4 ms·

> I can see how a skeptic might look at these reports and think "how convenient, all the fun drugs make people happier for a little while" And those skeptics

> I can see how a skeptic might look at these reports and think "how convenient, all the fun drugs make people happier for a little while" And those skeptics would be both right and wrong. Wrong in the sense that the antidepressant effect of ketamine lasts for some time after the drug leaves the system, so we know it's not just a temporary drug-induced effect. But somewhat right because the antidepressant effect isn't very durable, so it's mostly useful in emergency situations (suicidal tendencies) and for kickstarting conventional therapy. Even the rare patients who convince their doctor to prescribe ketamine multiple times per week over the long term usually encounter diminishing effects as tolerance sets in. Unfortunately, the high relapse rate presents a huge conflict of interest for these ketamine clinics, which are often more than happy to continue taking your money in exchange for ketamine sessions. The more ethical ones will insist that patients be enrolled in therapy and will educate them on proper maintenance antidepressant options if they choose. The less ethical ones will give patients a speech about how traditional medicine is bad and their only real option is to continue coming in for more ketamine. There are some horror stories from one of the local ketamine clinics here. I'm actually shocked they aren't more tightly regulated at this point.

criticaltinker 5y ago
I know you comment on a wide range of topics here, and perhaps you’re jaded by some personal experiences with local ketamine clinics - but IMO your tone comes across as unnecessarily pessimistic and a smidge anecdotal. Ketamine/MDMA/LSD/Psilocybin and their derivatives are on their way to being recognized as the safest, most effective, and widely available medicines - for nearly every common mental health disorder - currently known to humanity. Yes there will always be predatory behavior in healthcare, and regulation can help. And of course no medicine is 100% side-effect free or effective for everyone. But shouldn’t we be complaining that many of these substances continue to remain federally outlawed in the US despite a huge body of scientific evidence and multiple companies discussing phase 3 clinical trials with the FDA this year? I don’t really hear many folks calling for tighter regulation on these substances, especially given the current regulatory situation.
- PragmaticPulp 5y ago
  > Ketamine/MDMA/LSD/Psilocybin and their derivatives are on their way to being recognized as the safest, most effective, and widely available medicines - for nearly every common mental health disorder - currently known to humanity. This sounds like a utopian fantasy. Ketamine can be useful, but like I said it’s not a long-term solution. MDMA isn’t really safe for extended use. Even the MDMA enthusiasts will agree with that one. Psilocybin is being studied in conjunction with 10-20 therapy sessions. If you’re attributing the positive effects from studies to the drug alone, that’s incorrect. Someone taking MDMA or mushrooms on their own is nothing like what’s being studied. I’m optimistic about future research, but if you think Ketamine, MDMA, and Psilocybin are the safest and most effective drugs available for “nearly all” mental health issues then you’re not really discussing the research, you’re discussing a utopian fantasy. Even the researchers I know in this space aren’t anywhere near that idealistic. Let’s be realistic.
  - criticaltinker 5y ago
    I'm afraid you're misrepresenting this important area of research. > Psilocybin is being studied in conjunction with 10-20 therapy sessions For a quick reality check, you could take a look at Compass Pathways and their phase 1 & 2 clinical trial results [1][2]: > we have completed a phase IIb clinical trial of psilocybin therapy for TRD, in 22 sites across Europe and North America. This was the largest randomised, controlled, double-blind psilocybin therapy clinical trial ever conducted, and our topline data showed a statistically significant (p<0.001) and clinically relevant improvement for patients who received a single high dose of COMP360 psilocybin with psychological support That is a single dose along with a single therapy session, showing positive benefits lasting 12+ weeks. For treatment resistant depression (TRD), a notoriously difficult condition to cure and one that affects many people. There are literally no other drugs on the market that come close to the safety, efficacy, and durability profile that is being observed! Do you think the FDA granted breakthrough therapy status in 2018 because of some collective "utopian fantasy"? It's well known there are numerous indications for psychedelic assisted therapy showing great promise - from anxiety and addiction to end of life care [3]. It's not just psilocybin either, many of these psychedelic substances are pharmacologically related - so they act on similar receptors and areas of the brain, and thus have similar therapeutic profiles [4]. Let's be realistic. Your appeal to extremes is an uncharitable interpretation of my comment, and frankly your uninformed pessimism on this topic is a disservice to anyone interested in learning about or benefiting from these advances. [1] https://ir.compasspathways.com/news-releases/news-release-details/comp360-psilocybin-study-89-healthy-participants-published https://ir.compasspathways.com/news-releases/news-release-de... [2] https://ir.compasspathways.com/static-files/0f9fbce8-2619-438b-a6ba-5bbe2ba08cf6 https://ir.compasspathways.com/static-files/0f9fbce8-2619-43... [3] https://www.sciencedirect.com/science/article/pii/S0092867420302828 https://www.sciencedirect.com/science/article/pii/S009286742... [4] https://www.nature.com/articles/s41386-022-01297-2 https://www.nature.com/articles/s41386-022-01297-2
hiram112 5y ago
> But somewhat right because the antidepressant effect isn't very durable, so it's mostly useful in emergency situations (suicidal tendencies) and for kickstarting conventional therapy. Even the rare patients who convince their doctor to prescribe ketamine multiple times per week over the long term usually encounter diminishing effects as tolerance sets in. This is the unfortunate reality with all depression treatments, including SSRIs, Tricyclics, ECT, TMS, and even MAOIs. Most people who have treatment resistant depression that is "biological" i.e. not situational will end up requiring treatment for the rest of their lives. SSRIs are well known for "pooping-out" after some number of years, and most patients will end up cycling through different treatments, sometimes finding something that works well for a long time, and other times not finding lasting relief for years at a time while experimenting with "cocktails" of meds from different psychiatrists. The only problem with Ketamine at this time is that it is quite expensive as commonly provided (patented formulations, in-clinic requirements e.g. REMs, fusion providers, etc). If it turns out to be safe to use in lower doses via lozenges or some other compounded route, without the current associated high costs of administration and procurement, then there's no reason Ketamine can't end up being given out as a generic prescription to be used once or twice a week at just a few dollars / month, similar to what generic SSRIs or Tricyclics now cost. But I imagine the Pharma industry and the increasing number of very profitable infusion providers will do everything they can to ensure this doesn't become mainstream anytime soon.

criticaltinker 5y ago

I know you comment on a wide range of topics here, and perhaps you’re jaded by some personal experiences with local ketamine clinics - but IMO your tone comes across as unnecessarily pessimistic and a smidge anecdotal. Ketamine/MDMA/LSD/Psilocybin and their derivatives are on their way to being recognized as the safest, most effective, and widely available medicines - for nearly every common mental health disorder - currently known to humanity. Yes there will always be predatory behavior in healthcare, and regulation can help. And of course no medicine is 100% side-effect free or effective for everyone. But shouldn’t we be complaining that many of these substances continue to remain federally outlawed in the US despite a huge body of scientific evidence and multiple companies discussing phase 3 clinical trials with the FDA this year? I don’t really hear many folks calling for tighter regulation on these substances, especially given the current regulatory situation.

PragmaticPulp 5y ago
> Ketamine/MDMA/LSD/Psilocybin and their derivatives are on their way to being recognized as the safest, most effective, and widely available medicines - for nearly every common mental health disorder - currently known to humanity. This sounds like a utopian fantasy. Ketamine can be useful, but like I said it’s not a long-term solution. MDMA isn’t really safe for extended use. Even the MDMA enthusiasts will agree with that one. Psilocybin is being studied in conjunction with 10-20 therapy sessions. If you’re attributing the positive effects from studies to the drug alone, that’s incorrect. Someone taking MDMA or mushrooms on their own is nothing like what’s being studied. I’m optimistic about future research, but if you think Ketamine, MDMA, and Psilocybin are the safest and most effective drugs available for “nearly all” mental health issues then you’re not really discussing the research, you’re discussing a utopian fantasy. Even the researchers I know in this space aren’t anywhere near that idealistic. Let’s be realistic.
- criticaltinker 5y ago
  I'm afraid you're misrepresenting this important area of research. > Psilocybin is being studied in conjunction with 10-20 therapy sessions For a quick reality check, you could take a look at Compass Pathways and their phase 1 & 2 clinical trial results [1][2]: > we have completed a phase IIb clinical trial of psilocybin therapy for TRD, in 22 sites across Europe and North America. This was the largest randomised, controlled, double-blind psilocybin therapy clinical trial ever conducted, and our topline data showed a statistically significant (p<0.001) and clinically relevant improvement for patients who received a single high dose of COMP360 psilocybin with psychological support That is a single dose along with a single therapy session, showing positive benefits lasting 12+ weeks. For treatment resistant depression (TRD), a notoriously difficult condition to cure and one that affects many people. There are literally no other drugs on the market that come close to the safety, efficacy, and durability profile that is being observed! Do you think the FDA granted breakthrough therapy status in 2018 because of some collective "utopian fantasy"? It's well known there are numerous indications for psychedelic assisted therapy showing great promise - from anxiety and addiction to end of life care [3]. It's not just psilocybin either, many of these psychedelic substances are pharmacologically related - so they act on similar receptors and areas of the brain, and thus have similar therapeutic profiles [4]. Let's be realistic. Your appeal to extremes is an uncharitable interpretation of my comment, and frankly your uninformed pessimism on this topic is a disservice to anyone interested in learning about or benefiting from these advances. [1] https://ir.compasspathways.com/news-releases/news-release-details/comp360-psilocybin-study-89-healthy-participants-published https://ir.compasspathways.com/news-releases/news-release-de... [2] https://ir.compasspathways.com/static-files/0f9fbce8-2619-438b-a6ba-5bbe2ba08cf6 https://ir.compasspathways.com/static-files/0f9fbce8-2619-43... [3] https://www.sciencedirect.com/science/article/pii/S0092867420302828 https://www.sciencedirect.com/science/article/pii/S009286742... [4] https://www.nature.com/articles/s41386-022-01297-2 https://www.nature.com/articles/s41386-022-01297-2

hiram112 5y ago

> But somewhat right because the antidepressant effect isn't very durable, so it's mostly useful in emergency situations (suicidal tendencies) and for kickstarting conventional therapy. Even the rare patients who convince their doctor to prescribe ketamine multiple times per week over the long term usually encounter diminishing effects as tolerance sets in. This is the unfortunate reality with all depression treatments, including SSRIs, Tricyclics, ECT, TMS, and even MAOIs. Most people who have treatment resistant depression that is "biological" i.e. not situational will end up requiring treatment for the rest of their lives. SSRIs are well known for "pooping-out" after some number of years, and most patients will end up cycling through different treatments, sometimes finding something that works well for a long time, and other times not finding lasting relief for years at a time while experimenting with "cocktails" of meds from different psychiatrists. The only problem with Ketamine at this time is that it is quite expensive as commonly provided (patented formulations, in-clinic requirements e.g. REMs, fusion providers, etc). If it turns out to be safe to use in lower doses via lozenges or some other compounded route, without the current associated high costs of administration and procurement, then there's no reason Ketamine can't end up being given out as a generic prescription to be used once or twice a week at just a few dollars / month, similar to what generic SSRIs or Tricyclics now cost. But I imagine the Pharma industry and the increasing number of very profitable infusion providers will do everything they can to ensure this doesn't become mainstream anytime soon.