Ketamine: What’s God got to do with it?

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March 11, 2019 | 28 Comments


  1. This is fascinating … but a bit hard to grasp. I had a few questions:

    If the Spravato inhaler is unlikely to do what Ketamine injections do, is that because of the dose they’re using – or because inhaling the drug will affect people differently from injections? Or both?

    The #1 “caution” about Spravato expressed both by cheerleaders and critics is the risk of abuse and diversion. Mainly, that’s because they all seem to assume that it’s similar or identical to Ketamine injections. Which it’s not. (For one thing, its effects on depression were surprisingly weak in clinical trials, and not especially rapid either.)

    You seem to be saying that Ketamine does not cause dependence (or addiction). Is that based on the experiences of recreational drug users, or on the outcomes of using Ketamine injections in the clinic? And do we know whether snorting esketamine long-term (say, twice a week for 6-12 months) could cause dependence or withdrawal effects?

    Last question: What does it mean to say that a drug is “pro-convulsant,” if it does not in fact cause seizures when used in normal doses? Is there some sub-threshold seizure-like process being triggered in the brain? If so, what are its benefits – and what are its hazards?

    • Jo

      Who knows about Spravato. But the standard wisdom is that PCP and ketamine do not cause dependence. They give intriguing experiences that people might want to repeat because it was very very different but not because it was hugely pleasant and not because you are left craving it. “Strange drug that” – is a common response. For many people once is enough.

      Pro-convulsant sounds mysterious sure. Read the article. Basically it means tonic. There were two groups of drugs – one strengthens the nervous system – tonics – the other weakens it – sedatives. Strengthening the nervous system sounds a lot better than pro-convulsant but as with strychnine you can strengthen it all the way up to a convulsion. At least with strychnine you die with a fixed grin on your face.

      There are other ketamine cautions – as with everything its people who tell me about these things rather than the literature – one of the problems can be urinary difficulties. Seems to have a bladder irritant effect. Don’t know if this is when used too much or whether it can happen after a few exposures.


  2. Further output from Janssen ‘Carepaths’ giving more ‘details’ about ‘safety’ information …

    Welcome to Janssen CarePath

    We’re here to help with Janssen Medications

    At Janssen CarePath, we’re committed to helping you get your patients started on the Janssen medications you prescribed, finding financial assistance options, and providing ongoing support to help them stay on prescribed Janssen therapy.

    SPRAVATO™ is marketed by Janssen Pharmaceuticals, Inc.

    Important Safety Information For Spravato

  3. Thanks! I did hear an interview with addiction specialist Anna Lembke in which she described a guy she was treating for opioid dependence (recovered) and depression. He reported feeling more depressed; she suggested changing his antidepressant, but he asked if he could try ketamine instead. When she would not supply it, he got it off the internet — and began injecting several times a day. He ended up having several seizures and a Parkinson’s-like movement disorder that took at least a month to clear up. Not sure if he developed “ketamine dependence,” or if his K use was just an expression of an “addictive” or “compulsive” behavior pattern.

    As for PCP, it is maybe the ultimate “demon drug” in the USA, with a longstanding reputation for triggering horrible violence. The only case I know of where a murderer was found not guilty due to the influence of illegal drugs, involved a guy who smoked a joint that (unbeknownst to him) had been treated with PCP or Angel Dust. I’ve heard PCP is no longer used as an anesthetic because people would sometimes be very combative on “coming to.” But you never hear this about ketamine, which is still used for invasive scoping procedures, etc. I wonder what the difference is?

  4. Thank you very much Dr. Healy. You are always helping to think with a critical open perspective, alternative to the “evil pharmaceutical consensus” who wants to transform us in non thinking prescriber profesionals. I really appreciate your opinion, it helps me think my patients in my every day practice. Greetings from Argentina

  5. I know very little about Ketamine – other than of its use as a horse sedative! However, 12 years ago we provided a home for a heroin addict on his release from prison. he lived with us for over two years. He was in his forties, the son of a drug dealer, therefore he’d been around drugs for most of his life. He spoke of ketamine with fear – he’d used more or less all street drugs that would be available in north wales – but ketamine, he would not touch. He’d seen it used, and seen the effects on some of his mates – it was the state of those ‘mates’ once the ‘trip’ was over that frightened the life out of him. I therefore deduce that it’s not very nice stuff!
    Spravato may well be miles away from ketamine found on the streets I guess, therefore who knows the effects – positive or negative – in its use to treat depression. It is so innocently packaged, could it have a sting in its tail if misused? Also, is it possible that there could be side effects if prescribed to patients who are merely anxious or in life crisis, similar to what has happened with SSRIs?
    An afterthought – IF it became the drug of choice out in the community, then it would be much easier to detect than a few tablets I suppose. Allergy sufferers had better leave their nasal sprays at home if that happens!

  6. According to the FDA News Release – the FDA Gave Approval for the Release of Eskatamine (Spravato) on Tues 6th March to Janssen Pharmaceurtical Ltd ( NBC News page updated 7/3/19 )
    This despite one of the Boxed Warnings side effects cautioned against – is’ suicidal thoughts and behaviours’.
    ‘The nasal spray will cost $590 for a dose of 56mg and a dose of 84mg will cost $885. Insurance cover is anticipated’.
    The spray is to be given in conjunction with another anti depressant.

    ‘This is a pivotal moment in the history of mental health’ – we’ve heard that before.

  7. Ibogane is another similar option depending on where you are, or where you are able to go. It’s used to treat opioid and alcohol addiction. People report feeling as if they’ve completed significant emotional work after just a short treatment as opposed to spending years in recovery or on medication assisted treatment. Cravings are said to disappear. It’s the emotional healing piece that releases the person, so it doesn’t seem like something that would help with the kind of withdrawal we face with benzos, etc. I don’t know if it’s used for depression. Seems like it might, though a rather quick fix and is not without risks.

    • Dependence on SSRIs and benzos is quite different and as mentioned ketamine looks to me contra-indicated. There were a number of suicidal events in the trials – I wouldn’t be surprised if they were linked to this


      • Ketamine Infusions have changed my life. I wish they were covered by my insurance, however I am lucky enough to have the resources to pay for them. I have only had 3 and am going for my 4th tomorrow. I do use the nasal spray, and it is not the most pleasant method or feeling afterwards however the fact that this is the first time since I was 13 now 47, that I have zero SI says a lot. I have to be driven 2 1/2 hours to get this treatment, and thank God that I have loving people in my life. The only risks that I have had is my pocket book and long travel. I work in the Mental Health field and have gone through counseling, therapy and all the anti-depressants on the market. This actually worked…

  8. If this is the case, that Spravato is contra-indicated to SSRIs then surely this could lead to a legal minefield.

    There were deaths and suicides in the trial, with seemingly little relevance …

    This lawyer bigs up Spravato, but, he might not be so chipper if suicides start appearing after using the Esketamine in Spravato ..

    If someone is taking an SSRI, having a hard time and wrongly diagnosed with treatment resistant depression then in all likelihood, Spravato could tip the balance in the wrong direction?

    This could protect an SSRI suicide legal case against a manufacturer if the contra-indicated theory is unknown?


    The FDA has also expressed concern that patients could be harmed if they experience dissociation, or an out-of-body experience that can leave people less aware of their surroundings. In briefing documents submitted before the advisory committee meeting, the agency also noted six deaths — including three suicides — among patients who were taking the drug. But FDA reviewers said that given that the patients had severe illnesses and there wasn’t a pattern seen in the deaths, it’s “difficult to consider these deaths as drug related.”

  9. Reading about all the different outcomes seen from ketamine injections makes me appreciate how much we lose moving from a world in which there are good doctors and bad doctors who deal with such ambiguously-effective interventions, to a world in which there are no good and bad doctors, only certified doctors who follow the unambiguous guidelines. In one world, doctors may make mistakes, but may also learn from them; in the other world, there are no decisions and no mistakes by definition. All the decisions were made centrally and admitting they could be mistaken becomes an existential threat to the system.

    There’s a very strong centralization imperative I’m seeing everywhere that doesn’t make a lot of sense, not even business sense, necessarily. Boeing is in the news lately because they made a central decision, a guideline if you will, about how their autopilot will work, ostensibly to protect the public from potential pilot error… and that decision may have been mistaken. If a plane crashes due to careless or badly trained pilots, that is a serious problem, but not an existential threat to Boeing or to aviation; but if a plane crashes because Boeing made a centralized decision, that plane model will be grounded worldwide and the company’s stock price takes a plummet. Fortunately two crashed planes are not as easy to hide compared to thousands of drug wrecks, or else I imagine the people at Boeing would be seriously tempted. Rather than trying to design guidelines for the perfect autopilot, a better nefarious business strategy might be to save the effort and get people to accept a world in which pilots can be good or bad at what they do.

    (Sorry, I originally submitted this comment on the wrong post on DH’s personal blog… this is the comment for the right post.)

    • Hear, hear! Let’s go back to understanding that doctors, like the rest of us, are human! Humans make mistakes – and, generally. learn from them. Being the puppets of pharma and government, and believers of ghostwritten materials, has left doctors as being little more than robots – simply middle – men between the manufacturers and patients. How on earth is job satisfaction possible in such a scenario? It is no wonder that more and more doctors seem to have poor mental/physical health. I, too, would be bored to tears if not allowed to make decisions, by recalling from my experience and using such in the best interest of those in need. Having said that, I do feel that we, the patients, also have responsibilities – to tell our doctors, clearly, why we reject certain medications; to return unused medications with our reasons for not continuing with their use and asking for clarity concerning any medication that is suggested for our use. By doing so, we prove that we are ‘thinking beings’ and, thereby, less likely to be harmed by our prescribed medications. Our doctors are not robots – AND NEITHER ARE WE!

  10. Update:

    What is the SPRAVATO™ REMS (Risk Evaluation and Mitigation Strategy)?

    A REMS (Risk Evaluation and Mitigation Strategy) is a program required by the Food and Drug Administration (FDA) to manage known or potential serious risks associated with a drug product.

    The goal of the REMS is to mitigate the risks of serious adverse outcomes resulting from sedation and dissociation caused by SPRAVATO™ administration, and abuse and misuse of SPRAVATO™ by:

    Ensuring that SPRAVATO™ is only dispensed to and administered in medically supervised healthcare setting that provides patient monitoring
    Ensuring that pharmacies and healthcare settings that dispense SPRAVATO™ are certified
    Ensuring that each patient is informed about serious adverse outcomes from dissociation and sedation and need for monitoring
    Enrollment of all patients in the REMS (registry) to further characterize the risks and support safe use

    SPRAVATO™ is intended for patient administration under the direct observation of a healthcare provider, and patients are required to be monitored by a healthcare provider for at least 2 hours. SPRAVATO™ must never be dispensed directly to a patient for home use.

    • REMS strategies are a great way to bankrupt a health service while leaving pharma able to claim their drugs take the same proportion of health budgets as they took in the 1960s.


  11. They wouldn’t treat an animal like this. Ketamine was banned as a drug given to race horses . Want not waste not – millions of human beings are being diagnosed as severely depressed – Spravato!
    As nobody will be able to give truly informed consent to taking Spravato , there is no way of weighing up the risks , the information only states there are risks . People are being prescribed it while the risks are still being very heavily monitored – in effect they are the ongoing guinea pigs for the drugs company if as it it seems they not being informed they are part of continuing research called ‘monitoring’.. What would a person’s legal rights be if s/he was picked up in a dissociated state which can be put down to alcohol or illegal drugs, especially if
    over the two hours specified after leaving the clinic? People can end up being incarcerated in a prison or psychiatric unit where the situation will not be understood and the person not able to explain their state is caused by a legal drug’s side effects. If anyone agrees to being administered Spravato they should be offered a tag to use in the same way people with epilepsy and at risk of having seizures can use them. The dose is presumed to take takes two hours to settle down but there is no way of telling how long the adverse effects will last and no way of stopping them if they become severe and frightening – much like the effect of LSD and ketamine which have to run their unpredictable course over time and regardless of what is thrown up in altered states there is no antidote.

  12. Patrick D Hahn
    Yesterday at 06:07 ·

    Baltimore Sun

    For your consideration:

    Today, The Baltimore Sun published this opinion piece by Patrick D Hahn about the nasal spray antidepressant esketamine that the FDA approved on March 5. “The recommended course of treatment for this drug, which is to be administered only in a doctor’s office, is twice-weekly for one month, followed by weekly or biweekly treatments thereafter. It comes with a price tag of $4,720 to $6,785 for the first month of treatment and $2,360 to $3,450 per month thereafter, which means the cost of a year’s treatment could be as high as $44,735. This is the same stuff (admittedly in purer form) that you can buy in a nightclub bathroom for a good deal less. Disturbingly, there were three suicides in the trials, all in the treatment arm. This finding becomes even more ominous in light of the fact that actively suicidal patients were excluded from these trials.”

    Know Your Drugs

  13. I must leave my comment anonymously because I work in the field as a therapist, and I also have a history.

    PCP, is a drug with nasty consequences, I have seen this drug used illicitly, and as a drug counselor while in grad school, I noticed that its use is a rarity. Most drug users that I treated, only used it by accident. And when the did, were not happy with the experience.

    At one time it was associated with gang members, who used it, and I know of some that was shot while under the influence, and saw this happing to someone else, the other them.

    Which brings me to my point. PCP, and Ketamine, are dissociative anesthetics, that were initially developed for use in labor and delivery. But were discontinued for that because mothers post delivery could not bond with their infants. They did not know why there were in the hospital.

    Users who like the drug describe the experience as being voided out, or out in the “void”, and will typically need someone sober with them to keep them oriented or risk having a break.

    My perception is these drugs, disassociate pain, as if it is happening to someone else, and this could account for their effect on someone suffering from depression. The symptoms are still there but their are happening to the other me, not me but someone else.

    It was also found during clinical trials that a significant number of those tried on the drug PCP had subsequent psychotic breaks. I think that this is a significant risk also from Ketamine. For example John Lilly using it to talk to GOD, and curing his life long depression simultaneously.

    I think what is happening is that pharmaceutical companies are looking for a disease to treat with a drug that’s already approved.

  14. Ketamine was also used in a psychotherapeutic context (following the ban on LSD) by the Greek neuropsychiatrist Athanassios Kafkalides who came to very similar conclusions with Stan Grof regarding pre- and perinatal memories and the therapeutic potential of psychedelic-sssisted psychotherapy.

  15. Published in thebmj 23/12/19
    So there’s this thing called a ‘central registry’ proposed for Eskatamin ‘users’ who are flagged up as potential ‘abusers’ ehh?.
    It is medics who prescribe the stuff – which has actually been banned for use on horses.
    Why is there no central registry for following up all meds…Mcshane is in a position to set one up himself, but will he?
    Esketamine nasal spray—sold under the name Spravato—has been approved by the European Commission (EC) in combination with a selective serotonin reuptake inhibitor or serotonin and norepinephrine reuptake inhibitor, for adults living with treatment resistant major depressive disorder.1

    The spray, sold by Janssen (the pharmaceutical branch of Johnson and Johnson), will be made available for patients with the disorder if they have not responded to at least two different treatments with antidepressants.

    The approval comes despite criticism over the limited evidence base.

    Before the drug can be marketed in the UK, the Medicines and Healthcare Products Regulatory Agency (MHRA) has to review whether any additional safety requirements need to be implemented. The National Institute for Health and Care Excellence will also need to recommend the drug before it can be made available on the NHS.

    The EC decision follows approval from the US Food and Drug Administration in March.

    The European Medicines Agency,2 which recommended the treatment to the EC, said that studies had shown the drug, in combination, improves symptoms of major depression in both the long and short term.

    Nonetheless, it noted that there is a risk of “patients misusing this medicine or becoming addicted to it” and said it should only be available “under a special prescription and must be taken under direct supervision of a healthcare professional.”

    John Read, professor of clinical psychology at the University of East London, was one of 12 experts who wrote to the MHRA in October to express “grave concern” over esketamine potentially being approved in the UK.

    The letter, seen by The BMJ, said, “There have been no trials of the efficacy of esketamine in the medium or long term. The majority of the studies of this drug (almost entirely conducted by Janssen, the company attempting to license the drug) are only four weeks in duration.”

    Speaking to The BMJ, Read said that the group had had “no meaningful response” from the MHRA about their concerns. He warned that not enough is known about the long term effects of the treatment or the withdrawal effects.

    Two out of three of the short term studies used for approval of the drug in the US failed to find statistically significant reductions in depressive symptoms, and raised concerns over potential side effects.3

    Tackling any safety requirements the MHRA could implement, Read said, “It’s not safe until we know what the long term effects are. They can mess around the edges, but the only way to be safe is to withhold it until it has been properly tested. NICE is going to have to make a decision about whether it will be available on the NHS. I’m more confident that it will take an evidence based approach.”

    Rupert McShane, electroconvulsive therapy and related treatments committee chair at the Royal College of Psychiatrists, said the EC decision was a “step in the right direction” as esketamine could offer hope to patients who have not responded to conventional drugs.

    McShane, who has sat on advisory boards for Janssen and is an investigator on esketamine trials, said, “Let’s be clear: it is a drug, not a miracle, and it doesn’t work for everyone. We still have concerns around how use will be monitored to prevent abuse and are disappointed that the European licence did not impose a requirement for patients taking it to be entered into a central registry that would enable the long term outcomes to be tracked.”

    McShane runs ketamine clinics at Oxford Health NHS Foundation Trust

  16. Rapid response to:
    Re: Esketamine is approved in Europe for treating resistant major depressive disorder
    Dear Editor

    The MHRA has responded to my statement in the Mahase article (20.12.19) that we received ‘no meaningful response’ to our letter to the MHRA, signed by 12 experts, explaining why the evidence on the safety and efficacy or esketamine nasal spray is woefully inadequate. The MHRA spokesperson claims that it did respond to our letter.

    At the time of the statement, and the article, this was not true. In the seven weeks since our letter (31.10.19) we had received nothing but repeated, unfulfilled promises to respond in 18 days and guarantees it had been forward to the tight team etc.. At no point had our requests for minutes, committee membership, conflicts of interest, etc. been responded to. Only after the EU decision to license esketamine, and within hours of the BMJ article appearing, did the CEO write to us, on the evening of 20.12.19.

    We note that in their Rapid Response supporting the decision to license esketamine, they fail to identify a massive institutional conflict of interest. The MHRA is almost entirely dependent for its funding on drug companies.

    Competing interests: I was the lead signatory on the letter reported in the Mahase/BMJ article in question

  17. I have been diagnosed with depression at age 14. (23yo currently.) Long story short been on a lot of anti depressents, and switching them rapidly seemed to make me more refractal and worsened depression overtime. (Dr. Robert Mcmullen talks about this theory on his ytube channel). Eventually i tried the drug clomipramine, and bam, withing 5 weeks no more depression. I did this treatment along with rtms and eventually ketmaine.

    My questions:

    1. By having my brain introduced to ssri’s and snri’s did it make it so that clomipramine only worked well because the antidepressants somehow activated some sort of a depression, and clomipramine undid this activation. Or did clomipramine actual work well for me because of the mechanisms of action on my briain? And does clomipramine have a place for use in endogenous depression? Am i just going further down the rabbit hole of eventually using maoi’s and augmentations then inevitably suicide if i stay on these drugs?

    2. Same principal above. Did ketamine work so freaking well for me because of some antidepressant induced depression? or does ketamine have actual benefits to someone who is truly endogenously depressed. Is the role of ketamine,Tca’s and maoi’s just to treat ssri induced depression?

  18. I really enjoyed your article. You did an excellent job of explaining the history of psychiatric medications in a nutshell in a way a non-clinician can understand.

    I’m a 53 year old woman with treatment resistant depression. I’ve been depressed since I was in my early teens and have used almost every antidepressant available, often in combination with antipsychotics and mood stabilizers. I’ve had relief at times, but nothing lasting.i also have chronic pain from lyme disease.

    I had ketamine infusions which were amazing and helped me get unstuck. It didn’t last forever, but it helped get me out of a dark place. I now use ketamine troches from a compounding pharmacy and they help a lot with depression and pain.

  19. I haven’t tried the nose spray, but I have a friend who takes it for migraines and swears by it. Seeing as how I get amazing pain relief during infusion, it makes sense it would work for short term pain problems.

  20. Hi David – There’s a lot of talk in the withdrawal community about using Ketamine or trying it after a certain period of stabilization after psych med withdrawal. Is there any further information you could provide on timing of the people who experienced protracted withdrawal and tried Ketamine? For example, how long since there last dose and what does “made their problems worse” mean? Did they get sick or feel like they had a setback etc? Any further data even if anecdotal could help more people. Timing and symptoms or more descriptions would be greatly appreciated.

    More details?: “Finally, three were SSRI and medication free but had protracted withdrawal from SSRIs. In all three cases, ketamine made their problems worse.”

    • This was at least 6-7 years ago so hard to be specific. Ketamine can be wonderful for some people but offered no benefit in 3 people with PSSD and 3 with protracted withdrawal. Of the protracted withdrawal, two of the three were drug free and on on a very low dose. All three felt much worse – mentally and physically as though whatever little gains they had made were reversed.


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