4 ms·

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

by pharke 6y ago

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.

vajrabum 6y ago
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?
- WalterSear 6y ago
  They don't. Fwiw, the psychedelic effect of ketamine is separate from its antidepressant effect.
  - pas 6y ago
    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?)
    - WalterSear 6y ago
      * 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.
- pas 6y ago
  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-prescription/ https://slatestarcodex.com/2019/03/11/ketamine-now-by-prescr...
  - naasking 6y ago
    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.
    - charlieflowers 6y ago
      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.
ta1234567890 6y ago
> 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.
majormajor 6y ago
> 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.

by pharke 6y ago

vajrabum 6y ago

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?

WalterSear 6y ago
They don't. Fwiw, the psychedelic effect of ketamine is separate from its antidepressant effect.
- pas 6y ago
  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?)
  - WalterSear 6y ago
    * 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.
pas 6y ago
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-prescription/ https://slatestarcodex.com/2019/03/11/ketamine-now-by-prescr...
- naasking 6y ago
  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.
  - charlieflowers 6y ago
    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.

ta1234567890 6y ago

> 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.

majormajor 6y ago