disease because of some one else's moral values. These drugs have been used very successfully for addiction treatment. There has hardly been a time research and treatment have been going on outside the USA. My experiences, beginning in the 60' to the present though not as often as in the 60's is that it helps tremendously. And yes, the high part is part of why it works. Look at how popular Marinol is for people who use medical marijuana. It makes people sick. God meant these plants to be used for healing and the sessation of unbearable sadness.
Reply | Report Abuse | Link to thisSalvia is hardly a sensible choice as it is too intense and it is too short to gain any insight into anything. I started doing acid in 1967 and have not stopped psychedelics yet though with considerably less frequency. Salvia is nothing like it and it is not even like DMT; which is a short and intense experience. Salvia is more delusional than "trippy." It does nothing for my depression and all the others do. I have not tried K as it sounds boring and the idea of being stuck in some hole does not appeal. Weed also helps if it is an old school one with the cannabinoids high and the THC low. It is the THC that is causing problems that did not happen in the sixties and seventies. Greed, of course.
Reply | Report Abuse | Link to thisMerlin, I have multiple psychiatric disorders and I can tell you that medication is too slow for someone who is suicidal and too difficult to implement on a daily basis for someone deep into depression. Many mentally ill people cannot work so they do not have money to pay for a guru. Had we all had the good fortune to have perfect lives and be taught to mediate from an early age, it may take some credit. When it is free for the ill, it will be a service and not a product. Without meds I am unable to believe in anything and am in danger of killing myself. I did TM in the 70's and got sick of being told how much money I would make. I did not get into it in order to be come a suit and make more money. As a Buddhist I have found meditation to be valuable while I am meditating on the rare times I can quiet my mind but not otherwise. It is brain damage not a bad mood.
Reply | Report Abuse | Link to thisIt is not my assumption that everything has to have a man made pill. That is one terrifically insulting comment. I suspect you believe yourself to be so far above the rest of us that you think no one notices your "passive agressive" attitude. It is even more true that meditation is only one of many ways to achieve healing. A compassionate doctor who does not insinuate you are too stupid to realize there many paths to health and enlightenment. TM is not recognized as a legitimate path in India. It is a product that is marketted. It is not free but they tell you you will get rich if you mediate their way.
Reply | Report Abuse | Link to thisI am convinced that Effexor made me worse. The withdrawals alone should tell the pshrinks that it is dangerous. I was slammed on to a high dose by a big shot psychiatrist who told me there were no side effects to quitting or starting. Cymbalta, another antidepressant, turned me into a sloth without the benefit of helping with the depression. It also destroyed my ability to eat. Everything tasted like dirt. The dilemma of the mentally ill is trying to determine which is worse: disorder symptoms or drug side effects. Weed helps as long as I am able to keep away from all stressors. Ya, that will happen with a mentally ill person.
Reply | Report Abuse | Link to thisWhen you cannot enjoy what you always enjoyed, when you can only remember the negative because the hypocampus has shrunk, when you contemplate death as a way to cure the misery, to flee the hell of trying to keep going because some people do care even if you can no longer feel that then a few hallucinations, explained, and some giggles make a nice break and a few days of clarity before the fog takes over again.
When I take a psychedelic (not salvia) I feel normal, oddly enough. Even if hallucinating like crazy (Hmmmmm) I do not feel mentally ill. It is like being myself as I was before life and doctors ground me down. There is a clarity that makes me want to live and keep fighting the diseases. I do not feel the disorders in me when I am on a psychedelic. I can always feel them even when I am stunned on some med or other. The only time I feel whole and sane is on a strong psychedelic. Alas that all we can ever find now is mushrooms and my partner in crime cannot tolerate them.
The research from the trials in Canada back in the day is still out there. Erowid.com may have them. England also did testing and is at it again. There is an excellent documentary on the early days and what poor old Timothy Leary messed it up. Naive man. The documentary is Canadian. I believe it is Ibogaine they are using in BC now and primarily for addiction. I would give my left arm to get into a program with meds that I know work from my own experience, the experience of friends and the research of the past and present. There is also the anecdotal record of people finding it helps mental illness. If you consider mescaline, psychedelics have been in use for thousands of years.
Marijuana is like a spiritual asprin and could easily take its place in many disorders of the body and the brain as well as just help you get through the night without having to drink and destroy brain cells.
Mushrooms are not as predictable as LSD or mescaline. There are several different psychoactive mushrooms and the effects vary. They are a bit rougher due to the different chemicals in them. The taste is friggin' unbelievable. I wonder if you could even get most people to put them in their mouth after that first taste. Low doses do not take you into the psychedelic state and would be of little value. The benefit of acid over all the natural ones is that it is only one substance and its effects can be predicted though the content of the trip itself cannot be.
Reply | Report Abuse | Link to thisMetzner is still in the game and still believes in the value of LSD. He did not go the way of Leary.
I was diagnosed with Dysthymia as a teen... I have MAJOR DEPRESSION, and have suffered for years... I have been on almost all of the SSRI's, and Cymbalta with little or no relief!! I am so tired of living in this evil black hole called depression that I am desperate for something that REALLY works...if they were to tell me that new evidence shows that dog shit helps, I'd be willing to try it!! We need more research in depression!!
Reply | Report Abuse | Link to thisIsn't this what Timothy Leary began and why has it taken so long for this to be taken seriousloy??
Reply | Report Abuse | Link to thisI had a long term sex addiction (20 plus years) that finally ended after I took a large dose of Ibogaine. The Ibogaine stopped the overwhelming cravings. Now I am working though my depression with mushrooms, and having some success. The work is emotionally difficult (ie., can include "bad" trips), but very worth while. I feel very grateful to have discovered these these substances, even though they are illegal. It is the hallucinogenic (I prefer the term "visionary") nature of the experience where I feel my mind or consciousness is healing. In my opinion, these substances are safe when respected--used in a knowledgeable way and in a safe space. And, in my opinion, dried mushrooms don't taste that bad. Fresh mushrooms taste pretty good, like the common supermarket Agaricus mushrooms.
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