Psychoplastogens

[Loveall]

The term Psychoplastogen has recently entered the scientific field and seems to be getting some traction.

It is being used for drugs that promote structural improvements in the brain as seen here.

Natural psychedelics such psilocybin and DMT have been found to be Psychoplastogens, which is consistent with the many stories of positive personal transformation and growth in many documented examples across the nexus forum.

However, there is a concerning trend arising summarized in this statement (source):

...(psychedelics) have long been known to be abused for their mind-altering effects... Olson and colleagues are hopeful that new medications can be derived from the existing drugs that retain the psychoplastogen properties while eliminating the psychedelic effects.

This seems like a mistake rooted in a cultural bias against the psychedelic experience (considered sacred by other cultures) . Other researh (by for example Ronal Griffiths) has already shown that (1) the psychedelic experience itself can be beneficial and the risk of a negative trip very well managed by some simple but important set and setting preparations together with patient screening, and (2) abuse potential is minimal.

It is my personal experience that the psychedelic effects are a very important part of the self improvement process. Extenind this to an opinion I think that if you give non psychedelic Psychoplastogen to ruthless businessesmen and they will just become better ruthless businessmen. However, give them psychedelics and they may just become better people.

With the combination of deep emotional realizations followed by a neurological boost to integrate the experience, it seems like nature has already given us a perfect medicine. Maybe our job is to recognize that our culture has been arrogantly wrong about these compounds for decades.

Or am I wrong? Is the quest that has begun to find a non psychedelic Psychoplastogen motivated by this cultural bias against the psychedelic experience a good idea?

I can imagine more common sense non-judgmental motivation for modification such as helping patients that don't pass psychedelic screening. However, that is not what the argument seems to be.

 

[Grey Fox]

What constitutes use and what constitutes abuse? The concern expressed in the quote is that all non-medical use is abuse and must be eliminated. Its as though the CSA is shaping their understanding at a fundamental level.

This is why I have so much apprehension about the medical model now being applied to psychedelics. Many see recent developments as positive because psychedelics are being researched and sent down the pipeline for FDA approval. But to what end?

Will all of this lead to a blossoming of liberty? Or will it lead to a further entrenchment of the prohibitionist system, whereby psychedelics are dropped down to lower schedule classes and then locked there forever because of corporate greed and governmental corruption?

This system views personal exploration and self-directed healing and development as illegitemate uses for psychedelics. Everything must go through a doctor's oversight. If they can somehow strip enjoyment from the drug then even better.

The message is that these substances are far too dangerous to allow adults to access them for their own purposes. Like a child being overseen by a teacher or guardian, the state and the medical system must oversee us and only grant access to psychedelics for narrow, medicalized purposes.

To hell with that!

 

[KloudQ7]

I just read about some non psychoactive versions of ibogaine and ketamine. I think with both of them the conclusion was that the psychadelic aspect is an important part of how they work.

 

[Auxin]

I see two things at work in that quote.
As mentioned, religious and cultural discrimination is both rampant and historically fundamental to modern western medicine. Modern western medicine grew as a hostile isolationist organization expressly opposed to holistic, hygenic, and herbalist types of medical traditions. To the point that it took a century to even get their doctors to wash their hands, because other groups washed their hands. They now wash their hands and are grudgingly starting to admit that food might have some effect on health, but expect any improvement to western medicine from an outside source to take 100 years. For psychedelics its only been 50 years.
Also, anything not profitable is considered irrelevant to western medicine. The quote specifically alludes to that. New drug compounds, patentable ones, are needed. Its just like that study that proved that THH could be used to cure type 1 diabetes, but only if an equally potent derivative were found and patented.

Don't be a slave to western medicine.
Do your own healing.

 

[0_o]

The system is the same system that took LSD and MDMA therapy underground because it worked.
It is the same system that got NIDA funding to study using psychedelics to treat PTSD.
Same system that produced Hoffman and Shulgin, both trained chemists.


I see a lot of hating and judgemental dismissal here, but it has nothing to do with pursuing psychoplastogenic effects without psychedelia.

 

[Grey Fox]

That same system also produced all the medical professionals and researchers who think that psychedelic use is drug abuse. I'm pretty sure that they're in the majority. Hopefully that will change one day.

I think the discussion in this thread has been good. But you can disagree if you like.

 

[Psilosopher?]

Holistic healing isn't practiced in conventional western medicine, since western medicine is the culmination of data obtained through reductionism. Holism is on the other side of the spectrum. Doctors in western medicine aren't stupid, many are just naive regarding the value of psychedelics.

I've spoken to plenty of doctors as part of my profession. The few that i talked to about psychedelics were not only on board, but enthusiasts.

From all my experiences with psychedelia, i have a hard time believing you can obtain effective psychoplastogenesis without psychedelia. The whole mind bending nature of psychedelia is what enables altered perceptions, different viewpoints and ultimately synaptic connections.

It's all about that stigma associated with tripping. Apparently any one who trips is a degenerate loser who contributes nothing to society, even if they ended up designing the polymerase chain reaction (PCR) that revolutionised science or visualising the DNA double helix on LSD.

 

[Spiralout]

Well I think it's obvious that not everyone thinks psychedelics are "bad". Maybe Olson et al. think so.... but then again; I don't see them stating their definition of abuse . If abuse means people taking psychedelics whimsically, in high doses and just to get a kick (devil is in the details here); well wouldn't you think it would be a good idea if people didn't do that? If only for there sake? Sure , no one should be controlling anyone but educating people surely isn't a bad idea... And that's what they're going to have to do once they realize the best drugs ARE psychotomimetic.

As was mentioned before there have been plenty of professionals immersed in related fields and no shortage of intellectuals in all different fields , that have used psychedelics. There's chaos in the order and order in the chaos.

 

[0_o]

Take caution with blanket statement dismissals and judgement about entire groups of people.
It's never a good sign.
You won't find the scientific nor medical community with a consensus for or against psychedelics.
Strawmen are a lot less common than is oft believed.

 

[Loveall]

Well I think it's obvious that not everyone thinks psychedelics are "bad". Maybe Olson et al. think so.... but then again; I don't see them stating their definition of abuse . If abuse means people taking psychedelics whimsically, in high doses and just to get a kick (devil is in the details here); well wouldn't you think it would be a good idea if people didn't do that? If only for there sake? Sure , no one should be controlling anyone but educating people surely isn't a bad idea... And that's what they're going to have to do once they realize the best drugs ARE psychotomimetic.

I think abuse is a general term with a poor definition. I've seen definitions out there range from "provides pleasure" (e.g. Caffeine) to "has a negative impact in your daily life" (e.g. heroine). The term "abuse" is used in the Controlled Substances Act (CSA) where it seems like the vagueness of the term is 'abused' (pun intented).

Dr. Nutt provided a rational scale for negative drug effects. I believe his published work (with over 1000 citations) is the golden standard. You are right that psychedelics can be misused, but in terms of harm, they are in the low end of the scale (see figure below).

However, this cultural institutionalized bias against psychedelic effects continues. Here, we have a researcher (who should be aware of Dr. Nutts work) labeling them as abusive drugs and using that label to propose a substantial amount of effort to modify the psychedelic molecules separate out the Psychoplastogen effect.

That line of reasoning seems incorrect to me based on what we know of the measured abuse potential of psychedelics via Dr. Nutts work.

It is concerning because what I think is unsubstantiated bias is directing research efforts.

If the motivation was to make psychoplatostogens available to the segment of the population that cannot or does not want to have a psychedelic experience, I would have no concerns.

I think that motivation based on false premises is a bad motivation. It is disfunctional. It could lead to things like extending the war on drugs and dother disasters.

I would hope that by now researchers would reach a concensus. <Calling psychedelics drugs of abuse is disappointing in light of Dr. Nutt's work. Yet, there it is, in the middle of cutting edge neurological research.

 

[0_o]

Abuse is not the same as harm.
Psychedelics can be and are abused.
They can also be used.

Literal the word abuse means "improper use" so any discussion of use implies abuse and any discussion of abuse implies use.

however, they have psychedelic properties and have long been known to be abused for their mind-altering effects, including perceptual changes that some people find enjoyable and other people find terrifying. Thus, the continued development of these drugs as therapeutic agents will have to consider risks, potential benefits, and methods of administration carefully in well-designed clinical trials. Olson and colleagues are hopeful that new medications can be derived from the existing drugs that retain the psychoplastogen properties while eliminating the psychedelic effects.

The article that used the word abuse addressed the fact that some people find psychedelics episodes terrifying. It is a legitimate risk and issue.

This site itself puts a lot of effort into addressing the risks entailed in psychedelic use. It does so because such risks are genuine.

Is it closed minded to want to develop psychoplastogens that don't have the risks that psychedelics entail? I honestly don't see anything biased against psychedelics in that at all.

 

[Loveall]

Is it closed minded to want to develop psychoplastogens that don't have the risks that psychedelics entail? I honestly don't see anything biased against psychedelics in that at all.

I agree, that approach is not closed minded. I tried to explain that earlier.

In the quote you posted they also characterize the pleasurable effects of psychedelics as abuse.

The bias some researchers are showing is against the psychedelic experience. However, there is no reason to assume the psychedelic experience is one of abuse alone without therapeutical value in itself. Evidence indicates quite to the contrary: there are studies that claim the experience itself can be therapeutic (Ronal G. et al.). Yes, there are risks, and work has been done to diminish these risks by managing set, setting, and implementing screening with great results (Ronal G. et al.).

The way I see it, the positive long lasting effects from psychedelics seen in the research may come from two sources and/or their combination:

1) Psycological: Deep emotional release ocasioned during the acute phase (~8 hours)
2) Physiological: Increased neuroplasticity to improve brain function after the acute phase.
3) A synergistic combination of 1) and 2)

The proposition here is that researchers who discard 1) are being biased. Same would go for researchers that discard 2) (haven't seen that in our culture, but I guess a shaman from a different culture may have a bias against 2)).

So, setting the (manageable) risks aside which are a valid reason to pursue taking out 1) from the drug effects, any researchers claiming that 2) alone should be pursued because the psychedelic experience is an experience of abuse and nothing more are being biased and potentially missing an important part of the healing process. This bias is culturally based, as the psychedelic experience is considered criminal and not sacred. This bias against the psychedelic experience has infiltrated our laws and research in my opinion.

Notice how I'm trying to separate out the associated risks from the judgment on the experience itself. The former is a legimite reason to pursue drugs designed to remove the psychedelic experience from physcoplastogens, but the latter reason is culturally biased (in my opinion).

This drug engineering may pose a risk in itself. We know depression is caused by reinforcing negative patterns of thought that show up as tight-loop neurological circuits in brain scans. What if by removing the psychedelic experience that disrupts these patterns and jumping strait to neuro plasticity the negative patterns are simply reinforced with more connections? The result could be a person whose depression neural circuit has been strengthened (this last part is all pure speculation of course).

 

[0_o]

Examples abound of cases where psychedelics don't have significant positive effects.
A lot of white supremacists and other members of other hate groups take things like LSD which are extremely popular today.
Psychedelics are not inherently good or bad.
The psychedelic experience is not inherently good or bad.

Psychoplastigenic effects seem explainable as a function of neuropharmacology, not of the psychedelic experience.

In reading that paper i didn't notice any dismissal of the psychedelic experience.
It seemed honest. I rather like the idea of psychoplastic drugs that can be given to infants and children etc. I have seen a lot of people use a lot of psychedelics and it definitely isn't for everyone and sometimes there are serious issues including psychological trauma.
While those issues can be considered they cannot be eliminated entirely.

I agree that there are antipsychedelic biases in some people, however one of the serious issues is the lack of objective neutrality including from those who believe that psychedelics make people into better people, yet that had never been shown and there is plenty of evidence against it. When Nazi's take LSD they remain Nazi's... They don't become worse or better.

Ultra positive unrealistic psychedelic advocacy harms the cause of cognitive liberty through its inability to be honest about the sheer inert neutrality of psychedelics which despite being potentially beneficial are fundamentally powerful tools that can easily be misused and abused in myriad ways. To obtain the greatest benefit from these powerful tools we must ourselves transcend the naive and ignorant views not only of the anti-psychedelic camp but also it's reciprocal antithesis which is just as bad.

 

[dreamer042]

The thing is, we already have the psychedelics. They aren't going anywhere, in fact they are moving ever moar deeply into medical and therapeutic legitimacy. Anyone who wants to has easily been able to obtain the supplies and skills necessary to grow psilocybin in their bedroom for decades now. Institutionalized biases or not, psychedelics are here to stay.

Now what if you could pair psilocybin with a (non-psychoactive) analogue that would increase the psychoplastogen effects 10/100/1000 fold? Is this undesirable? If you could take a compound that will increase your ability to create and reinforce new neural pathways before learning a new skill at work, in the dojo, in the classroom, or any other venue where publicly tripping your bawlls off may not be appropriate, wouldn't that ultimately be a beneficial thing?

Psychedelics have already been as demonized as they possibly can be, it's not as though they can be made moar illegal than schedule 1, or as if that has had the slightest impact whatsoever on people's ability to obtain them. I think at this point we've crossed the line from needing to seek legitimacy and we've moved on to social integration.

 

[0_o]

Psychedelics have already been as demonized as they possibly can be, it's not as though they can be made moar illegal than schedule 1, or as if that has had the slightest impact whatsoever on people's ability to obtain them. I think at this point we've crossed the line from needing to seek legitimacy and we've moved on to social integration.

That's how I see it.
VOA just published an article about conservation of peyote!
Numerous NIDA funded studies have established psychedelics as having indisputable benefits when used in certain contexts for specific purposes.
The focus of harm reduction has expanded!
Microdosing... something that was experimental 15 years ago is now an established practice.
Though the antipsychedelic people speak loudly they are becoming a minority.

 

[0_o]

There is an issue I see as holding things back, it is the US vs THEM mentality.
There is no real divide.
We are all just people.

 

[Loveall]

Well here it is, a recent report on synthesis and search for psychoplastogens with lower psychedelic activity. Guess it was just a matter of time as we expected.

"Identification of Psychoplastogenic N,N‑Dimethylaminoisotryptamine (isoDMT) Analogues through Structure−Activity Relationship Studies"

Interesting read as they go into what molecular features occasion neuroplasticity and which ones occasion "hallucinations".

Adding an interesting quote from the paper below. Not sure how to feel about it, on the one hand the science is cool, on the other hand it feels like a sacred thing has been "adulterated". It will be interesting if one day DMT and then less hallucinogenic isoDMT derivatives are compared in people's therapeutic outcomes.

...this work is the first to demonstrate that a psychedelic compound (i.e., DMT) can be engineered to lack hallucinogenic potential while retaining the ability to promote neural plasticity

 

[dragonrider]

Didn't paul stamets suggest that lionsmane and niacin would increase the beneficial effects of psilocybes? The niacin was meant to improve the distribution of the active compounds throughout the body, i believe.

Has anyone here ever done this?

For me personally...i am going to take some acid and shrooms on either saturday or monday, and i am thinking about taking some chaga then as well. I have heard people say that chaga opens the third eye, so i'm thinking that if there is any truth to those claims, then you should surely feel "something" when you are tripping balls.

 

[Loveall]

Here is a new article discussing this topic with input from Rick Doblin (spoiler: he doesn't seem too warm to the idea of using resources to remove the psychedelic effects at this time).

The Future Of Psychedelic Medicine Might Skip The Trip

A hallucinogenic experience may draw people to LSD and psilocybin, but the mental health industry believes there's a $50 billion opportunity in turning these compounds into safe at-home medications—without the ego-dissolving ride.

www.forbes.com

 

[Loveall]

Here is a new article discussing this topic with input from Rick Doblin (spoiler: he doesn't seem too warm to the idea of using resources to remove the psychedelic effects at this time).

The Future Of Psychedelic Medicine Might Skip The Trip

Also, $27 million? Mindlusion could do it in exchange for some good quality vanilla beans ...