The problem with ketamine and suicidality studies is that suicides - thankfully don’t happen very often - so we have no direct evidence that ketamine prevents suicides. Of course if it would only alleviate suffering and wouldn’t increase the rate of suicides, that would be a win too.
0.5 mg/kg intravenous. For frame of reference, a small recreational dose is between 5-25 mg (insufflated[0]), and a larger recreational dose (for people targeting a "k-hole") is more like 50-100mg. For clinical depression (ie, not this study, but for a similar purpose), the fixed dose is 84mg (not weight-based).
So assuming a 75kg individual, that would be a 37.5mg intravenous dose, which is definitely going to provide a noticeable effect for any ketamine-naive user (ie, someone who does not already have a tolerance for the drug from recent prior use).
> The problem with ketamine and suicidality studies is that suicides - thankfully don’t happen very often - so we have no direct evidence that ketamine prevents suicides.
That's not really a problem - suicidal ideation is a strong enough predictor for suicidality and mental health that it's common to use as a biomarker. In other words, nearly anything that reduces suicidal ideation is presumed to reduce suicidality (on a large scale) - it's not necessary to wait months or years to see what happens (and in fact, depending on the specifics of the study, it can be considered unethical to do so).
Source: former clinical researcher and drug counselor
[0] bioavailability when insufflated is significantly less than other means of ingestion
About the first point, I still disagree with the parent comment. The standard 0,5mg/kg ketamine is given under 40 minutes. I've seen two patients receive it. The room was dimly lit, silent and peaceful, as to not induce or exacerbate any possible dissociative or hallucinative side effects. The patients didn't report any side effects at first and later reported a little sedation. I wouldn't be a able to tell with certainty if they had received a placebo or ketamine, and certainly not within minutes.
Source: psychiatrist in training
Edit: I still think we need hard data about anti-suicide effect and not just surrogate markers. Variability in suicidal ideation is suggested to be a predictor of suicide attempts [1]. If ketamine first gets someone better and later on they relapse, they could, in theory, be at increased risk for suicide. More long term data is also needed about it's long term effects. Note that I do think it's a good thing that ketamine is becoming more available! I will continue to suggest it for e.g. patients with treatment resistant and severe depression.
[1] https://www.sciencedirect.com/science/article/abs/pii/S01650...
And I'm not drug naive by a very long shot. On my 2nd infusion there was an older gentleman across the hall from me who had never had anything stronger than scotch whiskey. He was not having a good time at all.
7 days falling in and out of the K-hole while hallucinating is not as much fun as it sounds.
.5 mg/kg
I was numb all over, my lips tongue and throat were numb.
I melted in to the chair and felt like I was up down and sideways at the same time.
You would not be able to tell immediately but I put on my blindfold within 7 minutes due to effects starting.
You certainly notice the effects of IV K. So do other people when you start to talk to a hairbrush. It's a bit draining after a few days though, and not terribly fun.
How numb does it make you. My mouth and throat being numb was very surprising.
However, I have no idea how other sedations feel, so who knows if they are a good placebo. Could be.
A friend of mine did it last week and he described it as the most intense experience of his life. He’s 40 and he has experience with other drugs.
I think possibly you don’t know what you’re talking about?
A lot of people take amphetamines as a medically prescribed treatment for ADHD (and other conditions such as narcolepsy too). A lot of people take amphetamines recreationally. Studies done on the negative heath consequences for recreational users are largely irrelevant to medically prescribed users, because your average recreational dose is an order of magnitude (or more) higher than the average prescribed dose. Increase the dose ten-told, it acts like a different drug altogether.
Plus, the irregular dosing schedule of recreational users probably isn’t helping either. And many recreational users try to get the drug into their bloodstream as fast as possible (injection, snorting, smoking), while most prescription drugs aim to be released more gradually (oral route, sometimes even extended release or an inactive prodrug such as Vyvanse/lisdexamfetamine)
What you're saying applies in other cases, but in the case of ketamine, the recreational dose is one or two orders of magnitude lower than the clinical dose.
It was more intense and less intense at the same time because I did not know what to expect.
At home treatments with sublingual trockies have much less side affects, but differently still noticeable. Nasal spray is the weakest with just some minor body numbing.
this is not part of the definition of double blind. There maybe drug effects and there may be placebo effects. If you don't know and the person administering it doesn't know, then the effects you report or measure are what is being studied over the group of people in the study.
> 3. Within minutes it would become obvious to everyone in the room if the patient was injected with salt water or ketamine.
also not part of the definition of double blind.
[Edited to clarify.]
At 0.5mg/kg intravenous, there's no way that people wouldn't feel anything. It's not necessarily a "drug trip", but pretty much anybody can tell the difference between that large of a dose of ketamine vs. a saline solution.
For trials in cases like this, it's common to use a group which receives either a smaller dose of the drug or a drug that is intended to mimic some of the subjectively observable side effects.
I do not know what a trip is or is not supposed to be like but it was a very wild sensation.
It's common for those wordings to be used because often it literally is a handing over of drugs you're talking about - with sickness you're more likely to talk about the moment a medical person said to start using a drug than to tell people about the actual use because it's usually more interesting.
> 3. Within minutes it would become obvious to everyone in the room if the patient was injected with salt water or ketamine.
I think you’re mistaking IV infusion for injection. The dose is given slowly over 40 minutes, not as a rapid injection. The patient would barely have any of the drug in their system in the first few minutes. Given the short duration of action, it wouldn’t produce peak levels anywhere near what recreational users experience.
In the sessions I had with IV ketamine, it is very, very noticeable and fairly trippy. The eye mask and the music certainly help, but the ketamine is inducing some crazy sensations.
I don’t remember the exact dosages I received, but I remember it being in line with what I saw others reporting online from their experiences at a clinic.
I read it as the nurse preparing the IV's knew if it was a placebo, it doesn't really say that the same nurse administered the IV's.
For orally dosed RCTs, often the pill making process is the way the blinding is done -- i.e. they're either in brightly-coloured gelcaps or a film or sugar coating. If it is a double-blind RCT it must be double blind. All of this will have been explicitly examined in the ethics statement for a trial and very, very prescriptively laid out.
Can't you achieve all of those by having someone else create the bag and then label it for the patient. The "right medication" is the one they're receiving as part of the study.
It's not like what they need to do is different if it's ketamine or saline.
For that matter, a quick web search shows that at least some of the (injected) coronavirus vaccine trials were double blind. Seems like enough for someone in the next room to know if the maybe-ketamine injection is placebo, so they can unblind immediately in case of a bad reaction.
But I suspect that would take many years to get through the permitting apparatus, if it was at all possible.
The classic gold standard is to randomly assign subjects to groups. Then give one group a sugar pill, give the other group the treatment pill. Neither to patient, the person administering, or the person recording the results know who got the treatment who got the placebo. This is not possible with ketamine, psilocybin, MDMA, LSD, etc. That's fine, we can still build a strong body of experimental evidence of their efficacy. It bothers me when clearly non-blind non-mask experiments are labeled as double-blinded, which we see often in this body of research, this study included.
I'm not saying it's impossible to conduct good experiments on these substances. I'm saying that they require special considerations of internal validity and it's incorrect to call this study (iv ketamine vs iv saline water) double blind.
This really shouldn’t be labeled as double blind.
1.The nurse administering knew if it was placebo or active (for safety reasons).
2. It would immediately become obvious to the subject if they were injected with salt water or ketamine.
3. Within minutes it would become obvious to everyone in the room if the patient was injected with salt water or ketamine.
Some trails are impossible to be double blind. That’s okay, there are other ways to address concerns of internal validity. Pretending like this trail is double blind does not address any internal validity concerns, and only raises concerns about the researchers understanding of experimental design.