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

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

#21

Post by psychedelicnope » Sat, Jan 06, 2018, 3:31 PM UTC

TheAdamAndChe wrote: post #16

Anecdotally, one-time use of LSD(which acts similarly to psilocybin, primarily through 5-ht2a agonism) set me on a path to self improvement. I had depression for years during my puberty, teens, and early adulthood. I contemplated suicide regularly and had a pessimistic outlook on life. I dropped out of college in my first semester despite taking and passing multiple AP classes in high school because I didn't see the…

Also anecdotally, I took a fairly large amount of magic mushrooms once, and it was an awful episode that left me with anxiety attacks for many months afterwards.

I saw no life improvement from this experience, and regret having ever dabbled recreationally.

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

#22

Post by jimnotgym » Sat, Jan 06, 2018, 3:34 PM UTC

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 complete due to the stringent regulatory restrictions imposed around the class 1 drug

This seems insane. Lots of other prescription drugs would be illegal for me to buy, why is this reserved for mushrooms that grow in our lawn? 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.

I note that many people are concerned about the side effects of magic-mushrooms. Perhaps you could consider that weighed against the side effects of the Seroxat[1] which amongst other things can stop a man reaching orgasm, or stop you dreaming(!) for years after taking it, is addictive and clouds your judgment. It can turn you suicidal or homicidal.

I wont bother to list any of the others and their side effects, but I know I would try the mushrooms first, and I would urge my family to do the same if they needed help.

[0]https://www.theguardian.com/science/2016/may/17/magic-mushro... [1]https://www.theguardian.com/uk/2001/jun/11/highereducation.m...

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

#23

Post by TheAdamAndChe » Sat, Jan 06, 2018, 3:47 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…

> 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 of which could be patented. 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.

[1] https://en.wikipedia.org/wiki/5-HT2A_receptor#Agonists

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

#24

Post by QAPereo » Sat, Jan 06, 2018, 3:51 PM UTC

brudgers wrote: post #7

evidence indicates that psilocybin with psychological support may be effective for treating depression On its own, psychological support may be effective for treating depression. If you're depressed, a reasonable starting point for clinical treatment is clinical treatment. The abstract does not suggest that self-medication with magic mushrooms may be effective. Deciding to consume psilocybin on one's own is an orthog…

Was there no control group which received pspsychological support and not the psilocybin?

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

#25

Post by SimbaOnSteroids » Sat, Jan 06, 2018, 3:51 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…

Fentanyl and cocaine are both schedule II, I wouldn't be surprised if these were the same way.

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

#26

Post by code_duck » Sat, Jan 06, 2018, 3:56 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…

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 this is elucidating what those effects are in detail.

By 'amazing', I'm referring to how many researchers, users and therapists refer to properties of, the potential of, and experiences with MDMA, not my own perception, usage or beliefs. I agree that something called 'methylene dioxy methamphetamine' is a serious drug that should be only used under the direction of a professional. As far as safety of long term effects and neurotoxicity, I'd question that about many current, legal prescription drugs such as SSRIs.

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

#27

Post by naasking » Sat, Jan 06, 2018, 4:05 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…

> 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.

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

#28

Post by TheAdamAndChe » Sat, Jan 06, 2018, 4:12 PM UTC

code_duck wrote: post #26

TheAdamAndChe wrote: post #18

Earlier quoted context omitted.

> 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…

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 don't believe that's reductionist.

> As far as safety of long term effects and neurotoxicity, I'd question that about many current, legal prescription drugs such as SSRIs.

There may be undiscovered negative effects of drugs like SSRIs, but suggesting that the negative effects of such drugs compare to the already recognized dose-dependent neurotoxic effects of MDMA is a stretch. Its combination of monoamine release and reuptake inhibition causes much more severe neurotoxic effects than SSRIs.

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

#29

Post by monktastic1 » Sat, Jan 06, 2018, 4:28 PM UTC

indescions_2018 wrote: post #14

Joins other studies from NYU investigating psilocybin mitigation of anxiety in advanced stage cancer patients. As well as a comprehensive survey by psychiatrists at Johns Hopkins showing 84% of those who tripped describing the experience as somewhat beneficial: Survey study of challenging experiences after ingesting psilocybin mushrooms http://journals.sagepub.com/doi/full/10.1177/026988111666263... As federal dollar…

Just so people know, MAPS primarily funds MDMA studies. Psilocybin funding is coming largely from the Heffter Institute.

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

#30

Post by drb91 » Sat, Jan 06, 2018, 4:29 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.

This is ultimately politics, and it is easy to scare with images of people who behave in entirely unpredictable ways.

One underutilized method to fight this, IMHO, is illustrating how terrible that line of thought is when you can compare it favorably to getting drunk in almost every way—but most of all judgement. Drunk people are already ethical black holes.