I think the answer to that is to slowly increase the dose over a number of sessions. Starting out with microdosing to get used to the body feeling, then getting used to visual disturbances and the altered mental state, and then graduating to a level that can unlock new perspectives on self and the world. This absolutely has to be done by a trained professional with personal experience with the substance and who has assisted with other guided sessions. It's not going to be a prescription that a doctor can throw at the patient and then check up on in a few weeks time.

> This absolutely has to be done by a trained professional with personal experience with the substance and who has assisted with other guided sessions. It's not going to be a prescription that a doctor can throw at the patient and then check up on in a few weeks time.

That's pretty much how every treatment, for almost anything, should be.

Unfortunately, in most professional services (not just doctors), the people providing the service just have a few "recipes" on how to solve certain types of problems and then they just prescribe that. If your problem doesn't fall into any of their predefined categories, then good luck.

The typical interaction is: you have an initial session/interview where you describe your issue, then they immediately diagnose you (unless they require some additional info - documents/exams), and finally they provide their predefined solution. They never observe you in your daily routine to see what's actually going on, they don't study you to provide a personalized solution.

It's as if programmers would never debug a program, only get told by someone what the issue is and then they provide some library/api/piece of code that deals with what appears to be the issue from the outside.

> This absolutely has to be done by a trained professional with personal experience with the substance and who has assisted with other guided sessions. It's not going to be a prescription that a doctor can throw at the patient and then check up on in a few weeks time.

Seems like a bang-up business model, along with all sorts of other regular-meetings-with-the-professional therapies. Biologics on the pharm side, or just plain old therapy on the practitioner side.

Industry has plenty of practice with "every month or two" doses, so I wouldn't be so cynical in the attempts to remove the side effects. "Can you do it without getting high" is something that would greatly expand the audience and give people a better experience.

Ketamine is being used to good effect these days in major depression. I wonder if they ramp up the doses like that when using it?

They don't.

Fwiw, the psychedelic effect of ketamine is separate from its antidepressant effect.

Hm, could you elaborate on that please? Do you mean the separate as in stereoisomer-wise? Or do you mean that ketamin has multiple effects on the brain or central nervous system, and one is the antidepressant effect and the other is the tripping balls effect? (And obviously pharma would like to find out what's going on exactly in the first case or ... how to block the second case while still having the first effect happen?)

* the stereo-isomers have differing effects: s-ketamine being more inebriating and less anti-depressant, while r-ketamine is less inebriating and has a stronger anti-depressant effect.

* The inebriant effect can be modulated without altering the anti-depressant effect, at least in lab rats. Cannabis is one drug that does this.

* The pharmaceutical company that ran the clinical trials for esketamine likely did so because it is actually the least effective anti-depressant of the two entanomers, and less effective than regular ketamine. By trialing and patenting the less effective one first, they can then patent the more effective one later, and make money longer, by dragging their feet. Esketamine is currently a few hundred dollars a dose (every three days). My ketamine is $70 for ~6 week supply. Capitalism is wonderful.

* fwiw, ketamine triggers other pathways in the brain, including ones that are involved in attention deficit and wakefulness. It has the same effect as amantadine - an ADHD medication. I can't take it after 10 am or so, if I am going to get a decent night's sleep.

Off-label use is great, doctors love it, but ... trials don't show much.

" [...] esketamine’s results are at least as bad as any SSRI’s. If you look at Table 9 in the FDA report, ketamine did notably worse than most of the other antidepressants the FDA has approved recently – including vortioxetine, an SSRI-like medication."

https://slatestarcodex.com/2019/03/11/ketamine-now-by-prescr...

See later on in the article:

> Another possibility is that everyone made a huge mistake in using left-handed ketamine, and it’s right-handed ketamine that holds the magic. Most previous research was done on a racemic mixture (an equal mix of left-handed and right-handed molecules), and at least one study suggests it was the right-handed ketamine that was driving the results. Pharma decided to pursue left-handed ketamine because it was known to have a stronger effect on NMDA receptors, but – surprise! – ketamine probably doesn’t work through NMDA after all.

Case isn't closed yet.

Hah! Serves them right.

I think pharma pursued left-handed ketamine because they could patent it and charge a king's ransom for it, whereas your dog's vet has a bottle of right-handed ketamine for $5.

Meditation has similar effects - some people will have a single mind-blowing experience and a lot of their problems go away at once. Others practice for years and slowly whittle away at the sharper corners of their mind.

The problem is, you may not know what type of person you are going to be till ten years in. I suspect the same is true of psychedelic dosing: some of those soccer moms may need a strong depersonalization experience to get any real benefit from it. In some psychonauts it's going to trigger psychosis. I'm glad there's finally research being done in this area, the possibilities are certainly very exciting.

"The problem is, you may not know what type of person you are going to be till ten years in."

Very true. I used to fancy myself a psychonaut, then i got careless with 5-meo-dmt. Now i'm a teetotaler. Upon reflection i can't say i ever really liked tripping.

That’s probably true some of the time, but I think there’s a mode of mental health issues that I’ve experienced personally and seen in others who approach life with one foot on the gas and one foot on the brake. Basically, my hypothesis is that some people have contradictory impulses of desire and fear of stimulation and calm at the same time. You don’t have two groups of people (novelty-seeking HN crew vs vanilla soccer moms), but one type of person who is both and in conflict with themselves.

That's me. Easily overstimulated, yet drive myself to exhaustion because everything is too damn exciting. If you ask me it's a combination of high dopamine and high neural excitability/high connectivity. I think many programmers are like this and exist in a semi-permanent state of exhaustion.

This is a bad assumption on both ends (HN comments are most definitely not a bastion of free thought and expression.) but If people affected by PTSD can re-experience their trauma in controlled therapeutic settings using psychedelic compounds, so to can most others. Psychedelics are not for everyone, but they are certainly also not limited to chosen ones.

As a mini-side rant, I've found that people in the psychedelic community (defined as those that purposefully use psychedelics vs more spur of the moment usage) have pumped them selves up on their own identities as these "open minded explorers". I've actually found them to be belligerently dug in when faced with new evidence, information, and perspectives.

Source: I helped run a major city psychedelic community for a couple years

I honestly don't understand what happens to some people they trip. When I trip I get torn apart and question everything I believe in. After my first trip I thought wow if only everyone could experience this people would open their minds.

Then in time I met more and more people who regularly use psychs who were stuck in dogma. Recently I saw an interview with Dennis McKenna of all people who regularly trips (like his brother) and he just came across really disconnected like a dogmatic liberal like he was repeating what he had been told rather than thinking for himself.

It's been bothering me for a long time trying to understand it. I think the conclusion I have come to so far is that it opens your mind but only above whatever baseline you came from. The other thing is because the experiences have a feeling of being profound people who are not that open minded end up worshiping it and just fit themselves into that niche.

There's a long rant here, but it'll be pages worth of text. The short of it is that the so called leaders of the community are often accidental, untrained, uneducated, and largely unchecked. They say the right things and every one coalesces around them even if it's unsubstantiated gibberish (Terrance was the master of this and a total nut to be honest). It is very reminiscent of political dogma and zealotry (lets not pretend this is just a "dogmatic liberal" thing). Not to mention the big money they're pulling in from it now too (looking at you Bill Richards.)

There's no reason to continually trip, to take large doses, to try multiple psychedelics, etc. It's up to the individual to decide on what feels right for them. It is one of the most subjective and personal experiences you can have. Benchmarking against others is just...destructive really. No one in the community is saying that right now. It's just spiraling group think.

Yes essentially the leaders become like religious leaders. The problem is there is usually a kernel of truth to what they are saying which makes it easy to buy into if you're not thinking critically about it.