The weak science behind psychedelics
theatlantic.com
theatlantic.com
How we didn't see that normalizing business dealings with criminal enterprise and then selling diy testing kits at the pharmacy wasn't a good way to handle this is beyond me. We could have taken the hint that once they're legalized in 1-2 states the safety and quality across the US jumps for some unknown reason.
The state murdering someone because they were carrying around a plant is the antithesis of justice.
There's also something to be said for microdosing. It's still in the anecdotal phase afaik, but I found it very helpful for depression, anxiety and socializing.
There are extensive reports of heavy addictions being virtually vaporized through DMT. Obviously some measure of openness and desire to change is important, but I personally do not think the potential here is debatable.
I think the only reason these are grouped together is that ketamine is also seeing a renewed interest in research into microdosing as a depression remedy, but this seems to be mediated by a metabolite of ketamine and may be more of a direct remedy for a chemical imbalance than something like therapeutic trips. In other words, the grouping isn't psychopharmacological, but the zeitgeist of this moment in public perception of these drugs, which has been shaped by fifty-four years of the nonsensical logic of the prohibition enacted by the Controlled Substances Act in the US, some of the trappings of which have also been adopted by other nations, as often happens in a world where US policy has outsized influence both through trade and at gunpoint
Personally I'm skeptical of a lot of psychopharmacological interventions for complex disorders like clinical depression. SSRIs for example strike me as a series of remarkably irresponsible experiments with drugs that appear to permanently alter cognition on wide swaths of the population. I view psychadelics and possibly ketamine as not necessarily more effective overall, but far less dangerous in terms of unknown effects
But increased abuse and dependence was apparent from studies. The studies were manipulated by the Sacklers and when that wasn't enough they bribed the FDA to say that their drug was "believed to reduce the abuse liability."
The claim that a drug has some potential side effects simply has no bearing on the question of whether prohibition is good policy, because the case against prohibition isn't and has never been that any drug is completely risk-free or cures every disease or makes you shit rainbows or whatever nonsense, the claim is that adults should get to make those decisions for themselves
> Hallucinogen persisting perception disorder (HPPD) is a non-psychotic disorder in which a person experiences apparent lasting or persistent visual hallucinations or perceptual distortions after using drugs,[1] including but not limited to psychedelics, dissociatives, entactogens, tetrahydrocannabinol (THC), and SSRIs.[2][3] Despite being designated as a hallucinogen-specific disorder, the specific contributory role of psychedelic drugs is unknown.
https://en.wikipedia.org/wiki/Hallucinogen_persisting_percep...
So, from the get go the relation to psychedelics is pretty murky ?
Most hallucinogen users will experience some long-lasting effects, especially to their vision. The nature of it can vary. This can happen in only one use.
If by "precautions" you mean "restricting people's bodily autonomy and sending cops after people who don't comply", as is currently widespread policy, this is very clearly not very effective and either of the widespread direct harms caused by implementing these policies - not the least of which are the chilling effect they've had on basic research as well as a proliferation of erroneous psychopharmacological pseudoscience - and the obvious erosion of the fundamental right to self-determination and bodily autonomy would to me seem more than adequate to outweigh such a benefit even if it weren't a total fiction. Carceral prohibition is bad policy on principle and in practice
It came to my mind if we have equally solid research for the effectivity of drugs like antidepressants. They have fame of sometimes working and sometimes don't depending on the patient, and I guess the same could be said of many psychedelics.
I'm not at all against antidepressants, and I know several people who have been helped a lot by them. But if there are potential alternatives like ketamine and psychedelics that have lower risk of side effects (ketamine in particular is extremely safe taken in a therapeutic setting) and only need to be taken once to potentially see an immediate effect, even if the science is weak, shouldn't these at least be available for adults to try before putting them on antidepressants?
And my memory of reading up on this is that the current understanding of how ketamine works for treating depression is that it's something about the way the body processes & gets rid of the ketamine, it's not from the effects that the person taking it feels (unlike with psychedelics where it's the effects themselves that open up new neural pathways in the brain allowing therapy to potentially be more effective). And taking ketamine daily won't be more effective for treating depression. So I wouldn't expect many patients to go from the medical treatment to thinking "I want to start using this recreationally" (though if enough people get treated with it, of course a few people are bound to go down that path - but plenty of people already go down the path of choosing to use it for fun).
Empirical research is also research.
That said, I agree. We need more research, which would have happened a long time ago if it wasn't for criminalization.
The same could be said for almost any drug or intervention.
What is reproached to some of the parties here is to have a spiritual ideology, but that’s precisely what working with these medicines opens up. The healing that takes place is not so much physical, as it is psycho-spiritual, it’s the change in perception of the world - often in the direction of spiritual beliefs, that contributes to the betterment of the person’s mental health condition.
So you can’t isolate the two easily. It’s just tricky, and still this article raises important points.
But that's not the main way in which they are able to treat mental health problems, specifically not in the majority (I suspect all) actual scientific research on this subject, but also just for people using them outside medical trials.
The key thing, it seems, is that psychedelics temporarily (while you're under the influence) increase the connectivity between different neurons in the brain, and between different areas of the brain. That can help in two ways, the first of which is that some new connections can become not temporary, and keep existing for the foreseeable future. The other is that, while under the influence, those additional neuron connections allow the person to think in different ways than they normally do, to see ideas or problems from a different angle/perspective. And this difference is what allows the therapy administered at the same time as the psychedelic drug (or the self-therapy version of using a drug and then thinking about the subjects that are causing you distress in life) to potentially have a better chance of making a stronger change to how the person thinks about certain things than if the same therapy were provided without psychedelics enabling greater levels of rewiring of the brain.
Couldn’t it be that this is what’s being experienced as mystical?
And all the studies (that I'm aware of, at least) using psychedelics and therapy to treat mental health conditions don't use doses high enough for the kind of trips they can create those experiences - the goal is to have a strong enough effect that the brain and its thought patterns are more malleable than usual, but not so strong that the patient focussed on the trip rather than on the talking therapy.
It's definitely possible a patient could walk away from a session so impressed with its effectiveness that they describe it as magical, or even mystical meaning that it worked and they can't understand how it worked, but that's not at all what psychedelic users normally mean when using those terms.
edit: Actually, it's worth mentioning that there are other non-Western cultures using psychedelics to treat mental health issues, such as Ayahuasca ceremonies in various South American countries. I don't really know enough about these to talk about them in any detail, but I do know it's common for the people to take strong enough doses of Ayahuasca to have full, intense trips, and while I think there usually is a leader of the group who probably does some sort of conversations to help people with their trips, it's not like Western countries' talking therapy, and I suspect it's likely that some, maybe m many, people who find benefit from that sort of psychedelic experience are indeed getting it from what they experienced, thought, and felt, while tripping.
South America is non-western culture now? Lmao ok. Also, practically nobody uses Ayahuasca to treat mental health issues over here. That kinda thing is an extremely niche and small practice of usually affluent people. Ayahuasca retreats are super expensive and half of the people you see there are rich Americans looking for some anecdata to share in sites like this. Everyone else is using standard medicine and therapy.
I do however believe there are various cultures that do use ayahuasca unrelated to the sort of expensive retreats Americans might travel to.
And you're right that Western / non-Western was a poor way of explaining what I meant, but I'm not sure if there's a widely accepted good phrasing for what I meant which was really "countries or communities within countries whose cultures, including in healthcare, are more significantly unlike the cultures in Western Europe & North America than the cultural differences between countries & states within NA+EU".
In hindsight I probably should have just said "I believe there are completely different styles of psychedelic use for mental health such as with Ayahuasca but I don't know enough to say more about that"!
I think you’re misinformed on this. Most modern psychedelic research is not focused on actively participating in therapy during the psychedelic experience itself. Typical doses used in trials are actually very large — verging on a “heroic dose” in some cases. E.g. see: https://bigthink.com/series/the-big-think-interview/psychede...
“My therapeutic research with psychedelics is primarily used 'psilocybin,' which is the agent in magic mushrooms. The dose we now give to patients is anywhere from 30 milligrams to 40 milligrams, which Terence McKenna, who's the famous psychedelic bard would refer to repeatedly as the "heroic dose."
I'm sceptical of your claim that "MOST (emphasis mine) modern psychedelic research is not focused on actively participating in therapy during the psychedelic experience"
I don't have time to look into what the split between the two approaches is now days, but it's an interesting enough question that I'll definitely find some time to get my knowledge caught up in the near future. Almost certainly not fast enough for this HN thread to still be alive by the time I have, but I'll reply to you if/when I'm able to either agree that you were right or explain why wrong, in case you're interested and in case you notice when someone replies to an older comment or yours (which can be achieved with the handy HN Replies, built by a longtime HN reader, which I personally think is a great tool filling a gap that HN should have had as a default feature - https://www.hnreplies.com/ )
E.g. https://www.sciencedirect.com/science/article/pii/S0924977X2...
These drugs are generally much less addictive than alcohol, nicotine, opiates, and amphentamines, drugs which are considered to have medical uses of some sort and are not criminalized as energetically as the psychedelics, which is a bit odd.
I suppose if you want an orderly obedient population not given to asking difficult questions of the established authoritarians (such as 'why are we paying you taxes that you use to live in a big mansion with lots of servants'), then you might be concerned about psychedelic use for reasons having nothing to do with medicine. You might be afraid of losing control, of random ideas popping up and spreading through the population, a questioning of long-established social norms, etc. I really wonder if that's where the control freak hysteria on this topic comes from.
For example, it opens by claiming No psychiatric treatment has attracted quite as much cash and hype as psychedelics have in the past decade - really?? Nobody would seriously believe that, of the entire pharmaceutical world, the largest $ slice goes to psychedelic research. Not even close.
Or, Suggesting that people should get off proven medications in order to try MDMA or psilocybin is dangerous unless those drugs are backed by airtight evidence - this is an arguable claim, in the wording semantics, because it implies that it's standard for regulated medications to be risk-free, "airtight" idealisms with only good possible outcomes, when the reality is quite far from that! - a % of SSRI patients routinely experience seriously unpleasant or debilitating side effects and withdrawal ordeals. To exclude effective treatments by way of special, higher ethical barriers to entry is not necessarily scientifically sound practice.
That’s not what it said though. It said “no psychiatric treatment”. I’m a little behind on the antipsychotic pipeline but I’m not sure the statement as written - past decade, psychiatric - is too far off the mark.
Journalism is really a type of opinion piece, social lubricant in 2024. The purpose is so you and I have something to talk about and connect when we would not have other wise.
Did either of us learn anything? Of course not but only an idiot would expect to learn anything based on the title.
If I want to learn something I will just browse arXiv myself.
I seriously doubt there are any researchers that believe injecting someone with ketamine 27 times in a week is a good idea. The reality is people were profiteering from a vulnerable person, using fraudulent prescriptions [1].
I agree the science is weak, but it is promising [2]. Let's be more specific and avoid emotional language like in this article.
[1] https://edition.cnn.com/2024/08/20/us/matthew-perry-death-5-... [2] https://pubmed.ncbi.nlm.nih.gov/39106989/
The opioid epidemic helped erode away ethics in medicine, as many physicians partnered with drug-dealers/Sackler-family to exploit users knowing full well the "medication" had serious side-effects.
As I watch the squirrels getting high on the poisonous mushrooms, and howling at a passersby in the yard this time of year... it reminds one that the methodology of self-harm is an irrelevant detail.
Drug addicts have an endless supply of excuses why they think their behavior is justified. Indeed, there are an ecosystem of unethical people willing to help them along the wrong path.
I don't think people should go to jail for seeking an artificial cathartic experience, but rather be forced to join the Native shamans in a 2 week Datura fueled experience. However, facing insanity while hallucinating and rolling in your own excrement naked for 2 weeks is not popular for some reason... =3
The problem with saying this is that being high simply isn't a single thing. It’s a huge spectrum of experiences done for different reasons.
My experience with psychedelics is that they are extremely fun. Sure, it’s escapism - in the same way a funfair or a film is escapism. That doesn’t make it immoral. It’s not even clear that it’s self harm - certainly no more than horse riding is a form of self harm (statistically speaking).
Yes and no. He was being dosed under the supervision of a doctor, but he acquired the "extras" from some other people who saw him as an easy, vulnerable mark who would pay them a lot for it.
> That makes it an example of the kinds of abuse/misuse we could expect more of if these things become more widespread, if nothing else.
Sure, and that's something to consider, but I don't think we should stop testing things that could be lifesavers for some people because they can be misused.
If that's how we're going to do it, we need to go back to prohibition and just ban everything, including alcohol and tobacco. That certainly worked out well the last time we tried it...
Perry also didn't die of an overdose in the "traditional" sense: the large amount of ketamine in his system acted as a sedative and he drowned. If he hadn't gone in the water, he probably would not have died that day.
The integrity of most drug research is compromised by commercial incentive. Molecules like psilocybin, MDMA, and DMT can’t be patented. I am more skeptical of commercial evangelism than whatever is currently going on with psychedelic research.
The Atlantic is clickbait for the professional-managerial class.
The irony is when you're under the influence of psychedelics, "weak science" is the least likeliest thought you'll have.
We know psychedelics change perception and mood significantly. That should be the starting point. I'm surprised anyone bothers with placebos. Lab coats and data analysis only gets you so far. Leary was right, set and setting is crucial. We come from a 'billion years of evolution', and the idea is to reflect on your own humanity and consciousness. If you attempt that within a 4 walled room, you're asking for trouble.
Temporary loss of ego is a whole topic that needs to be part of the learning. Big doses push perception outside yourself. That effect alone is beneficial, if unsettling. If in doubt, avoid. Climbing a mountain or going on epic multi-day adventure in nature is healthier anyway if you have the opportunity.
I am someone who has suffered bouts of depression, sometimes severe with consistent thoughts of suicide, since I was a child. I had been in therapy for over a decade (which was immensely helpful for me), and I had tried a couple different antidepressants. This spring, partially due to some particularly bad sleep issues, I had an unusually bad bout of depression where I was borderline non-functional. As a "last ditch" effort I went in for ketamine infusion therapy at a clinic. Before the therapy they have you take a "depression assessment" questionnaire, the PHQ-9. The scores range from 0 to 27, and I went in as a 25 (basically, ready to jump off a bridge).
Without exaggeration, my initial ketamine session, which lasted about 2 hours, was the most profound experience of my life, and I firmly believe it saved my life. Not only that, it completely changed my understanding of my mental illness. Mental illness is hard to separate from your vision of "you", because if you, say, break your arm, nobody considers you a different person, but your mind is really what people most consider to be "you" - when it's broken, it's hard to not feel like you are broken. With my depression, the best way I could explain it is not just that things that used to make me happy no longer did, not even that I could no longer feel joy, but that I couldn't remember what joy itself actually felt like. When you can't even remember what the emotion of happiness feels like, existence feels pretty bleak.
What ketamine did for me is essentially "broke the damn", and I felt an enormous rush of actually being able to feel emotions again. The analogy I like to use is that my depression was like "brain atherosclerosis", i.e. my emotional channels were "clogged", and the ketamine therapy was like "brain angioplasty" - it felt like it broke up all the "clot" in my brain so that my neurons could talk to each other again and I could feel. It was the first time I actually understood my mental illness as a physical disease. At the end of my session I was literally balling for like 30 mins just because the flood of emotions felt so intense.
The next morning I was singing in the shower, and a couple days later when I retook the PHQ-9 I was a 3. It's been about 9 months since my first session, and while I don't always feel as awesome as I did right after it, I do feel like my completely changed view of my depression has made me much more resilient, and also much more willing to ask for help. In my initial series I had 4 sessions spaced over about 3 weeks (the recommendation for an initial series is 6, but for me after the 4th one I was like "no, I'm totally good" - I didn't want to "get used to" the ketamine trip because it was such a powerful experience for me). I had one "booster" session of ketamine about 3 months ago when I was feeling not great, and it was very helpful.
Now, I know that I was extremely lucky - my shrink calls me a "ketamine responder". The problem with depression is that it's not a disease, it's a symptom, and since doctors don't often know the underlying cause, a lot of the treatment is just "throw things at it and see what works". I have a friend that got very little depression release from ketamine, but TMS (transcranial magnetic stimulation) was what was helpful for him. So I'm very, very wary of ketamine getting oversold as a "wonder cure" - it may work for some people, but not others, and I've already seen how CBD and marijuana shops have popped up all over basically planning to cure every symptom under the sun since marijuana was legalized.
At the same time, I'm also wary of psychedelics being dismissed in a similar way to how they were dismissed and demonized about 50-60 years ago. I fully understand that the plural of anecdotes is not data, but I'm also not trying to find the statistically significant treatment for your average person - I'm just trying to not die. For me, I have all the evidence I need, and I feel it would be a tragedy to take away that option for other people before we know more.
I know, from repeated personal experience, that psychedelics (or mushrooms at least) can be highly effective against even severe depression.
They have been the single most effective anti-depressant that I have ever taken.
Now, I haven't had the depression curing wonder of an experience that some people claim;
It never pulled me out right out of it - but it pulled me back from suicide (on multiple occasions) and a single (rather large) dose is effective for 3 or 4 months before I find myself spiraling back down.
And if we're gonna have a conversation about anti-depressants that are being used despite scant evidence in their favour, perhaps we should start with SSRIs - which not only made my depression worse, but also left me almost asexual for ~20 years.
I write in only to say that I’ve taken MDMA under the guidance of a specialist, who had MAPS training and a lot of experience. MDMA is typically not considered to be a psychedelic, but it’s in-family with psychedelic therapy.
Two sessions, separated by about 6 months, helped me to see many relationships in my life in a new way. There was intention setting beforehand, and notes taken during session, and integration afterwards. All that seemed very important to the process.
Interested people could check out Julie Holland’s book on Ecstacy, or Rachel Nuwer’s book I feel love, or of course Michael Pollan’s wonderful book How to change your mind.
However, eating a piece of chocolate also makes you feel good. Doesn't mean chocolate is an effective treatment for depression. Whether psychedelics are effective treatments for various psychological conditions, I don't know. Whether the risks outweigh the benefits, I don't know.
I've grown more conservative about drug use over the past few years. I hope we keep up the research but it is very clear that -- as the article argues -- these drugs have been overhyped.
Sadly, hen and hens family desperately need help.
English needs a gender neutral pronoun because, imo, the gender of the pronoun person is almost never relevant (as in this case).
Being true to my culture, I felt it appropriate to appropriate it from another language.
How would you feel if the tables were reversed and you were being pushed into tripping instead of therapy?
These are the kinds of choices that we have to learn to respect, for all of us, which means less judging.
There may be other ways to help if that's really what you want to do.
But it would be wiser to base it on empathy and understanding than ego.
Agreed, but you need to keep it on a leash, or it will ruin your life.
I know more about the situation and you do, the person question is a relative I care for deeply.
I’ve only seen the opposite. I won’t touch them because my brain is poison, but the people I know who have, they are all in legitimately better places, and this is without regular redosing.
They try quite heavily to sell me in the idea of these things, but again, I know they just are not for me and my brain.
By whom?
(Replying to the comment that you made before completely rewriting it.)
You're completely wrong about the sugar pill (or at least whether or not it matters) - it's one of the issues with psychedelic medicines: there's no viable placebo at higher doses, and it's the higher doses that seem to have the deepest and longest lasting impact on depression.
Most people certainly aren't capable of having the same kind of experience without the substance, goes for all of the ones I mentioned and more.
And while we haven't been able to do the amount of science one could wish for, because of criminalization; there's plenty of experience out there and enough science to understand how the drugs deliver their effect.
Using psychedelics to improve anything (except maybe some forms of art) seems to me like when writers would drink to help them write. There's never going to be any rigorous evidence for any benefit.