Ketamine is Helping Alleviate Depression—Fast

A new study published in Nature shows just how quick relief is possible with ketamine.


Depression is a crippling problem that hijacks a patient’s neurochemistry, often making it impossible to “see the bright side.” While many potential therapeutic applications exist, there has been a longstanding quarrel between treating depression chemically or through interventions like talk therapy. While some psychiatrists are advocates for both, no silver bullet seems possible for all people who suffer from this condition.

One thing seems certain, however: the post-World War II mentality of pulling yourself up by the bootstraps is not working. Culturally we’ve probably swung in the other direction: from not talking about our problems to over-emoting on social media. That said, exposure is arguably better than suppression; the numerous online mediums for connecting with others is a boon in what was once a desert. 

Ketamine has long been touted as a potential therapy for depression. Popularly used as an animal tranquilizer (and street hallucinogen) a new study published in Nature shows that not only is ketamine a plausible means for treating depression, but its ability to immediately stabilize patients makes it of great value for those who might not have the willpower to wait weeks for another pharmaceutical to kick in. 

This is not to imply ketamine is a wonder drug. Its potentially damaging effects on memory and other cognitive functions is spurring researchers to investigate how it works in hopes of finding another similar course of treatment. But in the short run the results are promising.

The research was conducted at the Peter O’Donnell Jr Brain Institute in Dallas. One of the study’s authors, Dr Lisa Monteggia, states

Now that we have a target in place, we can study the pathway and develop drugs that safely induce the antidepressant effect.

Ketamine is responsible for blocking the N-methyl-D-aspartate (NMDA) receptor, which causes an immediate alleviation of depressive effects, while another metabolite in the drug helps the effects last for hours. This blockage is also what causes the hallucinogenic effects. 

For Monteggia, its rapid results is extremely appealing for patients who want quick relief. This is important for future research, she says.  

Because the (NMDA) receptor that is the target of ketamine is not involved in how other classical serotonin-based antidepressants work, our study opens up a new avenue of drug discovery. 

The efficacy of ketamine is not new. The World Health Organization includes it in its list of essential medicines. In 2013, Brent Miles began using it after hearing about it on NPR to treat his long history of bipolar disorder. He tried regular infusions over a six-month period, willing to give it a shot considering conventional pharmaceuticals had failed him over a period of decades. The therapists started with a low dosage. 

But this was the first treatment, a low dose, and it kind of wears off. It's not like you crash or anything. During the next treatment, they boost up the level that you're given, so it would start working successively, staggering. After that, I started feeling better.

Miles eventually worked in weekly talk therapy when he could afford it. The problem with ketamine, he says, is expense: $1,500 for a total of six infusions. With the publication of this study in Nature (and further accounts), hopefully that will change. If insurance companies need data before covering a drug, ketamine is prime for reimbursement. And that’s a good thing given how much depression we seem to be combating right now.

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Derek's next book, Whole Motion: Training Your Brain and Body For Optimal Health, will be published on 7/17 by Carrel/Skyhorse Publishing. He is based in Los Angeles. Stay in touch on Facebook and Twitter.

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Yale scientists restore brain function to 32 clinically dead pigs

Researchers hope the technology will further our understanding of the brain, but lawmakers may not be ready for the ethical challenges.

Still from John Stephenson's 1999 rendition of Animal Farm.
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  • Researchers at the Yale School of Medicine successfully restored some functions to pig brains that had been dead for hours.
  • They hope the technology will advance our understanding of the brain, potentially developing new treatments for debilitating diseases and disorders.
  • The research raises many ethical questions and puts to the test our current understanding of death.

The image of an undead brain coming back to live again is the stuff of science fiction. Not just any science fiction, specifically B-grade sci fi. What instantly springs to mind is the black-and-white horrors of films like Fiend Without a Face. Bad acting. Plastic monstrosities. Visible strings. And a spinal cord that, for some reason, is also a tentacle?

But like any good science fiction, it's only a matter of time before some manner of it seeps into our reality. This week's Nature published the findings of researchers who managed to restore function to pigs' brains that were clinically dead. At least, what we once thought of as dead.

What's dead may never die, it seems

The researchers did not hail from House Greyjoy — "What is dead may never die" — but came largely from the Yale School of Medicine. They connected 32 pig brains to a system called BrainEx. BrainEx is an artificial perfusion system — that is, a system that takes over the functions normally regulated by the organ. Think a dialysis machine for the mind. The pigs had been killed four hours earlier at a U.S. Department of Agriculture slaughterhouse; their brains completely removed from the skulls.

BrainEx pumped an experiment solution into the brain that essentially mimic blood flow. It brought oxygen and nutrients to the tissues, giving brain cells the resources to begin many normal functions. The cells began consuming and metabolizing sugars. The brains' immune systems kicked in. Neuron samples could carry an electrical signal. Some brain cells even responded to drugs.

The researchers have managed to keep some brains alive for up to 36 hours, and currently do not know if BrainEx can have sustained the brains longer. "It is conceivable we are just preventing the inevitable, and the brain won't be able to recover," said Nenad Sestan, Yale neuroscientist and the lead researcher.

As a control, other brains received either a fake solution or no solution at all. None revived brain activity and deteriorated as normal.

The researchers hope the technology can enhance our ability to study the brain and its cellular functions. One of the main avenues of such studies would be brain disorders and diseases. This could point the way to developing new of treatments for the likes of brain injuries, Alzheimer's, Huntington's, and neurodegenerative conditions.

"This is an extraordinary and very promising breakthrough for neuroscience. It immediately offers a much better model for studying the human brain, which is extraordinarily important, given the vast amount of human suffering from diseases of the mind [and] brain," Nita Farahany, the bioethicists at the Duke University School of Law who wrote the study's commentary, told National Geographic.

An ethical gray matter

Before anyone gets an Island of Dr. Moreau vibe, it's worth noting that the brains did not approach neural activity anywhere near consciousness.

The BrainEx solution contained chemicals that prevented neurons from firing. To be extra cautious, the researchers also monitored the brains for any such activity and were prepared to administer an anesthetic should they have seen signs of consciousness.

Even so, the research signals a massive debate to come regarding medical ethics and our definition of death.

Most countries define death, clinically speaking, as the irreversible loss of brain or circulatory function. This definition was already at odds with some folk- and value-centric understandings, but where do we go if it becomes possible to reverse clinical death with artificial perfusion?

"This is wild," Jonathan Moreno, a bioethicist at the University of Pennsylvania, told the New York Times. "If ever there was an issue that merited big public deliberation on the ethics of science and medicine, this is one."

One possible consequence involves organ donations. Some European countries require emergency responders to use a process that preserves organs when they cannot resuscitate a person. They continue to pump blood throughout the body, but use a "thoracic aortic occlusion balloon" to prevent that blood from reaching the brain.

The system is already controversial because it raises concerns about what caused the patient's death. But what happens when brain death becomes readily reversible? Stuart Younger, a bioethicist at Case Western Reserve University, told Nature that if BrainEx were to become widely available, it could shrink the pool of eligible donors.

"There's a potential conflict here between the interests of potential donors — who might not even be donors — and people who are waiting for organs," he said.

It will be a while before such experiments go anywhere near human subjects. A more immediate ethical question relates to how such experiments harm animal subjects.

Ethical review boards evaluate research protocols and can reject any that causes undue pain, suffering, or distress. Since dead animals feel no pain, suffer no trauma, they are typically approved as subjects. But how do such boards make a judgement regarding the suffering of a "cellularly active" brain? The distress of a partially alive brain?

The dilemma is unprecedented.

Setting new boundaries

Another science fiction story that comes to mind when discussing this story is, of course, Frankenstein. As Farahany told National Geographic: "It is definitely has [sic] a good science-fiction element to it, and it is restoring cellular function where we previously thought impossible. But to have Frankenstein, you need some degree of consciousness, some 'there' there. [The researchers] did not recover any form of consciousness in this study, and it is still unclear if we ever could. But we are one step closer to that possibility."

She's right. The researchers undertook their research for the betterment of humanity, and we may one day reap some unimaginable medical benefits from it. The ethical questions, however, remain as unsettling as the stories they remind us of.