Ketamine might help prevent suicide | Hacker News Reader

Ketamine might help prevent suicide

nytimes.com

193 pointsandrewl100 comments

I want to warn folks that the quality of street ketamine wildly varies and is not a suitable alternative to these kinds of treatments.

I have had on and off issues with dependency on this substance mainly due to my issues with depression and anxiety.

If anything, it works too well for these issues, and it’s incredibly easy to get used to the relief from the constant onslaught of struggle that these types of illnesses cause, just as I imagine an opiate would be relieving for someone with chronic pain.

I would urge a sense of critical importance to the understanding that the exciting part of these treatments is that in combination with psychotherapy they could cure, not treat these issues.

Unlike someone with chronic pain, it can be used, along with certain other properly-applied psychedelics like LSD, to help train the psyche into functioning without it.

It’s not, however, something for everyone, and while it worked for me, please excercise extreme caution in using this substance or recommending it to others.

I’ve had friends who did it for years and still killed themselves. Two of them.

So at the end of the day, I urge everyone with even the deepest-seated mental issues like this - this kind of change has to come from within, and any benefits an external tool provides should be for dedicated moments of healing and/or a focus on the mind, and, for lack of a better word, spirit.

I can create a throwaway email account to answer any questions anyone may have. Please don’t hesitate to reach out if you, or anyone close to you has problems with this substance.

Very valid points. But keep in mind that ketamine therapy is generally considered a treatment of last resort, for refractory depression, often after even treatments like ECT have failed.

From the article:

> Dr. Michael Grunebaum, a Columbia psychiatrist who studies ketamine, thinks the drug should no longer be relegated to a last-line treatment.

I find this argument interesting. Going through depression myself, waiting for an SSRI to be effective 6 - 8 weeks feels impossible if you want to end it all RIGHT NOW. That's kinda the point of suicide, is to end the pain ASAP.

Here's the thing, the SSRI didn't work out for me, now I'm going to try another medication, another 6 weeks before it's fully effective (It's not an SSRI though). I don't know if I can wait that long.

I still haven't gotten to other tiers of treatment in terms of medication - Antipsychotics, rMAOIs, etc.

Point is: I'm not sure a tiered approach for medication works well for everyone with depression, it's too time sensitive.

I agree. I can imagine... well, I don't have to imagine, I've been there: the prospect of months or even years long carousel of medications, trying and discarding one after another, hoping to get lucky on the next try... It's awful. I'd like to see ketamine and some others in careful but wider use. (modafinil for example works wonders for me and is also fast acting, definitely keeps me functional during depressive periods)

Yes indeed. 6 to 8 weeks is an eternity for someone who is deeply suffering. I personally think we are way too stingy with medicines these days. I also had a friend commit suicide while suffering from intense depression. He would no doubt be alive today if he had been giving what he needed right away, instead of being made to start with Prozac and then worked through a bunch of different "starter" antidepressants. Just give people what they need. There are worse outcomes than over-prescribing (death at one's own hand, for example).

Sadly, we don’t know enough about the brain to have any idea which medications are going to work or what it is people need right away. While you certainly could sedate people to the point of utter apathy by giving every shmiel who walks through the clinic doors high powered anti-psychotics it would be akin to treating a broken toe with amputation.

First line treatments like sertraline and fluoxetine are used because they take time to work and have generally tolerable side-effect profiles. E.g. in the case of patients with undiagnosed bipolar disorder, you run a lower risk of triggering a manic episode.

Why shouldn't the person be allowed to make their own choice after being properly informed of their options and having received their doctor's suggestion?

It's unethical, just like if a patient demanded their leg be amputated for a broken toe.

If the broken toe was inside a concrete cast that no one could see into, and there was no such thing as an X-ray machine, CT scan, MRI, or any other machine that could be used to verify the toe being the part that's broken.

If the doctor didn't listen to, or at all believe at least half the the stuff the patient actually said, and didn't need to.

If others had leg amputation performed and the leg grew back and on top of it we had evidence that leg amputation caused long-term damage when performed for other reasons. (Ketamine has long been used as an anesthetic precisely because the data we have suggests no long term damage from that dosage.)

If the patient had suicidal ideation and intent, because something hurt so much and we had no way of doing anything other than leg amputation, then why shouldn't we?

Until humanity manages to develop and deploy brain scanners that can actually see how much physical and emotional pain a person is actually in, then the leg amputation analogy is lazy and unhelpful because we simply don't have the same tools to address mental health because it's largely invisible.

Most doctors are still humans who negatively judge patients who drink heavily, who frequently miss appointments, who can't manage to get lab work done, who self-medicate with street drugs; those patients are judged as degenerates, not deserving of their help because they can't manage to take a pill, that doesn't seem to work for 6-8 weeks.

I mean, it's great that a hospital's ethic's board has reviewed the situation and determined that the best course of action is for people to suffer because they don't want the liability of, in this analogy, leg amputation, but in the meanwhile, people are being discarded by the mental health profession.

But what treatment are you thinking of here? Ketamine? Maybe after more research, trials and long term tracking of patient outcomes it can become a front line treatment. For now there's a reason it's a treatment of last resort. It's use in this way is not as well understood as traditional drugs. Use as an anaesthetic is a one-off. As with most substances, chronic use carries more complications. There's potential for cardiovascular issues. Also cognitive issues like impairments in creating new memories, accessing old memories, verbal memory, forgetting words, names... It makes sense to attempt treatments with a lower risk profile first, not for legal liability but patient well being. In the meantime there already is an immediate treatment available for those at risk of self harm: short and medium term hospitalization, which allows for more rapid trials of different medications at higher doses because the patient is under regular monitoring. Yes it still sucks, it's a crappy experience, but it is effective in getting most people stable enough to wait for longer term treatments to reach peak effectiveness.

> It's use in this way is not as well understood as traditional drugs

Traditional drugs are often a crapshoot anyway, and there's been plenty of harm from them. In the end, it should be the patient's choice in what path to take.

Yep, traditional drugs have their pitfalls too, but have had the advantage of rigorous trials that something like ketamine has not yet undergone. I'm glad it's an option, but there's really not a strong enough body of research for it to make it a first-line option. Yet. I hope that changes.

And, in the end, it is the patient's choice, within a certain circumscribed set of options. A good doctor works with the patient's needs. But it would be a very poor doctor that jumped to riskier options and less proven options first. The level of patient choice you're suggesting implies a level of informed patient that is frequently not the case. I rigorously research every single treatment option, discuss each one with my doctor, and we arrive at a course of treatment. But my doctor has indicated that I am, unfortunately, in the small minority in this respect. Your level of patient choice would invite all sorts of bad prescriptions to patients ill informed and, often, self diagnosed incorrectly-- a frequent issue leading patients to skew their conversations with doctors towards that incorrect diagnosis. In theory, in a perfect world, what you propose is fine. But we don't live in that place.

How do you know what he needed? There aren't "starter" antidepressants and "high-strength" ones. Prescribing him prozac first was giving him what he needed. I'm sorry you lost your friend, but it's not because he was denied some wonder drug.

Secondly, it's ridiculous to suggest we're underprescribing antidepressants. Completely the opposite. Mental health disorders require complex treatments involving therapy and lifestyle changes as well as medicines, but doctors will completely ignore that in favour of just writing a prescription after a 5-minute conversation. I say this with a lot of experience of mental health treatment: doctors hand out antidepressants far too easily.

I know it is trite, bit stay strong, things can get better. I have schizoaffective disorder and I did find a mix of medication that helps a lot, but it literally took 13 years to find the mix with a couple suicide attempts during that period. Check out some of the mental health subreddits, I am the founder of /r/schizoaffective.

Maybe ketamine is treatment of last resort, and LSD, because they’re most likely to actually work and the pharmaceutical-insurance industrial complex wants to rinse as many people through the ineffective drugs and therapies first.

Maybe I’m just being cynical, but if the standard treatments were effective perhaps we mental illness wouldn’t be so prevalent.

Of course, it’s complex and multifactorial, and there’s societal and cultural issues, and generational issues, we need to address too.

Exactly my thoughts.

Check out the book Ketamine for Treatment Resistant Depression.

It's a safe drug with a low incidence of serious side effects that could help a lot of patients. Researchers have shifted much of the research to Ketamine metabolites.

Their reasoning is that these metabolites have a lower side effect profile than the parent compound. It has been almost 20 years of small scale ketamine trials for depression with not much to show for it. Now, they would like to explore a diversion that may be less safe than a drug with a long history of safety.

I think there are a few reasons for this: 1) Depression isn't seen as a serious disease like cancer and 2) Ketamine is a cheap drug.

I thought because of its rapid efficacy it was moving towards, being proposed as being a Frontline intervention to reset.

SSRI are hugely problemmatical because they take time to ramp up and flush down. Mental health sometimes needs a course correct not a long-term hand on the tiller.

MDMA and psylocibin likewise: brief, sharp reset goal.

(That's what I read)

This is very misleading. Patients are seeking out this treatment from independent clinics that do not take insurance. They don't need a referral. The biggest consideration is patient ability to pay a lump sum up front.

Katamine may actually /be/ an opiate: http://slatestarcodex.com/2018/11/08/ketamine-an-update/

It is not an opiate, even if it has an affinity for the mu receptor (it may or may not) it is absolutely classified as an NMDA antagonist.

It has effects on the opioid receptors but is definitely not an opiate or opioid.

Additionally, it appears that the different isomers have different properties potentially for anti-depressive effects. The R- isomer seems to work better for it from what I’ve read. Know what isomer you’ve got is less common from street. A lot of people prefer S+ isomer for recreation though but it doesn’t help as much

The usage of ketamine in the trials for depression typically uses IV administration over a fairly long timespan with highly specific dosages. It is not comparable to street usage of the drug.

As with any psychotropic medication, one should do their research. Psychiatrists whom I’ve spoken with seem generally excited about the prospect of more rapidly acting agents for the treatment of depressive episodes, but with the caveat that data is not there yet to draw any conclusions. And, as with every other treatment for depression, psychotherapy + medication outperforms medication alone. There remains power in the talking cure.

> The usage of ketamine in the trials for depression typically uses IV administration over a fairly long timespan with highly specific dosages

That's surprising, I would imagine that therapeutically a longer term low dosage would be more interesting (that is, not through IV, though I'm not sure how Ketamine behaves in the digestive tract)

> (that is, not through IV, though I'm not sure how Ketamine behaves in the digestive tract)

The main problem with sustained use (abuse) of ketamine nasally are severe crippling stomach cramps (think agony, rolling around in pain screaming) and scarring of the bladder causing you to urinate every few minutes just a few drops due to bladder damage. In severe cases bladders stop functioning and in some cases removed altogether.

Urban legends are these are caused by the "drip" after snorting large amounts, so if you spit the drip out you are ok. No idea how true this is, but some people swore by it

The bulk of ketamine studies have used IV administration but that doesn't mean it's more effective than sublingual. There are several studies on oral, intranasal, and sublingual ketamine with positive results. There are also several doctors including mine that are prescribing it for use at home.

Also consider that many of the doctors administering ketamine by IV at $500 a pop are not psychiatrists. There is far too little written about these opportunists.

I suffer from serious depression. I have tried to kill myself. It comes and goes in waves.

I was able to try an experimental ketamine treatment in the hospital.

3 doses administered via IV every-other day. (Monday, Wednesday, Friday)

The first and third were failures for me. Nurses talking in the OR completely distracted me and "stole" my awareness.

But the second one was perfect. I was able to feel nothing. I was able to shut off my mind and enjoy the single most peaceful moment of my life.

As time & work permit I plan on doing this again. Especially now that I know I need to be blindfolded and have ear-plugs in. (this sounds dramatic, but it's what works for me)

It hasn't cured my depression, but it has given me hope. And that's more then I have ever had.

I hope you get the help you need.

I can’t recommend The Body Keeps the Score by Bessel Van Der Kolk enough, I wish this book had been out 10 years ago before my mom took her life.

Nonetheless, it’s been instrumental in helping me alleviate my anxiety and depression. I read it a year ago and I can’t imagine going back to the way I felt then.

Specifically I’ve done two forms of therapy — EMDR and Somatic Experiencing — that were recommended (among many others) in the book.

Seems to have really good reviews. Is it something worth reading for somebody without a depression or a trauma? Any insight that stuck with you the most? I'm sorry about your mom.

I honestly read the book just because I consider myself an autodidact and student of human nature and it sounded interesting. While reading I realized that the traditional psychotherapy I’d done since my mother’s suicide was mostly just a way to cope with the tragedy rather than to heal from it (coping is still better than nothing though IMO).

I’d say it’s still worth reading to better understand the people around you who seem to act in almost objectively “illogical/irrational” ways, even when presented with better solutions. Even though such behavior is typically self-destructive, this book helped me to see the “logic” of it (Eg some obese women are obese because they were abused as children and they unconsciously overeat/eat junk food to make themselves fat and unattractive to potential abusers, so without resolving that issue no amount of healthy nutrition knowledge will help them, they’ll always regress).

It’s also given me more empathy for those around me, instead of feeling like they’re doing things “to me” I’ve been able to keep the bigger picture in mind and realize that people mistreating you is typically just a sign that they have unresolved issues themselves (that doesn’t mean you just let it happen without saying anything, but the increased empathy helps me handle the situation better).

> Eg some obese women are obese because they were abused as children and they unconsciously overeat/eat junk food to make themselves fat and unattractive to potential abusers ...

I‘m not a big fan of these kind of „logic“ explanations. I think the explanation can be a lot more straightforward, like by being treated worthless your whole childhood you‘ve internalised this feeling and now continue to do the same to yourself.

But yes, it‘s really helpful to somehow understand or least get an idea why a person behaves in a certain way.

To my understanding, the logic is that there's a hormone called leptin which strongly guides your eating patterns, cravings, energy, etc. Stresses and traumas can affect your leptin levels, so particular stresses and traumas can cause you to eat more. This makes evolutionary sense, since if you're in a famine, or an ice age, you better stock up on as much food as you can. Move slowly, digest slowly, don't lose any of it, because you never know when you'll run out.

Sexual abuse traumas get interpreted by some bodies as the same kinds of stress signals as famine, raising leptin, causing overeating.

So I guess the broader point is that some of the "unconscious logic" going on inside us isn't just habits or odd personality traits, but actual chemical processes.

Note that I got all of this knowledge from reading a Pop Sci weight loss book. HN, let me know if you know better :-)

Yeah, I hear what you’re saying, the book goes more in depth, and again the question becomes — so you’ve internalized feeling worthless, what is the solution?

I believe the book provides a key to understanding how to resolve those feelings that traditional psychotherapy lacks (with its focus on identifying the problem and acting more logically, most people know exactly what they’re doing wrong, they don’t need you to point it out, they need to resolve the underlying issue — which typically seems to be some childhood trauma).

While van der Kolk et al. have certainly contributed a great deal to the study of trauma and helped popularise ideas that have been known within the academy, he remains a controversial figure and spends a great deal of the text going off on self-aggrandising tangents. If you’re interested in psychotherapy in general or the interpretation of the human experience through a psychological lens, I would recommend anything picking up one of Rogers, Yalom, Frankl, or Satir’s books.

I’m undergoing EMDR for PTSD from childhood trauma. It’s kind of amazing how well it has worked for me, much more so than I had expected (I was skeptical at first). It hasn’t completely wiped the feelings and memories away but they are much easier to cope with and process.

I’ve tried nearly everything - Medication, counseling, support groups. EMDR has been the most effective treatment I’ve found so far.

I did some sessions of a therapeutic approach similar to EMDR called Accelerated Resolution Therapy (ART). I too was skeptical, and amazed at how well it worked. When I told a friend about it, he pointed me at the "Memory Hackers" episode of Nova, which isn't about EMDR or ART, but discusses the science of rewriting memories, and helped ease my skepticism about the approach.

I just got the book and have read through part 1 already. Thanks, it's a great book, so far.

Best of luck with your depression. I'm sorry to hear you are suffering. NPR today had a piece on deep brain stimulation as a treatment for depression. Very preliminary research and very invasive but something is better than nothing. [0]

Also, Michael Pollan's latest book on psychedelics is very interesting and has a specific chapter about using psychedelics to treat depression. It might be interesting to you. [1]

0. https://www.npr.org/sections/health-shots/2018/11/29/6718660...

1. https://michaelpollan.com/books/how-to-change-your-mind/

FWIW, the antidepressant effects of ketamine (7-14 days long) are unrelated to the hallucinogenic effects (45-60 minutes long) experienced at time of administration. You could be unconscious during the “trip” part and the antidepressant part would still do its thing.

Fwiw, the therapeutic effect is caused by ketamine metabolites that are not the involved in the ketamine high.

Take a look at neurofeedback I had friend who had a similar background and it helped him get through a deep depression.

Can suicidal thoughts on daily basis categorized as depression or just a phase of life? I feel very disappointed at my current life condition and I feel like dying from the inside and feel numb sometimes. I cant afford a therapist at the moment but a lot of people are shrugging my issues as phase of life and I cant help it but feel dejected.

Think it’s quite normal to have issues as a phase of life. Regular Suicidal thoughts is however something to take seriously. But dealing with issues for me took breaking a bad pattern and progressively working towards a better goal. Earl nightingale “the strangest secret” is worth watching... for me what he speaks has become true. Things I know for a fact takes bad thinking away is Changa but it’s something you either neeed to educate yourself in very thoroughly or have guidance. Most other drugs are too dangerous for most especially if you are in a fragile state. Breaking bad patterns can be things like getting away from a girlfriend, having a new job, getting a new interest, o finding the place where people will listen to you ... for me slacklining did wonders as it’s almost like meditating.

What is slacklining? and Changa?

https://en.m.wikipedia.org/wiki/Slacklining

Walking on a line of dynamic webbing that kind of forces you to not to think about anything else.

https://en.m.wikipedia.org/wiki/Changa_(drug)

I have a post somewhere else in this thread where I describe it.

Thanks!

I have a similar story. It wasn't a phase. It was a daily occurrence for 2 decades. On a good day, it's easy to tell that voice to go to hell. On a day with depressive triggers... those suggestion cut deep, and deepened every spiral I'd find myself on.

I found a clean source, I get it tested independently. I take a few milligrams once every 1-4 weeks, depending on my stress / trauma load. Early on, I'd take some whenever the voice came back. Now I've learned what the edge feels like, I dose early enough to maintain silence.

I understand why pharmaceutical companies wanna keep this as a last resort. I've seen the treatment programs -- they're k-hole doses; nothing like what's been working for me. But there's no profit regimines like mine. And maybe it won't work more often than a placebo. But it's worked for me and that's what matters.

Have you ever tried a float tank? Most relaxing experience of my life. It's like a blindfold and earplugs but for all your other senses, too.

Psychedelics for this benefit should be done in environment without disturbances. That’s the reason I did them all alone and make sure the setting is perfect when I take others through a Changa trip. People who k-hole and do it them self build up or just take a big enough dose and often alone. For Changa even a mosquito can be a disturbance taking you out of the most perfect trip from a place you can never return.

I was a ketamine user for a long time. My use turned into a problem but I'm realizing that my use patterns were basically: Use, wait until depression returned, crave a cure from my depression, use.

In a clinical setting I'm sure that it's very helpful but for me the "crave a cure" caused me to not getting around to dealing with my issues of depression until after I had issues with ketamine that required intervention and left me alone with depression again.

I hope other people never go down that path. She is a cruel seductress and the draw of the sudden emotional changes is a lot to put on someone's psyche. If they're suffering, and then suddenly they aren't and they feel happy for the first time in a long time it's easy to make the association to powder = happy and that's a very powerful association for an animal/human psyche to put together.

For most people, street ketamine would scare the shit out of them but for anyone else they might get drawn in to basically constant cycles of self medication.

How is a constant cycle of medication any different from using common antidepressants like SSRIs? Sure, it would be great if we could cure depression without drugs, but if that isn't possible, obviously medication is important for those people to be able to live good lives.

Well in the case of an nmda receptor antagonist, the harm can be pretty high. For example, alchohol is an nmda receptor antagonist and is considered to have one of the highest social costs of any drugs.

How does it compare to the side-effects associated with the other anti-depressants, including extreme suicidal ideation?

I'm not sure what you mean by "social cost".

social cost = effects on family, close friends and relatives, and occasionally society in general.

The doses are acute so the side effects at reasonable doses are primary psychotomimetic effects without physical harm or other behavioral impact - it has a very short half-life and people will be basically sober by the time they leave from a treatment and the body will clear it in a day. The effects last beyond that because they cause a systemic brain change and psychological effect, not because there is a drug present.

Alcohol is an issue mainly due to how it interacts with Gaba receptors. Alcohol (and benzodiazepienes) binding with those receptors is what causes tolerance, physical addiction and withdrawal. Nmda receptors antagonists don't cause the same kind of issues.

You generally can not physically get addicted to nmda antagonists like ketamine. In fact nmda antagonists and modulators are being studied because "research suggests that N-methyl-D-aspartate (NMDA) receptor neurotransmission contributes to mediating the behavioural effects of alcohol and other drugs of abuse" https://www.ncbi.nlm.nih.gov/m/pubmed/11060803/

I want to make clear that I mean physical in the biological sense. It is still possible to form an addiction to these drugs. I only mean to say that it's rare to have dangerous withdrawal effects, unlike with alcohol.

That is true - alcohol is both nmda antagonist (the stumbly ataxia) and gaba agonist (effect on anxiety.) GHB IMO is not nearly as gnarly of a substance as alcohol because it sort of has a ceiling but withdrawal from any gabaergic is uncomfortable and potentially life threatening and nmda agonists are not, there are a lot of causes of bladder damage especially from ketamine, drowning, falling off buildings, loss of jobs, friends, family. Despite it's rather low physical harm profile (aside from the bladder damage) it's incredibly addictive and many people go wayyyyy wayyyyyyyy too far. I have lived it, and I've seen it. It has a very dark side.

I know the IV user in this film (they call him Chris on camera). This user is atypical but there are many people with extensive bladder damage and negative social effects. You'll have to take my word for it. I'm sure there is more research from china especially as it's very common drug used there. Police note (anecdotally) the typical user in north america has changed to middle aged and affluent as the price of street ketamine has gone up from maybe $25/g to +$90 https://www.snagfilms.com/films/title/drugs_inc_ketamine

I believe in its power as an antidepressant. I'm just concerned about the effects a bit. It will fuel research - it seems it's not ketamine but metabolites and effects on ganglial growth that spur the sudden changes to a depressed mind. And a new objective view on life and reality.

> I know the IV user in this film (they call him Chris on camera). This user is atypical but there are many people with extensive bladder damage and negative social effects. You'll have to take my word for it. I'm sure there is more research from china especially as it's very common drug used there.

That's not pharma grade ketamine. We have no idea what these drug users are taking.

The illicit nature of street ketamine is what sets it apart from SSRIs, for mainstream society. A random primary care physician (PCP) isn't going to send a prescription for it over to the local CVS/Walgreens pharmacy for convenient pickup over lunch. Which often means resorting to desperate measures, at heavy markup, in order to procure any amount, with an unreliable supply.

Self-medication can be problematic because it's non-objective, but it can easily lead to (psychological) addiction. The brain optimizes/skips a step - not-being-depressed looks a lot like actually being happy when compared to being depressed, so then there emerges this belief that the user needs to be high on ketamine constantly, which is when it becomes a problem.

GP post isn't arguing that no one should use ketamine, or any other medication that works. They are giving first-hand perspective that ketamine addiction is real, and having heard stories myself, I'm inclined to believe GP. It would be great if ketamine had to be prescribed by a doctor to avoid addiction, and that such a requirement didn't end up excluding those outside of mainstream society (often because of mental problems like, say, depression).

FDA approval of ketamine for depression will go a long way to improving the situation but for now one choice is to pay some $1500/session (not covered by insurance), to a clinic run by medical professionals risking their license. (Each session uses less than $20 of ketamine, so it's quite the markup!)

The other option is to buy street ketamine, which is a move of desperation, but looks a lot better than committing suicide.

I don't understand the objection int the article about the possible necessity of "booster" treatments though.

> A random primary care physician (PCP) isn't going to send a prescription for it over to the local CVS/Walgreens pharmacy for convenient pickup over lunch.

Most GPs won't write you a scrip for ADHD medication on a whim, either, but I wouldn't describe Vyvanse as "illicit." They just "know what they don't know" and so don't trust their own evaluation of you and think you should get a professional evaluation by a specialist (i.e. a psychiatrist, in this case.)

They're usually perfectly willing to continue prescribing after you've gotten a previous scrip from a psychiatrist, though. I suspect ketamine would be much the same, except that you'd need to get your scrip filled at the pharmacy of an inpatient hospital (since that's where they'd have it in stock), rather than the corner store.

It's the same story as, say, methamphetamine. Scheduled drug—but that doesn't mean you can't just get a prescription and get it filled. It's a lot of work to get that prescription (since methamphetamine is also a last-line treatment), but once you have it, any hospital pharmacy should have some in stock.

Where a future hypothetical ketamine prescription could be filled from, I can't say, but clinics charging $1500/session have it in nasal sprays and lozenge form, I'm hopeful that a corner store would eventually be able to fill it easily once one of the pharmaceutical companies manage to package it up in a form they deem lucrative. (Which will involve patenting some part of it, possibly the delivery mechanism, since ketamine itself is past patentable date.)

Depression is an insidious disease, and being able to fill it at the corner store, rather than having to go all the way to hospital (which can be a scary and frustrating experience) might make the difference between having the medication, and not.

Ketamine is hugely psychologically addictive though. It is like saying that opioids should be available to everyone that is in any pain. The level of addiction caused may be different because the opioid user has to contend with the negative association with withdrawal as well as the allure of the high itself, whereas ketamine is only one of those two. Dependence and addiction are not the same and ketamine is powerfully re-enforcing. I don't mean to trash this - I'm just trying to show a counterpoint and another perspective because there WILL be misuse as soon as prescriptions become available, and people (doctors) will not understand the degrees to which it can draw people to misuse until much later. There is already a black market to supply to the demand. If droves of people start acclimatizing themselves to ketamine, the market demand will increase and the black market will be there to fill that new demand, just like it did with heroin/fentanyl when pain was over-treated with opioids and droves of mom's and yuppies suddenly thought heroin sounded like a pretty good idea because they had already lost their opioid naivety.

So in turn, I put forward that we should hope a discovery of the mechanism of action and a way to put it to use without ketamine. Ketamine's action itself is assumed to _not_ the primary mechanism of action but rather a metabolite is (the experience has a part of it I'm sure - it's pretty fairly a psychedelic but the yin to LSD's yang) and scientists are working to find a drug that will have the same effect without the psychedelic dissociative qualities of ketamine (and it's monstrous allure which some people notice and fall for - but many don't)

Seems to me that only certain personalities thirst for ketamine after experiencing it. But that will all come to view in time because the black market is ready to supply to an increase in demand and it will happen that way once people start diverting ketamine. The black market will compete in that market. It will offer a product of similar quality (most clandestine on the street is close to 100% purity) but will find its competitive advantage is price and availability.

Yet another strong case for legalization.

> (Each session uses less than $20 of ketamine, so it's quite the markup!)

Are you sure? That is a lot of ketamine

You're right. An upper bound of $3/session is a better estimate.

Dosing regimens for ketamine to treat depression are still being worked out, especially because that still considered an "off-label" use by the FDA. Using the upper bound of 0.75 mg/kg [0] and a person weighing (again, upper bound) 300 lb, I calculate 100 mg dose/session, which is roughly $3 of ketamine (when procured by a doctor).

[0] https://www.ncbi.nlm.nih.gov/pubmed/28749092

It's very interesting that the most impactful and potentially revolutionary psychiatric drugs currently in trials are both illegal recreational drugs, MDMA and Ketamine.

I do wonder how many regular users of these drugs are (consciously or subconsciously) self-medicating, vs. purely using hedonistically. Although I can imagine the line is quite blurry.

Scott Alexander has talked about these drugs from a psychiatrist's perspective; his article on Ketamine gives a lot more technical speculation about its mode of action, plus links to academic papers, for anyone that's interested in digging more:

http://slatestarcodex.com/2018/11/08/ketamine-an-update/

Don't forget about psilocybin.

I was absolutely self medicating with mdma to deal with childhood trauma but it was also a hell of a lot of fun.

Interestingly I brought up child abuse on an email list I was on with people I met in the rave scene many years ago and literally all of them had a history of it. I had no idea. We never really talked about it even when we were taking mdma and having deep conversations but almost everyone said the mdma helped them deal with it.

I wonder what would happen if they stumble upon Alexander Shulgin's research on phenetylamines and tryptamines.

What other most impactful and potentially revolutionary revelations await us there ...

> It's very interesting that the most impactful and potentially revolutionary psychiatric drugs currently in trials are both illegal recreational drugs

History will not be kind to the War on Drugs. Aside from the millions of lives it directly destroyed, it also set back several fields of science 50 years.

I suffer from depression and anxiety. I take medication for it but the one thing that has helped more than anything has been cannabis. Unfortunately it's also hindered me quite a bit. I'm intrigued by this study but also suspicious... It seems a lot of "illicit" substances are being touted as possible depression aides, such as shrooms and MDMA.

Same stuff basically minus the cannabis. Honest question: did you check your hormone levels? Especially the testosterone and thyroid? I was browsing youtube couple of months ago when I came across this podcast [1] and everything that this guy talked about seemed like it was everything that I'm experiencing.

I went ahead and checked my hormones. Sure enough I'm low on testosterone with a measure of 3.2 where the lower limit is 9.6 with the upper of 23 so I'm just 30%~ of the lower limit. It may be a long shot but the chemistry checks out and I will give it a try.

[1] https://www.youtube.com/watch?v=_wlvoWASBD4&t=395s

P.S. Just read your bio so testosterone might be out of the question, still...check your hormones :)

Not sure why that should be surprising since unlike most anti depressants, club drugs have an immediate and dramatic effect.

Maybe I wasn't able to use cannabis moderately enough, but as my tolerance grew and I had to take more and more to feel the effects, my depression and anxiety got much, much worse.

These "illicit" substances work. I can only speak for myself, but the amount depression that can be caused from anxiety is enormous, and then there's MDMA, which provides a reference point for life without it -- which in turn reduces the depression. Life changing, but it was also in a therapeutic setting with all the proper controls.

It's interesting. You and other commenters refer to MDMA as providing an experience of being anxiety free, but the few times SWIM's rolled, I've experienced part of the time with a high level of anxiety (in fact, the first time I got a panic attack was while rolling). They still were amazing experiences that made me feel great afterwards.

*not in a therapeutic setting

Did the anxiety occur during the initial onset of the MDMA (aka the comeup)? The onset of MDMA creates strong physiological effects that can trigger anxiety. One way to mitigate this is to split the dose of MDMA into two equal parts, and taking them 10 minutes apart. This creates a more gradual onset that greatly reduces the feeling of anxiety for most users.

More discussion about MDMA anxiety: https://www.reddit.com/r/MDMA/comments/5v4h9z/panic_attacks_...

A) Studies have shown that if a person takes threshold amounts anxiety can happen. This applies to other psychedelic-like substances as well. One doesn't want to take too little, but also not too much! 80mg - 120mg is the sweet spot.

B) Was is pure? Unless you're sure, it was likely cut with something.

"I'm intrigued by this study but also suspicious... It seems a lot of "illicit" substances are being touted as possible depression aides, such as shrooms and MDMA."

I've done MDMA multiple times. I'm over 35. I did it recreationally with my spouse. I know the recreational doses and the theraputic doses are the same.

And boy, did it solve some stuff in my brain. All positive. I'm better equipped to deal with anxiety and depression than I was before. I was.. OK. With myself, with things, and so on. The next day and week or so after, it felt like by brain had been rinsed off, massaged, and gently put back in place. Now, this slowly lessened, but I was able to deal with stuff. It is really hard to explain: Like finally getting glasses and being amazed with how clear things were. I can only imagine how this would be in a clinical setting, with someone guiding your brain to deal with things you needed to deal with. Also, I found I like myself. That's not nothing.

Now, I've never done Ketamine, but I imagine results are similarly helpful for folks this is a good match with especially when you are in a clinical setting.

Yes it can really work wonders but it’s also easy to use recreational. Had a friend who only does cocaine as he loves being in control and hated on mdma... he is also the most negative person I ever knew and would usally end up in a fight anytime he walked out the door... he blames his ptsd. One time we got him to do mdma anyway and he changed to the most positive guy over nite... sometimes accused us of being negative suddenly even though that used to be his middle name. It had that effect for 1-2 months untill he was back to his old self.

I’ve seen both mdma and many other psychedelics have short term positive effects but they also had a downside as they are easy used recreational. Only thing I can swear by works wonders are Changa and is in a category where regular abuse is very unlikely. I’ve been around 100s of people the last 20 years where we all smoked daily.personally 100g+ month of bubble hash grade or o.g kush types heavy weed, had year long periods of doing extasy,cocaine,mdma,amfetamine every weekend. Occasionally did stuff like 2cb, mandrake root, phenibut, Kanna, kath, ghb, lsd, dmt, ketamine, some RCs and perhaps 50 shroom trips in my youth and a bit of opimum to end a nite on a festival after having mixed a bit of all of the above. Having a highly stressful job I got tinnitus and was waking around myself in circles I decided to make my own Changa (dmt from mimosa hostilis keeping nmt +hamalas(rima) from b.caapi+alkaloids of Passion flower + blue Lotus, African dream herb) and it instantly took my stress and tinitus away and forced me to sleep properly Which had Been years since.. and imo is one of the most dangerous things and I have often seen as a trigger for insanity . Also lost any cravings for weed + sugar and such and now have not touched anything for a few years don’t even care for a beer. I gave my product to about 80 people under my strict supervision and guidelines and they go through so many emotions laughing, crying, having internal conversations, being afraid, wanting to die, feeling love, not wanting to die all in a short time they come back and tell me it’s the most incredible experience ever, that it saved marriges, ended abuse, stopped suiacidal thoughts and gave a new perspective on life some who had given up on shrinks and medicine.. mostly a common effect of living more in the moment and forgetting the bad thought loops they had. Friend working at google Quit his job right after, gave away his things and went to live with aboriginals. Another came back from South America after doing ayhuasca, rape, sanga, Kampo and told me what I had made was what he had been looking for there ... it got so “known” that someone from Sting heard about it and came by to do it when touring my country ;) most have only tried dmt enhanced leaf so they can’t relate.. those who have tried the real deal have respect for it and for most it will be once in a life trip .. even the hardcore are not just doing it for good reasons even if it’s just 1 hour it’s also the most crazy psychedelic... I’d done well you will leave your body not even be aware of yourself anymore and go a other worlds or memories and “movies” so far out no words exists for what you experience :D even if it’s the most amazing experience in a life like sex with the universe I can stil live on the memories of it for years. It’s a drug I expect to hear more about in coming years when it becomes more known as it’s my experience it’s much more effective than mdma ketamine shrooms which I have seen way too many downsides with like excessive abuse and suicides

I recently did a therapeutic MDMA session and it was life changing. So much was stored in my body that it helped to release.

I hate providing any negative news for stuff that works for people butt... More and more trials are showing that if you block ampa, ketamine's acute depression curative properties are completely diminished. Aka, it might work, but it's probably not the right drug

https://clinicaltrials.gov/ct2/show/NCT02911597 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487269/

Personal ancedote: I know someone who has tried this treatment and it has worked for them. First time I’ve heard about ampa blocking.

IIRC (I forget where I read this), ketamine does one thing pharmacokinetically, but its main metabolites—norketamine and dehydronorketamine—have their own entirely-different pharmacokinetics (which aren't just less-potent versions of ketamine's.)

I don't know about "not the right drug"; but it might turn out to be considered a pro-drug.

This is important. I was considering a ketamine study but based on the results of naltrexone + ketamine I'm much more cautious and will wait for further studies.

Weird factoid about Ketamine: it seems to require being paired with the smell of a male to work: https://www.scientificamerican.com/article/sex-matters-in-ex...

In mice.

(Just pointing out that, as useful as rodent studies are, this isn’t a result that can be generalized to people.)

Have you seen any tests of this with people? Or heard any first hand witnessing about ketamine and males? I hear it is considered a drug to take when going to clubs.

Which reminds me of another quirky result: caffeine promotes wakefulness in fruit flies: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757164/

Without specific selective pressures, traits persist through species

No, but from the article you linked:

“Gould doubts that the sex of the person administering the drug affects how well it works in a depressed patient, but it's never been tested.“

It seems to be related to stress response, which the mice were experiencing in the presence of male handlers. One would assume the same issue isn’t present in humans unless they become anxious and stressed when men are around.

That said, it does have interesting implications for the drug’s relationship with stress; e.g., it might have stronger subjective effects in folks with high stress or stimulation levels at the time of administration.

This isn't a particularly good article. Psychiatrists in the UK are cautiously optimistic about ketamine, and things like TCMS, but they're worried about the widespread off-label prescribing in the US, especially when that's decoupled from other measures such as talking therapy or psycho-social interventions.

> The suicide rate has been rising in the United States since the beginning of the century, [...] And yet no new classes of drugs have been developed to treat depression (and by extension suicidality) in about 30 years, since the advent of selective serotonin reuptake inhibitors like Prozac.

Lack of access to new drugs is common across countries, yet many countries have seen falling rates of suicide. What's different about the US?

> After her suicide attempt, Louise’s psychiatrist suggested she try ketamine. She agreed, and received an infusion intravenously. Within hours, her sense of well-being improved. The hospital discharged her. Back home, she discovered that going to the market was no longer a “herculean task.” Getting her car washed wasn’t an insurmountable chore. “Life was better,” she said. “Life was doable.”

This is exactly the kind of thing that was being said about prozac - these are wonder drugs that make you better than well, and the current drug licencing rules are outdated because Prozac should be available to everyone not just ill people.

Ketamine will end up being moderately useful to some people. It will save a few lives. It's probably not a wonder drug.

The article makes no mention of the low risk paradox. Most people who die by suicide will have been assessed as low risk of death by suicide shortly before they died. I'm curious if these people would be given ketamine or not. And that's the people who were seen by MH professionals before they died.

> Here’s a sobering fact: Some studies indicate that suicide risk peaks soon after patients have been discharged from a medical facility.

This is a well known phenomena, which is why NCISH in the UK includes this in their ten ways to improve safety in MH services https://sites.manchester.ac.uk/ncish/

"Patients discharged from psychiatric in-patient care should be followed up by the service within two to three days of discharge. A care plan should be in place at the time of discharge."

> Lack of access to new drugs is common across countries

They didn't say "new drugs", they said "new classes of drugs." The point they were trying to make was that innovation (by big-pharma researchers, at least) in the anti-depressant space has stalled.

I think the article is confusing someone who's at the tail end of their life, and no longer interesting in continuing, with depression among people who'd otherwise go on to live a radically different life.

The two are not the same and treating anyone who is done with living as depressed or needing psychiatric intervention is short sighted.

I'm all for helping people who want help. Some people don't want help - they just don't want to break the hearts of those who care about them.

Suicide is not some grave sin and there is no God watching over us. It'd help to realize some folks get dealt a hand they don't want to play out to the bitter end. The stigma around somebody choosing to act as they see fit, including suicide, really needs to be released. Not so much for the folks who go through with it, but for those around them, that feel guilt, shame and all kinds of negative emotions as a result.

I do wonder if normalizing suicide as an option would cause exploitation based systems to implode. Imagine those miserable sweatshop workers. If they said you know what - I'd rather die than live like this, they'd actually have leverage to significantly improve their living conditions.

Great television programme, in Dutch, about using ketamine in the treatment of depression (and additionally, about using GHB in the treatment of narcolepsy): https://www.npostart.nl/dokters-van-morgen/30-10-2018/AT_210...

As a long-term treatment it's being considered as an alternative to electroconvulsive therapy, not SSRIs. It is still a dangerous drug with potential side effects, but that power to harm is exactly what doctors are exploiting to help.

For deeper dives into mechanisms, Mayo is doing interesting research into the biomarkers for ketamine responsive versus non-responsive patients: https://www.mayoclinic.org/medical-professionals/psychiatry-...

I remember covering this topic in a poster presentation at medical school. It's a perennial news article that, despite popping up on an annual basis, is always presented as a crazy new idea.

The fact that ketamine is a street drug makes it a prime topic for click-bait articles. It's a case of the usual bad science in media.

NYT is no better a source to cite for medical topics than the Daily Mail is for Computer Science!

IBT non-synthetic mescaline would prove to be a better choice. Medicinal on this continent for a thousand years.

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