Health and Medicine Neuroscience

Antidepressant Compound Located That May Come With Zero Side Effects


Ketamine is known to be able to reverse the symptoms of depression very quickly. It has been shown to treat depression in a matter of hours. Most antidepressant medications take a number of weeks or months for results to be reached. Sadly, the drug comes with many major side effects, such as hallucinations or even dissociation. Thankfully, researchers recently discovered a metabolite of ketamine that has successfully reversed depression within mice, with zero side effects. 

Todd Gould, a researcher at the Department of Psychiatry within the University of Maryland’s School of Medicine says this new information has the potential of becoming a major breakthrough that may offer the fast help of ketamine to sufferers of depression without all the risks. Most depression medications increase neurochemical levels in the brain. Most commonly, SSRIs are used but these drugs are only helpful to about half the patients they are prescribed to. Moreover, when the drugs do work properly, they do not take effect for up to two months. Ketamine does not work by increasing serotonin or norepinephrine levels, and offers help within just a few hours following first treatment.

Ketamine’s structure

Work for the project was done by scientists at the University of Maryland School of Medicine (UM SOM), the NIH National Institute of Mental Health (NIMH) , the NIH National Center for Advancing Translational Sciences, the NIH National Institute on Aging and the University of North Carolina.

Scott Thompson, co-author and UM SOM researcher says the team has been working for years to try to find ways to treat depression more effectively. He has spent over ten years studying the link between glutamate and depression and calls these results exciting vistas for a new generation of antidepressant compounds. It has been 30 years since the last generation of such meds were introduced.

Mice were used in these new tests to see how different ketamine metabolites effected the body. Metabolites are chemicals that are created when ketamine is broken down. Hydroxynorketamine ended up being the main focus of the study, which is shocking because it was previously believed to not have any psychoactive effects. When the transformation from ketamine to this metabolite was stopped, so were ketamine’s antidepressant actions. Hydroxynorketamine also showed antidepressant effects with zero of the side effects previously associated with treatment via ketamine.

Hydroxynorketamine’s structure

Co-author and NIMH researcher, Carlos Zarate says thanks to the newest research ketamine has been reverse-engineered to better understand its properties. He says this holds great promise for future developments of a much safer and wider scale treatment of depression. Ketamine is known to block the NMDA glutamate receptor. In the past researchers believed ketamine probably worked as an antidepressant in a very similar way. This was proven false upon the finding that hydroxynorketamine actually stimulates a glutamate receptor called the AMPA receptor. Whether or not the metabolite does so directly or indirectly is not certain at this time.

There are plans to continue testing of hydroxynorketamine and how safe it would be in human trials. Gould believes the metabolite will prove to be safe as it has already been in humans for years after administration by ketamine.

The study was published this month in Nature journal.

  • Chancho Bandito

    Nice, a horse tranquillizer that causes hallucinations, please cut the bull, reverse engineered a chemical WOW no way! Look there is only really two cures for treating depression….. positive outlook on life and a change of environment. Ketamine has been around for decades give it a rest with this NEW MIRACLE CURE FOUND!!!! Bull

    • Enaz

      You do realize you are essentially telling people to suck it up and be more positive? It’s not that fucking simple for everyone Sherlock. Most people depressed spend years and years trying to do exactly that, decades even.

      • Chancho Bandito

        You are not very intelligent Go seek reassurance somewhere else.

        • Danta

          By what methods did you come to such a conclusion? Your own personal observations? You must convince me of your position by some other method than personal attack, despite your convictions. In addition to the scientific consensus that chemical treatment methods for depression actually do work, there are millions of people who take the opposite position based on their own personal observations. Who am I to trust, as someone trying to believe the truth?

          What errors did these thousands of doctors and researchers make? How was the truth so blatantly disregarded for so long by those whose job it is to find it? To be credible, you must explain specifically why so many chemical treatments seem so effective above a placebo in double-blind studies. If you have some reason to ignore the scientific consensus on this issue in particular, let me know. Otherwise, you should know that most reasonable people will (and should) write you off as a crackpot.

          • Chancho Bandito

            What the kind of imbecilic debate do you think this is? are you an invalid?

        • Enaz

          Seeking reassurance? Your kidding right? This isn’t a popularity contest and I don’t have to have people agree with me. However you might want to consider that there is a good reason that you have no up votes and most replys are calling you out as ignorant.

          How is this about me being some sort of “protector” lol? I don’t necessarily have to care about the victims of depression to state what should be fairly obvious: that change of scenery and positive outlook is not always enough to treat depression and there is a place for medicine, especially medicine that has less side effects than drugs like ssri’s.

          Savior complex? So I guess your a psychologist now lol.

          A piece of advice: Try writing posts with more substance if you want to be taken seriously.

    • Carl

      Ugh. You know nothing. Stop writing words on the internet dude. If you’re going to be uneducated, don’t infect others with your dumbness. Depression is not cured by positive outlook any more than cancer is cured by aspirin. A depressed person could be in Disney World and still be depressed.

      • Chancho Bandito

        Fuckstick…… that what I said. Who was I calling out? nitwit.

    • confused

      You’ve obviously never dealt with depression before. It’s not that simple for those with clinical depression. You shouldn’t assume your capabilities are the same as everyone around you. You are lucky you can get by with a positive outlook and a change of environment, but not every one can. And please believe me when I say it’s not for lack of effort. By all accounts my life is great and I should be incredibly happy, but I still feel suicidal most of the time. I would most definitely be open to trying a medication that had zero side effects.

      • Chancho Bandito

        Once again you missed the point when ever article comes out with a new miracle drug its is inherently a dangerous thing. There are INHERENT side effects with every drug. Consider taking any drug once considering the side effects, remember no doctor can know everything about you, also consider taking microdoses 10 micrograms of lsd in the morning for depression, not some clickbait bullshit article.

        • Zack

          Ya the article was a bit misguided. You have a point. I doubt that the metabolite of Ketamine (that causes the antidepressant effect) has NO side effects. It probably has side effects but they haven’t yet looked into this because this is such a new discovery. What the article should have said is that the metabolite doesn’t have the DISASSOCIATIVE side effect that Ketamine has. That would be more accurate than saying it has “no side effects”.

        • Enaz

          LSD? Wow so “A psychedelic that causes hallucinations”? But I thought that “a positive outlook on life and a change of environment” are the only cures for depression?

          Joking aside I actually happen to agree with you on this one, LSD and other psychedelics like Shrooms have been shown to be very promising in recent years as far as depression is concerned.

          But why are ketamine and other drugs inherently bad while LSD is good? That is just asinine.

    • Sam Oakley

      ketamine is used by doctors on people as an anaesthetic, but yeah sure write ‘horse tranquilizer’ to try and make yourself look clever

      • Chancho Bandito

        It is, we use it in horse Hospitals. These people attacking me are really thick.

        • Zack

          Apparently it’s used as an animal tranquilizer. Didn’t know that. It has also been used as an anesthetic for humans and animals for many years. Now they’re discovering it has antidepressant properties. It’s not uncommon for a drug to be discovered to have multiple uses.

        • Enaz

          Yeah but you are implying that it is used mainly on horses when it’s actually used safely on people quite alot.

          You might want to work on the tone of your posts because stuff like: “horse tranquillizer that causes hallucinations” implys that it is only used on horses and makes it sound alot worse than it really is.

    • wikkiwikki

      You are part of the reason we need to build the wall. Go home, self centered twat.

      • Mectrid

        There’s no reason to build a wall. A wall is ludicrous just by suggestion, you should not support a wall. You do not live in ancient China and no one is attacking you from Mexico. You’d be better off building a wall around yourself, it’d do the world a lot more good.

        • wikkiwikki

          Again, You are part of the problem, not a solution. The United States of America is a nation of citizens, not immigrants. We encourage people to become legal tax paying citizens if they choose to be a part of The United States. There is no where on earth where you can go to as a foreigner and expect others to pay for your medical expenses, crimes you commit, food you don’t pay for or finances to pay for your own crotch spawn that you can’t afford to raise on your own….. Except for The United States of America, where even then it is ILLEGAL. Sure we may not be trying to stop Mexicans from visiting and spending their hard earned coin over here with us, but we also aren’t trying to let people extend their stay and live off the tax payers dollar.

          You are in fact the racist if you even suggest that we should not build the wall. I would like to not only further that point but also to back it up with a simple scene of events that unfolded three days ago in San Jose California. “Make America Mexico!!!” “America was never great.” As well as the terrorists there that were burning the American flag, while raising in support of the Mexican flag. Those who were at the protests burning American flags and violently attacking peaceful Trump supporters are in fact the racists and they have upgraded themselves to rioters and terrorists. What you seem to want is a bernout revolution. A world under bernout would be absolute hysteria.

          Grow up child.

    • Mectrid

      Wow, seriously get a clue and please talk less in future.

    • Charliemopps

      You didn’t even read past the first sentence. What an idiot.

      • Chancho Bandito

        You’ll get there

    • Zack

      Yes you’re right it has been known for decades that Ketamine has a profound effect on depression. This is old news. But what they’re saying is that they’ve singled out the metabolite which has the antidepressant effect without the dissoaciative side effects. This means that if they can synthesize the metabolite then it can be used more widely without having to worry about abuse potential. This means that if a pharma company can synthesize the metabolite they can they can patent it, put it through clinical trials and then finally make it available to the public (with a prescription of course).

      As for your statement about the cure to depression being simply a positive outlook on life and a change of environment I must say that you sound very ignorant regarding mental illness. It’s actually not as simple as “thinking positive” to pull yourself out of clinical depression. Well, it might be for some people but not for others. Not everyone is like you and for you to assume that anyone can pull themselves out of it, like you or someone you know did, is faulty logic. Some literally cannot pull themselves out of it and for you to trivialize their illness is silliness,

  • DonGateley

    Fingers crossed. This one could be huge.

  • Altaus9b

    Psychiatry and Psychology’s Epidemic of Junk Science: See the scientific journals, court cases, and top scientists speak out against the junk science, misleading research, lies about no side effects, and drug lords pushing dangerous drugs on people that could be treated with other proven techniques.

    • Enaz

      What other “proven techniques” would you recommend to someone with severe depression?

      • Chancho Bandito

        Medicine not Psychiatry and Psychology Pseudo-scientific garbage.

        • Enaz

          It’s not all “pseudo science garbage”, there is alot of evidence that ketamine can treat depression and sometimes there is no other choice but to resort to something like this (especially in the most severe cases).

          Preferably you should find a treatment that doesn’t involve pharmaceuticals but unfortunately sometimes they are left with no other choice.

          Maybe read up on the subject more, ketamine and similar drugs such as psychedelics. I understand that alot drugs have bad side effects but ketamine and similar drugs actually show alot of promise.

    • Chancho Bandito

      Yes finally someone gets it. This^^

    • Zack

      How is the fact that Ketamine has antidepressant properties junk science?

  • dalekaup

    When I was had clinical depression I started crying in the frozen food aisle and had to abandon my cart full of groceries and get the fuck out of there. It was oppressive and seemingly uncontrollable. I did manage to overcome it after 18 months having spent most of my life savings and ending up in prison. Sounds like this drug would have saved me a lot of trouble.

    • Enaz

      Sorry to hear that but at least you got over it eventually without drugs. But maybe it would have been better if you had a ketamine treatment. It too bad it’s so expensive a lot of people can’t afford that price.

    • c4p0ne

      No. You went through what you did and came out alive and well for a reason. You did this without submerging your grey matter in potentially destructive “medications” being peddled to you at your time of greatest weakness. You’re not only fortunate that this thing wasn’t around during those moments, but lucky that you didn’t somehow decide to go on any of the myriad other ruinous substances available. I’m not against medicine in general, I just think every option should be utterly exhausted before resorting to something that may end up making you even more depressed.. or worse. There’s good data to show how well-meaning doctors are being HEAVILY incentivized by private pharmaceutical monstrosities to ram their particular miracle-invention down the throats of people who would likely be better off without it. The process is truly diabolical in that these incentives are powerful enough to pervert the reasoning of even the most honest doctors, often times causing them to lie to _themselves_ in order to prematurely prescribe a substance that they wouldn’t have under normal conditions.

  • Charles Wright

    I have personally had 8 individual ketamine treatments for my severe depression which began in June of last year. It was all done via I.V. and the effects were ALWAYS profound. Any negative side-effects from the treatments were basically negligible, while there were many experiences of positive ‘after-glows’ and the like.

    From my perspective, it must be understood by ALL practitioners of psychiatry/mental health/healing of any kind that there cannot, nor should not, ever be a single cure-all for depression. Major depression is undeniably one of the worst possible conditions a person could ever deal with, and thus requires a fully comprehensive approach to ameliorate and ultimately cure in the mind-body system of each individual. That being said, I can honestly say that after years of experimenting with various therapies ketamine made a difference for me that was unprecedented.

    Not only is it believed to re-stimulate neural networks which have presumably atrophied, it creates a profound experience for the individual that, in itself, is extremely healing. Even though I had to pay for the entire treatment out of pocket it was worth every penny!

  • Zack

    The title of this article and some of it’s information isn’t accurate. The article makes it sound like the metabolite has no side effects. That’s not what scientists have discovered. What they discovered is that the metabolite of Ketamine (the one that causes the antidepressant effect) doesn’t have the DISSOCIATIVE or HALLUCINATORY side effects that Ketamine has. They didn’t discover that it has NO side effects. They discovered that it has no dissociative or hallucinatory side effects. In other words, the metabolite doesn’t make you “trip” or “hallucinate” like Ketamine does. This is huge because if it can be synthesized then it could potentially be prescribed without worrying about people abusing it.

    But I don’t know yet if it lacks the “side effect” of making you feel high/euphoric. They haven’t stated this much. If it turns out that it also doesn’t make you feel high then it likely has no recreational value and this is a good thing if we want it to be available to the masses and not a strictly controlled drug.

  • Cyclus

    They don’t understand that dissociation is the mechanism by which it works as an antidepressant.
    The dissociation gives you new perspective on your situation and reminds you of or gives you new insights.