News Psilocybin spurs growth of neural connections lost in depression

[mr peabody]

Psilocybin spurs growth of neural connections lost in depression

Yale | Neuroscience News | 5 Jul 2021

Summary: One dose of psilocybin, the psychoactive compound found in magic mushrooms, increases dendritic spine density within 24 hours. The neurobiological changes lasted for a month following psilocybin exposure. Additionally, mice subjected to stress showed behavioral improvements and increased neurotransmitter activity after psilocybin exposure.

The psychedelic drug psilocybin, a naturally occurring compound found in some mushrooms, has been studied as a potential treatment for depression for years. But exactly how it works in the brain and how long beneficial results might last is still unclear.

In a new study, Yale researchers show that a single dose of psilocybin given to mice prompted an immediate and long-lasting increase in connections between neurons.

The findings are published July 5 in the journal Neuron.

“We not only saw a 10% increase in the number of neuronal connections, but also they were on average about 10% larger, so the connections were stronger as well,” said Yale’s Alex Kwan, associate professor of psychiatry and of neuroscience and senior author of the paper.

Previous laboratory experiments had shown promise that psilocybin, as well as the anesthetic ketamine, can decrease depression. The new Yale research found that these compounds increase the density of dendritic spines, small protrusions found on nerve cells which aid in the transmission of information between neurons. Chronic stress and depression are known to reduce the number of these neuronal connections.

Using a laser-scanning microscope, Kwan and first author Ling-Xiao Shao, a postdoctoral associate in the Yale School of Medicine, imaged dendritic spines in high resolution and tracked them for multiple days in living mice.

They found increases in the number of dendritic spines and in their size within 24 hours of administration of psilocybin. These changes were still present a month later. Also, mice subjected to stress showed behavioral improvements and increased neurotransmitter activity after being given psilocybin.

For some people, psilocybin, an active compound in “magic mushrooms,” can produce a profound mystical experience. The psychedelic was a staple of religious ceremonies among indigenous populations of the New World and is also a popular recreational drug.

"It may be the novel psychological effects of psilocybin itself that spurs the growth of neuronal connections," Kwan said.

“It was a real surprise to see such enduring changes from just one dose of psilocybin,” he said. “These new connections may be the structural changes the brain uses to store new experiences.”

Psychedelic Spurs Growth of Neural Connections Lost In Depression - Neuroscience News

One dose of psilocybin, the psychoactive compound found in magic mushrooms, increases dendritic spine density within 24 hours. The neurobiological changes lasted for a month following psilocybin exposure. Additionally, mice subjected to stress showed behavioral improvements and increased...

neurosciencenews.com

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[Neuropharmacist]

Here's my quick take on the study:

 

[G_Chem]

This is interesting as I’ve said elsewhere I underwent chemotherapy with a few different “drugs” but one was good ol’ cisplatin, know to reduce dendrite density in the frontal cortex as well as just fuck up the brain in general.

I was left with severe depression and anxiety that had no rhyme or reason, I knew logically there was no reason for it but it felt truly like my brain wasn’t working.

It’s been just over 6mos now and through the use of LSD, Mescaline, Ketamine, DMT, and MDMA I feel I’ve gotten back to a place I’m happy with. I still have slight cognitive issues but no longer am I riddled with anxiety and depression.

Im a lucky one, cuz I knew of their neurogenesis potential long before I went through this. Many cancer survivors stay on benzodiazepines or opiates because they can’t handle the leftover mental issues, but those just create problems of their own.

Amazing times we live in!

Btw good to have you around @Neuropharmacist i learned some things from that video as well

-GC

 

[Neuropharmacist]

This is interesting as I’ve said elsewhere I underwent chemotherapy with a few different “drugs” but one was good ol’ cisplatin, know to reduce dendrite density in the frontal cortex as well as just fuck up the brain in general.

I was left with severe depression and anxiety that had no rhyme or reason, I knew logically there was no reason for it but it felt truly like my brain wasn’t working.

It’s been just over 6mos now and through the use of LSD, Mescaline, Ketamine, DMT, and MDMA I feel I’ve gotten back to a place I’m happy with. I still have slight cognitive issues but no longer am I riddled with anxiety and depression.

Im a lucky one, cuz I knew of their neurogenesis potential long before I went through this. Many cancer survivors stay on benzodiazepines or opiates because they can’t handle the leftover mental issues, but those just create problems of their own.

Amazing times we live in!

Btw good to have you around @Neuropharmacist i learned some things from that video as well

-GC

That is a very interesting observation. I hadn't really thought about cisplatin previously.

Glad to hear you enjoyed the video.

 

[patchoulirose]

I found this article a few weeks ago and this is what made me want to try shrooms. I am tired of all of the medication that does nothing. I'm tired of people talking to me for 15-an hour, but not really listening to what I'm saying. I'm ready to do this on my own (with supervision of course.)

 

[G_Chem]

I found this article a few weeks ago and this is what made me want to try shrooms. I am tired of all of the medication that does nothing. I'm tired of people talking to me for 15-an hour, but not really listening to what I'm saying. I'm ready to do this on my own (with supervision of course.)

Start a thread with any questions if you’d like We may be able to help. These drugs can remove the need for pharmaceutical medications, but it takes work and planning. Do you have some supervising the mushrooming?

-GC

 

[thegreenhand]

Fwiw there is some evidence that SSRIs may have an additional mechanism via some neurogenesis related function. That is, in addition to its primary effect of acute serotonin reuptake inhibition and eventual receptor downregulation. So psychedelics are not necessarily unique in this regard, though they certainly are noteworthy compounds to induce neurogenesis.

One more thing to consider is that not all neurogenesis is necessarily positive. It may, for example, lead to learning some sort of harmful behavior. I guess my point is to be cautious of the claims that neurogenesis implies antidepressant effects.

That said, psilocybin (and LSD) have been remarkably effective for my depression. Unfortunately, I struggle to tolerate them anymore though

 

[G_Chem]

Fwiw there is some evidence that SSRIs may have an additional mechanism via some neurogenesis related function. That is, in addition to its primary effect of acute serotonin reuptake inhibition and eventual receptor downregulation. So psychedelics are not necessarily unique in this regard, though they certainly are noteworthy compounds to induce neurogenesis.

One more thing to consider is that not all neurogenesis is necessarily positive. It may, for example, lead to learning some sort of harmful behavior. I guess my point is to be cautious of the claims that neurogenesis implies antidepressant effects.

That said, psilocybin (and LSD) have been remarkably effective for my depression. Unfortunately, I struggle to tolerate them anymore though

Some good points. I feel you’re right on about the learning behaviors part. I notice that substances that induce neurogenesis also seem to wipe out certain, less necessary, memories over time. I’ve felt this is part of their power to help us re-learn new healthy behaviors but it could also bring about new negative behaviors and thought patterns too.

My early life wasn’t super great so I’m not so hurt to lose those memories but I’ve thought it could be negative for someone who’s grown up comfortable and doesn’t need some intense restart.

It seems with drugs like SSRI’s the neurogenesis is truly the beneficial part of their effect, that’s why they say wait a few weeks. It takes that long for the new neurons to grow mature. But while they may do similar things, they’re ability to form long term dependence and nasty withdrawals make them not as good of options in my eyes.

In the end though the research time and again recently seems to point to the antidepressant aspect of many drugs relating to their neurogenic properties. I’ve yet to see many claiming anything negative in that regard but am open to seeing some.

The only thing that scares me about neurogenesis is the potential to have cancer happen from overgrowth of cells. I remember reading a Reddit post where a supposed researcher said cancer cells had a field day in the presence of DMT. I notice when I started using DMT regularly certain moles on my body began growing, I’ve yet to get them checked out but will soon. I’d hope my cancer doc would’ve mentioned them during my last bout but he ain’t a dermatologist either..

I’m finding it’s hard to win in this life, balance is the name of the game. Can’t have too much of anything.

-GC

 

[thegreenhand]

Some good points. I feel you’re right on about the learning behaviors part. I notice that substances that induce neurogenesis also seem to wipe out certain, less necessary, memories over time. I’ve felt this is part of their power to help us re-learn new healthy behaviors but it could also bring about new negative behaviors and thought patterns too.

interesting point about the memory loss. i've never considered that. my gut tells me that it makes sense some memories may be lost from a pure computational perspective. with such potentially significant changes in LTP and LTD. i'm gonna have to dive into pub med on that one...

My early life wasn’t super great so I’m not so hurt to lose those memories but I’ve thought it could be negative for someone who’s grown up comfortable and doesn’t need some intense restart.

my own theory is that most mental 'illnesses' are remnants of early childhood trauma. from that, i can definitely see how a mentally 'healthy' person might be negatively afflicted by psychedelics.

It seems with drugs like SSRI’s the neurogenesis is truly the beneficial part of their effect, that’s why they say wait a few weeks. It takes that long for the new neurons to grow mature. But while they may do similar things, they’re ability to form long term dependence and nasty withdrawals make them not as good of options in my eyes.

i dont know if i'd quite say that. while post synaptic 5ht receptor regulation is likely a primary mechanism of the SSRIs' antidepressant action, i would hesitate to conflate this with neurogenesis. when new neurons are borne out of STEM cells then we say that neurogenesis has occurred. receptor up/downregulation probably occurs in some form during this process but i dont think it's a biconditional statement. and yeah,,as you noted, SSRI withdrawal can be very nasty. but with a sufficient taper i don't reckon many ill effects would occur. the real problem is that most patients are not warned of this risk...

In the end though the research time and again recently seems to point to the antidepressant aspect of many drugs relating to their neurogenic properties. I’ve yet to see many claiming anything negative in that regard but am open to seeing some.

i would agree neurogenic properties are strongly tied to antidepressant effects. exercise's antidepressant effects may in fact be modulated by this.

The only thing that scares me about neurogenesis is the potential to have cancer happen from overgrowth of cells. I remember reading a Reddit post where a supposed researcher said cancer cells had a field day in the presence of DMT. I notice when I started using DMT regularly certain moles on my body began growing, I’ve yet to get them checked out but will soon. I’d hope my cancer doc would’ve mentioned them during my last bout but he ain’t a dermatologist either..

that's interesting about cancer cells and DMT. i've never heard of it but sounds perfectly reasonable. @Skorpio are you familiar with any of this research?

I’m finding it’s hard to win in this life, balance is the name of the game. Can’t have too much of anything.

brotha, ain't that the truth

 

[G_Chem]

I’ll respond more later, but some articles that seem to think neurogenesis plays at least the most important role (not to say monoamine modulation doesn’t do anything, just not the main route.)

Science | AAAS

www.science.org

Unraveling the Mystery of How Antidepression Drugs Work

New insights into how selective serotonin reuptake inhibitors work suggest they reverse inhibited nerve regeneration and connectivity that may underlie depression

www.scientificamerican.com

It seems lowered 5-HT overall increases neurogenesis too when looking at this study.

Reducing central serotonin in adulthood promotes hippocampal neurogenesis - Scientific Reports

Chronic administration of selective serotonin reuptake inhibitors (SSRIs), which up-regulates central serotonin (5-HT) system function, enhances adult hippocampal neurogenesis. However, the relationship between central 5-HT system and adult neurogenesis has not fully been understood. Here, we...

www.nature.com

Some would say serotonin would be higher with SSRI’s, only temporary until (like everything we put into our bodies) homeostasis sets in to fix things.

New Rat Study: SSRIs Markedly Deplete Brain Serotonin

Study helps explain SSRI "discontinuation syndrome"

www.psychologytoday.com

So it may be that the neurogenesis comes from significantly reduced 5-HT that accompanies long term SSRI use.

My recent research into drugs like flavonoids shows their antidepressant effects too are derived from their neurogenic properties. The more I read the more it seems neuron growth makes us happy one way or another.

-GC

 

[thegreenhand]

I’ll have to read through those papers. but yeah agreed that neurogenesis is a very strong candidate for the underlying general feature of all classes of antidepressants.

I just still hesitate to say that it’s always a good thing w.r.t countering depression. something like cancer (as you noted) could be considered neurogenesis. or even more simply it leads to maladaptive learning. I think we all know folks who went off their rocker after heavy psychedelic use, potentially from this neurogenesis induced learning

that said, i think

neuron growth makes us happy one way or another.

is a perfectly reasonable position to hold. I’ll just need some more convincing yet

 

[Skorpio]

that's interesting about cancer cells and DMT. i've never heard of it but sounds perfectly reasonable. @Skorpio are you familiar with any of this research?

Not familiar with it, did a cursory pubmed search and couldn't find anything germane with keys dimethyltrypamine and cancer and psychadelics and cancer.

Cancer is a complex enough set of diseases that i could imagine certain types being worsened by the increase in BDNF, as there are some cancers that are driven by high levels of that hormone.

However that is just me stringing things together and doesn't represent a tested hypothesis.

 

[patchoulirose]

Start a thread with any questions if you’d like We may be able to help. These drugs can remove the need for pharmaceutical medications, but it takes work and planning. Do you have some supervising the mushrooming?

-GC

Not yet G_Chem. I'm working on getting the items first. I do have someone in mind to supervise. I read some articles that it might be good to have water or a Gatorade type drink near by. I'm asking suppliers what they recommend for a first timer. Many have said tea is good. I also have my eye on some gummies.