[HN Gopher] With a nudge from AI, ketamine emerges as a potentia...
       ___________________________________________________________________
        
       With a nudge from AI, ketamine emerges as a potential rare disease
       treatment
        
       Author : hassanahmad
       Score  : 142 points
       Date   : 2021-08-07 15:55 UTC (7 hours ago)
        
 (HTM) web link (www.statnews.com)
 (TXT) w3m dump (www.statnews.com)
        
       | DoreenMichele wrote:
       | _" 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._
       | 
       | I like these people.
        
       | pizza wrote:
       | > Proof-of-concept for reasoning over medical knowledge graphs,
       | using miniKanren + heuristics + indexing.
       | 
       | https://github.com/webyrd/mediKanren
        
         | civilized wrote:
         | 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...)
        
           | rscho wrote:
           | 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!
        
           | mattmight wrote:
           | 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.
        
             | rscho wrote:
             | 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.
             | 
             | Congratulations to you and your team!!
        
             | civilized wrote:
             | 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.
        
               | rscho wrote:
               | https://youtu.be/d-Klzumjulo
        
       | JPLeRouzic wrote:
       | 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).
       | 
       | [0] http://www.alias-i.com/lingpipe/
        
       | tomato-sauce wrote:
       | 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.
        
         | wyre wrote:
         | 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.
        
           | gunshai wrote:
           | >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.
        
           | sandworm101 wrote:
           | 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.
        
             | stouset wrote:
             | 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.
        
             | chillwaves wrote:
             | because there was a profit motive to lie.
        
         | scythe wrote:
         | >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.
        
           | PragmaticPulp wrote:
           | > 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.
        
             | scythe wrote:
             | >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.
        
         | irthomasthomas wrote:
         | 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/
        
           | loeg wrote:
           | 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.
        
           | jfk13 wrote:
           | 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."
           | 
           | (https://www.drugabuse.gov/publications/drugfacts/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.
        
             | ctoth wrote:
             | 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.
        
               | irthomasthomas wrote:
               | I think the FDA are in this thread ;)
        
               | jfk13 wrote:
               | 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.
        
               | technothrasher wrote:
               | 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.
        
           | scythe wrote:
           | >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.
           | 
           | 1: https://jpet.aspetjournals.org/content/376/3/410.abstract
           | 
           | 2: https://jamanetwork.com/journals/jamapsychiatry/article-
           | abst...
           | 
           | 3: https://www.sciencedirect.com/science/article/pii/S0376871
           | 60...
           | 
           | 4: https://www.sciencedirect.com/science/article/pii/S0140673
           | 69...
           | 
           | 5:
           | https://link.springer.com/article/10.1007/s40122-020-00151-x
        
             | irthomasthomas wrote:
             | 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.
        
           | tomato-sauce wrote:
           | 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.
        
             | fsckboy wrote:
             | https://www.drugabuse.gov/publications/drugfacts/kratom
        
           | PragmaticPulp wrote:
           | 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.
        
             | skulk wrote:
             | 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.re
             | ddit.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.
        
             | bserge wrote:
             | I dunno about illegal drugs, they're illegal for a reason.
        
             | drooogs wrote:
             | 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.
        
               | cik2e wrote:
               | - 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.
        
               | drooogs wrote:
               | 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.
        
               | LordDragonfang wrote:
               | 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.
        
               | drooogs wrote:
               | 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...
        
               | netizen-936824 wrote:
               | 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.
        
           | gunshai wrote:
           | Come to Oregon where we just decriminalized the party.
        
           | parineum wrote:
           | >It is a herb harvested from the leaves of a tree
           | 
           | As opposed to heroin and cocaine right?
        
             | acchow wrote:
             | To clarify for other users, heroin doesn't come from
             | nature: that's morphine. We then take morphine and put it
             | through a chemical reaction.
             | 
             | And cocaine? Why is cocaine worse than alcohol?
        
         | dkersten wrote:
         | > and now ketamine
         | 
         | 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.
        
         | nickthemagicman wrote:
         | What there a really are no or very few side effects?
        
           | rscho wrote:
           | 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.
        
           | shadowgovt wrote:
           | (interpreting as "What if there really are no or very few
           | side effects?")
           | 
           | That would be great, but it would be something we learn on
           | the other side of controlled trials.
        
           | IBCNU wrote:
           | 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.
        
           | narag wrote:
           | 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.
        
             | stouset wrote:
             | 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.
        
         | DoreenMichele wrote:
         | _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.
        
         | mam3 wrote:
         | The side effects are super well documented on drug-positive
         | websites such as psychonaut wiki, erowid,... even r/drugs.
         | 
         | Just look for it
        
         | PragmaticPulp wrote:
         | > 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).
        
           | chillwaves wrote:
           | 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.
        
             | PragmaticPulp wrote:
             | 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.
        
               | chillwaves wrote:
               | > 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.
        
         | TulliusCicero wrote:
         | What we're seeing is data from studies. What we need is yet
         | more studies.
         | 
         | Yes, there's probably negative side effects, but that's true
         | for medicines in general.
        
         | stakkur wrote:
         | Michael Pollan would like a word. I think you're confusing
         | 'recent news' with 'a long history'.
        
         | samstave wrote:
         | I'm not sure how old you are, nor your familiarity with the
         | history behind Silicon Valley and "Drugs"
         | 
         | ---
         | 
         | > _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.
         | 
         | ---
         | 
         | 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"
         | 
         | Here is one article on it:
         | 
         | https://www.wired.com/2006/01/lsd-the-geeks-wonder-drug/
         | 
         | 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...)
         | 
         | Go microdose some shrooms for good measure.
        
         | okareaman wrote:
         | > 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.
        
           | monocasa wrote:
           | No, the messaging to the doctors was that there was
           | essentially no risk of addiction.
           | 
           | > This pain population with no abuse history is literally at
           | no risk for addiction
           | 
           | > There have been studies suggesting that addiction rarely
           | evolves in the setting of painful conditions
           | 
           | https://www.statnews.com/2017/05/31/opioid-epidemic-nejm-
           | let...
        
             | okareaman wrote:
             | 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.
        
           | raphlinus wrote:
           | 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.
           | 
           | [1]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2622774/
        
             | okareaman wrote:
             | > 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
        
           | amanaplanacanal wrote:
           | I thought the new idea was that people who took opioids only
           | for pain relief didn't get addicted, which in hindsight is
           | absolute nonsense.
        
             | okareaman wrote:
             | 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.
        
         | nicoburns wrote:
         | > 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!
        
           | pitaj wrote:
           | 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.
        
             | lumost wrote:
             | No one has had a good approach for opioid addiction since
             | the first cases of morphine addiction a century ago.
             | 
             | Banning opiate use results in deaths, restricting
             | prescriptions moves addicts to the black market, the status
             | quo results in more addicts.
        
               | nicoburns wrote:
               | 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.
        
               | bserge wrote:
               | I'm sure it works as well as described. /s
        
             | [deleted]
        
         | dghughes wrote:
         | >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.
        
           | Klinky wrote:
           | 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.
        
           | throaway46546 wrote:
           | 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.
        
           | ihunter2839 wrote:
           | "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.
        
         | standardUser wrote:
         | "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.
        
         | bawolff wrote:
         | > 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.
        
           | acituan wrote:
           | > 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_.
        
         | elevaet wrote:
         | One danger of chronic ketamine use is bladder damage.
        
           | dllthomas wrote:
           | But note https://astralcodexten.substack.com/p/drug-users-
           | use-a-lot-o...
        
           | chefkoch wrote:
           | You have to take really large amounts daily to get bladder
           | problems.
        
           | dkersten wrote:
           | 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.
        
         | funnybeam wrote:
         | A lot of the "fun drugs" were originally used for medical
         | purposes and only banned because people started using them for
         | fun
        
           | bserge wrote:
           | A real shame. But I guess if you let people learn personal
           | responsibility they won't need the government as much
           | anymore.
        
             | acituan wrote:
             | > But I guess if you let people learn personal
             | responsibility they won't need the government as much
             | anymore
             | 
             | Addiction is not a mere matter of personal responsibility
             | but a complex bio-psycho-social phenomena.
             | 
             | Oversimplified solutions from both sides of the argument
             | does the most harm.
        
               | bserge wrote:
               | What goes around comes around.
        
               | acituan wrote:
               | Funny enough this is an area we can exert personal
               | responsibility.
        
       | cupcake-unicorn wrote:
       | 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!
       | 
       | Here's the link to the github app they mentioned:
       | https://github.com/webyrd/mediKanren
        
       | rscho wrote:
       | 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.
        
       | cratermoon wrote:
       | Uh oh, here come the ketamine hucksters.
        
       | rscho wrote:
       | The video that explains it all for techies:
       | https://youtu.be/d-Klzumjulo
        
       | loceng wrote:
       | "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?
        
         | tartoran wrote:
         | Reminds me of minikanren and I think this may be related
        
           | rscho wrote:
           | it indeed is based on MiniKanren.
        
           | IBCNU wrote:
           | Yeah, I had the same thought. Also, these are two things that
           | absolutely _should_ be together haha...
        
           | tejtm wrote:
           | indeed they do share Will Byrd as their author
        
           | [deleted]
        
         | rscho wrote:
         | 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.
        
         | doit4thebitties wrote:
         | I worked at a biomedical informatics shop that did this very
         | thing by AI/ML 10 years ago. Essentially: automated
         | metanalysis.
        
           | rscho wrote:
           | 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:
           | 
           | https://skr3.nlm.nih.gov/SemMedDB/
        
         | dylan604 wrote:
         | 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.
        
           | edejong wrote:
           | 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.
        
             | cratermoon wrote:
             | 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.
        
               | cortezdecoy wrote:
               | "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.
        
               | cratermoon wrote:
               | 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>"
        
               | edejong wrote:
               | 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.
        
               | cratermoon wrote:
               | Thanks for the mansplanation.
        
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