Ketamine might become our secret weapon against depression

Ketamine is an anesthetic and analgesic drug, usually used on animals. It’s also popular as a party drug, typically known as “Special K”. Lately, more and more studies seem to support the drug’s value as an anti-depressant, but the risk for abuse makes it undesirable. This may set to change. Researchers believe they’ve found the specific brain circuitry that activates the anti-depressive effects of ketamine. Now, what can happen next is someone develops a drug that targets this pathway, and this pathway only. This way you get only the anti-depressive effects, minus the “K-hole”.


Ketamine comes both in liquid and powder form.

Special K

Short- and long-term effects of ketamine use include increased heart rate and blood pressure, nausea, vomiting, numbness, depression, amnesia, hallucinations, and potentially fatal respiratory problems. Following repeated use of ketamine, users may experience cravings for the drug. When high doses are used, the user may experience an effect known as the  “K-Hole,” an “out of body” or “near-death” experience.

Though ketamine may incur depression, in the right dosage and taken not too frequently the drug is a proven remedy for depression. It’s so effective that the positive effects can be felt in a matter of hours and can last for a whole week. Conventional anti-depressives take weeks to start working. For the chronically depressed pondering suicide, those weeks of waiting might be too long.  “It blew the doors off what we thought we knew about depression treatment,” says psychiatrist James Murrough at Mount Sinai Hospital in New York City.

Today’s most common antidepressants target the brain’s serotonin or noradrenaline pathways (some target both). Ketamine acts on the NMDA receptor, a component of the glutamate pathway, which is involved in memory and cognition.

The largest trial on ketamine’s anti-depressive effects was conducted in 2013 with 73 participants. Mere 24 hours after the first treatment, ketamine proved to reduce depression symptoms in 64% of patients who had tried three or more other medications with unsuccessful results. Other studies have confirmed the findings. “Feeling better faster, getting the mood to improve faster — that’s why ketamine is very promising,” said Alan Manevitz, MD.

Capitalizing on this sort of news, already a number of companies are developing their own patentable versions of ketamine. These include  GLYX-13 by Naurex or a nasal spray called esketamine by Johnson & Johnson. These companies are expected to soon release the results of their own field trials, which Nature reports are already promising.

The “K” pathway

The problem with Ketamine, and likely its derivatives, is that it has perilous side effects and the long-term effects are poorly understood. But what if we could jack up ketamine to work only as an anti-depressant and put everything else aside? It could be possible, says Daniel Lodge, Ph.D., of The University of Texas Health Science Center at San Antonio.

Lodge and colleagues used optogenetics and designer drugs in rats to localize the exact brain circuitry involved in ketamine anti-depression effects. The researchers found that activating the ventral hippocampus (vHipp)-medial prefrontal cortex (mPFC) pathway in rats causes antidepressant-like effects similar to those caused by ketamine, whereas preventing activation of the circuit eliminates the antidepressant-like effects of ketamine.

“The idea is, if one part of the brain contributes to the beneficial effects of ketamine, and another part contributes to its abuse and effects such as hallucinations, now we can come up with medications to target the good part and not the bad,” said Flavia R. Carreno, Ph.D., lead author of the study.

This sounds amazing. Ketamine truly sounds like a miracle drug against chronic depression, affecting millions everywhere. Now, there might be a way to make Ketamine 2.0. “The next step is finding a drug that interacts selectively with it. And we have some ideas how to do that,” Lodge says.

Reference: Activation of a ventral hippocampus–medial prefrontal cortex pathway is both necessary and sufficient for an antidepressant response to ketamine” F R Carreno, J J Donegan, A M Boley, A Shah, M DeGuzman, A Frazer and D J Lodge. Molecular Psychiatry, doi:10.1038/mp.2015.176. 1 December 2015

9 thoughts on “Ketamine might become our secret weapon against depression

  1. ziasquinn

    Definitely have to watch the long term effects. A lot of ADHD medications, like Vyvanse, were also initially being targeted as potential anti-depressants, except the anti-depressant effect didn’t last beyond 3 months.

  2. Charlene Wright

    Present treatment options for depression are simply not working. AD medications
    seem to be the “go-to” treatment, but if they performed as well as the
    pharmaceutical organizations say they did, depression rates would be dropping,
    not growing to be the global crisis that it is today. In my view, more
    organic treatment methods for depression like the “Destroy Depression System”
    ought to get more publicity, due to the fact it is created by someone who has
    actually experienced depression and recovered. It teaches seven natural methods
    which numbers show perform a lot better than present ‘treatments’. These types
    of treatment plans come with absolutely no negative side effects like
    prescription medication does, cost you next to nothing and most importantly, due
    to the fact the individual is curing them selves, they begin to sense like THEY
    are the ones restoring control over their life.

  3. disqus_ODRpz1oIp4

    Ibogaine can also deal with depression. A single dose will have this effect for weeks; sometimes months. It is also a proven way to break addictions to other drugs (about half the time, according to decades of journal literature). It is definitely not a party drug, and never used that way. It is powerful medicine.

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