[HN Gopher] With a nudge from AI, ketamine emerges as a potentia...
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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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