Best in Class Life Improvement

sapphire4 Apr 2024 1:51 UTC

68 points

Practical Health / Medicine / Disease Nootropics & Other Cognitive Enhancement

There is an enormous amount of crappy self-help advice. Most supplements do nothing. However, some substances and practices can dramatically improve your life. It’s worth being explicit about what those are in my experience.

The American medical system endorses all of these treatments and methods, and you can implement them with a doctor’s supervision. The only way I differ from the American medical system is that they operate under a paradigm of treating diseases or perhaps what might be better understood as serious deficiencies. But if a technique is powerful enough to help the ill it is plausible it can also help the well. Make your own choices and set yourself free. Before reading this advice, it is important to note that drug users use a lot of drugs.

In general, recreational drug users take their drugs at doses so much higher than psychiatric patients that they’re basically two different chemicals. A lot of our impressions of drugs, what side effects they have, and how dangerous they are get shaped by the recreational users, not the patients. This is sometimes even true for the doctors who are supposed to prescribe to the patients and give them good advice. While studies of recreational user populations can sometimes be helpful in flagging an issue for consideration, we should be judging the clinical risks based on studies of clinical populations.

Ketamine

Ketamine is extremely effective and extremely fast-acting. It often solves depression in a single day. Hence, it should be among the first things you try if you have mood issues.

From Scott’s writeup:

The short version: Ketamine is a new and exciting depression treatment, which probably works by activating AMPA receptors and strengthening synaptic connections. It takes effect within hours and works about two or three times as well as traditional antidepressants. Most people get it through heavily regulated and expensive esketamine prescriptions or even more expensive IV ketamine clinics. Still, evidence suggests that getting it prescribed cheaply and conveniently from a compounding pharmacy is equally effective. A single dose of ketamine lasts between a few days and a few weeks, after which some people will find their depression comes back; long-term repeated dosing with ketamine anecdotally seems to work great but hasn’t been formally tested for safety.
6: How effective is ketamine?
Pretty effective.
Studies find the effect of ketamine peaks about 24 hours after use. A meta-analysis finds that by that time, around 50% of patients are feeling better (defined as 50% symptom reduction) compared to less than 10% of patients who got a placebo. A more recent Taiwanese study finds roughly similar numbers.
Another way to measure effectiveness is through effect size statistics. The effect size of normal antidepressants like SSRIs is around 0.3. The effect size of ketamine is between 0.6 and 1.0, so about two to three times larger.

Ketamine is a psychoactive drug. The state it induces is hard to describe, but it can be psychedelic in its own way. My advice is to take enough ketamine that you are clearly quite high but not so much you are ‘out in space.’ Ideally, the experience won’t be very scary. Ketamine is very short-acting. The peak high should only last about 45 minutes, and the total trip should be under two hours. I recommend either doing a very simple breathing meditation (described in detail later in this document) or enjoying media you find uncomplicatedly pleasant. Watch a nature documentary about trees. Don’t watch one about predators. Listen to music that makes you happy.

It’s important to get your setting right. Moving around on ketamine makes people nauseous. So, have water and nausea meds (ondansetron or Dramamine) right next to you. In case you need it, I’d also have a puke bucket. Try to stay still and enjoy the happy trip. I strongly recommend dosing alone. Ketamine is safe, and the trip is not long. Whatever happens, you can easily wait it out. You need to be able to focus on yourself. It is highly unpleasant to manage someone else’s emotions while having a difficult experience. This can lead to serious emotional issues. It is also valuable to commit to handling your mind. Unless you accidentally take a very large dose of ketamine, you can handle it.

Scott recommends this person to obtain ketamine legally at a reasonable price of ~$250/month. Many people pay hundreds per session for ketamine clinics, which seems too expensive for most people. I will say the obvious and point out that a dose of 100mg of ketamine costs about $10 in California (100/gram is normal here). Mixing it with distilled water into a nasal spray is not hard since ketamine is water-soluble. I can only speak from personal experience, but I have spoken to multiple local testing services, and all of them report that ketamine is usually pretty pure. It’s not a drug with a high risk of dangerous adulterants. Unlike Scott, I recommend dosing only once per week. Ketamine definitely builds tolerance, and you do not want to abuse life-improving medications.

Adderall and other Amphetamines

Amphetamines give you mental and physical energy. They help you focus. Amphetamines consistently take the top spot in surveys of which nootropics and life interventions are the most effective. Many people are obsessed with their intelligence. But having more energy and focus is, for many purposes, similarly effective to being ‘smarter.’ Returns on effort are exponential, especially over short periods of time. Even if you seek creativity and deep insights, it helps you feel alert. If you genuinely fit the diagnostic criteria for ADHD, you will benefit even further. However, the fraction of people who would benefit from ‘more energy and focus on demand’ is not small.

If you haven’t read it, Scott’s write-up on amphetamines is quite thorough. Some amphetamines work better, but are all fairly similar compared to ‘not taking them at all.’ One non-trivial downside is that amphetamines are not exactly good for your heart. I am not sure why Scott’s write-up finds such small adverse cardiovascular effects. Get a heart rate and blood pressure tracker. If needed do some extra cardio to counteract any negative effects.

In Dune, the spice melange has huge mental benefits. The human computers depended on spice. Adderall isn’t as good as Spice, and it doesn’t extend your lifespan. But there is an important parallel. You can get high off spice, whereas it’s extremely hard to get high off forms of amphetamines like Vyvanse (it’s really an amphetamine prodrug), but you can take others in euphoric doses. It is an incredibly bad idea to EVER use amphetamines recreationally. Do not do this even a single time. Never get high off the spice! I am honestly not the biggest fan of commitments. Arguably, this article aims to set you free from many chains. But this is one time it pays to metaphorically sign the oath in blood and bind yourself to the mast. Never do it. You have been warned.

Exercise Regularly and Safely – You can get huge benefits with little effort or risk

I’m unsure how much I need to sell anyone on ‘regular exercise is good.’ But it helps with many mental issues. Elizabeth’s epistemic spot checks are not easy to pass. But the argument for exercise strongly improving your mental health in Exercise for Mood and Anxiety basically passes. I recommend both the spot check and the book for details. However, many people find it hard to get themselves to actually exercise, and it is VERY easy to cause yourself chronic health issues. Conveniently, the benefits of intense exercise aren’t much larger than those of regular but very low-intensity activity. Therefore, I recommend starting with daily walking and basic simple bodyweight exercises (pushups, burpees, leg raises, pull-ups if you can manage them). Listen to a podcast or audiobook. If your cardio is good, you can try adding elevation changes to your walk. Most people aren’t that strong. But if you can actually do 10-20+ pull-ups, you might need to add weight lifting. If you go for more intense training, do so because it’s fun or you are willing to take risks.

Romeo has a good write-up that advocates slightly more risk than I personally take (I don’t use weights; bodyweight only is safer). This quote captures his conclusions:

The basic idea that lifting twice a week and doing cardio twice a week add up to a calorie expenditure that gets you the vast majority of exercise benefits compared to extreme athletes holds up, especially when you take reverse causality adjustments into effect (survivorship bias on the genetic gifts of the extreme). Nothing I’ve encountered since has cast much doubt on this main takeaway.
What updates have I had, then, both in personal experience and in giving training advice to others, as well as any research that has come out since then?
A greater emphasis on injury prevention, as the disutility from injuries vastly outweighs the positive effects of chasing numbers. This one was sadly a foreseeable update with aging, and thus, I lose bayes points for it. I did get an injury deadlifting despite a substantial emphasis on good form and not pushing to the limit as many do.
Exercise selection and program optimization likely matter less than I thought, and research that has come out in the meantime has supported this.
One and two combined imply that there is no real downside to picking exercises with lower injury potential for the joints and back.

In Scott’s post about depression, he is asked which kind of exercise helps, and he answers:

Again, the most important answer is ‘whatever kind you will actually do.’ Almost all benefits come from exercising at all.

Everyone knows exercise helps a ton. But perhaps they think exercise has to be difficult. Or maybe they subconsciously know that exercising risks chronic injury. So, the important thing to realize is that you can get a huge benefit from exercise with little effort or risk. Hopefully, internalizing this helps you actually do it!

Semaglutide/Ozempic

Semaglutide is the real-deal weight loss drug we have been praying for. It works well for 70%+ of people. Losing and keeping weight off is so difficult that prior to ozempic, it was reasonable advice to preach acceptance or extremely restricted diets. Prior to Semaglutide, I used to assume that most of my friends who wanted to lose weight would fail. Now I assume they will trivially succeed if they get on the drugs. Here is how to get on Semaglutide:

I purchased sema, for myself and others, on this site: https://evolutionpeptides.com/products/semaglutide-10mg?variant=42834747326660. It has been a reliable supplier for me. Reliability can always change, but for now, it’s where I would go.
Start with a dose of 0.25mg. Increase your dose approximately every four weeks. Stay on lower dosages as long as possible. Tolerance can increase rapidly. For example, the official guidelines say to double your dose after each of the first two months of treatment. I would try to increase dosages more slowly.
Gray market semaglutide is sold as a powder. You need to mix it into a solution to inject. Search for reconstitution solution.
You also need needles. Any insulin needle will work fine but some hurt less than others. Here are the ones I use.
To make the solution, I draw 100 units of reconstitution (a ‘full’ vial) solution into the needle. I then squirt the solution into the sema vial and repeat this process again. This means 5mg of semaglutide per 200 units of solution. So, to do a 0.25 starting dose, I would inject 10 units of mixed sema solution into my deltoid. It doesn’t really matter if you inject into fat or muscle.

Semaglutide feels weird in many ways and makes many people nauseous. Fake Dr. Sapphire’s medical advice is to use gray market odansetron to manage nausea. But dramamine is OTC in the USA and most other countries and also works well. Don’t expect insanely rapid weight loss. It’s normal to lose 1-2 pounds a week, which is honestly quite quick!

Testosterone

I try to stick to very compelling arguments. Anyone who has read SSC/astralcodexten should know that interpreting studies and meta-analyses is difficult. High doses of testosterone dramatically boost strength, lean muscle mass, and sports performance. They make it much easier to lose fat while preserving muscle. In combination with other drugs, they make it possible to achieve ludicrous body types. The extreme doses of testosterone taken by bodybuilders are almost certainly highly unsafe. However, lower doses, such as those common in testosterone replacement therapy, also have significant effects. If you want to be stronger, leaner and/or more muscular, you should seriously look into supplementing testosterone.

I am honestly unsure how to accurately model the safety curve for testosterone. Merely having more lean muscle mass is plausibly bad for longevity since it puts more pressure on your metabolic system and causes more accumulated damage. However, there are studies showing the opposite in older people.

TRT doses of 50–200 mg intramuscular weekly injections seem safe enough to me. Injections work better than topical gels in most studies.

It’s worth being overt about how testosterone (exogenous or otherwise!) has many potential irreversible side effects. It metabolizes into DHT, which is the main cause of hair loss. DHT blockers to prevent this commonly destroy sexual function in men. Topical DHT blockers applied to the scalp are more promising for most men. Large doses of exogenous testosterone can shut down natural production, and this can persist even after you stop taking testosterone. Increasing your testosterone can also masculinize your appearance in tons of smaller and permanent ways. Testosterone can metabolize into hormones that cause breast growth, and breast growth does not go away on its own. All of these effects are much smaller with the TRT dosages I recommend.

Interlude: Buddhism, Meditation and Psychedelics

You are probably some combination of secular, mentally flexible, open to experience, and attracted to ‘dangerous’ ideas. Those are often lucrative traits, but they make meditation more dangerous. Let’s look at some quotes from Holly Elmore’s write-up of the long-lasting harms meditation caused her:

I’m just going to list the harms I am still dealing with today, about four years after ceasing serious meditation and two years after stopping meditating on purpose entirely.
Harm: relaxation-induced panic
Relaxation-induced panic is a horrible catch-22 wherein relaxing is a cue to panic and become vigilant again. It’s a symptom most often associated with PTSD, and it’s high up on the list of meditation harms tracked by Willoughby Britton.
Harm: loss of 3D vision
This is related to the loss of concepts. I can pop in and out of 2D and 3D vision at will, it’s just that 2D is the default, and 3D always feels more real. Whenever I pop into it, I feel suddenly aware that I have a back and that there are sounds behind me as well. I suspect it’s like tapping into the immersive UI model setting of the mind.
Harm: exacerbated neurological vision processing issues
Mindfulness made my visual snow worse by encouraging me to notice it.
Possible harm: difficulty hearing noise or processing speech
ar exams show that my machinery is good, and it’s so analogous to the visual processing issues caused by mindfulness that I think meditation contributed to it

Obviously Holly’s was an unusually pathological case. But the rationalist/secular-curious-nerd neurotype does genuinely seem at higher risk. Almost everyone, including the medical establishment, highly recommends meditation. Very few people are harmed, and traditional practice considers meditation quite safe and not in need of many warnings. So, it is very interesting to me that the meditation teacher who seems most popular among the rationalist community is Daniel Ingram.

Daniel is famous for popularizing the concept of the ‘Dark Night of the Soul,’ a harrowing and unpleasant stage that can last months or years! I do not wish to make any negative value judgments about the path Daniel and others follow. Different paths, or dharma gates in Buddhist lore, appeal to different people. However, this document aims to teach you consistently effective techniques to improve your health without sending you through dark nights.

Meditation, if done skillfully, is powerful. It has similar effects to psychedelic drugs. Psychedelics and meditation help you relax and see things from a new perspective. This is very useful to heal trauma. It also lets you become a generally happier and more serene person. However, it should be obvious from this framing that relaxing your priors and then making semi-random changes is not obviously beneficial. Many of the harms of meditation and drug use come from using them in an unstructured way. Perception is very strange. We all know about the blindspot, but many optical illusions show us the different ways the mind has to create the coherent reality we experience. Perhaps it is useful for some people to perform this deconstruction. But our goal is to instead cultivate serenity and peace. For this reason, I recommend basic counting breath meditation:

Sit comfortably, with your spine erect, either in a chair or cross-legged on a cushion.
Close your eyes, take a few deep breaths, and feel the points of contact between your body and the chair or floor. Notice the sensations associated with sitting—feelings of pressure, warmth, tingling, vibration, etc.
Gradually become aware of the breathing process. Pay attention to wherever you feel the breath most clearly—either at the nostrils or in the rising and falling of your abdomen.
Allow your attention to rest on the mere sensation of breathing. (There is no need to control your breath. Just let it come and go naturally.)
Every time your mind wanders in thought, gently return it to the sensation of breathing.
As you focus on the breath, you will notice that other perceptions and sensations continue to appear: sounds, feelings in the body, emotions, etc. Simply notice these phenomena as they emerge in the field of awareness and then return to the sensation of breathing.
The moment you observe that you have been lost in thought, notice the present thought itself as an object of consciousness. Then, return your attention to the breath—or to whatever sounds or sensations arise in the next moment.
Continue in this way until you can witness all objects of consciousness—sights, sounds, sensations, emotions, and even thoughts—as they arise and pass away.
Don’t fall.

Breathing deeply is fundamentally calming; it is the first thing people should try if they are having a panic attack. Focusing on the breath lets your thoughts arise without dwelling on them. If you have troubles, they will come to the surface, but we can very gently process them. This meditation naturally cultivates serenity and simple happiness, which is exactly what we want to cultivate when our priors are relaxed. There is no need to overdo meditation. Fifteen minutes a day, three to seven days a week, with occasional longer sessions, is plenty. If you start meditating substantially more make sure it’s actually helping.

This meditation can also be thought of as the strongest defensive magic. Much suffering in life comes from being overwhelmed by unpleasant thoughts or feelings. Practicing focusing on the breath and letting go is extremely helpful in normal life. Meditation can be very psychedelic, but if things become unpleasant, you can simply stop meditating. There is no reliable way to stop a psychedelic experience induced by something like LSD or shrooms. Before you can consider such substances, you need to practice your defenses. Breathe meditation can be fun, but it can also be quite boring. Don’t hurt yourself by holding an unhealthy posture. But you should consider this meditation training and practice; it doesn’t have to be fun to be helpful. However, at worst, the practice should be boring. If you start experiencing seriously negative mental states, stop meditating immediately. Your mind will rapidly return to normal if you stop promptly.

Our meditation goals rely on straightforward mechanisms:

1 - Practice letting go of thoughts and emotions by returning to the breath.

2 - Eventually, be able to let go of unpleasantness, even in difficult situations such as panic attacks or ‘bad trips.’ Knowing we can do this helps us feel safe.

3 - Cultivate serenity and gentle happiness.

If you become skilled at meditating, you can induce extremely euphoric states. This is helpful in moderation, but being too obsessed with these states is considered unhealthy. If you learn to reach such states, don’t make a big deal about them. They are great for ending panic attacks, but they aren’t our goal.

4 - Create a beneficial ‘relaxed prior’ mental state while being happy and safe.

For the most part, the techniques developed in classical Buddhism are powerful and work for their intended purposes. But it is highly unlikely that you share the goals of the people who developed those techniques. In classical Buddhism, when you become a monk or a serious lay student, you ‘take refuge’ in the Buddha, the community, and its teachings. You are taking refuge from the pain of existence/samsara. The core logic of Buddhism is true. If you undertake a fairly extreme set of behaviors and mental practices, you can be quite happy even in harsh circumstances. Knowing this can inspire peace and courage. If I were faced with very serious adversity, I would take refuge. Even if I was put in solitary confinement, I know that I could be peaceful and happy. People have remained tranquil while setting themselves on fire in protest. The way is tested; if you need refuge, it is always available. But I am currently happily living in Samara. Unless you sincerely intend to escape the pain of Samsara, whatever the sacrifices, you should be extremely cautious about following Buddhist practices unless you understand why they serve your actual goals.

I have tried to give an appropriate warning about the dangers of meditation. But I am not sure it is even possible to convey how powerful classical psychedelics (LSD, Shrooms, 5meo-dmt) can be. Some highlights from a survey of people’s experience:

Around 4.5% of respondents said the psychedelics caused them to experience psychosis, and another 4.5% said they might have had this effect.
Specifically, 74% said a psychedelic trip was in the top 20 most enjoyable experiences of their life; 61% said a trip was in the top 20 most meaningful experiences.
41% said they had one of their top 20 most frightening experiences on psychedelics, and 32% reported the same thing for mentally painful experiences.
The majority of respondents say that their psychedelic use caused at least some enduring (>6mo) personality change in them (~32% said “yes, very minor ones,” ~25% said “yes, moderately strong ones,” and ~7% said “yes, very strong ones”). The vast majority said these changes were positive.
More psychedelic trips are reported to be good than bad (depending on how you count it, there are about fivex-11x as many good as bad trips).

Doing intensive therapy on psychedelics has a long history, and there is a lot of interesting scientific research being done. If you have serious PTSD or other issues, perhaps that is something to look into. For those interested in the theory, I recommend the original work by Stanislav Graf. I have successfully worked as a facilitator before. But I am only willing to work with someone if they are already experienced with psychedelics or they already have done serious preparation. Taking a serious dose of a psychedelic is invoking interstellar overdrive. There is no way to do it reliably and safely, though you can minimize the risks. I recommend safer techniques first. You want to be as mentally strong as possible before you invoke full overdrive. If you go down this route, I strongly recommend using shrooms instead of LSD since shrooms last about half as long. I will discuss ketamine in more detail later, but adding ketamine significantly increases the odds you have a ‘good trip’ and is also strongly recommended.

The logic of this article required discussing full psychedelics. I will now move on to discussing the much safer substances I actually recommend.

MDMA

MDMA makes you feel happy and full of love. MDMA lasts about three to six hours with a two to three-hour peak. Drug onset and duration are always highly variable. There is very little risk of a ‘bad trip’ but should you feel strange effects I recommend the usual: focus on the breath and let go. This makes MDMA extremely useful for healing trauma. The FDA has approved MDMA-assisted therapy as a breakthrough treatment for PTSD. There is also significant research showing it is useful for anxiety, depression, and eating disorders. The studies are quite convincing, but I am a man of straightforward arguments, not interpreting studies. A substance that reliably induces happiness and love is obviously useful.

I recommend combining MDMA and meditation. Follow these steps:

Trip alone and sweetly ask people not to distract you from your goals.
Create an ideal cozy, pretty setting. Have tasty, nutritious food such as berries nearby.
Dose MDMA.
Watch happy media or listen to enjoyable music until you feel the effects hitting strongly.
Do 45 minutes of breathing meditation. As usual, simply let your thoughts arise and pass away.
Take a short break.
Do another 45-minute session.
Enjoy simple pleasures for the remainder of the trip.
Make sure you don’t have anything to do the next day.

In this protocol we are taking responsibility for our own mental health. You don’t need other people to help you process. Ultimately, only you can decide how to interpret the events in your own mind. Other people’s reactions are unpredictable, and we want the most reliable protocol possible. MDMA is very safe; you certainly don’t need a tripsitter. However, once you have entered the ‘come down’ phase, bonding with friends and loved ones can be helpful. But beware, anytime you add people to a drug experience, you have increased the variance, so be choosy.

The other protocol I recommend is based on MDMA’s extremely strong ability to facilitate bonding. Choose who you want to bond with wisely. Follow the same steps, except instead of meditating, spend time cuddling or having sex. MDMA is very effective at healing sexual trauma, making people more comfortable with sex acts they have internalized as shameful, or helping partners become more comfortable with each other.

Of course, a small amount of meditation can be useful to set your mind or course correct. If the bonding protocol feels even slightly ‘off,’ safely retreat to the meditation protocol. You never want to force intimacy. The bonding protocol’s only real ‘risk’ is that it works extremely well. It’s the sort of thing I recommend doing with your spouse or otherwise committed partner. We are trying to make our lives beautiful, not develop unwanted or unrequited feelings. It is worth noting that MDMA causes severe erectile dysfunction in many people. The ED goes away, but if you wish to have penetrative sex on MDMA, you might need Viagra. I would recommend taking the Viagra ahead of time since ED is quite likely during the session.

Some people feel like MDMA ‘overloaded’ their serotonin, and they feel somewhat more down the next few days after a session. This is normal. Of course, a ketamine session the day after MDMA can help. Unfortunately, MDMA interacts badly with SSRIs, and you absolutely should not use MDMA if you are taking one. I don’t recommend pausing or skipping antidepressants so that you can take MDMA. That does not strike me as a wise course of action. However, you can consider trying an SNRI instead. Many people respond better to SNRIs instead, and the information value of trying the swap is likely worth it anyway. You also need to skip any stimulants (such as Adderall) on days when you take MDMA.

There is substantial debate about whether MDMA, taken in reasonable doses, is neurotoxic. My personal review is that doing it once every one to three months is safe. MDMA definitely messes with your body’s heat regulation, which can harm your brain, so please only take MDMA somewhere cool. You definitely should not mix MDMA with other stimulants such as Adderall since the combination makes the heat/neurotoxic risk much more severe. If you are seriously working on your mental health, I would recommend monthly sessions. Once things are in better shape I would switch to once every three months. I recommend reading these reviews and coming to your own conclusions before dosing.

https://www.thedea.org/mdma-risks-science-and-statistics-technical-faq/mdma-ecstasy-molly-neurotoxicity-brain-damage/

https://dancesafe.org/drug-information/is-mdma-neurotoxic/#2

Appendix

Caveats policy:

There are many caveats I could have added. In general, I chose not to go into an even longer digression on Buddhism and different meditation practices. If AI safety has taught me anything, there is no way to discuss a potential danger without inadvertently pushing many people toward it. I’m aware I probably encouraged people to try psychedelics despite the extreme warnings. But most people have heard of psychedelics anyway, and the EV isn’t so bad. Many Buddhist practices are more obscure and have much worse expected value.

Drug Testing Resources:

https://dancesafe.org/product/ketamine-testing-kit/

https://dancesafe.org/product/mdma-testing-kit/

Neither kit is perfect, but it’s better than nothing.

https://www.sfaf.org/services/drug-checking-scope/

Services like the above exist in tons of cities and offer very high quality purity testing.

Drug interaction notes:

https://www.vice.com/en/article/padgjm/everything-you-need-to-know-about-mixing-mdma-and-antidepressants-safe-sesh

https://addictionresource.com/drugs/zoloft/how-long-stays-in-system/