The question was whether joe 6-pack would benefit from, or harmed by, exposure to the psychedelic experience.

There is much to be said for both.

But though i wasn't around in the 60's, my impression is that the net result of the psychedelic hype back then, still was positive. In spite of all the negatives that also where a result of what happened in those days.

If psychedelics would never have become that popular, LSD might have never become illegal.

But i think the positive impact psychedelics have had on our culture should not be underestimated either.

Maybe joe 6-pack was never meant to take psychedelics himself. But maybe just the realisation that he COULD, that if he would realy want to, there is a whole new universe waiting for him there, just around the corner, would be enough. Enough to be more open to all of the other possibilities he has.

Most likely: the one would, the other not so.
To be honest: I would not have given myself a good wide chance when looking back at myself half a lifetime ago.

The thing is there are very intelligent Joe 6-packs out there.

I think that in general, any group of people can be effectively conditioned to behave in a certain way: What we buy into when young stays with us, we seek to reinforce it as we grow for cognitive comfort. We also feed off each other and our group who are in a similar cultural construct. We will ignore the flaws and damage from our cultural tenets while focusing on the positives to validate our flawed beliefs.

Put a very intelligent baby in a Joe 6- pack culture and she will likely just end up being a very good Joe 6-pack. During the height of the Nazi regime, the intelligent people did not usually reject the Nazi ideology, instead they just became very good Nazis.

The shock I got from psychedlics was being shown how many of my preconceived notions that I held in high regard were really unfounded and ridiculous. For example, I used to think that science was the untilate authority in everything and that spirituality was a waste of time. Those arrogant notions where crushed in an instant by a pshychedelic brain with enhanced connections.

The hard part came after, coming to terms with how wrong and arrogant I had been for many years. That process is still ongoing.

We can now directly observe improved structural and functional neural plasticity afforded by psychedelics. In basic empirical terms, they seem to be psysically healthy and beneficial. The more difficult question is: How do we integrate enhanced individual conciousness with our flawed and vulnerable cultural constructs we tend to get trapped into? Facing this dilemma is hard at both the personal and collective level.

Good point !
The true risk with psychedelics is that they induce one's subjective sensation of reconnection with his own nature, his own authority and so this person will not respect any kind of paternalist authority based on imposition of social or moral rules anymore. He will become god himself, immortal and will only respect his own inspiration.

Psychedelics are the enemies of control over nature. Someone who want to control someone else (because of unconscious fear of himself) will want to control the use of psychedelics.

Diversity in unity is the true richness and it scares a lot of people to accept difference. We say "I am more this, or less that, he is not as ... as..." But the real truth is that we are just all different and all together. If you respect that you do not create rules to control what somebody is doing.

I ask to everyone who think that human laws over natural ones are useful to explain why. What justify controlling natural behaviors ?

An interesting follow up paper. Pretty strong neurogenesis in rats, and this time they saw improvements in learning too.

They still worry and discuss trying to remove hallucinogenic effects. If I understand the paper, they do not seem to even consider that the subjective experience could be synergistic with the neurogenesis they observe 🤷‍♂️

"N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo"


https://www.nature.com/articles/s41398-020-01011-0

To be clear, I think trying to remove the hallucinogenic effects while retaining the neurogenesis effects is a worthwhile research path. There are people for whom that may be a viable or preferred way to get therapeutical effects.

However, I do not understand why the hallucinogenic effects are not ALSO discussed as a path for further investigation. Especially since people are ALREADY doing that at John Hopkins and other places.

An open minded researcher would say:

1) We see clear neurogenesis effects with DMT
2) It would be interesting to separate out the hallucinogenic effects while retaining neurogenesis. Let's call such a drug SOMA.
3) It would also be interesting to study therapeutical effects from both SOMA and DMT. It is possible they are not equivalent. The results would shed light on the benefits or issues with the hallucinogenic experience itself. They could also inform the current social prejudice against the hallucinogenic experience by either confirmig it, contradicting it, or showing no significant effect in clinical outcomes.

The researchers in these kind of papers never get to 3). They seem to assume that SOMA is the way to go because the hallucinogenic experience is judged apriori to be unwanted. If so, they are carrying their external social prejudice into their research and NOT being good scientists. The apriori judgment is even more baffling in the light of other research and a lot of modern social data in the form of personal growth experiences.

Hi Loveall, they probably aim to make a pil after which one can go to work, drive, ... to satisfy a bigger market. Easier to get approvals from governments. Eliminating potential mishaps that happen when hallucinating, we know these things happen seldom but they do, it would link their pil to the very idea of danger. The triptan meds against migraines (Sumatriptan/Imitrex) worked without the hallucinations as we know them, maybe that is stuf that inspired them? Just guessing.
It would be very interesting for sure to see how much the 'trip' makes up for the benefits!

So the question appears to be whether sigma-1 receptor activation is intrinsic to the hallucinogenic effects. Here: https://www.ncbi.nlm.nih.gov/pubmed/7905926 we see that there is an overlap in affinity for S1R and 5HT2R with some compounds and here: https://pubmed.ncbi.nlm.nih.gov/9144641/ we see that it is (of course) possible to produce compounds that are highly selective for S1R exclusively.

Thus, it would appear to be relatively simple to answer the question regarding abolition of psychedelic, er, 'hallucinogenic' effects, by finding out whether a selective S1R agonist such as PD144418 supports structural and functional neuroplasticity (SFNP). If it turns out that S1R activation in absence of 5HT2aR activation does not produce SFNP, it would then be worth combining the s-S1R agonist with a selective 5-HT2a agonist and, conversely, examining whether there are any 5-HT2a agonists that do support SFNP.

While the Morales-Garcia et al. study does in a way examine this by co-administration of DMT with 5-HT2 antagonists, it is still not quite the same as examining the effects of a pure S1R agonist. Of course, if this is being done in order to abolish hallucinogenic effects it might seem like the S1R is a poor place to start considering it was discovered through the anomalous 'psychotomimetic' effects of several opioid compounds. However, it is unclear to me whether this effect could be accounted for wholly by their concomitant effect at NMDA receptors - which itself turns out to be implicated in neural plasticity, perhaps adding weight to the idea that 'hallucinatory' effects are part-and-parcel of SFNP.

This thread contains a lot of stuff related to sigma-1 receptors.