"The tool, called mediKanren, scanned millions of biomedical abstracts hunting for relationships between existing compounds and the gene involved in the disease."
Is this AI or someone put the effort into compiling a database and added automatic search function?
Isn't that all AI is in its current state? Just like computer chess. It knows the moves, and can calculate possibles and iterate through them way faster than a human. It's not like it is thinking for itself saying, what happens if I try this. The devs of the AI point it in a direction, and it sorts through things much more deeply and faster than humans.
All of that is great when we get useable information or even when it exhausts all options to no positive result. It's just another tool to find out answers. The term AI is used waaaay too broadly.
That was the state of AI in the 90's. AlphaGo Zero and AlphaZero have shown that it does not need to search exhaustively when it can search intelligently using reinforcement learning. The 'direction' is something the system learns and is not given by the devs.
Take out 'exhaustively', though, and everything parent comment said is correct. AI is just (big data + statistical inference) implemented in massively parallel ways using linear algebra.
"just" is always a weird modifier in these kinds of conversations. Most things can be reduced to "just" some basic operation(s). What is amazing is the complexity that emerges from those simple operations at scale.
Granted that emergent behaviors are important. The reason for injecting "just" is to counter the AI hype. Imagine if the headline read "With a nudge from linear algebra, ketamine emerges as a potential rare disease treatment". Dropping the word AI in there, in addition to boosting the articles SEO, will suggest to those with a casual interest that his must be a big deal, because "I've heard so much about how AI is solving <insert big problem here>"
Well, if you dive into data science and ML, you'll see it is much more than just a bit of linear algebra. Some topics (and as a data engineer, I am not an expert):
- Distributed computing
- Feature selection
- Budgeting / accounting of experimental design (these TPU clusters are not cheap)
- ML architecture
- Involvement of domain experts (multidisciplinary teams)
- Storage
The whole list is much longer, but just some topics to think about. For me the term "AI", although overly broad, come to mean the engineering and organisation needed to pull these kind of projects.
I don't think that's automated meta analysis. It's meta research, which is not the same thing. Take a look at the MediKanren papers. This is logic programming and it's not based on statistics, but first order logic.
In fact, it's a kind of expert system. But in the 80's, expert systems didn't have access to that:
This is logic programming. So AI in the symbolic sense. And much better suited to medical 'AI' in the current state of medical information retrieval capability than most of the statistical crap that gets all the hype nowadays.
GitHub says it's mostly written in Scheme and Racket! Would love to hear the story behind that... is this just one researcher's idiosyncratic choice, or are these languages providing some kind of material advantage in this application?
(I'm aware that Lisps have a long history in AI but I understood that to be kind of in the past at this point...)
Scheme is the ideal language for something like MiniKanren, because of its 'almost-purely-functional' nature and its powerful macros. MiniKanren is all lambdas at its core with clever macros sprinkled on top.
And also, Dan Friedman, Matt Might and Will Byrd are VERY clever people. So much for people complaning nothing useful ever comes out of Racket!
I'm the researcher mentioned in the article. We used Racket in part because before we transitioned into academic medicine, Will Byrd and I were in academic computer science with a focus on programming languages. Will was building up miniKanren to do lots of cool stuff in program synthesis and program analysis. When we jumped over, it felt natural to bring the power of relational reasoning to knowledge graphs over biomedical knowledge, and so mediKanren was born.
Im a big fan of your work, Mr Might! I'm just an MD with a hobby interest in logic programming, but FWIW I think that you guys have really captured how to use current medical information, a thing that the statistical approach still cannot achieve.
Knowing nothing about miniKanren, I'm curious if you feel its essence much better expressed in a LISP than an Algol-like language like Python? And will relational reasoning increasingly require people to return to LISP as an AI language?
Another question - would it be possible to visualize the exact chain of reasoning used by mediKanren to link ketamine to this disease? It would be wonderful to see exactly what the tool brought to the table that human researchers missed.
miniKanren definitely exploits a lot of the syntactic dexterity of Scheme/Racket/Lisp to do some really cool things -- or at least to express them more succinctly.
Yes, it is always possible, in fact, since logical arguments can always be rendered as proof trees.
I am also a big fan of yours Prof Might!
I am very passionate about genomics and rare diseases and your contributions (code, writings, setting up the PMI, and all the others too numerous to list them all here) in this oft neglected area have been very motivating and inspiring to me .
Wish more software folks were aware of and work on these important problems at the intersection of biology and software
It feels like in the last few years I have been constantly hearing about new research showing “fun” drugs as cures to a wide array of medical conditions. There’s marijuana for chronic pain, mushrooms for depression, mdma for ptsd, and now ketamine. They are often talked about as if they have little or no harmful side effects. I’m glad we are moving away from the incredibly destructive drug policies that have been in place for so long but I fear the pendulum may be swinging too far the other way. The opioid epidemic was largely caused by the idea of them being non addictive being heavy pushed by the pharmaceuticals industry. Are we going to see similar harms from these drugs a few years after they gain more popularity? So far the evidence doesn’t show anything near this level of harm. I’m just skeptical of anything that seems too good to be true.
The idea of the pendulum swinging too far is a huge over-reaction. The pendulum has 40 years of swinging back to a "normal" state if you include the overprescribed industry of prescribing mood altering drugs to suburbanites, adderall, etc. Yes, the boomer and gen-x generations were raised in a lie: their doctors told them they could take drugs without side effects. However, this is now well known.
Ketamine seems to be a commonly used drug in emergencies because it's a safer anesthetic than propofol when you don't know specifics about the patient and can't determine dosage.
Ketamine is the world’s most commonly used anaesthetic, or at least it was as of some years ago.
It’s on the WHO’s list of 100 essential medicines because it’s one of the very rare anaesthetics that doesn’t depress the respiratory system, making it extremely safe by comparison with many others.
There are. Hypertension, arrhythmia, confusion, delirium... Mostly at anesthetic or at least pain killer dosage, though. Ketamine can in fact be a dangerous drug when you don't know what you're doing.
Cannabis, psilocybin, and LSD have been used recreationally for decades with death rates approaching zero and there have been 0 cases of overdose. I was under the impression that these drugs were made illegal because their use promotes an anti capitalism mindset (see Timothy Leary being called the most dangerous man because of his research on LSD) and the medical industrial complex isnt able to extract as much money from them. I’ve never heard that opioids where once known to be non-addictive. Weren’t the Opium Wars started because China wanted Britain to stop selling them addictive opium?
It’s fair to be skeptical, but the data is not there. Cannabis, MDMA, and ketamine all have high potential for addiction and the latter two potential for abuse but it is possible to find Ketamine clinics for safe administration. I’m not familiar if there is public MDMA treatment available.
>Weren’t the Opium Wars started because China wanted Britain to stop selling them addictive opium?
Yes and out of the opium wars I believe is why the state of Hong Kong came into existence. China had contractual obligations to buy opium, I believe they ended up dumping it into the bay in sort of a Tea Party type scenario but it was the Chinese government who did the dumping.
The opium wars are pretty damn fascinating. OH and if I'm not mistaken it was a contractual obligations with the East India Trading company and the British government backed the EITC by making a trade blockade.
Oxycodone was pitched as non-addicting. Opioids generally were pitched as non-addicting because they were by prescription, under control of doctors. That protection scheme obviously failed miserably.
Oxycodone was created by a pharmaceutical company and marketed in a way that would earn them a profit.
Marijuana and psilocybin have been around for literal ages with widespread use. LSD and ketamine are synthesized, but we have decades of experience with them.
Sorry to burst your bubble but U.S. drug policy is not as progressive as you might think. Cannabis is still illegal under federal law. And right now America is petitioning the WHO for a GLOBAL ban on KRATOM, a herb which has been used in Asia for hundreds of years with no recorded deaths. It has been in use in Europe and America for a couple of decades and still there are no deaths recorded from pure Kratom use. Kratom can be used to treat or replace alcohol, cocaine and opiate addiction. It is a herb harvested from the leaves of a tree related to the coffee plant and has incredible pain relieving properties, as well as being a mild stimulant and mood regulator. For more info see this recent study https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612999/
And please tell the FDA and WHO not to ban this awesome herb. The deadline for comments is August 9th. https://www.americankratom.org/
Thanks for pointing this out. I don’t know enough about kratom to have an opinion on how it should be regulated. I will add a comment though. Just because I am fundamentally opposed to America regulating drug use outside of its territory.
Kratom is fundamentally an opioid. It happens to be cheap and relatively safe (consumed by ingesting large quantities of plant matter, rather than injection or insufflation of some extremely potent compound). I think opioids are over-vilified in general, and I'm on the side of legalization, but kratom isn't magic.
I'm not familiar with that "awesome herb", so I wondered what other sources might have to say.
While the numbers are small (unsurprisingly, if it's not nearly as widely known and used as some other substances), it may not be quite as innocuous as you seem to imply:
> "A 2019 paper analyzing data from the National Poison Data System found that between 2011-2017 there were 11 deaths associated with kratom exposure. Nine of the 11 deaths reported in this study involved kratom plus other drugs and medicines, such as diphenhydramine (an antihistamine), alcohol, caffeine, benzodiazepines, fentanyl, and cocaine. Two deaths were reported following exposure from kratom alone with no other reported substances."
> "In 2017, the FDA identified at least 44 deaths related to kratom, with at least one case investigated as possible use of pure kratom."
Actually, even the study you linked has some disturbing statements:
> Deaths attributed to the use of Kratom have been reported in Europe and the United States but not in Southeast Asia.
> The increasing trend in Kratom consumption in the West has corresponded with an increase in reports of Kratom-related exposures to Poison Control Centers in the United States, care received at a health care facility due to Kratom consumption, and association with overdose fatalities.
> Kratom was identified as the cause of death by a medical examiner in 91 of the 152 Kratom-positive deaths, but was the only identified substance in just seven of these cases.
This is the most reefer madness comment I have ever seen on Hacker News. Seven possible deaths with just Kratom and this justifies banning it?
How many deaths and ruined lives will those enforcing a Kratom ban be responsible for? Perhaps we should consult the history of bans of other drugs to get some idea.
Anyone claiming that their reason for adding yet another substance to The Forever War on Drugs is harm reduction should be laughed out of the room at this point.
I reckon that, because the Covid vaccine has been responsible for at least ten blood clots we should also set up a global ban to ensure nobody ever gets to take it.
If you're going to label scientific papers you don't like as a "wall of FUD" [edit: I see you've decided to remove this remark], I'm not sure there's much we can discuss further.
I didn't say it should be banned. Or that it shouldn't. I don't know enough to form an opinion on the question.
I just wondered how balanced and objective the post from irthomasthomas was, did a quick search for other points of view, and felt it was worth offering some additional comments for consideration.
The person you were replying to said nothing about banning it. They simply said that a little poking around showed the previous poster's description of it as completely harmless was possibly contested. Your knee jerk reaction that asking questions about a drug is the same as demanding a ban on it reveals a pretty strong bias on your end.
It seems to support the harmless claim. Basically water, coffee, red meat, sunlight and so on are more dangerous than kratom if you look at similar numbers.
Please don’t glorify Kratom as some sort of miracle herb without downsides.
Kratom is an opioid, full stop. People are under the mistaken impression that it’s less addictive because it’s less potent on a per-gram basis, but addicts simply end up consuming more grams to get similar highs.
It’s not a “mood regulator” in any magical sense other than it’s an opioid and opioids temporarily put people in good moods.
There are many communities dedicated to quitting Kratom and handling Kratom withdrawal, which is the same as withdrawing from other opioids (For instance: https://www.reddit.com/r/quittingkratom/ ).
Whether or not you think Kratom should be legal, we shouldn’t be glorifying it as a harmless substance that somehow defies the realities of every other opioid.
opioids are a large class of drugs with widely varying effects and potential for abuse. for instance, the active ingredient in Imodium is an opioid, but you don't see a lot of recreational Imodium users.
kratom is certainly not a miracle herb, but its characteristics do make it a lot less addictive and lethal than its more popular relatives. it's not unreasonable to think it might be used in replacement therapy, similar to buprenorphine.
Using Imodium as an example really hurts your case here. Loperamide (Imodium's active ingredient) isn't used recreationally because it's not psychoactive - or more accurately, it doesn't cross the blood-brain barrier. Meanwhile, you'd be hard pressed to find an opioid which does (as kratom obviously does) that lacks recreational users.
Occasionally people with opioid addictions actually do use loperamide at high doses to stave off withdrawals. But it does not have the same effects as ones that cross the BBB, correct.
that's exactly my point. maybe it wasn't worded well. "X is an opioid" does not imply "X is an extremely dangerous drug with high potential for addiction". not all opioids have psychoactive effects. some (eg, buprenorphine) do have psychoactive effects that are generally considered unpleasant by users. it's a large class of drugs...
- kratom is certainly not a miracle herb, but its characteristics do make it a lot less addictive and lethal than its more popular relatives.
Yea, that's what you read online. But after going 2.5 months without sleep (I would doze off for half an hour once a twice per night), 4 months of acute depression, and umm like a year of PAWS, I beg to differ. If you're going off of personal experience, congrats, you didn't abuse it.
Someone already linked the quitting kratom subreddit where you can hear all kinds of horror stories.
Finally, comparing Kratom to traditional opiods isn't all that useful. Kratom has a shitload of other active alkaloids and very little research on their effects. Saying it's less addictive than other opiodis is like saying you'd rather get hit by a car going 60 vs 100.
Personally, I would have been much much better off if Kratom had been illegal, and I am amazed it still is.
I've only tried kratom a couple times, many years ago. I can see how someone like me could have a severe problem with it, but I didn't find it to be nearly as addictive (to me) as heroin. I knew someone, like you, who had withdrawal symptoms for a very long time after quitting. I've also known a couple of the mythical "chippers", who've used heroin/oxy/etc occasionally over the course of many years without becoming addicted.
humans can become addicted to pretty much anything that's enjoyable. some things are probably much more addictive than others, but you can't really create a strict ordering of addictive substances/activities when every individual responds differently. is kratom less addictive than heroin? I would guess yes. is it more addictive than alcohol? I don't know, probably yes for some, no for others.
Compared to opioids peddled by pharmaceutical companies (who are, no doubt, responsible for the US pushing to get kratom banned), kratom _IS_ a miracle drug.
Edit: also, I'll bite on the r/quittingkratom link. The first upvoted thread I see is the following: https://www.reddit.com/r/quittingkratom/comments/ozuh1r/krat.... 90 grams per day for 10 years is an absolutely staggering amount of kratom to consume. (For reference, I would feel sick if I ate more than 4 grams at a time, and never felt the need to exceed 5 gpd.) And this person didn't even skip work during withdrawals. They claim the worst part is restless legs and not being able to sleep. Hardly seems comparable to a person quitting a heavy oxycontin habit.
"I dunno about illegal drugs, they're illegal for a reason. "
They're illegal for many reasons, which are mostly: stupid, unjust, racist, harmful, and hypocritical.
Alcohol is one of the most harmful "recreational" drugs, but it's still perfectly legal, and no one is seriously proposing we make it illegal again, despite all the violence, addiction, sickness, and death it causes.
Virtually all of the illegal drugs are less harmful than alcohol, and when they are harmful it's largely because they're illegal, as it means people can't reliably get what they thought they were buying, which leads to overdoses.
Not to mention all of the organized crime, imprisonment, and ruining of lives that prohibition causes (especially of the poor and minorities).
Also, some of the most illegal drugs that are classified as highly addictive with no medical use are literally orders of magnitude less harmful and addictive than for example meth, which is acknowledged to at least have some medical use.
Of course it was. I edited the comment because my thoughts on this are not welcome in "civilized society". God forbid people have some personal responsibility instead of relying on a system that tramples on the minority. But hey, it's a small minority, so fuck them, right.
I and many others definitely agree with you. I think we're just so used to the opposing view being expressed in full earnestness that the satire was missed by some.
Disclaimer: Don't start using opioids. You could become addicted and end up using street drugs and overdose and die.
But the physiological reality is most opioids are harmless if dosed correctly. They do tend to make people happier although often less productive or driven.
We should focus on harm reduction. If registered addicts can get a regular dose of a pure opioid in a safe setting they can often be productive members of society albeit maybe less so than if they had never became addicts.
People function for decades on methadone or buperenorphine therapies with few if any ill effects besides constipation.
I would like to see a society where people with refractory depression were given the option to try opioids. Often depressiom is caused by obsessive ruminations on topics of anxiety or social isolation. By supressing the subjective feeling of psychic pain opioids directly attack these problems at their root. SSRIs may be more indirect. I bet in many cases it would help.
Opioid tolerance is a real thing but we should be looking for ways to attenuate the tolerance formation process.
It is bizarre to me how current progressive circles push cannabis but demonise opioids.
In my opinion as a non-addict but somebody who has had limited experience with various opioids years ago I think they are the closest thing to a psychological wonder drug.
I wonder if they are so demonised because they actually work?
It is true overdose can be lethal but this is a dosing issue with unpure stree products not an inevitability.
> addicts simply end up consuming more grams to get similar highs.
That doesn’t really work with kratom. There’s a ceiling to the effects, unlike regular opiates (which kratom is not) and consuming more doesn’t produce stronger enjoyable effects. It tops out at about codeine level, or perhaps 1 hydrocodone.
>Kratom can be used to treat or replace alcohol, cocaine and opiate addiction.
This is a strange claim. Kratom alkaloids appear to be opioid receptor partial agonists [1]. De-escalation from opioids to kratom makes sense. Cocaine and alcohol addiction usually do not require "maintenance" post-rehab [2,3], unlike opioid dependence which is highly persistent [4], and this seems to muddy the story of a promising treatment [5] (it may compete favorably with buspirone and methadone) by mixing in stories of polydrug users who switched from cocaine to kratom.
I think kratom deserves further investigation not because it is so miraculous but because the options for effective management of opioid use disorder are extremely limited, so I would think defenses of kratom should focus on this application in particular. It is certainly much less deadly than true opioids.
Yep, addiction is a complex subject that we still know very little about. I recommend reading the study I linked to. And check out the kratom forums to read many personal accounts from people using kratom to quit alcohol, cocaine, heroine and more. Thanks.
> The opioid epidemic was largely caused by the idea of them being non addictive being heavy pushed by the pharmaceuticals industry.
I definitely think the pharmecuetical industry pushing drugs is a big problem. But that doesn't mean we should deny people treatments that work. Instead we should fix the actual problem: innapropruate presceiptions. Note that opiods are mostly not a problem here in the UK for example. We're much stricter about when they're used.
In any case, I think there's much less risk here. Ketamine is a somewhat addictive, but nowhere near as bad as opiods, and cannabis and especially psychedelics are pretty much not addictive.
It doesn't seem too good to be true to me. It seems obvious that the chemicals which clearly affect the mind are the ones which are likely to have some use for... affecting the mind in a positive way. They've at least cleared the first hurdle!
The US has been cracking down on opioid prescriptions to the point that a lot of people can't get opioids for when they really need them for chronic pain and even after surgeries!
In the meantime, opioid overdoses have continued to climb. Turns out that forcing people into the black market to deal with terrible pain is not a good policy.
Portugal seems to have found a decent solution: addicts can get easy access to legitimate supply, but non-addicts can't. Seems to have dramatically improved the situation there.
>I’m glad we are moving away from the incredibly destructive drug policies that have been in place for so long
The point of the polices was to counter the incredibly destructive result of the surge of cocaine, crack, heroin use in the mid 1970s and early to mid 1980s. And the deaths from the drug use and the gangs fighting over the spoils. It really was a war. Mexico didn't seem to make it, I think the drugs won.
I know for some people these days it's cool to poo poo the so-called "war on drugs" but to Gen X who lived through the surge it was not a great time. Every day some news of deaths, fights, we were constantly reminded of it. Something had to be done and the free-for-all didn't seem to be working. I guess just like psychology you hear of examples where the stern family raises a wild child and the carefree family raises a straight-edge child the program backfired.
Drugs are chemicals just as is water and yes if a drug is useful then study it and use them for good if possible. But to others it seems many view all drugs as holy and that they can do no wrong is ridiculous.
"The point of the polices was to counter the incredibly destructive result of the surge of cocaine, crack, heroin use in the mid 1970s and early to mid 1980s."
This would be plausible if the policies were focused on those drugs exclusively. However, I see the draconian policies targeted towards cannabis, hallucinogens, and amphetamines as pretty ample evidence that the "war on drugs" had much wider ambitions than curbing the usage of these hard narcotics.
Edit)
To your point of folks speaking harshly of our current drug policies - look at where we are now, 50 years later. A nationwide opioid crisis created by pharma companies. A generation, if not two, of young men and fathers locked up in prison with little to no room for upwards mobility. Communities, already economically deprived, losing stability, obliteration of the nuclear family core, and enduring oppressive policing policies. So yes, I think its entirely fair for a new generation to shit on the war on drugs. Even if the policy was formed with good intentions (which is, frankly, debatable), it is still bad policy.
The "War on Drugs" did little to solve the social causes of drug addiction and dealing, and mainly focused on expensive law enforcement operations and penalizing impoverished people further. With the opioid epidemic, white-collar drug dealers were free to make huge profits getting people addicted, with little repercussions for decades. The "War" was targeted to a very specific demographic.
Ironically you are describing the consequences of the "war on drugs" which started in 1971. Many overdose deaths are directly related to the unknown quality of black market drugs. There would be no gangs "fighting over the spoils" if it were legal. You are conflating the consequences of prohibition with the consequences of drug use. That isn't to say all drugs are good, but as we learned in the 1920s prohibition is assuredly worse.
Thanks for saying this. The parent comment just shows how deeply the propaganda has worked. There would be no gangs fighting and much lower levels of overdose and abuse if you could pick up your cheap, clean, legal cocaine/heroin/etc. at an official dispensary if you needed it. Portugal is showing the way.
I totally agree with the perspective in that blog. I just wanted to mention one of the known dangers of chronic ketamine use in the spirit of harm-reduction, because I don't think the bladder damage risk is that well-known, and sometimes people become seduced by the charms of ketamine and end up taking the drug far more often than when they set out.
From what I've read about people using Ketamine for antidepression, they tend to use a very small dose at as long an interval as possible while still being effective, while the reports of bladder damage seem to be when people use large quantities (a few grams) per day for months. That is, if you're using it medically, rather than for recreation, its probably not a risk. Even recreationally, unless you're abusing it, its likely not a big risk.
I think a big part of the issue is that you quickly develop a tolerance to Ketamine, so if you're a daily user, there's a strong tendency to up the dosage to maintain its effect. If you're a casual user or are careful to spread it out to avoid tolerance buildup, I think it can be avoided.
With that said, you're absolutely right that it is a danger that needs to be kept in mind, but from what I've read, if you're not abusing it, the risk seems low.
You're right, taken in a medical context there would be no risk of this. Just wanted to put the bladder damage risk on the radar, so that people are aware that there are physical consequences to abuse. You know, a lot of people self-medicate and there's a fine line between self-medication, recreation, and abuse.
>marijuana for chronic pain, mushrooms for depression, mdma for ptsd
Is it that much of a surprise that psychoactive drugs treat psychogenic symptoms? In the particular case of pain, the two major available drug classes -- opioids and benzodiazepines -- mimic the activity of addictive recreational drugs opium and alcohol. THC is used per se instead of derivatives because of its price and safety record (contrast opium/alcohol).
For depression/PTSD, psychiatry has thrown the kitchen sink at these conditions. It's more "newsworthy" when MDMA is used for PTSD than propanolol even though both serve essentially the same purpose: allowing the patient to discuss the traumatic experience without experiencing the emotional effects of that trauma, by blocking them physiologically. In this case, "blocking negative emotions" is a naturally desirable effect of a recreational drug (propanolol also blocks many positive emotions, rendering it less fun). Modifying emotions in depression doesn't seem like a surprise either, although psychedelics can be unreliable here (and this is well-documented). I expect some negative side-effects to appear, but I disagree that this is much of a change from the norm, except insofar as it upends a taboo. Methaqualone got its start treating insomnia, and the medical history of amphetamine is too long to fit in this comment.
In fact, during the early history of psychedelics, there were developed "less recreational" analogues of the major drugs, such as diethyl-psilocin ("ethocin") and 5'-methoxy-MDA ("MMDA") which were considered as possibly safer adjuvants to psychotherapy. The rediscovery of these agents might benefit more from attention on their history of bona fide therapeutic use, rather than on their recreational past. Perhaps we shouldn't be so surprised when some psychiatric medications turn out to be recreational, and mitigate the consequences pragmatically, rather than reflexively recoiling from anything resembling euphoria. One thing you learn from Infinite Jest is that the mere materialism of emotion is especially unnerving insofar as it applies to happiness, but reality isn't going away anytime soon.
What happened in this article with ketamine is quite different: test-tube evidence uncovered an effect that modifies a rare hereditary condition. I think the story here is really more about data-mining, and ketamine just happens to be interesting.
> Is it that much of a surprise that psychoactive drugs treat psychogenic symptoms?
The surprising part is the growing narrative that these psychoactive drugs are basically miracle cures without downsides.
Drugs like LSD are being explored as adjuncts to intense therapy spanning many sessions, but the pop-science portrayal of these drugs ignores that intense therapy and instead imagines that tripping on mushrooms or LSD is a cure for psychiatric illness. It also ignores the fact that bad trips are a very real possibility and worsening of psychiatric illness is not uncommon among illicit users of these drugs. There are plentiful reports of psychedelics causing weeks or months of dysphoria or even precipitating long-lasting episodes of major depression, and it’s not hard to find them either.
If we want to get anywhere with these substances, we need to quit exaggerating their positive effects and downplaying their negatives. That’s a setup for failure when they’re further studied and the reality can’t match the unreasonably loft pop-culture presentation of these drugs as miracle cures that act alone without any downsides.
It is, as the grandparent comment said, reminiscent of the early days of opioids when we were bombarded with stories about how they were miracle cures without downsides. The truth is that they’re helpful in controlled circumstances but can be harmful when overdosed or prescribed without supervision, which doesn’t sound that different then the situation with drugs like ketamine.
>we need to quit exaggerating their positive effects and downplaying their negatives.
Who is 'we'? Sure, the media exaggerates the benefits of psychedelics. You can also find plenty of stories exaggerating the benefits of electric cars, veganism, meditation, antioxidants, or martial arts, among other things.
The media loves a narrative with a miracle -- how is that the "surprising part"?
>the early days of opioids
The early days of opioids were in the nineteenth century. I certainly don't recall being bombarded with stories about them. The post-mortem of the opioid painkiller crisis (the "codones") focused on deceitful marketing from pharmaceutical companies aimed at physicians, not pop-psych puff pieces for a lay audience. There is no shortage of exaggeration in the cornucopia of cannabis clickbait, but the situation is not comparable.
Inaccuracy in pop-sci is lamentable, but not historic, and usually the only thing that comes of it are bins of discarded magazines.
> Are we going to see similar harms from these drugs a few years after they gain more popularity?
I think we’re already starting to see this on a smaller scale.
One of my friends is a therapist who does a lot of social work predominantly for low-income people coming from difficult situations. She encounters a lot of people who have become heavily dependent on marijuana under a mistaken impression that smoking multiple times every day is a good treatment for depression or anxiety. Many of them are under the impression than marijuana is a wonder drug that treats everything from psychiatric illnesses to cancer. Meanwhile they’re clearly too impaired and unmotivated to get their lives together due to being constantly high. She spends a lot of time convincing people to moderate their consumption or even abstain entirely. The results are great if she can convince them to stop, but that’s a difficult task.
More worrisome is the increasing number of parents she sees who are trying to medicate their juvenile children with marijuana. Some of the stories she tells about parents who are convinced they’re doing their kids a favor by giving them THC edibles before school (supposedly for anxiety) are downright tragic.
There is a growing mistrust of pharmaceutical companies and mainstream psychiatry that mirrors the rise of things like anti-vaxxers and belief in essential oils. Many companies are rushing to fill this demand for alternative medicine with products and services ranging from pushing heavy THC consumption to ketamine clinics that will give ketamine to anyone willing to pay a few hundred dollars per dose.
In the case of this article the discovery of ketamine’s actions is more likely to spur development of new molecules that can be used without the obvious side effects of ongoing ketamine treatment (which is not as harmless as it sounds when repeatedly dosed over a lifetime).
Did you ever compare the side effects of marijuana to the popular antidepressant, antianxiety and ADHD medications being given to children?
> There is a growing mistrust of pharmaceutical companies and mainstream psychiatry that mirrors the rise of things like anti-vaxxers
This statement seems to ignore the crisis brought by narcotic drugs. People should be skeptical of pharmaceutical companies. There is a long history of their drugs killing people. It's really not worth my time to post it all, but feel free to do a little research yourself.
Comparing them to antivaxxers is inflammatory and inaccurate.
There’s a lot of “whataboutism” when it comes to marijuana, but it doesn’t negate the fact that heavy daily marijuana usage is a net negative for mental health and produces worse long-term depression scores than abstaining.
And yes, she generally refers people to psychiatric treatment under the guidance of doctors who can monitor and adjust medications over time. Outcomes on mainstream depression and anxiety medications are far more positive and the people do much, much better after getting proper treatment with proper medications.
There is no comparison. Marijuana is not an effective depression treatment even though it may temporarily dull feelings and emotions. Long-term studied outcomes are poor.
> the fact that heavy daily marijuana usage is a net negative for mental health
citation required.
There is no comparison because you are speaking in anecdotes, not data.
Even if it is a "net negative" is it a bigger net negative than the cognitive effects of anti depressants?
How is it "whataboutism" when the two are being used to treat the same illnesses, but you only look at the negative effects of marijuana in a vacuum, while at the same time lauding pharmaceuticals.
>Marijuana is not an effective depression treatment even though it may temporarily dull feelings and emotions.
That describes how my teenage Lithium prescription felt far better than it does marijuana use. Though perhaps they have better pharmaceuticals now than they did 20 years ago.
"They are often talked about as if they have little or no harmful side effect"
Unlike all those "unfun" drugs? I think side effects are part and parcel of virtually all drugs. Do we need a special all-caps disclaimer anytime a drug is mentioned to remind people that side effects exist? If we did, most of the biggest disclaimers would be reserved for fully-legal, commonly-prescribed drugs.
> They are often talked about as if they have little or no harmful side effects.
Most drugs have side effects, including all the legal pharmaceuticals. E.g. normal antidepressants aren't without risk.
Anyways, that's why its important to study them - see where they lie on the risk-benefit trade-off curve.
> The opioid epidemic was largely caused by the idea of them being non addictive
I don't know which idiots thought these were non addictive. Like there was even the opium wars faught over this point in the 1800s. We've known of the danger since the 1700s.
> Most drugs have side effects, including all the legal pharmaceuticals. E.g. normal antidepressants aren't without risk.
Risk/no-risk dichotomy is misleading in that those categories do not consist of homogeneously comparable members. Nausea from an SSRI is not the same as triggering a first psychotic episode from psychedelic drug use, or pushing your neuroticism a standard deviation higher from stimulant abuse or getting stuck in opioid addiction.
SSRI's are also linked to hallucinations and suicide. Of course not all drugs are the same, some are more risky than others, but its not like legality corresponds to the risk.
I'm not saying that popular drugs are risk free. They definitely aren't. That's why its important to study them and understand what the risks are so people can make informed decisions about them (under the supervision of a doctor)
Ketamine has been in medical use for a long time as an anesthetic and has also been shown to be beneficial for depression in recent years. Its not "now" Ketamine.
I'm not sure how old you are, nor your familiarity with the history behind Silicon Valley and "Drugs"
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>The opioid epidemic was largely caused by the idea of them being non addictive being heavy pushed by the pharmaceuticals industry.
False - there was never the "idea" that these were non-addictive - it was an active, malicious, evil fucking LIE.
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One of the co-founders of Cisco, and one of the fathers of the Border Gateway Protocol (BGP), (as well as RIP, etc) - - which is aurguably the foundations of routing which makes the Internet possible, stated, in response to Hoffman's 100th birthday celebration (the discoverer of LSD):
(Paraphrased, mostly: "I was opposed to drug testing of employees at Cisco as we scaled -- if it weren't for LSD we wouldn't have been able to come up with many of the complex concepts behind BGP"
I know first hand how much Drug/"anti-Culture" is imbued in Silicon Valley, computing in general.
I have done many a drug with many a people who have built the shit that the world lives and thrives on daily.
There is a STARK difference between a mood altering suppressant such as an opioid and expand nootropic drugs, such as LSD and Shrooms. Both of which are IMO some of the most important psycho-actives we have.
You are touching something (your machine) and consuming content (netflix etc) built by many people who have benefited, and thus had you benefit, from their experiences with 'altered-conscious'....
The Sackler Family is an evil piece of shit family that should be worse than in prison....
But The internet and Computing as we know it, would not exist if it were not for people who do not accept the simplicity of base reality and can operate at higher levels at times with the help of LSD/Shrooms.
its funny how one may equate "harmful addiction" with the USE of such substance.... in fact, my counter-culture DNA has shown me my entire life - that "the establishment" literally is quelling human growth because of the fact that using these reveals the fragility and tenuous control they actually have.
In fact, I am sitting here with a book that one of my best friends just sent me - "The Fabric of Reality" (by David Deutsch) and in all likelihood, this evening you will be using tech that he has helped build...
The only thing that is "too good to be true" is when someone else tells you definitively that you must do and act "this way" because we said so. (Look at the fucking state of the world at this moment -- you think that all these governments and institutions know what the fuck they are talking about? - no...)
> The opioid epidemic was largely caused by the idea of them being non addictive being heavy pushed by the pharmaceuticals industry
That's not true. The new idea was that a manageable addiction was preferred to chronic pain. The theory was that addiction to opioids could be managed. That turned out to be not the case. People started selling pills and buying street heroin and it spiraled out of control.
People didn't suddenly forget centuries of experience that narcotics were addictive. They thought that making them time release and long lasting they could manage the addiction. Pharmacies did downplay the cleverness of people when they want to get high. People found they could crush the pills and snort them for a quick rush. Those who weren't addiction prone found they could sell their pills for $80 a pill. It was off to the races after that.
The real crime here wasn't trying to help those in chronic pain with a manageable addiction, it was the incredibly long time it took for pharma companies and govt regulators to do anything about the crisis, even as some pharmacies in Florida and West Virginia were selling millions of pills, far more than their local communities would warrant. The suspicion is that a lot of money was being made, so why rush to intervene.
Managing acute pain is different from chronic pain. The 'new idea' you refer to is that people who get opioids in hospitals don't get addicted. Of course, the important difference is that when people get better after surgery their life is generally goin in a good direction. It's easy to stop using opioids when you are finally able to walk, work, move, live, love again.
Chronic pain is basically the opposite. Where depression is almost guaranteed, and susceptibility to addiction is very high.
A single letter written 40 years ago did not cause the opiod epidemic. It was part of a movement to reassess the use of pain medication to ease chronic pain. By movement I mean it was part of a change in the zeitgeist among doctors and pharmaceutical companies. No doctor read this letter and said to themselves, well I guess narcotics are not addictive anymore and I can prescribe them without concern. I don't know why people want to make reductive arguments.
It absolutely did, the article even goes into how new printings of the same journal now come with a public health warning because of the number of times it was cited, how it had subsequently been debunked, and the overall effect it had on the industry.
It is true. The claim was that the risk of addiction was extremely small. One of the ways this idea was pushed was cherry-picking a study that showed no addiction among 10k burn victims treated with opioids. Minimizing the risk of addiction was also a major component of the guilty plea and fine.
Obviously any reasonable person with a knowledge of opioids could see that these claims were BS, but it's remarkable what motivated reasoning can do, especially when there's profit involved.
> The opioid epidemic was largely caused by the idea of them being non addictive
the parent comment said "non addictive" which I said wasn't true. You said
> The claim was that the risk of addiction was extremely small
which is another way of saying they thought they could manage addiction that did occur. They thought this because they had a time-release pill which made the risk of problematic addiction "extremely small" as you say
So far the evidence doesn’t show anything near this level of harm. I’m just skeptical of anything that seems too good to be true.
People with rare diseases (and their families and caretakers) get excited about anything at all actually helpful, especially if it comes through official, approved medical channels, because they suffer a whole helluva lot every single day while listening to the medical community promise "cures" that never seem to arrive. It's an amazingly hard psychological thing to live with.
On a Cystic Fibrosis list years ago, a parent said "My child turns 18 today. The life expectancy now is 36. When he was born, the life expectancy was 18."
So gains get made but these are people who need a miracle cure and needed it "yesterday" who are, instead, getting incremental improvements at what feels like a glacial speed while they live tormented lives.
So, yeah, they get excited. But that doesn't mean they are going to all throw caution to the wind and jump on the band wagon. Some that do -- or seem to -- are basically "already dead anyway" if they don't try something new and are happy to take a gamble in hopes of one last hurrah and at least it's more data for others like them if it doesn't help them.
I think the harmful opoids were created due to heroin being illegal. The pharmaceutical version is purified and more potent in general, helping enshrine it as the go to for smuggling due to its smaller size/volume and then cut once it's imported to its destination. Just an opinion tho.
I recently got my full genome sequenced via a website called nebula.org. I don't have any backgrounds in genetics but I was playing around with the raw data with some github apps. Thanks so much for this - I may be able to link this app in to my custom data. That would be so awesome if we could hook this up to personal genetics results. Even people who aren't sick do have mutations and it would be so cool seeing AI running some kind of search on their personal genome and suggesting a drug for that!
A drug for what? I don't see how running an AI on your genome to find drugs for a non-existent genetic disease you don't have because the AI just hallucinated it.
Some 15 years ago someone (sorry I forgot who) in Waterloo university published a paper about how to use a search engine to discover hidden relations.
It was something like this:
1. Search for the key word "A"
2. Find new keywords (b,c,..) that are associated with "A" (I did this with lingpipe [0]
3. Search each the new keywords (b,c, ...)
4. Find for each of them their associated keywords (finding (s, t, ...)
5. Repeat 3.
6. repeat 4. finding (z, x, ...)
7. If in (z, x, ...) one of them is associated with "A" then you discovered an hidden relation between "A" and one of the members of (s, t, ...) (hidden if it did not appear in the initial search).
I am surprised people here seem mostly interested in discussing drugs when the object of this article is the materialization of the wet dreams of all the ML fanboys out there. Reasoning over medical information that actually works! Isn't that remarkable?! Of course, it's symbolic and not statistical 'AI' so it doesn't tickle the deep learning hipsters announcing AGI as just around the corner.
"In these patients, that gene is sort of running at 50% capacity: One copy’s broken, the other copy’s working,” explained Might. “So the tool, when it sees that, says, ‘OK, well, maybe I can make the functioning copy work twice as hard to compensate.’”
Woo! Biohacking at its best.
I do something sort of similar by eating hot peppers regularly. It opens up a different chanel than my defective chanel and helps me keep my chronic edema down to a dull roar, among other things.
To prepare the kids and their parents, the Seaver center sent stickers to practice applying to the kids’ chests, so they could get comfortable with the sensory experience of ECG readings.
On reading this article, it must be so hard for parents to see a way forward for treating their child's condition, but be roadblocked by either funding, or study participation criteria. If I observed my child have such a profound change as Mateo did, I think I might be incentivised to continue seeking these drugs for their treatment.
I know that it would be absolutely a criminal act to purchase ketamine illegally and administer it to my child, or to find a shady doctor who prescribe it off-label. I wonder how often these scenarios come up? And how often parents go out of their way to seek unapproved medicines (much like the AIDS Buyer's Clubs of the 90s).
“I advise strongly against trying to pursue ketamine, commercially or clinically, because of safety concerns and the risk of losing our opportunity to study it rigorously,” said Kolevzon [the clinical director]
Research to gain quality evidence is good, but sometimes other considerations outweigh that. Visible improvement in the sufferers of a rare disease may be such a case.
Is this AI or someone put the effort into compiling a database and added automatic search function?
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