TylerJay

Karma: 956

TylerJay 8 Apr 2014 15:49 UTC
36 points
in reply to: JoshuaFox’s comment on: Open Thread April 8 - April 14 2014
I can’t speak for others, but I love HPMoR. I honestly believe it’s one of the best pieces of fiction I’ve ever read, so I’ll try to describe my own reasons.
1. Tropes and Plot Devices: I’ve read a lot of sci-fi and fantasy and HPMoR avoids a lot of the downfalls of the genre such as dei ex machina, whiny/angsty heroes, and phleboninum/unobtainium. Eliezer is familiar enough with common tropes that he does a great job of applying them in the right contexts, subverting them interestingly, and sometimes calling them out and making fun of them directly.
2. The First Law of Rationalist Fiction: Roughly, that characters should succeed by thinking in understandable, imitable ways, not by inexplicable powers or opaque “bursts of insight” that don’t really explain anything. After hearing this ideal stated outright and seeing it in practice, a lot of other fiction I’ve read (and, unfortunately, written) seems a lot less satisfying. Eliezer does a fantastic job at giving a look into the characters’ minds and letting you follow their thought patterns. This makes it even more satisfying when they succeed and even more crushing when they fail.
3. Application of the Sequences: As someone who had read the sequences more than once before reading HPMoR, it was both fun and enlightening to see the ideas put into practice in a high-stakes scenario. As someone who was familiar with the ideas beforehand, I got to smile and “get the reference,” yet also be surprised by the application. I honestly believe that I’ve started applying rationality to my real life more after reading MOR and seeing examples of how to do it.
4. Balance of Power: I think MOR does an excellent job of maintaining a balance of power between the characters. At times, you think your protagonist is horribly weak and at other times, they appear very strong, though perhaps in a different way from the other characters. The conflict is never one-sided.
5. The Characters: The characters are dynamic, multi-faceted, and sometimes morally ambiguous. You never fully understand their goals or motives, but they are there and they are consistent. Even the “dark” characters have certain insights to share that sound “bad”, but are nonetheless seductive and often hard to argue with.
6. The World and the Lore: As a long-time Harry Potter fan, seeing this kind of adaptation of the world is just fun. It’s a rich world in which to set a story and Eliezer does a great job expanding the lore, making some of it grittier, and making a lot of it much deeper and more mysterious. While he had a great platform to start from, the world-building is fantastic.
Overall, the story is incredibly entertaining and fun to read. It has a lot more to offer than most fiction out there. I love it.

TylerJay 31 May 2014 20:27 UTC
24 points
on: Brainstorming for post topics
A while back, I read “The Little Book of Common Sense Investing” by John Bogle, the founder of Vanguard and creator the first index fund. It’s an analysis of why index funds are a better option than actively managed mutual funds.

I’ve had some highly-upvoted comments on the merits of index funds on the past, so I’ve considered doing a writeup on it to give LessWrong a summary since it seems that a lot of people around here know that they’re supposed to be good, but don’t really understand all the reasons why. Is there any interest around this?

Edit: Thanks for the positive response. I’ll work on it and try to get it out in the next couple weeks. Does anyone have any input on whether it would be appropriate to post in Main?

TylerJay 29 Aug 2011 21:26 UTC
24 points
on: Help Fund Lukeprog at SIAI
Something about Help Fund Luke, The Summer Challenge, and HPMOR just got a $50 donation out of a 20 year old starving student. Feels good.

[Meta] Post-meetup reports and discussion

TylerJay21 Dec 2013 4:11 UTC

23 points

14 comments1 min readLW link

TylerJay 1 Jul 2014 17:54 UTC
23 points
on: Open thread, 30 June 2014- 6 July 2014
Some people treat LessWrong as just a philosophical exercise, but “Rationality” and its little brother “Critical Thinking” really can make you a rockstar in the corporate world if you so choose. I’m going to give a bit of background on some things that I’ve managed to accomplish in the last couple years by thinking when no one else would, then I’d hope to get some feedback and suggestions for future optimizations. Feel free to skip to the “-----------” below if you want to skip my brag section, though I am writing it to help give an idea of the landscape.

At the SaaS startup I work at, I’ve worked in a few different departments. I started in Support and decided we needed training videos and better articles to reduce the load on Support reps, so I made them and set up a process for forwarding people to the appropriate video/article instead of answering questions directly. This saved Support Rep’s time.

When I moved into Account Management and Implementation, every new client account needed a minimum of 5 hours of AM training time. I decided this was inefficient and recorded some more training videos, then set up an LMS so our clients could do self-paced training and designed an implementation process around it. I measured engagement after certain time periods and there was no difference between the live trainings, so we kept it. This has saved thousands of hours of AM time over two years. I noticed that another call we did with every client was the same questions and the same responses, so I wrote a supplementary Rails app “wizard” so that clients could go through that themselves, saving another hour off of every implementation.

I’ve recently moved into the Sales department and I’m looking for ways to optimize this department as well, both with logistics and tools and proven sales strategies. The first thing I did was set up a way for SalesForce to generate our contracts automatically instead of Sales people having to fill them out each time which will save our Sales team 15-30 minutes a day each. Low-hanging fruit.

Does anyone have any suggestions for things that I could look into to optimize our Sales department?

Every current “best practice” seems to be based on anecdotal evidence and I’ve already seen my company royally screw up A/B testing by peeking and retiring options early, so I don’t trust that anything is based on an empirical foundation.

Some of the issues I’ve noticed are:
1. Meetings are set in advance by a qualification team. Sometimes we have no-shows. I’m looking to reduce that. What resources are available about encouraging people to keep commitments? If i’m going to test things, like a call or email the day before, 2-3 days before, etc. as a reminder and collect data, how much data would I need for meaningful results? How should I randomize? Would I need to adjust for other factors? (ex: small prospects miss more meetings in general)
2. “Demos” currently have a very basic structure: Get background and identify problems ⇒ Do a Demonstration ⇒ Quote pricing ⇒ Follow Up. Already, adding the question “What’s it going to take to make this happen?” has been hugely effective in identifying the real obstacles and what to do next. I have considerable Sales experience, but in a non-tech industry, so I don’t know what will transfer. If I decide to test whether doing a Need Satisfaction Selling Cycle or a simple Feature-Description-Benefit sales approach is better, how would I collect data?
3. Are there any non dark-arts Sales techniques for Enterprise (B2B) Sales that are backed up by science? (I’ve read Influence, but I’m dealing with whole organizations here)
Any other ideas to try or test would be great. Thanks!

TylerJay 2 Feb 2014 19:43 UTC
22 points
on: How can I spend money to improve my life?
If you wake up before the sun rises (or have blackout shades), would recommendI this gradual-wakeup light alarm clock. I bought it after seeing someone link it on LessWrong. If your morning wakeups are abrupt, I highly recommend this. For the 30 minutes before your set alarm time, it gradually brightens the light. Then if you’re not awake yet by the time the sound comes on, it’s birds chirping VERY softly that slowly gets louder. I usually actually mistake them for real birds in my half-asleep state. Its a much more pleasant way to get up in the morning and personally, I feel a lot better when I do.

I also have a Vitamix that I use usually twice a day and I absolutely love it. Great quality and really easy to clean.

TylerJay 21 Jan 2014 7:23 UTC
22 points
in reply to: Said Achmiz’s comment on: Rationalists Are Less Credulous But Better At Taking Ideas Seriously
An index fund is intended to go up or down y the exact same amount as the entire exchange as a whole. For example, you might hear that the S&P 500 rose a total of 7% last year. If that happened, then your index fund would go up by 7%.

The main reason people don’t invest in index funds is because they want to “beat the market.” They see some stocks double or triple within a year and think “oh man, if only I’d bought that stock a bit earlier, I’d be rich!” So some people try to pick individual stocks, but the majority of laypeople want to let “experts” do it for them.

Mutual funds generally have a fund manager and tons of analysts working there trying to figure out how to beat the market (get a return greater than the market itself). They all claim to be able to do this and some have a record to point to to prove that they have done it in the past. For example, fund A may have beat the market in the previous 3 years, so investors think that by investing in Fund A over an Index fund, they will come out ahead.

But unfortunately, markets are anti-inductive so past success of individual stocks, mutual funds, and even index funds is no guarantee of future performance.

If you look at the performance of all funds over the past 20+ years and correct for survivorship bias (take into account all the funds that went out of business as well as the ones that are still around today), it becomes very clear that almost no mutual funds actually beat the market in terms of your ACTUAL RETURN when averaged over each year.

The final big problems with actively managed funds are fees and taxes. Actively managed funds charge higher percentage rates each year to cover their work. That’s how they make money. They also tend to sell a percentage of your stocks each year and buy new ones in their attempt to beat the market. This gives a certain “portfolio turnover” percentage and the higher that is, the more you have to pay in taxes (capital gains), which lessens your return even more.

The bottom line is that mutual funds claim to be able to beat the market and many do in any given year. People chase the money and pay more in capital gains and fees to try to make a higher return. Over time though, the index fund beats all others in terms of total return over time.

TylerJay 8 Oct 2013 0:23 UTC
21 points
on: Rewiring my Brain: (gentle) Help Appreciated
As a philosophy major who picked up CS after graduating, I have a recommendation:

If you want to start programming, start programming. The gaps in your knowledge will become apparent when you get to a problem you can’t solve BECAUSE you don’t understand the math behind it, and then you can backfill. Chances are you can develop a pretty solid grasp on the basics of programming before you get to that point.

This is not to say that taking math and science beforehand is a bad thing, but often people get hung up on prerequisites to the things they want to do and never get started.

My first course on programming was an earlier version of this course on edX: https://www.edx.org/course/mit/6-00-1x/introduction-computer-science/1122

It was far and away the best online class I’ve ever taken. Extremely high quality, designed specifically for the MOOC format, difficult enough that I had to really work hard, but doable with enough effort.

They’re actually making it a part of a CS core series that looks like it will be very comprehensive.

Good luck!
What links here?
- TylerJay's comment on Self-Study Questions Thread by TylerJay (29 Jan 2014 17:17 UTC; 4 points)

TylerJay 1 Sep 2014 18:13 UTC
19 points
in reply to: Dorikka’s comment on: Open thread, Sept. 1-7, 2014
There are a number of 3rd party tools that allow you to upload your 23 and me raw data for analysis. Here is a list

TylerJay 23 Oct 2014 17:23 UTC
18 points
on: What supplements do you take, if any?
I used Cronometer for about 6 months until I found a few variations of my weekly food intake that got me to average out to 100% of the daily micronutrients I wanted each day. It comes with the RDAs as preset thresholds, but you can modify your targets as needed. (I used Yvain’s Word doc and some of the other submissions to the minerals contest to set better targets).
I eventually got it to the point where the only supplements I was taking were:
1. 3.5g total ultra-high-purity, independently lab-tested EPA/DHA caps to get my n-6:n-3 ratio close to 1:1 (though that is now replaced with wild canned pink salmon 3x/week)
2. A quarter of a low-dose chelated zinc tab (I was having a hard time getting 100% of from natural foods)
3. The smallest piece I could possibly break off of the lowest dose tab of no-flush Niacin available a few times a week (This was the only B vitamin I couldn’t get 100% of through natural food, but all available supplements were mega-doses)
4. The RDA of Vitamin E (mixed tocopherols) for a little while, until I decided I probably don’t need it (Tocopherols only seem to occur in nature along with polyunsaturated fats, n-6 mostly, and since my diet was intentionally extremely low in n-6, I didn’t really get much. Personally, I think its function is just to prevent oxidation of polyunsaturates, so I stopped worrying about it. Also, suffered the same “megadoses only” problem as Niacin.)
5. Some KCL salt or potassium caps (Oddly, potassium supplements are not allowed to contain over 3% RDA in the US)
I also occasionally take magnesium citrate supplements, even though I get enough through food, because I find they help with jaw-clenching which I do while I sleep, and ¹⁄₄ of a 3mg melatonin tab to counteract the “white/blue light before sleep suppressing natural melatonin production” problem. I bought some lithium orotate a while back, but haven’t tried it yet

Getting away from vitamins/minerals, I use some no-added-vitamins Whey powder to help meet daily protein goals on days where I eat less or no meat and to rapidly refuel after weight training. I also occasionally cycle creatine to help with my weight training. (The benefits are very real and zero side effects.)

I take supplements during my feeding window (I do a ¹⁶⁄₈ Intermittent Fasting protocol which I love) but am conscious of micronutrient absorption competition. Most supplements will upset my stomach if it’s empty.

I decided to use them after tracking my micronutrient intake on Cronometer and seeing that my intake of some is below the levels I want them (with my goal being general health and longevity). I decide to continue using them if it is not a large cost, doesn’t take too long, and doesn’t cause any negative side-effects. (I stopped multivitamins because they were causing digestive issues, their effectiveness has not been substantiated by science, and the epidemiological correlation between multivitamins and all-cause mortality.)

I have some preferred vendors, but more important is the specific form of the supplement for bioavailability (for example, chelated zinc/magnesium > zinc/magnesium oxide). For certain types of supplements, the manufacturing process (and therefore the vendor) is more important because of the initial source (like EPA/DHA fish oil caplets. Have to be careful to get ones that have negligible amounts of toxins and heavy metals) and Melatonin (animal product and hormone).

A heuristic/methodology I use is to look up possible problems with things from the people who demonize them most (usually vegans and ancestral health / paleo people, but also sometimes Conventional Wisdom and government like in the case of Raw Milk) and then research their claims and learn more about the topic in general along the way. If I gauge the downsides to be negligible and the potential benefits good enough, then I give myself the OK to go for it.

I tracked everything meticulously for a long time, so now I have a pretty good idea of what most common foods contain, but now I’m a bit more relaxed about it all, knowing that my diet gives me well over 80% of the amount of everything that I want.

Hope this was helpful. Let me know if you have any followup questions.

TylerJay 6 Jun 2014 16:00 UTC
18 points
in reply to: Lumifer’s comment on: [meta] Policy for dealing with users suspected/guilty of mass-downvote harassment?
Well, if this is really the goal, then maybe disentangle downvotes from both post/comment karma and personal karma while leaving the invisibility rules in place? Make it more of a “mark as non-constructive” button that if enough people hit it, the post becomes invisible. If we want to make it more comprehensive, it could be made to weigh these votes against upvotes to make the show/hide decision.

TylerJay 15 Mar 2014 21:46 UTC
18 points
on: What are you working on? March / April 2014
After writing this, it seemed more appropriate for the Bragging Thread, but I haven’t seen one in a while, so I’m posting here. I’m just really excited and wanted to share with someone.

I just completed the last programming assignment in Coursera’s Algorithms course from Princeton. I worked on it for 6 hours straight this morning and just submitted it for full credit, passing all the tests. It was one of the harder assignments so far, but I finished it much faster than the others on which I averaged about 10-12 hours of work. Best of all, I didn’t encounter any bugs that took me more than a minute or two to find and fix which is big for me and seems like evidence that my skills are improving.

I had never programmed in Java before this course, but it feels natural to me now.

On top of that, I feel like the Algorithms course is giving me a whole new perspective on languages like Python and Ruby which I use more often. For example, I had never questioned their automatically resizing arrays and I’d never understood how dictionaries/hashes worked, but now I know how much there is going on under the hood.

Self-Study Questions Thread

TylerJay29 Jan 2014 1:32 UTC

17 points

66 comments1 min readLW link

TylerJay 21 Apr 2014 16:31 UTC
17 points
on: LSD, Meditation, Enlightenment, and Ego Death
I don’t really have any recommendations, but I do have a story. LSD was actually one of the catalysts that helped me find out about the idea of AGI and the LessWrong community. The story ended up a little long, but I figured I’d share if anyone was interested.

When I was 17, I started experimenting with LSD. I tried successively higher doses until one day I had a very strong experience. I often describe LSD as something that forces you to “drop your filters,” the idea being that we take in so much sensory data at any moment, we can’t possibly process all of it at once. So what we do is we categorize things into more general levels of organization. Instead of looking at each discrete sight quantum (“pixel” for lack of a better word) of a tree, we instead see the general shape, color, texture, and classify it as a “tree” in order to save processing power. LSD inhibits this process, making you look closer and actually see the details. I suspect that this is why some people report having a better appreciation for nature and natural beauty after taking LSD.

As a parallel to this phenomenon, LSD makes you take a closer look at yourself, your actions, and your trajectory in the same fashion. For me, it started all the way at the beginning, at the level of individual atoms and molecules. At the time, I had a basic understanding of physics and evolution. During my trip, I looked at the sand and saw how it moved in the waves, then started chasing the details of what I was seeing all the way down to atoms and molecules (mentally, of course). Then I started visualizing a rough outline of how the first replicators might have come about; how many would be dashed against the rocks and destroyed. But eventually some would get more complicated and have a slightly higher chance of surviving. At this point, it’s all about survival and being able to replicate. Certain variations would make them more likely to survive, but often these would require more energy, like locomotion. Eventually, they would get larger and the energy demands would be greater and they would have to have more purposeful movements to obtain food. Once we’re at the point where they have brains, reward centers would develop to guide their actions to make them more likely to survive and replicate.

While many of my ideas at the time were not quite right, if not wrong entirely, I think this was the first time that I’d intuitively understood the idea of evolution. So eventually I got to the point in this process I was imagining where survival needs are all taken care of and I thought about how people would have those reward systems still in place and that might not be a good thing.

I started asking myself, “What is the next ‘noble’ step to take”. I remember that that was the way I phrased the question at the time. I pictured people getting to this stage and then just falling into a cycle of trying to bliss out their reward systems and never advancing. I didn’t yet understand the philosophical idea of objective vs subjective morality. I wondered if there was some “right” thing for people to do once they got to this step. What should happen next?

Well, I never got past that point on my trip, but I had gotten to the point where I could start asking the right kinds of questions. Once I was back in a sober state of mind, I took to the internet and started searching. Eventually, I found Eliezer’s Levels of Organization in General Intelligence, the technical details of which were over my head, but I learned from it. I was amazed at what I was finding, so I googled the author. That brought me to Yudkowsky.net which lead me to LessWrong and the sequences. I read through all of them and they gave me the foundations of my current understanding, along with helping me realize that AGI is quite possibly the most important problem in the world.

I was amazed with how often one of the articles in the sequences would directly address a question or an uncertainty I had spent a lot of time thinking and wondering about. However, more important than answering the questions, they helped me phrase them the right way.

So my deep wisdom on LSD is that it opens doors, but it won’t get you through them. It can help you see things with fresh eyes, without your filters, and gives the opportunity to reshape your understanding if you choose to.

TylerJay 6 Aug 2014 16:03 UTC
14 points
on: Roles are Martial Arts for Agency
After reading Benito’s rephrasing of the point...

Your identity/role, in near mode, seems to tell your System 1 what to be thinking, and your System 2 can change what identity/role you’re running at a given time.

I immediately had the same reaction as Lumifer:

There is a trade-off, of course: your reaction is fixed by training and it’s not necessarily appropriate to the specific situation.

A carefully crafted role (or set of roles) that allows your System 1 to function the way you want it to in most circumstances, while being a huge improvement for most, will still have problems if it is restricted only to System 1 responses. The appropriate reaction is sometimes to switch to System 2 where one can go through all the methods of rationality, not to just perform certain habits or responses that rationality has shown to be better than the default.

At first, this seemed contradictory to me, as many of the high-value things on LW seem to be System 2 processes. But then I realized that many of the habits of rationality involve training your System 1 to fire up your System 2 in the right circumstances and it seems that this could be crafted into the Roles that we try to adopt. For example, not “flinching away” from an Ugh Field. Noticing when you are about to do it and kicking over to System 2 to do something about it. If you see yourself as the kind of person who does this (and practice of course) then I don’t see why that can’t be a part of the Roles that you train.

Excellent article Eneasz!

TylerJay 20 Jan 2014 21:02 UTC
14 points
on: [link] Why Self-Control Seems (but may not be) Limited
If this model is true, then that would seem to support the effectiveness of So8res’ “goal hacking” strategy. If you can convince yourself that working towards the instrumental goal (eg. of “having worked out today”) is a want-to task, then you would feel less depleted and could either do it longer or be better able to perform your next have-to task. Or, if you’re performing these kinds of tasks after work, convincing yourself that they are “want-to” tasks could help you complete them even in your “have-to depleted” state.

However, I still can’t quite shake the intuition that there is something being depleted just by doing “hard” mental work, even if it feels like a “want-to” task. Though, this proposed model does help explain how I can sometimes come home from a full day of work and get absorbed in a programming project for another 6 hours.

Thanks for posting these, Kaj. If the standard model of resource depletion is in fact wrong, then this is very important information for people to base their anti-akrasia strategies on.
What links here?
- Kaj_Sotala's comment on [link] Why Self-Control Seems (but may not be) Limited by Kaj_Sotala (21 Jan 2014 7:49 UTC; 12 points)

TylerJay 6 Jan 2015 15:07 UTC
13 points
on: Low Hanging fruit for buying a better life
I’m going to focus more on entertainment in terms of real products as I expect this category to be underrepresented in this thread:

Spotify Premium: ~$10/mo, unlimited commercial-free music streaming (+ ability to sync to mobile for offline listening). They have an enormous library. I have essentially stopped buying albums because they are all available on Spotify (might not be as useful if you listen to really obscure music, but it’s worth searching their library before buying a subscription. You may be surprised what they have. I just bought my dad (a huge audiophile and musician) a 6 month subscription for his 65th birthday and he just downloaded Rolling Stone’s top 10 albums of the year that he otherwise would have bought and is really happy with it.

Netflix: Unlimited streaming is ~$7/mo, which is all I have. They have a large library and are starting to become content producers as well as just aggregators. Of course if you’re easily seduced into binge-watching when you really want to be doing other things, it might not be a good idea. Personally, I get a lot of enjoyment out of it and it’s cheaper than one movie ticket a month. Lots of classic movies as well as more modern stuff. However, it’s relatively easy to “run out” of stuff to watch on Netflix, at which time you can just cancel your subscription.

Roku: If you don’t have a Smart TV, it’s the best of all of the 3rd party options (FireTV, AppleTV, Chromecast, etc.). Get the “Roku 3”, it’s under $100 and has access to a lot of streaming services. The best feature is “Universal Search” where you search for a title and it looks across all of the different streaming services and lets you find the cheapest (or free) offerings. (Not offered as far as I know with any of the other products because they all push their own content stores first).

Aux-port/Cigarette-lighter Car Bluetooth Adaptor: ~$30-$40. Gives you in-car bluetooth if you don’t already have it. I recommend the Belkin one on Amazon. It’s been well worth the price in terms of added convenience for me.

Windshield/Dash Suction-Cup Mount for Smartphone: Cheap. If you use your phone for driving directions, it’s much more convenient (and a lot safer) than having the phone in your lap. Keep in mind that in some areas, it may be illegal to mount it to the windshield.

Radar Detector: ~$200 – $700. Get either a Valentine or a Cobra. They’re about the cost of one speeding ticket and can help you avoid tickets. (This is not an endorsement of driving too fast of course). Valentine is simple but effective and indicates front or back direction of radar source. Expensive, but no bells and whistles. Cobra has a wide range of products with a wide range of prices. Not directional, but has lots of bells and whistles like learning false positives, traffic-cam alerts through GPS, and connection to a network for crowd-sourced data (think Waze, but for stuff like speed traps). Again, these may be illegal in your area—make sure to check first.

Tablet/e-reader: I prefer to read textbooks on a tablet and other books on my Kindle Paper-white. Had an iPad provided by my previous employer before I left and I’m really missing it more than I thought I would for textbooks. I’m looking into a new tablet and really want one with good palm-rejection and a stylus for taking notes (If anyone has suggestions, please let me know).

Textbooks: I give myself a monthly education budget and buy a new textbook (and sometimes solutions guide) every couple months. There are also free options of dubious legality like libgen.org or libgen.info. e-textbooks go great with tablets.

Wake-up light / Dawn Simulator Alarm Clock: ~$100 Some love em, some (like Eliezer) don’t get any benefit from them. I kept a sleep journal for a month and it seems to work for me. I’m in a much lighter sleep when the alarm finally goes off (if I don’t wake up naturally from the light). If you’re techy, you can build your own with an arduino or raspberry pi pretty easily. On that note...

Arduino / Raspberry Pi: ~$30-$40. Very fun if you want to learn DIY electronics. Arduino is a microcontroller whereas raspberry pi is a full computer. I’m just getting started learning embedded systems and electronics myself (taking a class on edX starting this month called “Embedded Systems”. If anyone else here on LW is planning on taking this, let me know).

My favorite fiction Novel (aside from HPMOR): The Shadow of the Wind—by Carlos Ruiz Zafon. Great story, deep characters, a love story, a mystery, and some of the most beautiful prose I’ve ever seen.

Nice sunglasses: $15 - $300. Get some brown/amber-tinted, polarized lenses with a nice lightweight aviator frame. You’ll never look back. May be a bit hard to find at the lower price point, but not impossible.

Hope some of this was helpful!

TylerJay 5 Aug 2014 15:52 UTC
13 points
in reply to: TheMajor’s comment on: Open thread, August 4 − 10, 2014
You might be interested in reading Gwern’s page on Archiving URLs and Link Rot

TylerJay 5 Apr 2011 21:40 UTC
12 points
on: Rationality Quotes: April 2011
The north went on forever. Tyrion Lannister knew the maps as well as anyone, but a fortnight on the wild track that passed for the kingsroad up here had brought home the lesson that the map was one thing and the land quite another.

--George R. R. Martin A Game of Thrones

TylerJay 3 May 2015 21:50 UTC
11 points
in reply to: [deleted]’s comment on: Open Thread, Apr. 27 - May 3, 2015
The risks of one-time MDMA use can be roughly sorted into two categories: “Normal Risks” which apply to everyone and “Edge-Case Risks” which only apply to certain people (though it may not always be clear, as we will see, if you are at risk for one of the edge-cases). I will give a very brief and oversimplified description of how MDMA is processed by the body and the effects it has, and then I will describe some of these risks. I didn’t have time to put together sources and citations (especially as this was written from memory + fact checking), but my hope is that this will help people understand what the risks are and some of the mechanisms of action so that they can do more informed research into the topic.

Basic Neuroscience Background Information

In the human brain, where two neurons meet is called the Synapse. In reality, there is actually a small gap at the synapse between neurons called the synaptic cleft. When a signal traveling down a neuron reaches the end, it causes a release of neurotransmitters into the synaptic cleft. These neurotransmitters fit like keys into keyholes called receptors on the second neuron. Depending on which keyholes/receptors are activated/filled, the second neuron takes some action like firing or not.

You can visualize this by holding your right fist up and then making a “C” shape around it with your left hand (they should be close, but not touching. While maintaining this, hold your elbows out to the sides. Each of your arms is a neuron. Your forearms are the “Axon” which is the path the signals travel down and the space between your hands is the synaptic cleft. A signal travels from your left elbow to your left fingers which causes them to release neurotransmitters into the space between your left hand and your right fist. All over your right fist are small keyholes called receptors that are shaped to specifically fit certain neurotransmitters. The neurotransmitters float around in the gap for a while, some of them fitting into the keyholes, and some of them being reabsorbed by your left hand to be used later. (This reabsorption process is called “reuptake” by the way) If enough of the keyholes on your right fist are filled, then a signal travels from your right fist down to your right elbow, at which there is another synapse and the same thing happens.

Now, on your fist (or the “receiving” end of a synapse) you have a lot of receptors, but not all of these receptors are “on” or “active” at any given time. Your body maintains homeostasis by regulating the amount of active receptors for a certain neurotransmitter in response to the amount of that neurotransmitter that is typically produced. For example, I might produce (or rather, release) slightly less serotonin than you on average, but my body will deal with that by activating more serotonin receptors. In that case, our expected number of serotonin receptors that are filled with serotonin molecules at any given time would be roughly the same, so there would be no difference between us in that respect.

The last piece of background information we’ll need is to explain “free radicals”. You learned in high-school chemistry how atoms have electron shells/orbitals that “want” to have a specific number of electrons in them. This applies to molecules as well. When a molecule is missing an electron, it goes crazy and tries to steal one from its neighbors. A molecule in this state is called a “free radical”. If it’s pull is stronger than a neighbor’s, then it takes one of the neighbor’s electrons and calms down while the neighbor then goes crazy and becomes a free radical itself, looking to steal an electron from another molecule. This causes a chain reaction and can be very damaging to sensitive structures in your body like DNA or receptors in the brain.

The definition of an “antioxidant” is a molecule that can give up at least one of its electrons to a free radical without becoming a free radical itself, thereby ending the chain reaction. Free radicals are produced by pretty much all metabolic functions, so they are unavoidable to a certain extent. Your body uses antioxidants from your diet and endogenous antioxidants to counter this process every second of every day. Typically, it does a pretty good job and your body maintains homeostasis.

MDMA Mechanism of Action and Pharmacokinetics

MDMA causes excess release of Serotonin, Dopamine, and Norepinephrine into the synaptic cleft, though its action is primarily on Serotonin, so that’s what I’ll mostly focus on here.

So when you take MDMA, your neurons release excess serotonin into the synaptic cleft. This causes more binding to serotonin receptors which causes more firing of those neurons. This leads to the euphoria associated with MDMA use. However, your body wants to maintain homeostasis, so it starts turning off serotonin receptors. That way, even though there’s more Serotonin, there are less places for it to bind, which reduces activity. Then your MDMA wears off and your neurons are actually releasing less serotonin than before. This, coupled with less active serotonin receptors leads to considerably lower serotonin activity. This is associated with the anhedonia, anxiety, and depression that sometimes follow MDMA usage for a few days. However, nothing I’ve just described is permanent, so your body will eventually up-regulate your serotonin receptors again, your serotonin stores will replenish, and you’ll be back to normal.

However, this excess activity at the Serotonin receptors also creates excess free radicals. These free radicals can actually damage serotonin receptors (break them permanently) so that they can never be reactivated. In a single, modest dose, this is likely negligible, though with a single super-dose, it is significant. This highlights the important of having antioxidants available to your brain throughout the MDMA trip. A study was done on monkeys where they gave them super-does of MDMA, some with a Vitamin C injection and some without, and found significant brain-damage reduction (as in, blocked the vast majority of brain damage) in the Vitamin C group. (sorry, I can’t find the study right now.)

So, with chronic use or higher doses, this kind of damage becomes more and more of a problem and leads to brain lesions in the serotonergic neural pathways, and is Normal Risk #1

When your neurons absorb MDMA, it has effects on the Monoamine Oxidase system. Therefore, taking MDMA with Monoamine Oxidase Inhibitors (MAOIs) is extremely dangerous and can be life-threatening. Do not take MDMA if you are on MAOIs (and make damn sure you check if any meds you are on or recreation drugs you take are MAOIs). This is Edge-Case Risk #1

Your body breaks down MDMA largely through the CYP450 family of liver enzymes—primarily CYP2D6, but also CYP3A4 and possibly some others to minor extents. Therefore, if these enzymes are inhibited or otherwise not fully functional, your body will not be able to eliminate MDMA (or will do so much more slowly) which can lead to overdose and amplification of the detrimental effects on your brain, cardiovascular system, and more. Inhibition of CYP450 enzymes can be caused by certain medications (like Tagamet/Cimetidine or Ritonavir) or foods like grapefruit and grapefruit juice. This is Edge-Case Risk #2a. Certain people may also have genetically-impaired CYP2D6 activity which can lead to similar complications. This is Edge-Case Risk #2b

TylerJay

[Meta] Post-meetup re­ports and discussion

Self-Study Ques­tions Thread

[Meta] Post-meetup reports and discussion

Self-Study Questions Thread