Ketamine reduces depression symptoms within hours. Here’s how the psychedelic drug works so fast

Most antidepressants take around three weeks to take effect, while studies consistently show ketamine works within hours. However, the mechanism which makes the drug work has remained unclear. Now, researchers from the Paris Brain Institute have discovered one answer that explains ketamine’s lightning-fast course of action.

Close to a third of depression patients don’t respond well to conventional therapies, with doctors classifying them as having treatment-resistant depression (TRD). Mental health issues can be aggressive, which makes finding effective treatments population absolutely imperative. To explore this, the researchers conducted their clinical study with 26 TRD patients and 30 healthy controls. Both patients and healthy participants had to estimate the probability of 40 “negative” events that could possibly occur in their lives, such as getting into a car accident, having a doctor diagnose them with cancer, or misplacing their wallet.

Study authors then revealed the risks associated with each event occurring relative to the general population to each participant. After, the team posed the same question to them in order to see how their thoughts changed when presented with the statistics. Their results show that after receiving information to help put things in perspective, the healthy participants changed their answers to reflect more realistic outcomes. Unfortunately, the answers from depressed patients didn’t show this trend.

The researchers then distributed ketamine to TRD patients and repeated this experiment. They received three doses of ketamine within one week, but it didn’t even take that long to notice a positive change. Just four hours after receiving the first dose, the patients were able to think much more optimistically. They were less sensitive to upsetting information and had a firmer grasp on receiving new facts in a similar way to the healthy controls.

These findings suggest that improvement in depressive symptoms among TRD patients after receiving ketamine indicates an association between greater clinical outcomes and the mechanistic changes that the brain undergoes.

“In other words, the more patients’ belief updating ability was increased, the greater the improvement in symptoms was,” explains Dr. Hugo Bottemanne and researchers say in a media release.

This research is the first of its kind to shine a light on the cognitive mechanism involved in the rapid effects of ketamine therapy. It helps neurologists and healthcare professionals have more confidence in alternative antidepressant therapies that may soon support a greater number of patients. The team also points out that more research is imperative, largely due to the many side-effects that ketamine can cause. Careful consideration and individualized dosing may help better study this drug and apply it in widespread clinical practice.

The findings are published in the journal People.

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About the Author

Shyla Cadogan

Shyla Cadogan is a DMV-Based Registered Dietitian. She is a recent graduate of the University of Maryland, College Park with a degree in Nutrition and Food Science and has published research on food insecurity in Maryland. She holds specialized interests in integrative nutrition, hormone health, and gastrointestinal health.

Comments

  1. This sounds good, I have read long ago that LSD (a psychedelic) in low doses and supervised was good for alcoholism. Psychedelics just get a bad reputation.

    1. Psychedelics should get & have a bad reputation.
      Ketamine aka the date rape drug.
      Imagine the subsequent brain damage.

      1. The doses used to treat TRD do not produce effects seen at higher doses. Spravato (esketamine) is FDA-approved for TRD and major depression with suicidal ideation. Do your research before commenting on subjects you know nothing about.

      2. Ketamine is not a psychedelic, it is a dissociative.
        Psychedelics have never been linked to brain damage or physical harm.
        GHB and roofies are date rape drugs.

        Every single thing you said was misinformation.

  2. Maybe I’m crazy 😉 but it never took 3 weeks for an antidepressant to alleviate my clinical depression. With Paxil, I felt normal in a few days- 3?

    After being on Paxil for a couple years, I realized I hadn’t been restored to normal: I simply didn’t feel much of anything when I should have. No joy, no normal anxiety (which is necessary for making necessary changes).

    I switched to effexor and found it to be the answer for me. I believe it stabilized me and my emotions to a normal degree. I experienced its effects within less than a week.

    I want to add that I also received cognitive behavioral therapy for about 4 years. This was very instrumental in my stabilization! A pill does not change erroneous thinking which leads to anxiety and depression. It doesn’t teach coping strategies either.

    Before I went on medication, I struggled through at least 2 years of therapy. I continued therapy, but I didn’t need it to the same degree.

    I must say that I was angry at my therapist for convincing me subtly not to use medication. I was raising two young daughters after a relatively easy separation where my husband helped to support me so the girls had two “equal” lifestyles. But I was not available to them in my depression and anxiety and they suffered greatly. I should have had the medication from the get-go for their sakes.

    1. Wow, that’s intense. Thank you for sharing your experience. Every person is unique, but by sharing what we’ve been through, slowly we can help one another out of the tunnel that is depression.

    2. I think you may be missing the inner workings of ketamine.
      Its a psychedelic usually administered intravenously. Not an anti-depressent pill.
      I personally know someone very close to me that I took to all of their 6 ketamine sessions.

      Anti-depressants were not working. They were suicidal.

      after even just one session they did a complete 180 in their emotional and mental stability.
      its been a few months since and this person is still completely different – in a really good way.

      I cant say its a cure as there isn’t super long term studies done on it yet. However, the clinic said they have not had any patient return for further treatment after the normal 6 sessions.

  3. ECT is often much quicker at relieving depression than traditional antidepressant treatments.
    Ketamine is an anesthetic used with animals and sometimes young children. Psychosis can be a side effect. Ketamine is similar to PCP, a NMDA antagonist. PCP often results in symptoms like schizophrenia. In fact animals treated with PCP are used as a model of schizophrenia with animals.

  4. MORE ways for BIG PHARMA MACHINE to make $$$$ at the cost of harming innocent people.
    Ketamine, the date rape drug, the elephant pill.
    The man who created this saying, ketamine makes people lose all inhibitions… (not a direct quote)

    1. You are an idiot, ketamine is not the date rape drug. It Is is a commonly used anesthetic agent used in operating rooms and icu patients every day. You are confusing it with several other drugs

  5. It should be a crime to dispense ketamine.
    Ask all of the women who were drugged & raped by ketamine.
    Justifying the use of ketamine in the name of “mental health” , to me is negligence.

    1. For the love of all things holy, the doses used are infinitesimal compared to doses associated with abuse/misuse. Just stop.

  6. I appear to be the only person who has actually completed ketamine therapy. It’s been in medical use since the Vietnam War, a top-line accident/wound treatment. I tried every new med, twice a week talk-therapy since Prozac. None worked. The first ketamine iv produced instant, incredible, life-changing results. My MD is a Professor at a major medical school who did much of the work getting the spray-delivery approved by the FDA. My provider is a board certified anesthesia specialist for over two decades who still works daily in OR’s. It works, it works extremely well. None of the prior posters have any experience with it, are posting drivel. Big Pharma is fighting its approval; it will revolutionize psychiatric treatment (and end the need for meds). Insurance is assisting by refusing to cover. In Dallas treatments are about $500 per. My provider usually gets great results with ONE IV, one or two a year after that. It works, it’s worked for every friend with my issues I’ve sent to them.

  7. I have invested in AXSM, which makes Auvelity, which uses a different route than SSRI’s do. It apparently works in around a week. See how it works….

  8. As a person who has taken the treatment I can say the article is spot on. I immediately felt a profound change. That change has lasted over four months so far. I had been in therapy almost thirty years to no avail. This treatment changed my life.

  9. I find it interesting that the commenters thus far do not reference TRD. If you have not personally or had a loved one suffer from TRD – its really hard to read your comments full of disdain and hate towards ketamine. Clearly some of you have suffered trauma associated with the drug “date rape,” etc. The use of ketamine to treat TRD does not happen lightly. It is not an RX you get filled and take home. It is a micro dose of the drug administered in a controlled clinical setting under the supervision of doctor. And absolutely yes, big pharma is making money from it as it does on hundreds of thousands of life saving drugs. All I can tell you from first hand experience is that this TRD patient who tried everything but electro shock therapy does not want to kill herself today. And that is a miracle. I take an antidepressant, see a psychotherapist once week and receive ketomine treatment every two weeks. I will go to fewer and fewer ketomine treatments as I continue to show stable improvement. I firmly believe my recovery is a result of ALL three treatments. I dud not understand what happened to me when I went down to the dark hole of depression. Today, I am out of bed, I manage my family and I even have a job interview next week. Not possible two years ago. My kids call it the “mom’s back tour” – would not trade it for the world.

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