Psychedelics Promote Structural and Functional Neural Plasticity

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082376/

"SUMMARY

Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders."

 

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082376/

 

"SUMMARY

Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders."

"potential" and "developing" are key words regardless of anyone's opinions re such.  Such words convince me of nothing as they do not denote any sure thing or solid assurance of safety.  My words here are pure logic, no attack.

http://www.maps.org/images/pdf/history_of_psychedelics.pdf

"potential" and "developing" are key words regardless of anyone's opinions re such.  Such words convince me of nothing as they do not denote any sure thing or solid assurance of safety.  My words here are pure logic, no attack.

On one hand it's great to think that there might be some kind of pill or potion we could take to make all of our symptoms go away, but on the other hand most of us are only here because we took a pill to try to make all of our issues go away. And that pill had close to half a decade track record of supposed "safety".

I for one won't be standing in line for any clinical trials.

"potential" and "developing" are key words regardless of anyone's opinions re such.  Such words convince me of nothing as they do not denote any sure thing or solid assurance of safety.  My words here are pure logic, no attack.

 

On one hand it's great to think that there might be some kind of pill or potion we could take to make all of our symptoms go away, but on the other hand most of us are only here because we took a pill to try to make all of our issues go away. And that pill had close to half a decade track record of supposed "safety".

 

I for one won't be standing in line for any clinical trials.

Yes, "supposed" in regards to safety is always key to keep in mind as well.  Two heads are better than one at conveying some things.   

https://www.erowid.org/references/refs_view.php?A=ShowDoc1&ID=6318

Abstract:

Hallucinogens (psychedelics) are psychoactive substances that powerfully alter perception, mood, and a host of cognitive processes. They

are considered physiologically safe and do not produce dependence or addiction. Their origin predates written history, and they were employed

by early cultures in a variety of sociocultural and ritual contexts. In the 1950s, after the virtually contemporaneous discovery of both serotonin

(5-HT) and lysergic acid diethylamide (LSD-25), early brain research focused intensely on the possibility that LSD or other hallucinogens had

a serotonergic basis of action and reinforced the idea that 5-HT was an important neurotransmitter in brain. These ideas were eventually proven,

and today it is believed that hallucinogens stimulate 5-HT2A receptors, especially those expressed on neocortical pyramidal cells. Activation of

5-HT2A receptors also leads to increased cortical glutamate levels presumably by a presynaptic receptor-mediated release from thalamic

afferents. These findings have led to comparisons of the effects of classical hallucinogens with certain aspects of acute psychosis and to a focus

on thalamocortical interactions as key to understanding both the action of these substances and the neuroanatomical sites involved in altered

states of consciousness (ASC). In vivo brain imaging in humans using [18F]fluorodeoxyglucose has shown that hallucinogens increase

prefrontal cortical metabolism, and correlations have been developed between activity in specific brain areas and psychological elements of the

ASC produced by hallucinogens. The 5-HT2A receptor clearly plays an essential role in cognitive processing, including working memory, and

ligands for this receptor may be extremely useful tools for future cognitive neuroscience research. In addition, it appears entirely possible that

utility may still emerge for the use of hallucinogens in treating alcoholism, substance abuse, and certain psychiatric disorders.

Conclusions:

The tools of today’s neuroscience, including in vivo

brain imaging technologies, have put a modern face on

the hallucinogens. Scientists can no longer see them as

‘‘magic’’ drugs but rather as 5-HT2A receptor-specific molecules

that affect membrane potentials, neuronal firing

frequencies, and neurotransmitter release in particular areas

of the brain. One can now begin to speculate in reasonable

ways about how these cellular changes transform our

perceptions of reality and produce ASC. It is intellectually

satisfying, although perhaps not at all surprising, that the

neuroanatomical substrates that are apparently most affected

by these substances are the ones of most interest to consciousness

researchers and cognitive neuroscientists. Very

clearly, the substrates in the brain that are affected by

hallucinogenic drugs play crucial roles for us as conscious

beings in constructing our reality and in defining exactly

who we are in relationship to the rest of the world.

One must keep in mind that these substances came to our

attention in the first place only because of their unique and

powerful effects on the human psyche; to forget about the

behavioral consequences of hallucinogen-altered neurochemistry

is to miss the main point. There will be profound

importance in understanding how hallucinogens transduce

effects in neuronal systems that provide for the perception of

ordinary states of reality under one set of biochemical

circumstances but which under another allow what can only

be described as an ineffable state of mystical consciousness.

The implications of ‘‘stimulating 5-HT2A receptors in the

brain’’ go far beyond simply modifying membrane currents

and neuronal firing frequencies. If everything that we are

and can ever hope to be is somehow inextricably wired into

the brain, then molecular tools that modify these circuits in

predictable ways will be powerful levers to help us understand

better how mind originates from brain states. Make no

mistake, neuroscientists today who study depression,

schizophrenia, or the palette of other psychiatric disorders

do not simply abandon their curiosity when someone asks,

‘‘What is consciousness?’’ Since before recorded history,

our species has been on a never-ending quest for meaning in

life, and there is no reason why neuroscience should not be a

part of that search.

The failure of much of modern science to envision

hallucinogens as key ingredients in our efforts to understand

the nature of consciousness and the human mind is what has

allowed society to view these molecules for so long only as

dangerous drugs of abuse. It is quite unfortunate that legal

restrictions have kept these extremely interesting substances

from receiving more extensive clinical study, but there are

hopeful recent signs that this situation may be changing.

Coupling psychological assessments with in vivo brain

imaging, as in the work of Franz Vollenweider and his

colleagues, Efie Gouzoulis-Mayfrank, and a few others, is a

positive move forward toward correlating changes in alterations

in mood and thinking with brain function. The recent

discovery by Pettigrew that hallucinogens have dramatic

effects on binocular rivalry and MIB promises further

insight into other cognitive processes. The effects of hallucinogens

on working memory demonstrated by Vollenweider,

Gouzoulis-Mayfrank, and others, and clinical

studies of the potential medical value of hallucinogens in

OCD and terminal patients, may signal that this field is

finally reaching a maturity that will lead to many important

new discoveries about what is called ‘‘the mind’’ and how

the brain generates it.

The philosopher in each of us yearns for greater understanding

of who we are and why we are here. Irrational fear

of inquiries into the nature of consciousness and conscious

experience must be put aside, and hallucinogens should be

recognized for what they are: tools that will ultimately help

us to understand ourselves. The answers lie in further

research for somewhere in the complexity of the brain exists

the source of answers to all questions about ourselves. In the

coming years, we may look forward to substantial progress

in understanding how hallucinogens affect brain function,

how those changes alter perception and cognition, and

ultimately whether these ancient healing substances have

medical value and wisdom to impart to our modern age."

"potential" and "developing" are key words regardless of anyone's opinions re such.  Such words convince me of nothing as they do not denote any sure thing or solid assurance of safety.  My words here are pure logic, no attack.

 

On one hand it's great to think that there might be some kind of pill or potion we could take to make all of our symptoms go away, but on the other hand most of us are only here because we took a pill to try to make all of our issues go away. And that pill had close to half a decade track record of supposed "safety".

 

I for one won't be standing in line for any clinical trials.

I imagine some thought the same about Polio vaccinations & many other scientific accomplishments over the years and generations. 

"potential" and "developing" are key words regardless of anyone's opinions re such.  Such words convince me of nothing as they do not denote any sure thing or solid assurance of safety.  My words here are pure logic, no attack.

 

On one hand it's great to think that there might be some kind of pill or potion we could take to make all of our symptoms go away, but on the other hand most of us are only here because we took a pill to try to make all of our issues go away. And that pill had close to half a decade track record of supposed "safety".

 

I for one won't be standing in line for any clinical trials.

 

I imagine some thought the same about Polio vaccinations & many other scientific accomplishments over the years and generations.

I'm grateful polio vaccinations and other scientific accomplishments have proven themselves. 

I imagine some thought the same about Polio vaccinations & many other scientific accomplishments over the years and generations.

I'm sure you are right, but there is a difference between preventing a debilitating illness with a vaccine and trying to use a drug to "fix" the neurological damage that was done by another drug.

Thanks for posting this.  It was very interesting to read through.

You are welcome. I thought of you when I decided to post it.

It may be difficult reading for some, here is a related NY Times article that abbreviates the research into a human interest type story:

https://www.nytimes.com/2018/05/01/us/ecstasy-molly-ptsd-mdma.html

Edit: Name of Article is, "Ecstasy as a Remedy for PTSD? You Probably Have Some Questions."

More on it here.  Not my bag, I don't think, lol, but very interesting nonetheless.  Who'd have thunk, eh?

http://www.benzobuddies.org/forum/index.php?topic=155161.0

http://www.benzobuddies.org/forum/index.php?topic=207647.0

following.  I am interested in these kinds of remedies and medicines.

Thanks F1

SS