Increased amygdala responses after psilocybin for treatment-resistant depression • Hacker News Board

Re: Increased amygdala responses after psilocybin for treatment-resistant depression

#31

Post by monktastic1 » Sat, Jan 06, 2018, 4:38 PM UTC

TheAdamAndChe wrote: post #18

code_duck wrote: post #6

While researching microdosing last year I learned that psilocybin and SSRIs have similar mechanisms of action, so I’m very happy they did this research. Anti-depressants are very popular drugs, and psychedelics have been suppressed culturally and legally, much like marijuana. I think there is definitely a place for ‘medicinal mushrooms ‘. Like MDMA, it’s an amazing substance psychologically.

> psilocybin and SSRIs have similar mechanisms of action This is incorrect. An SSRI is a selective serotonin reuptake inhibitor[1]. It works through decreasing the reuptake of serotonin from the synaptic cleft back into the presynaptic cell, effectively increasing utilization of existing serotonin. It has limited short-term psychoactive side-effects compared to psilocybin, which is mostly a powerful agonist of certai…

> but just claiming it's "amazing" is being reductionist.

This seems a bit parochial. The results that MDMA is showing for PTSD can certainly be called "amazing," even when the dangers are taken into consideration. That's why it has been given Breakthrough Therapy designation by FDA. So it seems reasonable to summarize this as "it's an amazing substance psychologically."

Re: Increased amygdala responses after psilocybin for treatment-resistant depression

#32

Post by code_duck » Sat, Jan 06, 2018, 4:53 PM UTC

TheAdamAndChe wrote: post #28

code_duck wrote: post #26

Earlier quoted context omitted.

Similar as in 'act on serotonin', which is close enough for me and most people. Like the article says, they actually have somewhat of an opposite mechanism. Thanks for the details. Your analysis of SSRIs is detailed, but not of psilocybin - saying they make you 'trip' and that's all is a bit reductionist too, wouldn't you say? They do have lasting psychological effects beyond that, and thankfully research such as thi…

> saying they make you 'trip' and that's all is a bit reductionist too, wouldn't you say? That's not all I said. First I compared the pharmacodynamics of the two(reuptake inhibition leading to better utilization of existing serotonin of SSRI vs direct serotonin receptor agonism of psilocybin), then I compared the psychological effects(fewer acute psychiatric effects in SSRI vs the "trip" of psilocybin). I personally…

I don't doubt that one would not want to take MDMA daily or regularly, and I doubt it will ever be prescribed or used like that - at least not in recreational doses. Their potential in large doses seems to be in therapeutic intervention.

If you know, I'd love to hear more about the mechanisms of psilocybin in the way you described SSRIs - I've done some reading but my understanding is certainly at the layman level.

Hopefully we will see research about related substances that exhibit therapeutic qualities with less toxic drawbacks.

Re: Increased amygdala responses after psilocybin for treatment-resistant depression

#33

Post by gt_ » Sat, Jan 06, 2018, 5:03 PM UTC

TheAdamAndChe wrote: post #23

jimnotgym wrote: post #22

This is fascinating as this is the plague of our generation. depression is such a debilitating condition, and in the UK mental health care has fallen to the level where it doesn't really exist outside of prescription medication. There was an earlier study in the UK [0] which showed similar effects, again on a small sample. The following interested me > A clinical trial, which took years and significant money to compl…

> It makes me wonder if the real resistance to this research is that an unmodified mushroom medicine would not be patentable, and it would be financially catastrophic to big pharma if people stopped taking their medication and grew their own more effective ones. Many of the antidepressant and psychoactive/psychedelic effects are caused by 5-ht2a receptor agonism, and many novel 5-ht2a agonists have been made[1], most…

Sounds questionable. Many substances with high abuse potential are used by medicine, and alcohol has no medical benefits that I know of but creates loads of problems everywhere I look. I don’t feel like I’m making any non-obvious points.

Re: Increased amygdala responses after psilocybin for treatment-resistant depression

#34

Post by ttul » Sat, Jan 06, 2018, 5:10 PM UTC

gt_ wrote: post #33

TheAdamAndChe wrote: post #23

Earlier quoted context omitted.

> It makes me wonder if the real resistance to this research is that an unmodified mushroom medicine would not be patentable, and it would be financially catastrophic to big pharma if people stopped taking their medication and grew their own more effective ones. Many of the antidepressant and psychoactive/psychedelic effects are caused by 5-ht2a receptor agonism, and many novel 5-ht2a agonists have been made[1], most…

Sounds questionable. Many substances with high abuse potential are used by medicine, and alcohol has no medical benefits that I know of but creates loads of problems everywhere I look. I don’t feel like I’m making any non-obvious points.

You obviously have never done mushrooms. You can’t abuse mushrooms. They are non addictive and self limiting.

Re: Increased amygdala responses after psilocybin for treatment-resistant depression

#35

Post by cle » Sat, Jan 06, 2018, 5:12 PM UTC

naasking wrote: post #27

TheAdamAndChe wrote: post #23

Earlier quoted context omitted.

> It makes me wonder if the real resistance to this research is that an unmodified mushroom medicine would not be patentable, and it would be financially catastrophic to big pharma if people stopped taking their medication and grew their own more effective ones. Many of the antidepressant and psychoactive/psychedelic effects are caused by 5-ht2a receptor agonism, and many novel 5-ht2a agonists have been made[1], most…

> The issue is abuse potential. Most of these drugs can be used to "trip," or have a psychedelic experience, meaning it would likely be made illegal very quickly. But why is tripping considered abuse? Particularly in cases where overdosing is difficult or impossible (like with marijuana). These requirements just seem asinine.

Because in the late 60s and 70s, US politicians needed scapegoats to blame for the social unrest, and the psychedelic movement with prominent figureheads like Timothy Leary was an easy target. Demonizing and criminalizing their drugs of choice gave them cause to imprison them and break up their social movements. So campaigns and institutions were established to proselytize the dangers of whatever drugs they were using, and laws were written and regulations established which simultaneously criminalized those drugs. Because the US political system is very slow moving and hard to course-correct, those institutions, regulations, and propaganda continue to this day.

Re: Increased amygdala responses after psilocybin for treatment-resistant depression

#36

Post by 0xcde4c3db » Sat, Jan 06, 2018, 5:14 PM UTC

naasking wrote: post #27

TheAdamAndChe wrote: post #23

Earlier quoted context omitted.

> It makes me wonder if the real resistance to this research is that an unmodified mushroom medicine would not be patentable, and it would be financially catastrophic to big pharma if people stopped taking their medication and grew their own more effective ones. Many of the antidepressant and psychoactive/psychedelic effects are caused by 5-ht2a receptor agonism, and many novel 5-ht2a agonists have been made[1], most…

> The issue is abuse potential. Most of these drugs can be used to "trip," or have a psychedelic experience, meaning it would likely be made illegal very quickly. But why is tripping considered abuse? Particularly in cases where overdosing is difficult or impossible (like with marijuana). These requirements just seem asinine.

> But why is tripping considered abuse? Particularly in cases where overdosing is difficult or impossible (like with marijuana). These requirements just seem asinine.

It's heavily associated with '60s counterculture in general, and more specifically hippies. Some users were starting to talk about entirely new (to them) kinds of spiritual experiences that didn't fit with Western religious traditions. Prohibition was seen as a valid tool for keeping these "subversive" people under control and blunting their effect on wider society.

Re: Increased amygdala responses after psilocybin for treatment-resistant depression

#37

Post by gt_ » Sat, Jan 06, 2018, 5:16 PM UTC

Despite being intensely skeptical of anything veering towards association as causation, I have always insisted that a psilocybin trip when I was 20 years old was overwhelming responsible for a series of achievements and positive changes in my life in the years following.

My lack of words or explanation for this has left me embarrassed to talk about it. Seeing these studies is bringing up a lot of dormant curiosity.

Re: Increased amygdala responses after psilocybin for treatment-resistant depression

#38

Post by gt_ » Sat, Jan 06, 2018, 5:20 PM UTC

ttul wrote: post #34

gt_ wrote: post #33

Earlier quoted context omitted.

Sounds questionable. Many substances with high abuse potential are used by medicine, and alcohol has no medical benefits that I know of but creates loads of problems everywhere I look. I don’t feel like I’m making any non-obvious points.

You obviously have never done mushrooms. You can’t abuse mushrooms. They are non addictive and self limiting.

Maybe you meant to reply to the parent of my comment?

Re: Increased amygdala responses after psilocybin for treatment-resistant depression

#39

Post by tpm » Sat, Jan 06, 2018, 5:47 PM UTC

jimnotgym wrote: post #22

This is fascinating as this is the plague of our generation. depression is such a debilitating condition, and in the UK mental health care has fallen to the level where it doesn't really exist outside of prescription medication. There was an earlier study in the UK [0] which showed similar effects, again on a small sample. The following interested me > A clinical trial, which took years and significant money to compl…

Currently, there is an application at the European Medicines Agency (EMA) for a large clinical trial of psilocybine therapy for the treatment of otherwise treatment-resistant depression, 400 patients in 8 European countries. As far as I know, it has not yet been approved, but I am optimistic.

http://www.appliedclinicaltrialsonline.com/compass-pathways-...

Re: Increased amygdala responses after psilocybin for treatment-resistant depression

#40

Post by b6 » Sat, Jan 06, 2018, 5:53 PM UTC

gt_ wrote: post #37

Despite being intensely skeptical of anything veering towards association as causation, I have always insisted that a psilocybin trip when I was 20 years old was overwhelming responsible for a series of achievements and positive changes in my life in the years following. My lack of words or explanation for this has left me embarrassed to talk about it. Seeing these studies is bringing up a lot of dormant curiosity.

> My lack of words or explanation for this

I wouldn't feel bad about this at all. I'm comfortable that there are many very important things that can be understood but cannot be conveyed to others using language. You can tell someone the capital of France, but not what it was like when your child was born, maybe because one is a concept and the other is an experience. I've had a lot of indescribable but very valuable experiences too (LSD).