> They gave volunteers ketamine while they were under general anesthesia, theoretically preventing the participants from going on a trip.
Maybe it's the trip that helps.
Maybe it's the trip that helps.
"Future studies of novel antidepressants with acute psychoactive effects should make stronger efforts to mask treatment assignment to minimize the effects of subject-expectancy bias."
Instead of pondering if their method is at fault for their negative result, the conclusion is to double down and working even harder at masking the effects.
That line just says people should do better at this in future to get more accurate results. It's not a statement about the ultimate form the treatment should take.
I believe benzodiazepines have also been tried as an active placebo but I don't remember what the results were.
No idea about deliriants like atropine/scopolamine, but in low doses, they were traditionally used to spice up beer (hence Pilsen named for Bilsenkraut, black henbane), so I could imagine short antidepressant effect there too.
It does, and this observation led to the development of dedicated antidepressant drugs. There are several such cases where interesting side effects turned out to open a world of possibilities, including an anti-TB drug that also led to antidepressants, and of course Viagra.
"find something that has a similar trip but does nothing" is actually equivalent to the original problem.
But it's also doubling down on the assumption that the subjective effects aren't the source of the benefit.
'Schenberg points out that people often report dreamlike and visual, auditory, and affective experiences under anesthesia. “Maybe people who had dreamlike experiences during the anesthesia had more improvement than the people who didn’t,” he says.'
So maybe the trip does indeed help, but evidently it is not necessary to be able to remember if you had one to get the reported benefits.
A common example would be ADHD stimulants, where the early stimulating and mood-boosting effects disappear over time while the concentration-enhancing effects mostly remain. This leads a lot of patients to assume the medication isn’t working because it doesn’t feel like those first few doses, which can lead to discontinuation or abuse.
Ketamine has a similar story arc. The antidepressant effect doesn’t require full blown dissociation, but so many headlines and fame-seeking authors have hyped it as “psychedelic medicine” that some patients assume it isn’t working until they disassociate/hallucinate. This can create a sort of nocebo effect where patients may actually be improving but they think they’re not because they didn’t have the wild hallucinations they read about in some exaggerated internet article.
I think a possible reason why medical research prefers a pill that works forever for continued use is that if you buy something cheap twice in your life and it fixes whatever needs fixing the pharma industry can't make money off of you the same way they can put you on antidepressants for life. I'm not in the medical field so I'm just speaking out of my ass based on personal anecdotes though.
Perhaps if you are looking for something profound or want a change of mindset, psychedelics might be able to help you reach it - similar to how shamans used psychedelics to talk to their gods or whatever - but if you're just looking to have fun that's what you'll get
Anyway if you take drugs to party and then go to a party, you'll party. If you take drugs and do therapy you'll do therapy. If you take drugs just to see what happens and you're open to whatever happens, things will happen. Maybe you'll just have an oddly memorable time and you ponder what it means, slowly altering how you think about other things for the rest of your life.
Drug discovery is difficult enough that the pharma companies don't have the ability to make a meaningful choice between fix-once-and-you're-set-for-life versus manage-symptoms-forever.
How do you test a medication that only needs to be taken once or twice? This is very challenging to study scientifically.
Psychedelics bridge the gap between medication and therapy. A trip is not guaranteed to be therapeutic, but a trip with proper guidance it's more likely to be.
How can we know which aspects of that guidance are useful, and which are superfluous?
It's going to take a lot of work to get to the level of certainty that our medical system expects for medication.
Most vaccines you only take once, you can still test if they work or not. Same with poison antidotes and things like that. Like I said, I'm not a doctor, but the fact that it's only once doesn't seem like the problem.
How do you measure depression? How do you know what changed it, or how much?
How are you quantifying "frequently"? Does that necessarily mean that the recreational effects cannot themselves be therapeutic?
After some time, the novelty of the experience wears off, and you start to get more familiar with the limitations of medication. That's disappointing. Disappointment feels bad. Again, this is not caused by the drug itself, but by the surrounding experience.
ADHD itself is riddled with secondary experiences: they make up the name itself! People with ADHD do not struggle to pay attention, we struggle to direct it. Hypoactivity is a reaction to living without enough simulation. Neither is a direct symptom of the disorder, but they are ubiquitous enough to
People who live with undiagnosed/untreated ADHD are likely to end up with a lot of trauma. That trauma is unaffected by medication.
So if you start taking ADHD medication, you need to know what it does and doesn't help with. Medication can't make up the entirety of treatment, just like cognitive behavioral therapy can't replace medication.
I'm not sure, isn't that kind of what's being shown by this study? Or like, is there levels of disassociation that you're distinguishing between? Are you able to enumerate those levels for those of us who are unfamiliar with disassociation?
Unfortunately, this means that the standard way of doing medicine research, with control group and placebo, is unlikely to ever be applicable to this area of research, and that a new epistemiology of medical research has to be developped for it. I find it super interesting.
(side note: if the idea of meditation as active engagement with "ways of looking" is intriguing you, I highly recommend looking up the teachings of Rob Burbea)
One of the people using it said it basically had cured her self-perception issues; she had been bullied for her looks as a child and internalized that she was ugly. But as an adult when she saw her younger face in the app, she realized immediately how the characterization of that face as ugly was just the perception of child bullies.
And it wasn't something that photographs could do for her -- it was the fact that it was her younger face superimposed on her current body, and that it was moving as she moved which gave her a new "way of looking" as you put it. In a sense, AI gave her a chemical-free trip.
To start with the negative:
She's basically fooling herself. She's avoiding the real problem of "not accepting herself for who she is, abd changing what can be changed"
IMO, The filtr only shows her a big lie, merely suppressing the pain, and not helping solve the real psychological problem.
On the positive hand, the filter allowed her to break a deeply-ingrained false belief about he past, which helps with one's healing journey.
The question is: does she believe her current looks are pretty?
It isn't a sure-fire cure, but apparently it offers enough relief to enough sufferers.
https://mirrortherapy.com/how-does-mirror-therapy-relieve-ph...
The trip is (also) the chemistry!
They are not looking at creating a "trippy" experience per se, but rather to generate an experience that produces a potential shift in the way to relate with the world
Or if you don't count oxygen as a drug: Breathwork (Holotropic Breathwork, Quantum Light Breathing, Shamanic Breathing, Rebirthing, etc.).
Never tried but I heard that multi-day retreats in complete darkness can also induce some kind of (visual) trips.
One of the core concepts of Rob Burbea I mentionned above is the idea of "imaginal middle way", which, in short, consists in seeing mental images as "neither real nor not real", "simultanously discovered and created". Going deeper into that topic would require way too much text and time for a simple comment here, but I can tell from experience that this way to engage with imaginative faculties can have deep and long lasting effects. And the important aspect here is that, while engaging with the image, one is constantly balancing between reification (considereing the image, for instance of a divinity, as having independent reality) and disdain (considering the image as "just made up").
The "chemistry" side of the debate would be that the trip is a side effect of the substance modifying neurological pathways (or similar), but what is actually important are those physical modifications to the brain, not the experience.
The "trip" side of the debate would be that the only important thing is the experience, and that whether it is induced by drugs, fasting, meditation, prayer, video games, etc. does not matter that much.
Obviously, there is also the possibility that both sides are valid: the fact that the experience can be transformative in itself does not prevent the physical effect of the molecule on the brain to be beneficial as well. There is even the possibility that one of the two has a positive effect, while the other is rather negative.
Thank you! Yes, the trip is caused by activation of the HTR2A receptor. It is not magic. everything you experience is both affected by and affects the biology of the body.
You know, I have a fried, diagnosed with depression 15 years ago, tried everything, nothing worked. Know what they finally found her problem was? Familial (genetically caused) hypoglycemia.
We cannot even diagnose depression, it is still too subjective nad personalized. Stop looking for these one size fits all miracle cures and look at your own body.
(FYI, you mean to use the word “propel” in place of “propulse” above… they aren’t synonymous, surprisingly.)
On one side it showed me (after a long time) how you can be very empathic for all people around you and also reminded me or showed me how really good happiness feels.
And while the effects lasted a little bit for 1-2 weeks, it also is something I know I could do again if I like to.
This definitely gave me an additional/new viewpoint.
In this trial, there was a 50% response rate and 40% remission [1], whereas in a meta-analysis of previous unblinded trials there was 40% response and 30% remission [2].
[1] https://www.medrxiv.org/content/10.1101/2023.04.28.23289210v... [2] https://pubmed.ncbi.nlm.nih.gov/35688035/
So it's not that this trial wasn't effective, just that the placebo effect is very effective, and it likely resulted in the improvements seen.
[1] https://www.theonion.com/study-dolphins-not-so-intelligent-o...
This is such a stupid study, I hope they didn't anesthetize people just to study this
Why not? Apart from potential side effects of anesthesia, this sounds like a great study to find the mechanism of ketamine helping depression.
Bingo. If they were going to study the effects of some drug on amputees, it would be better if they didn't amputate limbs to test it. People don't have a good understanding of the damage from general anesthesia, so it's probably easier to get them to agree to do this study (and therefore perhaps easier/cheaper than selecting people already undergoing general anesthesia, and coordinating with the anesthesiologist and controlling for confounding factors like why they're being anesthetised in the first place)
But ethically, it would be much better if they didn't put people under to perform a stupid study on them, since it is damaging to the people getting anesthetized.
It can produce some sensory distortions, but anyone who is going into a full “k hole” is almost certainly taking too much. It’s not a case of more is better.
https://slatestarcodex.com/2019/03/11/ketamine-now-by-prescr...
The notion that the trip is the therapeutic element seems oddly frightening or threatening to a lot of people.
… Or at least it’s not what they’re looking for. The quest is for a pill that works deterministically without any need to involve consciousness.
Part of it comes down to overall scientific responsibility and being careful about defining the scope of the claims and conclusions. I haven't seen the final paper here, but if the Conclusions section says "This research indicates that ketamine given while patients are already sedated with general anesthesia doesn't not appear to provide a benefit for patients suffering from depression." then that's great.
If their Conclusions section says "By isolating ketamine-the-substance from the ketamine trip by administering the substance while the patient is under general anesthesia, this work demonstrates that there is nothing inherently anti-depressant about ketamine and that ketamine treatment for anti-depression is no better than placebo.", that's going to potentially have a huge ripple effect.
Throughout this thread there's a fair bit of discussion about "the trip is the treatment". The first conclusion leaves a number of other lines of inquiry open for exploration. The second conclusion opens the door for funding agencies and physicians to put an end to additional research and terminating treatments that are potentially effective.
Scientific communication absolutely must be very careful with the breadth of the claims and state them loudly and explicitly. While journal and conference proceedings have historically been generally only consumed by other practitioners of a field, now that everything is online and accessible to the general public there is definitely an increased burden for clear communication with explicit, conservative, narrow unless otherwise warranted conclusions.
The result of years of "altered state of mind" anti-drug propaganda. There is a significant perception that "altering your state of mind" is immoral (even though we do that every day, all day, and in fact even some foods can "alter your state of mind"). If cannabis could actually cure cancer just by smoking it, there are some people who would respond "well now we need to take the 'high' out of it, because getting 'high' is wrong". These type of people would never accept that the "high" might be the actual mechanism of psychological action, especially with psychedelics and dissociatives, where the user probably won't be able to interact with what passes for objective reality.
For example, DMT is very useful for, among other things, learning more about life and death. If the beliefs are correct, and DMT is released in the brain at the point of death, then DMT itself could be good preparation for the weirdness that happens at and before death (like Alzheimer's or dementia). Taking the "trip" out of DMT would make it completely useless.
This is probably a straw man. The immoral part comes from some percentage of the trippers ending up doing things like climbing naked up power lines to steal the copper for future trips.
It's a question of whether society should tolerate the % damage that occurs versus the % high it gives those not participating in the damage.
You're committing the same error people did when they declared cannabis and LSD as scheduled 1 drugs in the same category as heroin.
By this line of thinking might as well avoid taking aspirine, because sounds like ketamine and is also a drug.
Climbing power lines, lmfao.