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"Talks a good game about freedom when out of power, but once he’s in – bam! Everyone's enslaved in the human-flourishing mines."

Adderall Risks: Much More Than You Wanted To Know

[Previously in series: Antidepressant Pharmacogenomics: Much More Than You Wanted To Know; SSRIs: Much More Than You Wanted To Know, etc. This is all preliminary and you should not take it as a reason to change successful medical care. None of this necessarily applies to your particular case and you should talk to your doctor if you have questions about that.]

I. Confessions Of A Gatekeeper

I didn’t realize how much of a psychiatrist’s time was spent gatekeeping Adderall.

The human brain wasn’t built for accounting or software engineering. A few lucky people can do these things ten hours a day, every day, with a smile. The rest of us start fidgeting and checking our cell phone somewhere around the thirty minute mark. I work near the financial district of a big city, so every day a new Senior Regional Manipulator Of Tiny Numbers comes in and tells me that his brain must be broken because he can’t sit still and manipulate tiny numbers as much as he wants. How come this is so hard for him, when all of his colleagues can work so diligently?

(it’s because his colleagues are all on Adderall already – but telling him that will just make things worse)

He goes on to give me his story about how he’s at risk of getting fired from his Senior Regional Manipulator Of Tiny Numbers position, and at this rate he’s never going to get the promotion to Vice President Of Staring At Giant Spreadsheets, so do I think I can give him some Adderall to help him through?

Psychiatric guidelines are very clear on this point: only give Adderall to people who “genuinely” “have” “ADHD”.

But “ability to concentrate” is a normally distributed trait, like IQ. We draw a line at some point on the far left of the bell curve and tell the people on the far side that they’ve “got” “the disease” of “ADHD”. This isn’t just me saying this. It’s the neurostructural literature, the the genetics literature, a bunch of other studies, and the the Consensus Conference On ADHD. This doesn’t mean ADHD is “just laziness” or “isn’t biological” – of course it’s biological! Height is biological! But that doesn’t mean the world is divided into two natural categories of “healthy people” and “people who have Height Deficiency Syndrome“. Attention is the same way. Some people really do have poor concentration, they suffer a lot from it, and it’s not their fault. They just don’t form a discrete population.

Meanwhile, Adderall works for people whether they “have” “ADHD” or not. It may work better for people with ADHD – a lot of them report an almost “magical” effect – but it works at least a little for most people. There is a vast literature trying to disprove this. Its main strategy is to show Adderall doesn’t enhance cognition in healthy people. Fine. But mostly it doesn’t enhance cognition in people with ADHD either. People aren’t using Adderall to get smart, they’re using it to focus. From Prescription stimulants in individuals with and without attention deficit hyperactivity disorder:

It has never been established that the cognitive effects of stimulant drugs are central to their therapeutic utility. In fact, although ADHD medications are effective for the behavioral components of the disorder, little information exists concerning their effects on cognition…stimulant drugs do improve the ability (even without ADHD) to focus and pay attention.

I cannot tell you how much literature there is trying to convince you that Adderall will not help healthy people, nor how consistently college students disprove every word of it every finals season.

That makes “only give Adderall to people with ADHD” a moral judgment, not a medical one. Adderall doesn’t “cure” the “disease” of ADHD, at least not in the same way penicillin cures syphilis. Adderall will give everyone better concentration, and we’ve judged that it’s okay for people with terrible concentration to use it to overcome their handicap, but not okay for people with already-fine concentration to use it to become superhuman.

We could still have a principled definition of ADHD. It would be something like “People below the Nth percentile in ability to concentrate.” Instead, we use the DSM, which advises us to diagnose people with ADHD if they say they have at least five symptoms from a list. The list has things like “often has difficulty sustaining attention” and “often has difficulty organizing tasks”. How often? You know, often! And if you work as a Senior Regional Manipulator Of Tiny Numbers, you’re going to have attention problems a lot more “often” than the rest of us.

So the DSM criteria are kind of meaningless, but that’s fine, because people can just lie about them anyway.

There are whole websites for this: How To Convince Your Shrink You Have ADHD, How To Get Your Doctor To Prescribe You Adderall In Five Easy Steps, et cetera. But I can’t imagine most people need them. Just talk about all the times in your life that you had attention and concentration problems, and if your doctor asks you a more specific question (“Do you often lose things?”) you give the obvious right answer (“Wow, it’s like you’ve known me my whole life!”).

Aren’t psychiatrists creepy wizards who can see through your deceptions? There are people like that. They’re called forensicists, they have special training in dealing with patients who might be lying to them, and they tend to get brought in for things like evaluating a murderer pleading the insanity defense. They have a toolbox of fascinating and frequently hilarious techniques to ascertain the truth, and they’re really good at their jobs.

But me? At best, I can have a vague suspicion you’re not telling the truth. And how many patients genuinely in need of treatment do I want to risk accidentally rejecting just so I can be sure of thwarting you? A lot of 100% honest psychiatric patients’ stories are pretty unbelievable, really, and I don’t want to have to treat every patient like a convicted murderer. Unless you give me some specific reason to doubt you, I start with the assumption that you’re telling the truth.

Think about how wasteful all of this is. We throw people in jail for using Adderall without a prescription. We expel them from colleges. We fight an expensive and bloody War on Drugs to prevent non-prescription-holders from getting Adderall. We create a system in which poor people need to stretch their limited resources to make it to a psychiatrist so they can be prescribed Adderall, in which people without health insurance can never get it at all, in which DEA agents occasionally bust down the doors of medical practices giving out Adderall illegally. All to preserve a sham in which psychiatrists ask their patients “Do you have ADD symptoms?” and the patients say “Oh, yeah, definitely,” and then the psychiatrists give them Adderall. It’s like adding twenty layers of super-reinforced concrete to a bunker with a wide-open front door.

(Also, if by some chance a psychiatrist doesn’t give a patient Adderall, that patient practically always goes to another psychiatrist, and that next psychiatrist does. Trust me, no matter how unsuitable a candidate you are, no matter how bad a liar you are, somewhere there is a psychiatrist who will give you Adderall. And by “somewhere”, I mean it will take you three tries, tops.)

Psychiatrists’ main response to this perverse and unwinnable system is to give people Adderall, but feel guilty about it. Somebody should do an anthropological study on this, but my preliminary observations:

Some people will lecture their patients on how Medication Can Never Address The Root Cause Of A Problem, and the patient will agree that Medication Can Never Address The Root Cause Of A Problem, and then the psychiatrist will give them Adderall and feel good about it.

Some people will discuss alternative options, like behavioral treatments, or non-stimulant medications, and the patient will come back in a month and say that the behavioral treatments didn’t work, and then the psychiatrist will give them Adderall and feel good about it.

Some people will give their patients a formal test where they have to answer questions like “I often have trouble concentrating – strongly disagree, disagree, neutral, agree, or strongly agree?” Then the patient will give whatever answers get them Adderall, the psychiatrist will add up all the answers and score the test and find that it means the patient needs Adderall, and then the psychiatrist will give the patient Adderall and feel good about it.

Some people will occasionally find some little issue with one patient’s story, deny them Adderall, and then ride out the moral high for weeks, feeling so virtuous that they can give the next few people Adderall and feel good about it.

Some people will demand multiple evaluation sessions, lots of laboratory tests, make a patient tell them their whole life story. And after learning that they had a bad relationship with their stepfather in 8th grade and still have sexual hangups over that time they ejaculated prematurely with Sally one time in freshman year, the psychiatrist will give the patient Adderall and feel good about it.

I have been guilty of all of these at one time or another. I still wrestle with these issues a lot. The latest step in my evolving position was reading Kelsey’s blog post about having ADHD and trying to get Adderall. Her doctor gave her a list of things she had to do before he would give her Adderall, and she – having ADHD – got distracted and never did any of them.

(by my calculations, that decreased Kelsey’s effectiveness by 20%, thus costing approximately 54 billion lives.)

So lately I’ve been trying to be smarter about all this. What about good old consequentialism? Most people will get some benefit from Adderall, but it’s a powerful drug with a lot of potential risks. Maybe I should figure out exactly how bad the risks are, and then I can figure out how bad people’s concentration problems would have to be for the risks to be outweighed by the benefits.

Trying to discover the risks of Adderall is a kind of ridiculous journey. It’s ridiculous because there are two equal and opposite agendas at work. The first agenda tries to scare college kids away from abusing Adderall as a study drug by emphasizing that it’s terrifying and will definitely kill you. The second agenda tries to encourage parents to get their kids treated for ADHD by insisting Adderall is completely safe and anyone saying otherwise is an irresponsible fearmonger. The difference between these two situations is supposed to be whether you have a doctor’s prescription. But what if you are the doctor, trying to decide who to prescribe it to? Then what? All they tell you in medical school is to give it to the people who actually have ADHD – which, I repeat, is kind of meaningless.

This post records my attempt to figure out something better. Apologies for the length.

II. Medical Risks

Most people on stimulants will have some minor side effects. Feeling jittery, feeling cold, feeling sick, leg cramps, arm cramps. Some will feel “like a robot” or otherwise psychologically uncomfortable. But these don’t discourage me from giving stimulants to people who need them. If someone needs the drugs, let them try them, see how many side effects they get, and decide for themselves whether it’s worth it.

I’m much more concerned about side effects that are permanent and dangerous. These people give us a list:

Sounds pretty bad. On the other hand, I’ve prescribed Adderall to lots of people and none of them have ever gotten any of these things, except mild hypertension. How common are these, really?

The best source for exact numbers is the guidelines by sinister-sounding European organization EUNETHYDIS. I’ll use US medical database UpToDate as a secondary source. Both lump together Adderall and Ritalin – something I’ll be doing too throughout most of this essay, except where it becomes important to distinguish them.

Seizures: EUNETHYDIS doesn’t believe this happens at normal doses. They write:

There are occasionally concerns that, as with other psychotropics, ADHD medications may lower the seizure threshold so as to cause seizures in previously seizure-free individuals. However, in prospective trials, retrospective cohort studies and post-marketing surveillance in ADHD patients without epilepsies, the incidence of seizures did not differ between ADHD pharmacotherapy and placebo [relative risk (RR)] for current versus non-use for methylphenidate, 0.8; RR for atomoxetine, 1.1

UpToDate is so unimpressed by this that they don’t even mention it. If you ask them about seizure risk for ADHD medications, they start telling you about bupropion. Overall I wouldn’t give these medications to people with a known seizure disorder without a neurologist’s approval, but they seem pretty okay otherwise.

Hypertension: Broad agreement from both sources that stimulants cause hypertension. EUNETHYDIS says 1-4 mm systolic, UpToDate says 3-8 mm.

The main problem with hypertension is that it increases risk for things like heart attacks. I calculated an average 40 year old’s risk of heart attack and got 1% over 10 years. Adding on an average Adderall-related increase in blood pressure, I got 1.1%.

What about in high-risk adults? I calculated risk for a 60 year old smoker with high cholesterol and high blood pressure. He has a 30.5% base risk of heart attack. Then I added in a typical Adderall-related rise in blood pressure, and he ended up at 32.0%. So Adderall only increased risk by about 1/1000 per year, even in this worst case scenario. Also, I never meet 60 year old smokers asking for Adderall. Overall this seems not too interesting.

I haven’t looked into other hypertension-related problems like kidney disease as much, but these seem like things you’ll hopefully have a lot of warning about and be able to talk to your doctor about whether to stop stimulants over.

Heart Attack and Stroke: My usual sources fail me here, but BioMed Central Cardiovascular Disorders comes to the rescue. They review three major studies on stroke and heart attack in stimulant patients.

Study #1 finds that stimulant users have 3x more risk of transient ischaemic attack (a small mini-stroke that does no lasting damage), but no increased risk of stroke.

Study #2 is the best and biggest study, and finds that stimulants actually reduce heart attack and stroke. They suspected “healthy-user bias”; that is, only healthy people would use such a supposedly-dangerous medication.

Study #3 is the most recent, and found no increased risk of heart attack or stroke.

UpToDate writes:

Patients receiving stimulant therapy visited the emergency department or clinician office more frequently than those who were not treated with medications because of cardiac symptoms (10.9 versus 9.1 events per 1000 patient-years, adjusted hazards ratio 1.2, 95% CI 1.04-1.38) [26]. The cardiac symptoms included syncope, tachycardia, or palpitations. However, the group that received stimulant therapy was more likely to receive other psychotropic medications (antidepressants and antipsychotic agents), be male, and be non-Hispanic. The incidence of fatal and serious cardiac abnormalities was low and not different between the two groups, and was similar to the rates seen in the general pediatric population.

The 1/1000 extra ER visit per patient year sounds bad, but “palpitations” means “your heart feels like it’s beating in a weird way”, and Adderall clearly causes this, so my guess is this is mostly just people feeling this and freaking out. I have had patients call me after feeling this and freaking out, and we dealt with it, and they were fine. If I hadn’t been available, maybe they would have gone to the ER and turned themselves into a statistic.

There might be some bias in these studies, but overall there doesn’t seem to be much evidence this is worth worrying about unless your risk of heart attack or stroke is already really high.

Psychosis: I saw this a lot when I worked in inpatient. Somebody would take five times the recommended dose, or take more Adderall every time they felt tired until they hadn’t slept for a week, and then they would start hearing voices or feeling like something was crawling on their skin. After a day or two off Adderall, and a night or two getting a normal amount of sleep, they’d be fine. Take enough stimulants and you will become psychotic – but it’s rare on prescribed doses, and it usually resolves pretty quickly.

What dose can cause psychosis? Amphetamine-Induced Psychosis says:

Early studies demonstrated that amphetamines could trigger acute psychosis in healthy subjects. In these studies, amphetamine was given in consecutively higher doses until psychosis was precipitated, often after 100–300 mg of amphetamine. The symptoms subsided within 6 days.

Compare this to the standard daily dose of Adderall of about 10 – 60 mg.

Can psychosis ever happen at normal doses? EUNETHYDIS is skeptical. They write:

Data from population-based birth cohorts indicate that self-reported psychotic symptoms are common and may occur in up to 10% of 11-year-old children. In contrast, the prevalence of psychotic symptoms in children treated with ADHD drugs from RCTs is reported as only 0.19%. While this very low observed event rate in trials is likely to reflect a lack of systematic assessment and reporting, there is no compelling evidence to suggest that the observed event rate of psychotic symptoms in children treated with ADHD drugs exceeds the expected (background) rate in the general population. In the US FDA analysis, ADHD drug overdoses did not contribute significantly to reports of psychosis adverse events.

So basically, “kids are always kind of weird, studies say kids aren’t weird on Adderall, clearly they’re not paying attention, but it doesn’t look like things got any worse.”

UpToDate links these people, who say:

We analyzed data from 49 randomized, controlled clinical trials in the pediatric development programs for these products. A total of 11 psychosis/mania adverse events occurred during 743 person-years of double-blind treatment with these drugs, and no comparable adverse events occurred in a total of 420 person-years of placebo exposure in the same trials. The rate per 100 person-years in the pooled active drug group was 1.48. The analysis of spontaneous postmarketing reports yielded >800 reports of adverse events related to psychosis or mania. In approximately 90% of the cases, there was no reported history of a similar psychiatric condition. Hallucinations involving visual and/or tactile sensations of insects, snakes, or worms were common in cases in children.

I think their use of “psychotic events per person-year” is misleading. Their study includes 5717 people, which means that for them to have 743 person-years each person must have been monitored for two months or so. But if you’re going to get psychotic on stimulants, usually it’s right after the stimulant is started. That means it might be better framed as “11/5717 patients had a psychotic event”, or even “one in every five hundred patients had a psychotic event”. Note that this matches the 0.19% number given by EUNETHYDIS. And the most common psychotic event was a feeling of snakes or insects on the skin which resolved after the drug was stopped, so we’re not talking “person is forever schizophrenic” here.

Also, I feel like EUNETHYDIS makes a good point with the “kids are always weird” thing. Here’s one of the psychotic events mentioned in the paper:

A spontaneous report from the manufacturer of Strattera (atomoxetine) described a 7-year-old girl who received 18 mg daily of atomoxetine for the treatment of ADHD. Within hours of taking the first dose, the patient started talking nonstop and stated that she was happy. The next morning the child was still elated. Two hours after taking her second dose of atomoxetine, the patient started running very fast, stopped suddenly, and fell to the ground. The patient said she had “run into a wall” (there was no wall there). The reporting physician considered that the child was hallucinating. Atomoxetine was discontinued.

Have these people ever seen a child?

The methylphenidate prescribing information suggests an 0.1% risk of psychosis, which matches the other two studies pretty well.

Does stimulant psychosis always get better after the stimulant is discontinued? My strong impression is “yes”, but I am told that this study claims 5% to 15% of stimulant psychosis patients do not recover. I cannot find the full text to figure out exactly what they mean, and it looks like it was done on chronic meth addicts rather than prescription users.

So a few lines of evidence converge on 0.1% – 0.2% of children who use prescription stimulants become psychotic. I don’t know numbers for adults, but a few people who have read drafts of this article mention they have personally seen someone get psychotic on Adderall, which seems anecdotally to argue for a higher rate. I don’t know if those people were using it correctly or using anything else alongside it. Of people who get psychotic on Adderall, perhaps 5-15% stay psychotic after discontinuation (I predict this is about meth-heads and exaggerated).

Aggressive Behavior: This is just going to be the same as psychosis. Adderall isn’t going to magically turn gentle old grandmothers into killing machines. If you’re already a kind of violent guy, and you take a lot of Adderall, maybe it’ll push you over the edge.

Sudden Death: This is usually cardiovascular – something goes very wrong with your heart and it stops beating without warning. But UpToDate writes:

Reports of unexpected deaths of children receiving stimulant therapy have led to concerns that these medications increase the risk of cardiovascular (CV) adverse events, including sudden unexpected deaths (SUD) [1,2]. However, large cohort studies have not shown an increased risk of serious CV adverse events in children treated with stimulant therapy compared with the general pediatric population…

Among adult patients who are either current or new users of stimulant medications, there appears to be no increased risk of serious CV events. This was illustrated in a large retrospective cohort study of adults (age range 25 to 64 years) based on data from four large health plans that was done in parallel with the study performed in children discussed above [3,16]. Multivariant analysis demonstrated a lower risk of serious CV events (defined as myocardial infarction, stroke, and sudden cardiac death) in individuals who were current users of stimulant therapy versus nonusers (relative risk [RR] 0.83, 95% CI 0.72-0.96). In new users of ADHD medications compared with controls, the risk of serious CV events was even lower (RR 0.77, 95% CI 0.63-0.94). However, there may be a modest amount of healthy-user bias that favored the current users of stimulant therapy. To adjust for this potential bias, a multivariant analysis that compared current users with individuals who had used stimulant therapy more than one year ago (defined as remote use) found no difference in the risk of serious CV events (RR 1.03, 95% CI 0.86-1.24). The crude incidence of serious CV events in the overall cohort was 1.34 per 1000 person-years. These results showing no increased risk of serious CV events are consistent with previously discussed studies in pediatric patients.

And EUNETHYDIS:

when the number of patient-years of prescribed medication was incorporated into the evaluation, the frequency of reported sudden death per year of ADHD therapy with methylphenidate, atomoxetine or amfetamines among children was 0.2–0.5/100,000 patient-years [99]. The analysis of 10-year adverse-event reporting in Denmark resulted in no sudden deaths in children taking ADHD medications [5]. While it is recognised that adverse events are frequently under-reported in general, it is likely that sudden deaths in young individuals on relatively new medications may be better reported. Death rates per year of therapy, calculated using the adverse events reporting system (AERS) reports and prescription data, are equivalent for two ADHD drugs (dexamfetamine and methylphenidate): 0.6/100,000/year [37]. (The accuracy of these estimates is limited however, for instance because in moving from number of prescriptions to patient-year figures assumptions must be made about the length of each prescription). It seems likely, using these best available data, and assuming a 50% under-reporting rate, that the sudden death risk of children on ADHD medications is similar to that of children in general.

Despite this, I am always very wary prescribing stimulants to anyone with any history of heart problems. I always make these people go see a cardiologist. The cardiologist always says yeah, sure, whatever, but it makes me feel a lot better.

In General: Probably the most informative passage I’ve seen on the medical risks of stimulants is this one from Misuse Of Study Drugs:

In 1990, there were about 271 emergency room reports involving methylphenidate, 1,727 in 1998, and 1,478 in 2001 [32]. The total number of emergency department visits resulting from use of all psychotherapeutic CNS stimulants was 4091 in 1998, 3644 in 1999, 3336, in 2000, 3146 in 2001 and 3275 in 2002 [33]. There are approximately 25 emergency room deaths per year among up to 3 million users of prescription stimulant drugs (including both those medically prescribed and not prescribed these drugs). Thus, the likelihood of dying from such drugs appears to be approximately 1 in 120,000.

But isn’t 25 deaths per year still bad?

Here’s another passage from the same source:

Intravenous use of prescription stimulants is particularly dangerous. In particular, intravenous (IV) abuse of methylphenidate may result in talcosis. Talcosis is a reaction to talc, a filler and lubricant in methylphenidate and other oral medication. This inflammation reaction occurs in the lungs and related consequences include lower lobe panacinar emphysema.

People aren’t dying because their psychiatrist gave them Adderall 10 mg bid. They’re dying because they ground it up, injected it into their bloodstream, and had their lungs turn into talc. The people dying of stimulant use are doing things so horrifying you could not possibly imagine them even if you took ten times your prescribed dose of Adderall and used all of it to focus on writing a report on the most horrifying ways you could possibly use Adderall. Did you know that 13% of Massachusetts college students have ground up Ritalin and snorted it up their nose? Did you know the first case report of Ritalin abuse involved a patient who was taking 125 Ritalin pills daily? All of these people are out there, and still only 25 people die of stimulant-related causes per year!

My impression is that, in particularly at-risk people, stimulants may add +1/1000 to the risk of heart attacks per year, and +1/10,000 risk of long-term psychosis. Everything else in this category can be rounded down to zero.

III. Addiction

What about addiction risk?

The data on this are really poor because it’s hard to define addiction. If a prescription stimulant user uses their stimulants every day, and feels really good on them, and feels really upset if they can’t get them…well, that’s basically the expected outcome.

Wilens et al finds that over ten years, 10% of adolescents surveyed got high on their medication, and 22% sometimes used more than prescribed. Does that mean those 10% or 22% are “addicted”? Not really – some of them probably have a tough day one time, so they take two Adderall that day and no Adderall the day after. As for getting high – well, a lot of people get high on alcohol who aren’t alcoholics, and a lot of people get stoned who nobody would call addicted to marijuana.

A lot of studies in this area ask the kind of different question of whether children put on stimulants are more likely to be addicted to drugs in general as adults. Most of them find these children are less likely, which is hypothesized to be an effect of successfully treating their ADHD.

And there’s a book on narcolepsy which apparently claims that between less than 1% and 3% of people taking stimulants for that condition get addicted, but I can’t track down their methodology or really anything beyond one reference. And narcoleptics are a different population than ADHD patients and results might not generalize (though that number sounds kind of right).

I don’t think there are good data here, but my intuitions and personal experience is that “addiction” of the sort you get with heroin or tobacco is very rare, at least when responsible people without a personal or family history of addictive behavior take stimulants as prescribed. Most people agree the risk is lower for extended-release stimulants (eg Adderall XR), and very low for Vyvanse.

IV. Tolerance

Tolerance is when you keep needing more and more of a drug to get an effect. In the worst cases, your baseline changes so that you need the drug to feel normal. The concern is that long-term use of Adderall will make your attention naturally worse, so that medicated-you is only as good at concentrating as unmedicated-you was before, and unmedicated-you is even less attentive.

We know tolerance occurs over the short-term, and we encourage patients to take a few days off Adderall every week or two to let their bodies reset. More concerning is whether it happens over the space of years, where people’s bodies adjust in a more permanent way.

The best study of this phenomenon was the Multimodal Treatment of ADHD (MTA) study, which randomized children to be treated with stimulants or “behavioral therapy” (eg learning coping skills, etc). Behavioral therapy for ADHD is not very good and I interpret it as a nice way of saying placebo.

For the first year, the kids getting stimulants did much better on all metrics than behavioral-therapy-only. For the second year, they did a little better. By the third year, they were the same. In the eighth year, which was as long as anyone kept checking, they were still the same.

This is pretty concerning. It sounds like over three years people’s bodies built up some tolerance to stimulants, after which they provided no further benefit. The only saving grace is that there’s no evidence of stimulants ever making people worse than normal (even on people who stopped the medications later).

People have critiqued this study on the grounds that although they started off giving the experimental group stimulants vs. the control group behavioral therapy, any patient could switch treatments at any time and many of them did. By year three when the groups equalized, only 66% of the medication group was on medication, and a full 43% of the therapy-only group was. So maybe this just drowned out any original effect?

The authors of the study are not convinced:

It is tempting to conclude that intensive medication management beyond 14-months could have resulted in continued differences between the randomly assigned treatment groups…In a previous multimodal treatment study where medication was carefully titrated and monitored for two years, treatment gains were maintained for the entire period. However, after 14 months the MTA became an uncontrolled naturalistic follow-up study and inferences about potential advantages that might have occurred with continued long-term study-provided treatment are speculation. Moreover, with one exception (math achievement), children still taking medication by 6 and 8 years fared no better than their non-medicated counterparts despite a 41% increase in the average total daily dose, failing to support continued medication treatment as salutary (at least, continued medication treatment as monitored by community practitioners)…Finally, a previous analysis of the MTA data through 3 years did not provide evidence that subject selection biases towards medication use in the follow-up period accounted for the observed lack of differential treatment effects.

Thus, although the MTA data provided strong support for the acute reduction of symptoms with intensive medication management, these long-term follow-up data fail to provide support for long-term advantage of medication treatment beyond two years for the majority of children—at least as medication is monitored in community settings.

As far as I can tell, pretty much everyone has ignored this, using the usual range of meaningless excuses like “Well, treatment must be individualized to the patient”.

This is very tempting, because for example I have a lot of patients who have been on stimulants for decades, are still very excited about them, and think they’re doing great. Every so often these patients go off their stimulants, are very unhappy, and insist on going back on them again. They say that pre-stimulant, they were scatterbrained and always losing things and missing appointments and failing to do work, and now, after ten years of stimulant treatment, they feel great.

We can imagine ways these people are wrong. Maybe the stimulants worked for the first three years, stopped working so gradually they didn’t notice, and now they only notice the difference between being on stimulants (baseline), and immediate post-stimulant withdrawal (very bad). But this would require a lot of people to be really wrong about their internal experience.

I asked a question on the Slate Star Codex survey about this. People on Adderall more than one month were asked to tell me whether they had no tolerance problems, some tolerance requiring dose escalation, or high tolerance that made the medications stop working entirely. The preliminary results:

Adderall for between one month and one year: (n = 124)
62 (50%) No tolerance, worked as well as ever
57 (46%) Some tolerance, or required dose escalation, but still worked well in general
5 (4%) High tolerance, stopped working

Adderall for one to five years: (n = 117)
33 (28%) No tolerance, worked as well as ever
78 (67%) Some tolerance, or required dose escalation, but still worked well in general
6 (5%) High tolerance, stopped working

Adderall for more than five years: (n = 59)
23 (39%) No tolerance, worked as well as ever
33 (56%) Some tolerance, or required dose escalation, but still worked well in general
3 (5%) High tolerance, stopped working

All three categories were evenly divided between “no tolerance” and “some tolerance but still worked well”, with only about 5% saying the tolerance became a big problem. This matches my clinical experience. So either I’m right, or the problem where they get confused and forget their baseline is affecting my survey-takers.

There are occasional claims that magnesium or some other substance can help reverse Adderall tolerance. As far as I know these have never really been investigated.

So: there’s no good evidence that taking Adderall will actively make your ADHD worse in the long run. There is good evidence from clinical trials that benefits will decrease to zero over the space of a few years, apparently contradicted by the personal experiences of doctors and patients. Overall not sure what to do with this one.

V. Neurotoxicity

There’s some evidence that amphetamines can cause permanent cellular damage, but it’s not clear whether this happens in humans at typical therapeutic doses.

If you give rats very high doses of IV amphetamines, they accumulate so much dopamine in the cytoplasm of their neurons that it causes oxidative stress and destroys dopaminergic nerve terminals. This doesn’t happen to rats at doses matching human doses of Adderall. But it does happen at those doses to squirrel monkeys. At least this is the claim:

Adult baboons and squirrel monkeys were treated with a 3:1 mixture of D/L–amphetamine similar to the pharmaceutical Adderall for 4 weeks. Plasma concentrations of amphetamine (136±21 ng/ml-1) matched the levels reported in human ADHD patients after amphetamine treatment lasting 3 weeks (120–140 ng/ml-1) or 6 weeks in the highest dose (30 mg/day-1) condition (120 ng/ml-1). When the animals were killed 2 weeks after the 4-week amphetamine treatment period, both non-human primate species showed a 30–50% reduction in striatal dopamine, its major metabolite (dihydroxyphenylacetic acid (DOPAC)), its rate-limiting enzyme (tyrosine hydroxylase), its membrane transporter and its vesicular transporter. These consequences are similar, if not identical to the effects of neurotoxic doses in rodents.

I’m not really sure what they’re getting at here – surely they’re not saying just one month of Adderall permanently decreases striatal dopamine by 50%? But it sounds like something bad is happening, and since humans are more like monkeys than rats, maybe there’s cause for concern.

What would it look like if people got this kind of brain damage? One likely possibility is Parkinson’s disease, a condition caused by poor dopaminergic function in the brain. If you were going to tell a story about how Adderall could cause long-term neurotoxic damage, it would look like gradual decrease of brain dopaminergic function without obvious effects through most of the lifespan (since most people have dopaminergic function to spare). As the patient got older and started naturally losing brain function, Parkinson’s would appear. This happens to genetically and environmentally predisposed people anyway (which is why old people get Parkinson’s so often), but in this scenario amphetamine use would present an extra risk factor.

Several studies have shown that meth addicts do have higher rates of Parkinson’s disease. This one says people hospitalized for meth addiction are 60% more likely to get Parkinson’s than people hospitalized for other reasons. This one finds Parkinson’s rates three times higher in meth addicts compared to non-drug-users.

What about at therapeutic doses? This article claims there was a study that found people who used Benzedrine and Dexadrine (early forms of prescription amphetamine) in the 1960s have rates of Parkinson’s Disease about 60% higher than non-users today, but I can’t find the study itself and I don’t know the methodology. Another study finds similar results. Since both ADHD and stimulant addiction are very hereditary, you could make an argument that people who already have problems with their dopamine system are more likely to get Parkinson’s later on. There’s a little bit of conflicting evidence for this. Also, ADHD patients might have three times the rate of dementia with Lewy bodies, a condition closely related to Parkinson’s. On the other hand, there doesn’t seem to be any genetic connection. Overall my guess is this is not what’s going on.

About 1-2% of people will get Parkinson’s if they live long enough. If Adderall increases that risk 60%, then presumably it could cause a 1% absolute increase in risk.

Some people claim various substances (magnesium, minocycline, etc) will protect your brain from amphetamine neurotoxicity. None of these have been studied in anywhere near the depth they would need to be to make me feel comfortable with this.

The good news is that as far as anyone can tell, Ritalin doesn’t cause these problems, even if you give it to rats at super-high doses. It seems to be a difference in the mechanism of action. I’ve been talking about Adderall this whole post because it’s the most commonly-used stimulant and some studies have suggested it’s more effective for a few people, but this might be a strong argument in favor of starting with Ritalin and only switching to Adderall if Ritalin fails.

So overall there is plausible, but not incontrovertible, evidence linking Adderall to a somewhat increased risk of Parkinson’s disease in old age.

VI. Summary

My impression is that the risks of proper, medically supervised Adderall use are the following:

1. High risk of minor short-term side effects that might make you want to stop taking the medication with no long-term issues
2. Extremely low risk of serious medical side effects like stroke or heart attack, except maybe in a few very vulnerable populations
3. Maybe one percent risk, but not literally zero risk, of addiction if patients are well-targeted by their doctors and use the medication responsibly.
4. Perhaps one in five hundred risk, but not literally zero risk, of psychosis. Some anecdotal evidence suggests it is more common than this. Most of these cases will be mild and resolve quickly. Some people find a very small number of cases of stimulant-induced psychosis may be permanent, though I still find this hard to believe.
5. Some evidence for tolerance after several years, though most patients will continue to believe it is helping them. No sign of supertolerance where it actually makes the condition worse.
6. Plausibly 60% increased relative risk (+~1% absolute risk) for Parkinson’s disease with long-term use; this is unlikely with Ritalin.
7. Unknown unknowns.

Of these, I find the psychosis, tolerance, and Parkinson’s to be the most concerning. My most likely change after doing this research is to prescribe my patients who need stimulants Ritalin instead of Adderall. Most people find both stimulants work about equally well, and it seems potentially slightly safer. Given that the increased risk is only 1% in absolute terms, is still unclear, and may be incurred after only a few weeks of use, I’m not planning to force my patients who are currently happy on Adderall to switch to Ritalin right now.

I am pretty upset about the overall terrible state of this research. In particular, nobody except the MTA takes the possibility of tolerance seriously, and the MTA results really ought to have inspired a lot more soul-searching and hand-wringing than they actually did. The numbers on addiction and psychosis are inexcusably terrible given how easy they would be to collect. Getting good data on the Parkinson’s risk would be harder, but one so-far-unexplored possibility would be to compare past prescription Adderall history to past prescription Ritalin history in Parkinson’s patients to adjust for the potential ADHD confounder. I really think somebody should do this.

Despite all this, I compare these risks to the risks of eating one extra strip of bacon per day and decide that overall this is not enough for me to stop prescribing stimulants to patients who I think might benefit from them. These are about the standard level of side effects for a powerful medication and I think there’s a major role for these in ADHD treatment as long as patients are well-informed about the risks they’re taking.

PS: I don’t accept blog readers as patients, and I won’t prescribe you Adderall just because you liked this post.

A History Of The Silmarils In The Fifth Age

[Spoiler warning for The Silmarillion]

I.

The Silmarillion describes the fate of the three Silmarils. Earendil kept one, and traveled with it through the sky, where it became the planet Venus. Maedhros stole another, but regretted his deed and jumped into a fiery chasm. And Maglor took the last one, but threw it into the sea in despair.

Well, Venus is still around. But what happened to the latter two? Surely over all the intervening millennia, with so many people wanting a Silmaril, they haven’t just hung around in the earth and ocean?

After some research, I’ve developed a couple of promising leads for the location of the Silmarils in the Fifth Age.

II.

I previously sketched out the argument that Maglor’s Silmaril probably belongs to a Los Angeles crime lord.

The movie Pulp Fiction centers around a mysterious briefcase. We’re never told exactly what’s inside, but we get some clues:

1. It’s described as “so beautiful” and captivates anyone who looks at it
2. It shines with an inner light
3. When Jules and Vincent are trying to get it, all the shots aimed at them miss, implying they’re miraculously immune to bullets, implying that they’re on some kind of divine quest.
4. Marsellus Wallace really wants to get it, and keeps killing anyone else who has it

So far this is only suggestive, but there’s more. While searching for the briefcase, Jules (!) keeps quoting a verse:

The path of the righteous man is beset on all sides by the inequities of the selfish and the tyranny of evil men. Blessed is he who, in the name of charity and good will, shepherds the weak through the valley of the darkness, for he is truly his brother’s keeper and the finder of lost children. And I will strike down upon thee with great vengeance and furious anger those who would attempt to poison and destroy my brothers.

They describe this as Ezekiel 25:17, but it isn’t. In fact, it isn’t anywhere in the Bible, and it doesn’t match any Biblical story. This isn’t from the Old Testament at all. It’s a description of the life of Maglor in the Silmarillion!

During the First Age, Maglor ruled “Maglor’s Gap”, a valley which connected the lands of the Elves and the lands of Morgoth. Maglor held Maglor’s Gap for 450 years until Morgoth finally conquered the valley; Maglor led the retreat of his people, thus “shepherding the weak through the valley of darkness”.

He fled to the fortress of his brother, Maedhros, in Himling, where he helped defend Maedhros’ lands and people in battle – making him “his brother’s keeper”.

In the ensuing battles, he captured the young Elrond and Elros, who had been orphaned after their parents fled across the sea, and adopted them – making him “the finder of lost children”.

As for “striking down with great vengeance and furious anger those who would attempt to poison and destroy my brothers”, that’s about as Noldor as it gets.

What is going on here, and why do we keep finding these connections to Maglor?

Maglor is unique as possibly the only Noldo still remaining in the world. According to Wikipedia:

Maglor, along with Galadriel and Gil-galad, was the greatest surviving Noldo at the beginning of the Second Age. There is speculation that he remained even after the Third Age in Middle-earth, forbidden forever from returning to Valinor.

If he were still alive in our times, he would remain bound by his oath and be hunting the Silmaril. So: could Marsellus Wallace, the mysterious gang boss who wants the briefcase so badly, be Maglor himself? Given that the name “Maglor” is a Sindarinization of his birth name “Makalaure”, “Marsellus” doesn’t even sound like much of a pseudonym.

The main argument against this point is that Tolkien’s elves are usually depicted as fair-skinned and lithe, but Marsellus Wallace is shown in the movie as a big black guy. Does this disprove the theory?

It would, unless Marsellus were under some kind of magical glamor to hide his true appearance. And there’s actually some evidence for this.

There’s one character in Pulp Fiction who is clearly able to cast illusion-related magic: Mia Wallace. In the parking lot of the restaurant, she tells Vinnie “Don’t be a…”. Then she traces a square in the air with her finger, and the square appears in glittering light. Marsellus Wallace is married to someone who can cast visual illusions.

But why should we believe Marsellus’ appearance is itself such an illusion? Well, in the scene with Jules and Brett, Jules puts a gun to Brett’s head and asks him what Marsellus looks like. Brett says he looks like a tall bald black guy, which seems to satisfy Jules.

The hit men try to play this off as some kind of intimidation thing, but they’re just going to shoot Brett anyway – there’s no need to intimidate him. It would only make sense if they’re actually checking how Marsellus appears to Brett – ie whether a certain illusion he’s projecting is working. When they follow up with “Does he look like a bitch?“, this is their foul-mouthed way of asking whether he looks androgynous. When Brett confirms that he looks masculine, this seems to satisfy the hit men, who then go ahead and shoot him. Unclear why they’re expecting the illusion to fail in Brett’s case, but it seems like if it has they’ll need to interrogate him further and maybe track down anybody else who might have learned too much.

How is Mia Wallace able to cast these illusions?

I would guess that “Mia” is actually Maia, ie one of the Maiar who is sent from Valinor to guide Elves and Men with their good counsel and magic powers. There’s a previous example of a female Maia marrying an elflord to guide him: Melian and Thingol. Mia is following in this tradition, and just as Melian granted Thingol’s kingdom invulnerability to attack, so Mia grants Maglor/Marsellus the ability to look like a big muscular black guy.

We actually have further proof of this in the movie. Mia overdoses on heroin and goes unconscious. It looks like she goes a really long time without breathing. You get anoxic brain injury in like four or five minutes; Mia was out way longer than that. But once they give her adrenaline, she instantly and completely recuperates in a medically implausible way. Suffice it to say that she’s proven beyond a shadow of a doubt that she doesn’t have a human circulatory system, and given us at least strong evidence that she is literally immortal.

I would guess that Maglor survived, found his Silmaril, lost his Silmaril again, and that Pulp Fiction is an account of him getting it back. “Quentin Tarantino” is probably a made-up pen name for a group of elvish historians – the name “Quentin” obviously deriving from “Quendi”, the elvish word for elves. “Tarantino” is more obscure, but it may be a reference to Tar-Atanamir, the Numenorean king who refused to die when his time came – something which must carry a lot of metaphorical associations for any elves remaining on Earth.

If all of this is true, Maglor’s Silmaril probably remains with Maglor in his Los Angeles mansion.

III.

The fate of Maedhros’ Silmaril is less clear, but one promising possibility is linked with the fate of Utumno.

Utumno was the fortress of the dark god Melkor before the First Age. It was built in the far north of Middle-Earth, “upon the borders of the regions of everlasting cold”. Tolkien Gateway writes that “the frigid temperatures of the northern regions were thought to originate from the evil of [Melkor’s] realm”.

What was Utumno like? Like most of Tolkien’s villains, Melkor was at least partly a technologist; his realm was one of forges and smithies ceaselessly building weapons for his war against the gods. This page describes it as “a fortress for war, with many armories, forges, dungeons and breeding pits.” Some of the descriptions sound like it was emitting pollution, destroying the land around it: “The lands of the far north were all made desolate in those days; for there Utumno was delved exceeding deep, and its pits were filled with fires and with great hosts of the servants of Melkor.”

Who manned these factories? Enslaved elves. As per the book, “All those of the Quendi who came into the hands of Melkor, ere Utumno was broken, were put there in prison, and by slow arts of cruelty were corrupted and enslaved”.

Eventually the gods decided enough was enough and marched against Utumno with a mighty host led by Tulkas, God of War. He wrestled with Melkor, defeated him, and bound him with a mighty chain.

What happened to Utumno after this? The Silmarillion is vague, but in retrospect it’s super obvious. What happened to the magical factory at the North Pole run by elves? Everyone knows the answer to that one!

Presumably Tulkas and the other gods, after defeating Melkor, decided it was poetically appropriate to turn Utumno from a place of darkness to a wonderland of holiday cheer. The elves agreed to stay on to help, and they repurposed Melkor’s forges to create toys for children around the world.

“Santa Claus” supposedly derives from St. Nicholas, on the grounds that “Santa” means “saint” and “Claus” is short for “Nicholas”. But “Santa” means a female saint; a male saint is “San”. Santa is male, so a more reasonable derivation would be “San Tulkas”. Once a year, Tulkas goes forth and distributes the toys created by the elves of Utumno.

(remember, the Silmarillion describes Tulkas as a huge bearded man who “laughs ever, in sport or in war, and even in the face of Melkor he laughed in battles before the Elves were born”. And remember, of his wife Nessa, it says “Deer she loves, and they follow her train whenever she goes in the wild”. Having deer follow your family around everywhere seems sounds pretty annoying, but at least it gives you a ready-made supply of draft animals.)

Since we never see Santa’s workshop, it must be hidden from the world in the same manner as the Undying Lands. How does Tulkas cross back into the mortal world to deliver gifts?

The only successful example of such a journey we have from Tolkien is that of Earendil, who travels from Middle-Earth to the Undying Lands using a Silmaril worn on his brow. Later, even after the two worlds are separated entirely, he is able use the same Silmaril to voyage through the sky in his flying boat. “The wise have said that it was by reason of the power of that holy jewel that they came in time to waters that no vessels save those of the Teleri had known”. So presumably any living being with a Silmaril upon their head can fly through the gulfs between the worlds safely.

Tulkas is a god and should have no trouble finding the only unclaimed Silmaril, the one Maedhros dropped into a chasm in the earth. His main issue would be preventing the surviving Noldor from learning what he has and invoking their vendetta. He would have to disguise it as something else, something so ridiculous that the stick-up-their-ass Noldor would never think to identify it with their holy jewels.

So…

Rudolph the Red-Nosed Reindeer
Had a very shiny nose
And if you ever saw it
You would even say it glows…

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Preregistration Of Hypotheses For The SSC Survey

[This post is about the 2018 SSC Survey. If you’ve read at least one blog post here before, please take the survey if you haven’t already. Please don’t read on until you’ve taken it, since this could bias your results.]

I’m preregistering my hypotheses for the survey this year. So far I’ve glanced at Google’s bar graphs for each individual question but haven’t started exploring relationships yet, so I’m not cheating too badly. I’ll still look for things I haven’t preregistered, but I’ll admit they’re preliminary results only. This is the stuff I’ve been thinking about beforehand and will be taking more seriously:

1. I plan to replicate the general thrust of last year’s results reported in Can We Link Perception And Cognition on the sample of new people who didn’t take the survey last year. In particular, I’m expecting that weirder, more autistic, more liberal, more schizophrenic, and more transgender people will be more likely to display unusual patterns of perception (hollowness or ambiguity) in the Hollow Mask illusion. I expect this to become much more obvious since I’ve included three examples of the illusion this year including one that seems to give a wider diversity of results.

1a. I plan to replicate the results from last year that people who were better at noticing duplicate “the’s” are more likely to display unusual patterns of perception on the Hollow Mask illusion.

2. I plan to conceptually replicate Mitchell et al’s study showing that autistic people are less susceptible to the Shepherd Table Illusion.

3. I plan to conceptually replicate Caparos et al’s study showing that politically further-right people are more likely to use global processing on a Navon task (eg when there’s an H made of tiny Es, they see the H more than the Es).

4. I plan to investigate a general construct of “first sight and second thoughts” that involves people being better able to see what’s actually there, and less susceptible to illusions, priors, stereotypes, and assumptions. This will involve correlations between the two Duplicate Thes illusions, the Hollow Mask illusion, the Shepherd Table illusion, the Cookies illusion, the Parentheses palindrome, the Map riddle, the Surgeon riddle, the Switched Answers task, the Cognitive Reflection test, and the Wason task.

4a. If I can figure out how to get a common factor out of all of these, I plan to see if it’s the same thing I’m looking at in 1, and how it relates to the same groups.

4b. Whether this relates to a general willingness to believe strange or unpopular things. Check vs. AI risk concern and HBD support.

5. I plan to investigate a general construct of “ambiguity tolerance” that involves people being okay with a superposition of different conflicting ideas. This will involve correlations between ambiguous results on the Hollow Mask illusion, the Spinning Dancer illusion and the Squares-Circles illusion, and with answers to the questions from the Tolerance Of Ambiguity and Tolerance of Uncertainty scales.

5a. Whether perceptual ambiguity relates to cognitive ambiguity. I want to check whether people with high ambiguity tolerance on the optical illusions are more likely to say their political opponents have some good points, are less likely to say their political opponents are evil, and are less likely to say the existing political system is justifiable. Also if they’re more likely to enjoy puns.

5b. To what degree this is the same construct as (1), and is stronger among the same demographic groups.

5c. I also want to see if people with high ambiguity tolerance give less extreme answers on questions in general. I’ll probably use Ambition, Social Status, Romantic Life, and Morality for this, just because these seem like complicated questions there’s no obvious right answer to.

5d. I plan to confirm previous studies showing low ambiguity tolerance correlates with conservative philosophy; check vs. Political Spectrum 1-10. I predict that this will be stronger for populists than for “business conservatives”, so I expect the low ambiguity correlation will be weak for generic conservatives, stronger for Trump supporters, strongest for people who identify as alt-right.

6. I plan to investigate whether autistic people are more likely to give process-centered rather than person-centered answers to the two political categorization questions (categorizing Nazis, categorizing civil disobedience on gay marriage). That is, neurotypical people will be more likely to categorize based on which side wins, and autistic people will be more likely to categorize based on what procedures were followed (eg violence, civil disobedience).

6a. I also want to investigate how these correlate with political views. I may end up controlling for this as a confounder in (6) above.

6b. This is a totally wild out-of-left field idea, but I suppose I should check how these relate to the Navon figures since they’re both about categorization.

7. I plan to confirm or disprove, once and for all, whether our community has more older siblings. For lack of a fancier way to do this, I’ll take the set of all people who have exactly one sibling, and see what percent of them are older vs. younger. If it’s significantly above 50% older, I’m going to interpret this as a birth order effect. I’ll do the same with the set of people who have two siblings, three siblings, etc, and combine them all for a final determination. Half-siblings will be ignored. If you have any problems with this methodology, tell me now.

7a. If I find we’re disproportionately older, try to use subgroups to figure out where the effect is stronger or weaker, to try to find exactly what’s going on. For example, are Less Wrongers more older-skewed than SSC readers in general?

7b. Birth order by autism, Openness, and IQ/SAT.

7c. One traditional birth-order claim is that younger children are more rebellious, so check birth order vs. people who think system needs to be fine-tuned or destroyed.

8. I plan to conceptually replicate studies showing that the more older brothers (but not younger brothers, or older or younger sisters) you have, the more likely you are to be gay.

8b. See if this predicts anything else: bisexuality, transgender, gender non-conformity, political leftism, autism, possibly ‘first sight and second thoughts’, possibly ‘ambiguity tolerance’.

9. I plan to see whether people with ADHD are more likely to prefer the buzzing city aesthetic to the quiet village aesthetic, more likely to rate themselves as more risk-taking, and more likely to describe themselves as ambitious.

10. I plan to investigate the hypothesis about sexual harassment mentioned here: that it’s higher in gender imbalanced industries only due to potential-perpetrator-to-victim ratio. I predict that in relatively gender imbalanced industries (in terms of survey categories, all three Computers fields, Finance, Physics, and Mathematics) compared to relatively gender-balanced industries (Health Care, Psychology, Art, Law, Biology), a higher percent of women will report being harassed at work, but the percent of men reporting harassing at work will remain the same.

10b. I predict that the more people identify with social justice, and the more positively they feel about feminism, the more likely they are to report both being harassed and harassing others, due to more awareness and lower threshold to report. I predict poor social skills and autism spectrum will predict more likely to say one is a harasser, due to causing unintentional offense. I predict people who are harassed more at work will also be harassed more outside of work.

11. A long time ago, I randomized people into groups and made them read articles on AI risk to see how it changed their minds. The effect mostly persisted after one month. Since those groups were randomized by birth date, and I asked respondents their birthdates, I plan to see if those effects continue to persist after a year.

These are mostly conceptual descriptions of what I’m going to do rather than algorithmic descriptions of exactly how I’m going to process the data. Part of that is that a lot of this involves statistical techniques at the limits of my abilities and I’m going to have to see if I can actually do them. Most important, I would like to learn enough about factor analysis to actually check for a General Factor Of First Sight/Second Thoughts, and a General Factor of Ambiguity Tolerance. If I have them, I’d like to use them to see if they correlate with the other things I’m wondering if they correlate with. If I can’t make this work or beg someone else to do it for me, I’ll just eyeball the correlations between individual questions, see which ones are highest, and maybe take an average of those questions or something.

Mostly I won’t be doing anything fancy or with too many branching paths to the data, but I plan to operationalize autism in two ways. First, a scale where professional diagnosis equals 3, self-diagnosis equals 2, family member equals 1, and no personal/family history equals 0. Second, the Autism Spectrum Quotient test I made people take at the bottom of the survey. I’m not at all confident these will correlate more than a weak amount, but I’ll try it and see. I might also try some kind of average of the two measures. Since there are a few things I expect to be correlated with autism – mathematical careers, bad response to clothing tags, poor social skills – I might check to see whether the first measure, the second measure, or the combination does a better job of predicting these, and stick with whichever one does. I’ll try not to base which measure I use on any of the variables I’m actually testing.

Please Take The 2018 SSC Reader Survey

If you’re reading this and have previously read at least one Slate Star Codex post, please take the 2018 SSC Survey.

This year’s survey is in three sections. If you’re strapped for time, just take Section 1. If you have a little more time, take both Sections 1 and 2. If you have a lot of time, take all three sections. Each section will take about ten minutes. There’s some more information on the survey itself.

You can talk about it in the comments, but don’t read them until you’re done taking the survey.

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Links 12/17: Silent Site, Holy Site

The world’s largest hotel is in Saudi Arabia, hosts 10,000 guests, and looks pretty much how you would expect the world’s largest hotel in Saudi Arabia to look.

Legends of Chinese immigrants in California, unsourced, sometimes a bit implausible. “John the Chinese laundry man was the laughingstock of Weaverville, California. For months he washed the Anglo miners’ clothes and never charged a penny for his services. But a year later one of the miners came across John wearing fine clothes in Sacramento. He had washed enough gold dust out of pants cuffs and shirttails to set himself up for life.”

Common vs. Specific Factors In Psychotherapy – Opening The Black Box. Key quote: “Neither variability in competence nor adherence [to the principles of the therapy involved] was related to patient outcome…extent of training might also not be relevant to outcome.”

Magic cards with @dril quotes as text. EG 1, 2

The size of a nation’s legislature tends to be about the cube root of its population. Also, the US House of Representatives is “one of the world’s most undersized” legislatures.

Sam Altman on the increasingly repressive climate in the Bay Area; makes some of the same points as my article about Kolmogorov complicity, but better, and with more personal experience. Tyler Cowen’s response. Related: GSS survey data shows high IQ predicts “free speech absolutism”.

Related: Heterodox Academy offers OpenMind, “a free, online platform designed to depolarize communities and foster mutual understanding across differences”.

More on the link between autism and transgender, with a few more studies than I’d seen before. Although only 5-10% of autistics have gender dysphoria, up to 25%-50% of transgender people may be autistic.

Late Christmas shopping idea: gravitational distortion placemats.

Contra Turkheimer and others, a new team finds no tendency for environmental influence on intelligence to be stronger in the poor, not even in the United States. [EDIT: Or maybe it doesn’t contradict Turkheimer, just show his results don’t extend to adults]

Also, even though the obvious evo psych explanation for bitter taste is that it’s supposed to warn us of potentially toxic molecules, there’s no real relationship between bitterness and toxicity.

The New I-66 Tolls Offer Great Insight Into Commuter Psychology. Commuters okay with a road being illegal to use (except for certain groups), but angry when it was legal to use but with a very high toll.

People Learned To Survive Disease; We Can Handle Twitter. Interesting take on cultural evolution including a micro-review of new James Scott book.

Some rare good news: the grad student waiver tax will not be in the final tax bill.

This month in the FDA: liberalization of rules on genetic tests like 23andMe (official statement, media summary). Related: probably legal for police to get your DNA from a genetic testing company if you’re a suspect; some good discussion of the exact warrant requirements buried in the Reddit comments. 23andMe has announced they will fight any such requests; unclear what other companies will do.

No, it’s not just your imagination: recent mystery interstellar asteroid Oumuamuamuamuamuamuamua does look kind of like a spaceship. Some good discussion in the comments here. And Robin Hanson on what it might teach us about interstellar space.

Venus only has one earthquake every hundred million years or so, but it’s a doozy.

Was James K. Polk the greatest US president? And Garrett Jones on which US president made the largest positive contribution to global income (hint: it’s James K. Polk)

The 100 most-discussed scientific papers of the year. A combination of health-relevant, politics-relevant, clickbaity, and groundbreaking new science. My girlfriend is lead author of #16.

The latest thing AI is outperforming humans at, this time very close to my heart: fantasy cartography. Example here. H/T Gwern.

Related, though you’ve probably seen it already: DeepMind has made an AI that can learn to play at superhuman level in various games including chess, Japanese chess, and Go – after just a few hours of practice.

Related: MIRI’s 2017 fundraiser. For those of you who don’t know, they’re a research institute that looks into the possibility of future AI superintelligence and how to make it safe for humans. I can vouch for them as good people; see also Zvi Mowshowitz’s I Vouch For MIRI.

Percent of people in different countries on who think life is better vs. worse than fifty years ago. More vs. less market freedom seems to be pretty big explanatory variable; being in Latin America doesn’t help.

This article purports to rank all generals and prove that Napoleon was the best. It’s gotten a lot of coverage, but it seems trivially wrong to me – as far as I can tell, it gives each general credit for their win vs. loss record, but doesn’t adjust for number of battles. So a general who fought 30 battles and won 50% would be “better” than a general who fought 10 battles and won 100%. As such, I can’t endorse it – but it’s a cool way of looking at things and I hope someone tries something similar and does it right – which would probably involve starting with a prior that each general is average and treating each battle as a new piece of Bayesian evidence.

We often hear that the amount parents talk to their baby is vital in explaining their development and life outcomes, so Scientific American profiles a South American tribe where parents practically never talk to their babies. But how many people from that tribe get into Ivy League colleges, HUH SCIENTIFIC AMERICAN?

In the IGM poll of economists, which I’ve cited a few times here as a good measure of expert opinion, top economists generally favor repealing Net Neutrality. H/T Buck, who writes that “if you think that repealing net neutrality is clearly bad, I’d love to bet you about it. Betting is a tax on bullshit and I feel like the internet is particularly full of bullshit at the moment; I’d like to do my part to clean it up a little while also hopefully making a little money. I’d love to hear your concrete predictions about how the world will be worse as a result of the repeal of net neutrality. I’m willing to spend at least a thousand dollars betting on this topic.”

Bay Area politicians die as they live: causing delays for local commuters.

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OT91: Opaean Thread

This is the bi-weekly visible open thread. Post about anything you want, ask random questions, whatever. You can also talk at the SSC subreddit or the SSC Discord server. Also:

1. Some people arguing at length against my post on taxes and on harassment. But comment of the week is Cameron Mahoney on pharma scams.

2. New ad for for the AI Safety Reading Group, meets every Wednesday night on Skype.

3. Related: MIRI is holding their annual fundraiser.

4. Some very minor updates to the Mistakes, Comments, and Predictions pages on the top.

5. I know many people left Patreon because of their plan to levy big fees on small donations. Patreon has since said they’re not going to do that. If you left my Patreon because of that, you may want to un-leave. I was considering switching from a per-post to per-month donation system anyway , just because most people program their per-post donations so they only count for the first few posts per month anyway, but I’m not sure. I’ll probably include a question on the survey about what people prefer.

6. Speaking of which, I’ve been busy working on a new survey. Expect it out in a few days to weeks.

7. Merry holidays to everyone!

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Classified Thread 4: Vinson Classif

This is the…monthly? bimonthly? occasional?…classified thread. Post advertisements, personals, and any interesting success stories from the last thread.

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What To Make Of New Positive NSI-189 Results?

I.

I wanted NSI-189 to be real so badly.

Pharma companies used to love antidepressants. Millions of people are depressed. Millions of people who aren’t depressed think they are. Sell them all a pill per day for their entire lifetime, and you’re looking at a lot of money. So they poured money into antidepressant research, culminating in 80s and 90s with the discovery of selective serotonin reuptake inhibitors (SSRIs) like Prozac. Since then, research has moved into exciting new areas, like “more SSRIs”, “even more SSRIs”, “drugs that claim to be SNRIs but on closer inspection are mostly just SSRIs”, and “drugs that claim to be complicated serotonin modulators but realistically just work as SSRIs”. Some companies still go through the pantomime of inventing new supposedly-not-SSRI drugs, and some psychiatrists still go through the pantomime of pretending to be excited about them, but nobody’s heart is really in it anymore.

How did it come to this? Apparently discovering new antidepressants is really hard. Part of it is that depression has such a high placebo response rate (realistically probably mostly regression to the mean) that it’s hard for even a good medication to separate much from placebo. Another part is that psychopharmacology is just a really difficult field even at the best of times. Pharma companies tried, tried some more, and gave up. All the new no-really-not-SSRIs are the fig leaf to cover their failure. Now people are gradually giving up on even pretending. There are still lots of exciting possibilities coming from the worlds of academia and irresponsible self-experimentation, but the Very Serious People have left the field. This is a disaster, insofar as they’re the only people who can get things through the FDA and into the mass market where anyone besides fringe enthusiasts will use them.

Enter NSI-189. A tiny pharma company called Neuralstem announced that they had a new antidepressant that worked on directly on neurogenesis – a totally new mechanism! nothing at all like SSRIs! – and seemed to be getting miraculous results. Lots of people (including me) suspect neurogenesis is pretty fundamental to depression in a way serotonin isn’t, so the narrative really worked – we’ve finally figured out a way to hit the root cause of depression instead of fiddling around with knobs ten steps away from the actual problem. Irresponsible self-experimenters managed to synthesize and try some of it, and reported miraculous stories of treatment-resistant depressions vanishing overnight. Someone had finally done the thing!

There are many theories about what place our world holds in God’s creation. Here’s one with as much evidence as any other: Earth was created as a Hell for bad psychiatrists. For one thing, it would explain why there are so many of them here. For another, it would explain why – after getting all of our hopes so high – NSI-189 totally flopped in FDA trials.

I don’t think the data have been published anywhere (more evidence for the theory!), but we can read off the important parts of the story from Neuralstem’s press release. In Stage 1, they put 44 patients on 40 mg NSI-189 daily, another 44 patients on 80 mg daily, and 132 patients on placebo for six weeks. In Stage 2, they took the people from the placebo group who hadn’t gotten better in Stage 1 and put half of them on NSI-189, leaving the other half on placebo – I think this was a clever trick to get a group of people pre-selected for not responding to placebo and so avoid the problem where everyone does well on placebo and so it’s a washout. But all of this was for nothing. On the primary endpoint – a depression rating instrument called MADRS – the NSI-189 group failed to significantly outperform placebo during either stage.

Neuralstem’s stock fell 61% on news of the study. Financial blog Seeking Alpha advised readers that Neuralstem Is Doomed. Investors tripped over themselves to withdraw support from a corporation that apparently was unable to handle the absolute bread-and-butter most basic job of a pharma company – fudging clinical trial results so that nobody figures out they were negative until half the US population is on their drug.

From last month’s New York Times:

The first thing you feel when a [drug] trial fails is a sense of shame. You’ve let your patients down. You know, of course, that experimental drugs have a poor track record – but even so, this drug had seemed so promising (you cannot erase the image of the cancer cells dying under the microscope). You feel as if you’ve shortchanged the Hippocratic Oath […]

There’s also a more existential shame. In an era when Big Pharma might have macerated the last drips of wonder out of us, it’s worth reiterating the fact: Medicines are notoriously hard to discover. The cosmos yields human drugs rarely and begrudgingly – and when a promising candidate fails to work, it is as if yet another chemical morsel of the universe has been thrown into the dumpster. The meniscus of disappointment rises inside you: That domain of human biology that the medicine hoped to target may never be breached therapeutically.

And so the rest of us gave a heavy sigh, shed a single tear, and went back to telling ourselves that maybe vortioxetine wasn’t exactly an SSRI, in ways.

II.

But the reason I’m writing about all of this now is that Neuralstem has just put out a new press release saying that actually, good news! NSI-189 works after all! Their stock rose 67%! Investment blogs are writing that Neuralstem Is A Big Winner and boasting about how much Neuralstem stock they were savvy enough to hold on to!

What are these new results? Can we believe them?

I’m still trying to figure out exactly what’s going on; the results themselves were presented at a conference and aren’t directly available. But from what I can gather from the press release, this isn’t a new trial. It’s new secondary endpoints from the first trial, that Neuralstem thinks cast a new light on the results.

What are secondary endpoints? Often during a drug trial, people want to measure whether the drug works in multiple different ways. For depression, these are usually rating scales that ask about depressive symptoms – things like “On a scale of 1 to 5, how sad are you?” or “How many times in the past month have you considered suicide?”. You could give the MADRS, a scale that focuses on emotional symptoms. Or you could give the HAM-D, a scale that focuses more on psychosomatic symptoms. Or since depression makes people think less clearly, you could give them a cognitive battery. Depending on what you want to do, all of these are potentially good choices.

But once you let people start giving a lot of tests, there’s a risk that they’ll just keep giving more and more tests until they find one that gives results they like. Remember, one out of every twenty statistical analyses you do will be positive at the 0.05 level by pure coincidence. So if you give people ten tests, you’ve got a pretty good chance of getting one positive result – at which point, you trumpet that one to the world.

Statisticians try to solve this loophole by demanding researchers pre-identify a primary endpoint. That is, you have to say beforehand which test you want to count. You can do however many tests you want, but the other ones (“secondary endpoints”) are for your own amusement and edification. The primary endpoint is the one that the magical “p = 0.05 means it works” criteria gets applied to.

Neuralstem chose the MADRS scale as their primary endpoint and got a null result. This is what they released in July that had everybody so disappointed. The recently-released data are a bunch of secondary endpoints, some of which are positive. This is the new result that has everybody so excited.

You might be asking “Wait, I thought the whole point of having primary versus secondary endpoints was so people wouldn’t do that?” Well…yes. I’m trying to figure out if there’s any angle here besides “Company does thing that you’re not supposed to do because it can always give you positive results, gets positive results, publishes a press release”. I am not an expert here. But I can’t find one.

The pattern of positive results shows pretty much the random pattern you would expect from spurious findings. They’re divided evenly among a bunch of scales, with occasional positive results on one scale followed by negative results on a very similar scale measuring the same thing. Most of them are only the tiniest iota below p = 0.05. Many of them only work at 40 mg, and disappear in the 80 mg condition; there are occasional complicated reasons why drugs can work better at lower doses, but Occam’s razor says that’s not what’s happening here. One of the results only appeared in Stage 2 of the trial, and disappeared in Stage 1 and the pooled analysis. This doesn’t look exactly like they just multiplied six instruments by two doses by three ways of grouping the stages, got 36 different cells, and rolled a die in each. But it’s not too much better than that. Who knows, maybe the drug does something? But it sure doesn’t seem to be a particularly effective antidepressant, even by our very low standards for such. Right now I am very unimpressed.

III.

Except…why did their stock jump 67%? We just got done talking about the efficient market hypothesis and the theory that the stock market is never wrong in a way detectable by ordinary humans.

First of all, maybe that’s wrong. My dad is a doctor, and he swears that he keeps making a lot of money from medical investments. He just sees some new medical product, says “Yeah, that sounds like the sort of thing that will work and become pretty popular”, and buys it. I keep telling him this cannot possibly work, and he keeps coming to me a year later telling me he made a killing and now has a new car. Maybe all financial theory is a total lie, and if you get a lucky feeling when looking at a company’s logo you should invest in them right away and you will always make a fortune.

Or maybe the it’s that it’s not investors’ job to answer “Does this drug work?” but rather “Will investing in this stock make me money?”. Neuralstem has mentioned that they’ll be bringing these new results in front of the FDA, presumably in the hopes of getting a Phase III trial. FDA standards seem to have gotten looser lately, and maybe a fig leaf of positive results is all they need to give the go ahead for a bigger trial anyway – after all, they wouldn’t be approving the drug, just saying more research is appropriate. Then maybe that trial would come out better. Or it would be big enough that they would discover some alternate use (remember, Viagra was originally developed to lower blood pressure, and only got switched to erectile dysfunction after Phase 1 trials). Or maybe Neuralstem will join the 21st century and hire a competent Obfuscation Department.

I don’t know. I’m beyond caring. The sign of a really deep depression is abandoning hope, and I’ve abandoned hope in NSI-189…

…which just leaves me even more time to be excited about SAGE-217, the novel GABA-A positive allosteric modulator that just passed Phase 2 trials! This one is going to be great!

[EDIT: Wait, is SAGE-217 just a weird attempt to rebrand benzodiazepines? Surely it’s got to be more than that, right?]

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Tax Bill 3: Don’t Mess With Taxes

I.

Thanks to everyone who commented on my last two posts, especially the many people who disagreed with me. Two things I will admit I got mostly wrong:

1. I was wrong to say there was “no case” for the tax bill. Aside from all of the minor provisions which can be good or bad, the case for slashing corporate rates is that they’re more distortionary and less efficient than other forms of taxation. Thanks to everyone who pointed this out to me.

2. Several people brought up problems with the article saying CEOs say they will just give the money back to shareholders, most notably that giving money back to shareholders may stimulate the economy in other ways.

But two things I still think are true:

1. Seriously, guys, I admit I don’t know as much about economics as some of you, but I am working off of a poll of the country’s best economists who came down pretty heavily on the side of this not significantly increasing growth. If you want to tell me that it would, your job isn’t to explain Economics 101 theories to me even louder, it’s to explain how the country’s best economists are getting it wrong. You may find this book review relevant.

2. I stand by my claim that I care less about economic growth than about where the money goes. That includes caring less about distortionary taxation, deadweight loss, and all those other concepts.

Suppose Alice is an effective altruist who supports whatever charity you think is most important and does a really good job of it. Every dollar she spends saves multiple lives. She lives in a town of 1000 people where nobody else is an effective altruist and everyone else just lives a pretty decent life and spends their extra money on, I don’t know, breeding virtual cats or something.

A demon places a curse on Alice’s neighbor Bob. Every time Bob pays a dollar in taxes, it destroys a random two dollars’ worth of wealth somewhere in the town.

The town elders meet and decide that for some reason they have to lower taxes either on Alice or Bob. The economic case for Bob is overwhelming – taxes on him are especially inefficient because of the extra wealth they destroy.

Still, I would want a tax cut for Alice. It seems like the only important thing that happens at all in this town is Alice’s charitable donations. The amount I care about this town’s utility focuses pretty much entirely on that. We could give the break to Bob, and have a nominally better economy, but it would just lead to more people buying virtual cats. It could be that the extra two dollars’ of wealth destroyed by Bob’s taxes was some sort of useful machinery, and so taxing Bob harms economic growth. Again, it is hard to care, except insofar as that hurts Alice, the only person in town whose wealth matters much for anyone’s utility.

I can imagine a world in which Bob’s curse was stronger, and every dollar Bob was taxed destroyed a million dollars in value, and soon any tax on Bob meant the citizens of the town were starving to death and all of them including Alice went bankrupt. But right now the tax on Bob isn’t big enough to be worse for Alice than a tax on Alice, and since Alice is the only important person in this situation, I don’t care.

I can also imagine a world where a wise economist comes to town. She says “Alice’s work is the most important thing in this town, but taxing Bob destroys wealth for no reason. Some of the town elders support tax breaks for Bob, and others support tax breaks for Alice. But we can give the tax break to Bob, and then all the people who saved $2 each from the curse not being activated can give $1.50 to Alice. That way Bob is better off, Alice is better off, and potential curse victims are better off.”

This is the best argument in favor of wealth creation instead of redistribution. But right now we’re not doing that. We just create the wealth and then don’t redistribute it, except through charity, which is a rounding error, and taxes, which everyone agrees this bill causes there to be less of. If we actually had Pareto-optimal wealth redistribution, then of course, create as much wealth as possible and redistribute it Pareto-optimally. Since we don’t, we’re kind of stuck.

My takeaway from this story is that in societies with a lot of marginal-value-of-money inequality, economic growth is potentially less useful than working to keep the money with people who can spend it on higher-marginal-value things. Consider three variables:

1. How low is the marginal utility of money for the person holding the average dollar, if no efforts are made to redistribute it?

2. How much economic growth are we sacrificing by choosing redistribution?

3. How high a marginal utility of money do we get by redistributing it?

Point 1 is why I stress the research showing increasing inequality eg most money going to people rich enough not to really have much use for it.

Point 2 is why I stress the economists saying that the gains from cutting corporate taxes really won’t have that much effect on growth.

Point 3 is the one I’m least sure about. If the government were a perfect effective altruist, it would be no contest – them having the money would be thousands of times more effective than random corporations (or even random middle-class people) having it. Even if the government were to give the money as a tax break to the working classes, it still seems really obvious to me that the increased utility swamps any effect from higher economic growth. In reality, the tax cut is being funded by increasing the deficit. I don’t know whether that means we need to compare it to whatever is bad about having a higher deficit, or else take as a given that the deficit has a certain amount of slack, and then compare it to other things we could do with the same money.

Imagine the government went $100 billion into debt to build a giant bronze statue of George Washington. Should we be debating whether running up the deficit is really that bad? Should we be debating the artistic merit of giant bronze statues of Washington, and whether it’s actually a pretty good statue that boosts tourism in the area? Or should we be comparing it to the best possible use for that money?

(added: I would be 100% happy with a bill that cut corporate taxes exactly this much, then raised taxes somewhere else in an equally progressive way, causing there to be the same amount of taxes with less distortion)

II.

The fairest thing I can think of is to compare this use of $100 billion to just spreading $100 billion evenly among all the government’s existing priorities.

Suppose that this tax cut was vastly better at stimulating economic growth than any reasonable person expects, and it increased growth by 1% per year. Then it would create $200 billion in value. With extreme good luck, 3% of that might go to the poorest quintile, giving them an extra $6 billion.

Or suppose the government keeps the $100 billion and distributes it evenly according to its existing priorities. Half of the budget is entitlement programs, and 32% of those go to the poorest quintile, so they would get an extra $16 billion.

I’m sure these numbers are wildly off. But it’s hard to come up with remotely plausible numbers in which the poor and working-class are better off with the tax bill than without it. I think the assumptions I plugged in were overly generous: the bill won’t really increase growth 1%, and although poor people have 3% of income they get much less than 3% of economic gains. Still, even under these generous assumptions, this bill gives poor people less money than the default case of not doing it.

One could argue that poor people are better off with $6 billion in actual money than $16 billion in government programs purporting to help them. But although I agree there’s a multiplier, I don’t know if it’s this big. And government programs would also disproportionately help the poorest of the poor, compared to economic gains which would disproportionately help the richest of the poor.

I think the marginal utility from an extra dollar to the poor (and the working class, etc) is orders of magnitude higher than the same dollar going to something else. So if you want to get me to support the tax bill, don’t tell me yet another reason why you think it would make the economy more efficient. Tell me why I’m wrong about this.

[EDIT: Commenters point out I was mistaken about the speed at which this would compound. See here. If the real growth from the bill was as high as 1%, it would probably be better for the poor than the lost government spending; if it were lower, it would take several decades to break even. So the best way to convince me to support this bill would be to find a plausible estimate of what level of growth is expected. My best guess from the economist poll is still “approximately zero”. ]

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Response To Comments: The Tax Bill Is Still Very Bad

There was some good pushback on yesterday’s article on taxes. But sorry, I’m still right.

Many people responded with generic low-tax anti-government positions. Fine. Let’s say the government is definitely bad and taxes are definitely too high. The current tax bill is still not the right way to do tax cuts.

Budget director Mick Mulvaney claims that the richest 20% of people pay 95% of income tax; the Wall Street Journal‘s numbers are a little lower, at 84%. Total income taxes are $1.8 trillion, so the poorest 80%’s share comes out to somewhere between 90 and 280 billion. This is around the same order of magnitude as the $100 billion in tax cuts in the current GOP bill. So it looks like one alternative to this bill, no more or less costly, would be to halve income taxes for the bottom 80% of the population, maybe anyone making less than $100,000.

Is there any reason to prefer the existing GOP proposal to this one?

The only argument I can think of is that corporations are good because they make investments are hire employees and stimulate the economy. But…

First of all, the IGM Forum asked the nation’s top economists whether the current tax bill would substantially raise GDP. 51% said it wouldn’t, 36% said they weren’t sure, and only 2% (= 1 economist) thought it probably would.

Second, as Marxist and anti-corporate a site as Forbes notes that A Corporate Tax Cut Won’t Boost Economic Growth, because they went around and asked a lot of CEOs whether they were going to invest the tax cut in cool economic-growth boosting stuff, and the CEOs mostly said no, they would probably just increase shareholder dividends.

Third, for the past few decades there’s been a weird uncoupling between economic growth and the fortunes of most people in the developed world. I won’t insult your intelligence by re-posting the same graph you’ve seen a thousand times, but this isn’t subtle. If all the economists and all the CEOs are wrong, and we get a 3% boost in GDP over a decade or something, I expect when I open a holo-newspaper in 2027 it’ll be about how mysterious it is that average middle-class salaries are still pretty close to their 1970s level. I don’t think you have to be a communist to believe that economic growth that just goes to a tiny subsection of the population isn’t all that useful. You just have to be a utilitarian.

(I guess expanding the economy can also give us cool technology, but I would like rather less cool technology for a while, actually).

But most important, if all of this is wrong – if the CEOs are lying and really they’ll spend the money on investment, and the economists are wrong and really corporate investment will turbo-charge the economy, and the past few decades of economic history are wrong and some of the gains of a turbo-charged economy go to the poor and middle-class – then the good thing that happens is that poor and middle-class people have more money.

…which is the same thing that would have happened if you had just lowered the taxes on the poor and middle-class directly, you moron. It’s also what would happen if we spent it on welfare for the poor, on health care for the middle class. God help me, even Bernie’s free college tuition would save a couple people from student loan debt.

For the corporate tax cut to be a better idea, it would have to turbo charge the economy so dramatically that even after accounting for the low chance it will work at all, the amount taken off the top by executives and shareholders, and the poor ability of economic turbo-charging to ever reach the working class, it still puts more money in the hands of people who need it than just giving them the money would. I am not an economist and I don’t know as much about multipliers as I should, but I have not heard anyone seriously assert this.

Last week I criticized socialists who prefer funding complicated government programs that might eventually help poor people, to just giving poor people the money. I feel like this is the same sort of issue. Some sort of complicated scheme in which we make corporations much richer and hope this is good for the poor and middle-class in some way is a lot less certain than just giving poor and middle-class people more money.

Spending the tax money on social welfare programs would help give poor and middle-class people more money. Expanding the EITC would give poor and middle-class people more money. Cutting personal income taxes in lower brackets would give poor and middle-class people more money. This tax bill doesn’t do any of those things, and it costs the money that would make doing any of those things easier.

It’s sometimes unfair to compare real government programs to the most effective possible government program; everything fails by that measure. But this tax bill seems so much worse than even other tax cuts that I think it’s fair to judge it as a tremendous opportunity cost.

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