Some Experiments I’d Like Someone To Try With An Amnestic
A couple years ago, I had a great conversation at a research retreat about the cool things we could do if only we had safe, reliable amnestic drugs—i.e. drugs which would allow us to act more-or-less normally for some time, but not remember it at all later on. And then nothing came of that conversation, because as far as any of us knew such drugs were science fiction.
… so yesterday when I read Eric Neyman’s fun post My hour of memoryless lucidity, I was pretty surprised to learn that what sounded like a pretty ideal amnestic drug was used in routine surgery. A little googling suggested that the drug was probably a benzodiazepine (think valium). Which means it’s not only a great amnestic, it’s also apparently one of the most heavily prescribed drug classes historically, and used recreationally—which puts very strong lower bounds on the drug’s safety in practice, and means it’s probably readily available.
With that in mind, here are some experiments I’d love for someone to try (and report back on) using benzodiazepines.
Tests
IIUC, benzodiazepines (at the right doses) specifically block long-term memory formation: someone on the drug can keep things in working memory just fine, and can recall everything they already knew just fine, but basically won’t remember new information past a few minutes.
One very broad class of tests which such drugs open up is: put someone in a situation, see what they do for a minute or two, wait 5 minutes for them to forget, then repeat. Assuming their behavior is highly reproducible, that gives an ideal platform for testing interventions.
I’m particularly interested in seeing this approach applied to IQ tests.
The individual items on a typical IQ test fit comfortably in the few-minutes-long window allowed by the amnestic. So, basic test: give a few questions from a standard IQ test, repeat the questions five minutes later, and hopefully the person’s responses are highly reproducible. Ideally, this would eliminate essentially all the usual test-retest variance seen on IQ tests, as well as the “learning the test” issues.
Assuming that baseline works (i.e. results are very highly reproducible with little variance), the effects of interventions should be much easier to measure than they typically are in psych studies. Start with the basics: track room temperature and lighting, blood glucose and oxygenation, ventilation, background noise. As those change, measure the effects on performance on IQ test items. Run the test a few times on different days and in different places, and try to nail down the exact sources of all the variance seen day-to-day and place-to-place. Tracking down the causes of all that “everyday variance” is where most of the value would be.
Once performance on different days is very precisely predictable, move to bigger interventions. Have the participant exercise in the middle of testing, or get a second participant and have them work together under the drug’s effects, or tell the participant to “think step-by-step”, or whatever other ideas you have. With the baseline sources of variance all nailed down, all this stuff should be much more precisely measurable than in the sort of studies typically done by research psychologists.
Implementation Notes
This is presumably the sort of thing which is tough to get past an institutional review board these days, but easy to do yourself over the weekend with a friend or two. So it’s exactly the sort of scientific project perfectly suited to LessWrong.
Unless you’ve used benzodiazepines before and know what dose you need, you should probably google around for dosing guidance. Note that this use-case is different from the standard recreational use-case; you might want doses closer to those used for surgery, which IIUC are typically larger. (Fortunately wikipedia says you’re unlikely to kill yourself by overdosing on benzodiazepines alone, but definitely don’t mix them with e.g. alcohol.)
Obviously do the experiment(s) with someone you trust, and it’s probably a good idea to record the whole thing.
Lastly, I’ll emphasize again: the primary value here would be in tracking down the sources of “everyday variance” in performance. That means finding some set of variables (think things like room temperature, blood glucose, some measure of how well you slept the night before, etc) such that you could walk into a random room on a random day, take measurements of those variables, and predict basically-perfectly your performance on an IQ test in that particular room on that particular day under the effects of benzodiazepines. You want to account for basically-all of the test-retest variance.
Important notice: benzodiazepines are serious business: benzo withdrawals are amongst the worst experiences a human can go through, and combinations of benzos with alcohol, barbiturates, opioids or tricyclic antidepressants are very dangerous: benzos played a role in 31% of the estimated 22,767 deaths from prescription drug overdose in the United States.
If you’re experimenting with benzos, please be very careful!
@habryka this comment has an anomalous amount of karma. It showed up on popular comments, I think, and I’m wondering if people liked the comment when they saw it there which lead to a feedback loop of more eyeballs on the comment, more likes, more eyeball etc. If so, is that the intended behaviour of the popular comments feature? It seems like it shouldn’t be.
See also discussion here.
Yeah, seems like a kinda bad feedback loop. It doesn’t seem to usually happen in that the comments I’ve seen upvoted in that section usually don’t get this extremely many upvotes on a comment this short.
I don’t have a great solution. We could do something that’s more clever and algorithmic, which doesn’t seem crazy but I am also hesitant to do because it’s a lot of work and also I like more straightforward and simple algorithms for transparency reasons.
IDK, I think this comment warrants the level of karma. OP is proposing messing around with a drug class that kills thousands of people per year. Even only counting benzo overdoses that don’t involve opioids, it kills ~1500 people per year. Source: https://nida.nih.gov/research-topics/trends-statistics/overdose-death-rates (you can download the data from that page to see precise numbers).
It’s not often that a forum comment could save a life!
Even though I think the comment was useful, it doesn’t look to me like it was as useful as the typical 139 karma comment as I expect LW readers to be fairly unlikely to start popping benzos after reading this post. IMO it should’ve gotten like 30-40 karma. Even 60 wouldn’t have been too shocking to me. But 139? That’s way more karma than anything else I’ve posted.
I don’t think it warrants this much karma, and I now share @ryan_greenblatt’s concerns about the ability to vote on Quick Takes and Popular Comments introducing algorithmic virality to LW. That sort of thing is typically corrosive to epistemic hygeine as it changes the incentives of commenting more towards posting applause-lights. I don’t think that’s a good change for LW, as I think we’ve got too much group-think as it is.
Yeah, seems right to me. If this is a recurring thing we might deactivate voting on the popular comments interface or something like that.
Here’s a quick mockup of what that might look like.
In my head you the voting UI is available after you click to expand and then scroll down to the bottom of the comment.
Added: Oops, I realize I did the quick takes, not the popular comments. Still, the relevant changes are very similar.
The comment being referenced may be of a very rare type. I have never been on Lesswrong, and rushed down to the comments section to type something, and found someone else having said it more eloquently than I wanted to. Normally we have a lot of entropy in the group thinking (which I love). This may just be a rare type of case.
I had heard, 15+ years ago (visiting neuroscience exhibits somewhere), about experiments involving people who, due to brain damage, can no longer form new memories. And Wiki agrees with what I remember hearing about some cases: that, although they couldn’t remember any new events, if you had them practice a skill, they would get good at it, and on future occasions would remain good at it (despite not remembering having learned it). I’d heard that an exception was that they couldn’t get good at Tetris.
Takeaway: “Memory” is not a uniform thing, and things that disrupt memory don’t necessarily disrupt all of it. So beware of that in any such testing. In fact, given some technique that purportedly blocks memory formation, “Exactly what memory does it block?” is a primary thing to investigate.
There was an era in a scientific community where they were interested in the “kinds of learning and memory that could happen in de-corticated animals” and they sort of homed in on the basal ganglia (which, to a first approximation “implements habits” (including bad ones like tooth grinding)) as the locus of this “ability to learn despite the absence of stuff you’d think was necessary for your naive theory of first-order subjectively-vivid learning”.
(The cerebellum also probably has some “learning contribution” specifically for fine motor skills, but it is somewhat selectively disrupted just by alcohol: hence the stumbling and slurring. I don’t know if anyone yet has a clean theory for how the cerebellum’s full update loop works. I learned about alcohol/cerebellum interactions because I once taught a friend to juggle at a party, and she learned it, but apparently only because she was drunk. She lost the skill when sober.)
Some comments:
The word for a drug that causes loss of memory is “amnestic”, not “amnesic”. The word “amnesic” is a variant spelling of “amnesiac”, which is the person who takes the drug. This made reading the article confusing.
Midazolam is the benzodiazepine most often prescribed as an amnestic. The trade name is Versed (accent on the second syllable, like vurSAID). The period of not making memories lasts less than an hour, but you’re relaxed for several hours afterward. It makes you pretty stupid and loopy, so I would think the performance on an IQ test would depend primarily on how much Midazolam was in the bloodstream at the moment, rather than on any details of setting.
Thanks! Fixed now.
Another class of applications which we discussed at the retreat: person 1 takes the amnestic, person 2 shares private information with them, and then person 1 gives their reaction to the private information. Can be used e.g. for complex negotiations: maybe it is in our mutual best interest to make some deal, but in order for me to know that I’d need some information which you don’t want to share with me, so I take the drug, you share the information, and I record some verified record of myself saying “dear future self, you should in fact take this deal”.
… which is cool in theory but I would guess not of high immediate value in practice, which is why the post didn’t focus on it.
it’s extremely high immediate value—it solves IP rights entirely.
It’s the barbed wire for IP rights
O man, wait until you discover nmda antagonists and anti-cholinergics. There are trip reports on erowid from people who took drugs with amnesia as a side effect so...happy reading I guess?
I’m going to summarize this post with “Can one of you take an online IQ test after dropping a ton of benzos and report back? Please do this several times, for science.”
Not the stupidest or most harmful ‘lets get high and...’ suggestion, but I can absolutely assure you that if trying this leads you into the care of a medical or law enforcement professional, they will likely say something to the effect of ‘so the test told you that you were retarded right?’ In response to this, you, with bright naive eyes, should say ‘HOW DID YOU KNOW?!’ as earnestly as you can. You might be able to make a run for it while they’re laughing.
For those who don’t get the joke: benzos are depressants, and will (temporarily) significantly reduce your cognitive function if you take enough to have amnesia.
this might not make john’s idea pointless, if the tested interventions’s effect on cognitive performance still correlates strongly with sober performance. but there may be some interventions whose main effect is to offset benzos effects whose usefulness does not generalize to sober.
Temporary implies immediately reversible and mild.
People who are on benzos often have emotional regulation issues, serious withdrawal symptoms (sometimes after very short courses potentially even a single dose), and cognitive issues that do not resolve quickly.
In an academic sense, this idea is ‘fine’, but in a very personal way, if someone asked me ‘should I take a member of this class of drug for any reason other than a serious issue that is severely affecting my quality of life?‘, I would answer ‘absolutely not, and if you have a severe issue that they might help with, try absolutely everything else first, because once you’re on these, you’re probably not coming off’.
yeah, agreed—benzos are on my list of drugs to never take if I can possibly avoid it, along with opiates. By temporary, I just mean “recoverably”. many drugs society considers sus or terrible I consider mostly fine if risks are managed, but that generally involves how to avoid addiction, and means using things at non-recreational-does levels. Benzos are hard to do that with because, to my cached understanding, the margin between therapeutic and addictive doses is very small.
But Eric Neyman’s post suggests that benzos don’t significantly reduce performance on some cognitive tasks (e.g. Spelling Bee)
Yeah there are definitely tasks that depressants would be expected to leave intact. I’d guess it’s correlated strongly with degree of working memory required.
I think this is a really interesting idea, but I’m not comfortable enough with drugs to test it myself. If anyone is doing this and wants psychometric advice, though, I am offering to join your project.
This sounds like a terrible idea.
Though, if you’re going to be put under sedation in hospital for some legit medical reason, you could have in mind a cool experiment to try when you’re coming around in the recovery room.
i was sedated for endoscopy about 10 years ago,
they tell you not to drive afterwards (really, don’t try and drive afterwards)
and to have a friend with you for the rest of the day to look after you
i was somewhat impaired for the rest of the day (like, even trying to cook a meal was difficult and potentially risky … e.g. be careful not to accidentally burn yourself when cooking)
I drew a bunch of sketches after coming round to see how it affected my ability to draw.
“I drew a bunch of sketches after coming round to see how it affected my ability to draw.”
What was the result?
The linked post suggests that your assumptions about memory are wrong:
He had training effects from multiplying the two numbers despite not having a memory of the first time he multiplied them.
Oh yeah, I guess that could be a learning effect. When reading it I assumed the lack of need for repeating the numbers was just because the drug was wearing off.
Yeah, that’s my best guess. I have other memories from that period (which was late into the hour), so I think it was the drug wearing off, rather than learning effects.
My wife was put on benzodiazepines not long ago for a wisdom tooth extraction, same as the author of that post. She did manifest some of the same behaviours (e.g. asking the same thing repeatedly). But your plan to make people in those conditions take an IQ test has a flaw: she was also obviously high as balls. No way her cognitive abilities weren’t cut down to like half of the usual. Not sure if this is a side effect of the loss of short term memory or a different effect of the sedatives, but yeah, this would absolutely impact an experiment IMO.
Obviously, you could also test nootropics this way.
One class of variance in cognitive test results is probably, effectively, pseudorandomness.
Suppose there’s a problem, and there are five plausible solutions you might try, two of which will work. Then your performance is effectively determined by the order in which you end up trying solutions. And if your skills and knowledge don’t give you a strong reason to prefer any of them, then it’ll presumably be determined in a pseudorandom way: whichever comes to mind first. Maybe being cold subconsciously reminds you of when you were thinking about stuff connected to Solution B, or discourages you from thinking about Solution C. Thus, you could get a reliably reproducible result that temperature affects your performance on a given test, even if it has no “real” effect on how well your mind works and wouldn’t generalize to other tests.
This should be addressable by simply taking more, different, cognitive tests to confirm any effect you think you’ve found.
I think the proposed method could still work though. A substantial fraction of the pseudorandomness may be consistent on the individual person level.
The type of pseudorandomness you describe here ought to be independent at the level of individual items, so it ought to be part of the least-reliable variance component (not part of the general trait measured and not stable over time). It’s possible to use statistics to estimate how big an effect it has on the scores, and it’s possible to drive it arbitrarily far down in effect simply by making the test longer.
You can actually use this to do the sleeping beauty experiment IRL and thereby test SIA vs SSA. Unfortunately you can only get results if you’re the one being put under.
How would it do that? If they learned the test in advance, it would be in their long-term memory, and they’d still remember it when tested on the drug.