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SSRI neurogenesis vs Psilosybin neurogenesis?

JohnBoy2000

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Apparently both work to activate BDNF.

Are the two remotely comparable in terms of outcome?
 
As far as being "remotely" comparable, I would say yes for sure they are, given that as you say they have some shared if not entire equivalent receptor activity. Beyond that, especially in terms of "outcome" it's very hard to say because they are typically used in such different ways even in the context of targeted psychotherapy. I would say that on the face of it if the beneficial aspects of Psilocybin-induced neurogenesis could be nailed down then this probably has an advantage over SSRIs in that a single dose can potentially be used to trigger lasting changes, whereas SSRIs obviously require a fairly sustained course of treatment. SSRIs of course also have a bigger issue with "neurological dependence", so to speak, or "discontinuation syndrome", to put it in the polite parlance of the pharmaceutical industry. Hard to say if the reason for that is inherent to their mechanism of action or just a result of the relatively longer exposure required, but given that the neurogenesis is probably not separable from the need for a longer course of treatment there's a disadvantage in this regard.

On the other hand, for all the hate SSRIs get they're still likely a more "slow and steady" route to the same or a similar result - any powerful psychedelics come with an acute and immediate psychological risk even in the most well planned therapeutic environment, which is not really comparable to the slower onset of undesirable side effects that might be caused by SSRIs.

So in answer to your question, in my opinion yes they are "remotely comparable" but beyond that I don't think there is enough data to say. Off the top of my head though the few ongoing experiments into using psilocybin to treat psychological disorders (which may or may not be linked to BDNF problems) generally show superiority over current SSRIs in terms of outcome, but there is a skewing of the statistics here in that SSRIs have a vastly larger sample size but are probably also overprescribed due to the machinations of pharmaceutical capitalism, and psychedelic research is still something done with great care and a lot of pre-emptive filtering of unsuitable candidates who might not react well to this kind of treatment.
 
As far as reducing depression and downgrading 5-HT2a, they are similar.

BDNF isn't always good. It depends on the region. In the VTA/nucleus accumbens, it's likely not good. A better example is in malignant brain tumors. We don't want cells of that kind being nourished and grown.

With SSRIs it's mostly in the dendate gyrus of the hippocampus, if memory serves (no pun intended). With psilocybin I'm not sure. Pubmed or GoogleScholar is a good place to start.

Well one is known to work fast and the other slow. In terms of adverse effects, no one has had a bad trip on an SSRI. But people generally don't feel blunted after a psilocybin experience. SSRIs are safer.

In not too long they will be offering psilocybin clinics to the greatly treatment-resistant depression cases. But that's no excuse to use it otherwise.
 
interesting that there are a lot of articles saying psilocybin can help depression. in my case, it exagerated and actually turned me back to alcohol. even though, again in articles and various people's reports, it supposedly helps with addiction too. very strange
 
.. any powerful psychedelics come with an acute and immediate psychological risk even in the most well planned therapeutic environment, which is not really comparable to the slower onset of undesirable side effects that might be caused by SSRIs...

True but afaik, the dosage required for psychedelics to promote neurogenesis/treat MDD may not necessarily be the same as that for their other risky psychological effects. In fact, they seem to promote neurogenesis at doses order of magnitude lower than used "recreationally" ("Psychedelics Promote Structural and Functional Neural Plasticity"). This is case at least for certain tryptamines. For example, pinoline (a restricted 5MeO-DMT basically) is a robust promoter of hippocampal neurogenesis in rodents. Even at trace concentration ie at limit of detection with current instruments, it robustly increases neurogenesis in rodents (cf this ref). Which means at this dose, it may probably hardly show other undesirable side effects. I don't know about DMT/psilocybin dosage range for MDD which I doubt it has been studied (no money to be made since you can't patent them!)

Since both SSRIs and 5HT2a/c psychedelics are serotonergic and the latter are obviously more potent promoter of neurogenesis/anti-depressant action, one might assume that psychedelics target for neurogenesis is more specific than SSRI, making them potentially much safer than SSRI for MDD, with higher therapeutic index. SSRIs increase level of serotonin thus indiscriminately activating any and all 5HT receptors that may happen to be around, resulting in increased neurogenesis among other effects of stimulating 5HTRs (at least 14 subtypes of 5HTR with all sorts of different functions are known and more may be discovered!). You can imagine how activating them indiscriminately will have serious side-effects. While psychedelics are more selective (most with activate 5HT2a receptor subtype specifically. Whether this specific 5HT2aR stimulation cause neurogenesis, I don't know. But if SSRIs cause neurogenesis by indirectly activating 5TH2a, then there is no point using SSRIs for MDD when microdose (or rather nanodose) psychedelics will work fine. It is like using a sledge hammer to open a door (SSRI) v using a smartcard key to enter (Psychedelics).. Both will get you same results but one is gonna be costlier than the other!

Edit: oh sorry, dead link! here is the link: "Neurogenic Potential Assessment and Pharmacological Characterization of 6-Methoxy-1,2,3,4-tetrahydro-β-carboline (Pinoline) and Melatonin?Pinoline Hybrids" https://pubs.acs.org/doi/10.1021/acschemneuro.5b00041
 
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I'd say its not the psilocybin that helps depression but whatever power it activates. That hallucinogens act at the borderline between pharmacology and spirituality, or something like that. Just cause animals too have some reactions on it doesn't mean that it's only purely abstract. Stuff like that doesn't work every time, not for every one and might also do the complete opposite (although that opposite might be turned again into its opposite in future, and so on).

But I get what you say, I'm interested in that too.

(sorry was meant to be a reply to asecin)
 
In my opinion psilocybin acts as disruptor of your automated thoughts and habits - a thought-brain-chopper, so to speak. In this context you are forced to experience the world in a new unfamiliar way, which can help to break out of endless cycles of rumination and automated behavior. Under the right conditions psychedelics can yield new starting points for a change in behavior, lifestyle and living itself. SSRI's are not meant to give somebody new experiences or perspectives. They are used to stabalize and help the person to be in the condition to make changes. Neither psychedelics nor SSRI's can solve problems. They are nothing but tools and therefor can't replace a experienced psychotherapist or coach. But they are still usefull in their own way.

On a side note: Most of the time a critical observation of somebodies "life" or actual conflict is needed in order to work on a solution benefitting the person. It is not possible to break out of habits, which are so automatised that they are not viewable by the person himself. An outside observation is needed to realize and work on these existing psychological barriers. Psychedelics can be able to give somebody a new "perspective", but the interpretation of this new view itself can be dangerous depending on the interpretation of the said person. A good minded rational guide would be really helpfull to get best out of somebodies psychedlic experience. In my case I don't care if I experience highs or lows and therefor don't mind if I trip on my own or in a group. Experience is experience and shows that I am still alive.
 
Oh yeah, on the good and the bad. That it's not possible to break out of completely automatised habits but also not if one is shattered enough not to understand the concept of criticism anymore.

I'd say the same about dissociatives. They too are 'thought-brain-chopper's as well as anxiolytics, antidepressants, (in some cases, like MXE/O-PCM socially connecting and disinhibiting), bad to your bladder (unavoidably?), uh- dissociatives, etc.. but work over a very different mechanism yet achieve part of much the same goal. So it's more about that what happens downstream than the MOA in first line. Isn't it?
 
True but afaik, the dosage required for psychedelics to promote neurogenesis/treat MDD may not necessarily be the same as that for their other risky psychological effects. In fact, they seem to promote neurogenesis at doses order of magnitude lower than used "recreationally" ("Psychedelics Promote Structural and Functional Neural Plasticity"). This is case at least for certain tryptamines. For example, pinoline (a restricted 5MeO-DMT basically) is a robust promoter of hippocampal neurogenesis in rodents. Even at trace concentration ie at limit of detection with current instruments, it robustly increases neurogenesis in rodents (cf this ref). Which means at this dose, it may probably hardly show other undesirable side effects. I don't know about DMT/psilocybin dosage range for MDD which I doubt it has been studied (no money to be made since you can't patent them!)

Since both SSRIs and 5HT2a/c psychedelics are serotonergic and the latter are obviously more potent promoter of neurogenesis/anti-depressant action, one might assume that psychedelics target for neurogenesis is more specific than SSRI, making them potentially much safer than SSRI for MDD, with higher therapeutic index. SSRIs increase level of serotonin thus indiscriminately activating any and all 5HT receptors that may happen to be around, resulting in increased neurogenesis among other effects of stimulating 5HTRs (at least 14 subtypes of 5HTR with all sorts of different functions are known and more may be discovered!). You can imagine how activating them indiscriminately will have serious side-effects. While psychedelics are more selective (most with activate 5HT2a receptor subtype specifically. Whether this specific 5HT2aR stimulation cause neurogenesis, I don't know. But if SSRIs cause neurogenesis by indirectly activating 5TH2a, then there is no point using SSRIs for MDD when microdose (or rather nanodose) psychedelics will work fine. It is like using a sledge hammer to open a door (SSRI) v using a smartcard key to enter (Psychedelics).. Both will get you same results but one is gonna be costlier than the other!

Edit: oh sorry, dead link! here is the link: "Neurogenic Potential Assessment and Pharmacological Characterization of 6-Methoxy-1,2,3,4-tetrahydro-β-carboline (Pinoline) and Melatonin?Pinoline Hybrids" https://pubs.acs.org/doi/10.1021/acschemneuro.5b00041
Very interesting! Thank you for that.
 
Is anything known about this assumption, that the bulk of downstream activity from an SSRI is unneeded and just dangerous? Always thought it was about 5-HT1a and 2a being labelled as responsible for side effects (although it might be one further step down, that activation of 5-ht1a leads to more 5-HT able to activate 5-HT2a ...? When I got onto venlafaxine first, I meant to recognize some distinct signs I've learned later that it's known as HPPD. Can't really remember but I guess my first dose of mushrooms was before the first SSRI, jurt mirtazapine was even earlier and this one might (potentially?) upregulate 5-ht2a, doesn't it? Also I did just overshoot the dosage for shrooms massively, leading to bad trips. Later, equipped with a precise scale (but the mushies being banned now) I've experienced thrice or so with synth tryptamines and none of them actually caused any of the intense anxiety I feared from remembering my mushroom experiences (not all of them were bad, of course, but always only truffles had chances for a good one. Still wonder if it was only about potency, because I've of course also tried a low dosage (more than microdosing) and it caused the same, just less visual activity.

Well my last experience is with fresh truffles, while on other stuff (O-PCM and residual cannabis) which I didn't tolerate. But at first I felt like I kind of 'needed' the truffles, and began to like their unique taste - so much, that I chewed much more than I should have. Maybe I just should have stopped at the right point. And of course, not doing pot when I have a history of anxiety (was a deliberate attempt to dive again into visuals I never got again from dissos alone for very long).
 
Not really. As far as I know the downregulation is what leads to the BDNF of the hippocampus, the major center of memory. People have a more positive bias on their memory...hence antidepresant effect. I'm sure it's more complicated than that though.

It's 5-HT partials that are known as anxiolytic.

Both agonists and antagonists of 5-HT2a lead to downregulation. Past that, I don't know how it works.

Sometimes, the anxiety, even intense as it may be, can be worked through during the experience. I think it's about just being completely honest during the experience. Letting things go. That sort of vibe. But sometimes the message is to just stop tripping.

For NMDA antagonists, ketamine has the most antidepressant effect, but other NMDA antagonists have some antidepressant effect. Part of it is due to metaboliates being AMPA agonists. Ketamine has a litany of effects taht aren't fully elucidated. Given that its metabolites offer significant effects, it's largely a mystery. Except that abusing it can cuase major problems...just because ketamine and psilocybin have antidepresant effects, doesn't mean it's by the same mechanism.

My opinion is that yes, psychedelics can calibrate your path, but that meditation offers the real enlightenment, imo.
 
True but afaik, the dosage required for psychedelics to promote neurogenesis/treat MDD may not necessarily be the same as that for their other risky psychological effects. In fact, they seem to promote neurogenesis at doses order of magnitude lower than used "recreationally" ("Psychedelics Promote Structural and Functional Neural Plasticity"). This is case at least for certain tryptamines. For example, pinoline (a restricted 5MeO-DMT basically) is a robust promoter of hippocampal neurogenesis in rodents. Even at trace concentration ie at limit of detection with current instruments, it robustly increases neurogenesis in rodents (cf this ref). Which means at this dose, it may probably hardly show other undesirable side effects. I don't know about DMT/psilocybin dosage range for MDD which I doubt it has been studied (no money to be made since you can't patent them!)

Since both SSRIs and 5HT2a/c psychedelics are serotonergic and the latter are obviously more potent promoter of neurogenesis/anti-depressant action, one might assume that psychedelics target for neurogenesis is more specific than SSRI, making them potentially much safer than SSRI for MDD, with higher therapeutic index. SSRIs increase level of serotonin thus indiscriminately activating any and all 5HT receptors that may happen to be around, resulting in increased neurogenesis among other effects of stimulating 5HTRs (at least 14 subtypes of 5HTR with all sorts of different functions are known and more may be discovered!). You can imagine how activating them indiscriminately will have serious side-effects. While psychedelics are more selective (most with activate 5HT2a receptor subtype specifically. Whether this specific 5HT2aR stimulation cause neurogenesis, I don't know. But if SSRIs cause neurogenesis by indirectly activating 5TH2a, then there is no point using SSRIs for MDD when microdose (or rather nanodose) psychedelics will work fine. It is like using a sledge hammer to open a door (SSRI) v using a smartcard key to enter (Psychedelics).. Both will get you same results but one is gonna be costlier than the other!

Edit: oh sorry, dead link! here is the link: "Neurogenic Potential Assessment and Pharmacological Characterization of 6-Methoxy-1,2,3,4-tetrahydro-β-carboline (Pinoline) and Melatonin?Pinoline Hybrids" https://pubs.acs.org/doi/10.1021/acschemneuro.5b00041

Is there any academic data that would allude to that?

So this psychedelic hysteria is actually well founded and goes beyond some stoners trying to promote their culture?

I've been following this dude in England by the name of David Nutt, who raves about the benefits of psychedelics but - for whatever reason I never paid much attention to that specifically until recently.
 
Oh yeah, on the good and the bad. That it's not possible to break out of completely automatised habits but also not if one is shattered enough not to understand the concept of criticism anymore.

I'd say the same about dissociatives. They too are 'thought-brain-chopper's as well as anxiolytics, antidepressants, (in some cases, like MXE/O-PCM socially connecting and disinhibiting), bad to your bladder (unavoidably?), uh- dissociatives, etc.. but work over a very different mechanism yet achieve part of much the same goal. So it's more about that what happens downstream than the MOA in first line. Isn't it?

Downstream spiritually?
Or neurologically?
 
Yeah, that's the question ;) probably both. I'm pretty sure that we have some receptor for every feeling, including spiritual ones.. yet doesn't that explain why we actually feel that feeling when its receptor gets activated.
 
Is there any academic data that would allude to that?

So this psychedelic hysteria is actually well founded and goes beyond some stoners trying to promote their culture?

I've been following this dude in England by the name of David Nutt, who raves about the benefits of psychedelics but - for whatever reason I never paid much attention to that specifically until recently.
David Nutt is a very smart guy and a renowned scientist who has a vast amount of experience in psychoactive-orientated fields, from big pharma to advisory roles for the UK government. There is actually tons of academic data on the potential benefits of psychedelics, besides that directly linked to in the post you quoted, and there is a ton of ongoing research... I can't speak for worldwide although I'm sure there are similar organisations based elsewhere, but The Beckley Foundation in the UK (with which David Nutt is associated) is helping to organise and fund multiple interdisciplinary studies into psychedelics in collaboration with various world-renowned universities, while working to promote the importance of ending prohibition worldwide. This is a highly credible organisation supported by accomplished scientists, as well as many equally credible people in related fields, and it is not the only one of it's kind...

So yes, this psychedelic "hysteria", is actually very well founded, and goes far beyond "some stoners trying to promote their culture" as you so dismissively phrased it...
 
David Nutt is a very smart guy and a renowned scientist who has a vast amount of experience in psychoactive-orientated fields, from big pharma to advisory roles for the UK government. There is actually tons of academic data on the potential benefits of psychedelics, besides that directly linked to in the post you quoted, and there is a ton of ongoing research... I can't speak for worldwide although I'm sure there are similar organisations based elsewhere, but The Beckley Foundation in the UK (with which David Nutt is associated) is helping to organise and fund multiple interdisciplinary studies into psychedelics in collaboration with various world-renowned universities, while working to promote the importance of ending prohibition worldwide. This is a highly credible organisation supported by accomplished scientists, as well as many equally credible people in related fields, and it is not the only one of it's kind...

So yes, this psychedelic "hysteria", is actually very well founded, and goes far beyond "some stoners trying to promote their culture" as you so dismissively phrased it...

I like to adopt a healthy scepticism.

Fact of the matter is - only time I've ever really been around people that took these kinds of drugs, was at school, or in a party environment - and the outcome was nothing I thought desirable.

If there's therapeutic use - which the like of David Nutt adamantly claims there is - that's aces.

But then Freud was adamant as to the therapeutic benefits of cocaine way back when.
As it happened - cocaine basically works off the monoamine hypothesis but - it's obviously limited in it's day to day applicability.

I'd like to think mushrooms and dissociatives do hold promise - but some explanation beyond basically "tripping" out of ones day to regimental thought patterns that may in fact precipitate depression or cognitive impairment, and in actual fact alleviate or ameliorate an actual neurological dysfunction brought on by environmental stressors or genetic disposition etc - would go a lot further as to alleviating my healthy scepticism.

Despite this "patent" talk and profits, dollars and the financial bottom line - I have a reasonably difficult time believing that big money tycoons across the world - especially in this day and age of information availability - conspire to basically hold a percentage of the population ill, and from a humanitarian point of view, would fail to take straight forward steps of licencing a worthwhile drug - if there was a profound benefit to be had.

That being said - if the like of David Nutt and his research team are successful in their endeavours, I'd be the first to shake his hand.
 
The other fact to consider is - every news article that references the next generation of pharmacological treatment for mental illness, seems to almost consistently cite either psilocybin, or ketamine - as being the next "big things".

What my problem is is, 5ht2a agonist or NMDA blocker - I mean - what's the actual neurological implication?

So, psilocybin increases neurogenesis in the hippocampus....
And ketamine via action potential inhibition - somehow implicates downstream catecholamine release (I assume via it's action on GABA neurons - how else would it work?).

Neurogenesis and increase in BDNF is already implicated via currently marketed agents;
And catecholamines also...

So - "next big thing" - what we basically seem to be falling back on is this "tripping balls" hypothesis.

Which - just for me personally - yeah, I mean, it doesn't convince my sense of logic that there's something truly novel here.
 
I appreciate your points, to an extent, but honestly I don't really see as much of a disconnect between the "tripping balls" hypothesis, as you call it, and the idea that their might be something genuinely useful about psychedelic drugs as you seem to assume there must be. "Tripping balls" is obviously the extreme end of the acute effects of these substances but it may well be on the same spectrum as any hypothesised sub-perceptual neurological benefit. There may well be benefits and dangers along the entire spectrum of dosage, although the risk:reward ratio will inevitably vary, and is invariably still very unclear to us no matter what dosage bracket we look at.

As I see it there are a couple of things that seem to be a given. Firstly, there are significant entrenched social biases against the use of psychedelic substances, for any reason, recreational or therapeutic, and in most places significant legal consequences to ignoring these biases. Secondly, a significant quantity of scientists and a significant quantity of scientific evidence suggests that these substances warrant a closer look and further research - however the first issue is a significant barrier to anyone being able to properly investigate the second.

To me this is the important issue here - there is potential for research into these substances that could be of huge benefit to many people, but there are considerable legal barriers, mostly based on archaic and frankly insane reasoning, that gets in the way of this. I won't pretend to know what's going on neurologically because obviously it's not yet clear to anyone, but that's the whole point of doing this research. I don't personally believe that any psychedelics, psilocybin, ketamine or something else are "magic elixirs", and no serious scientist would make any such claims. But they do offer a glimpse into an alternative approach to the current chemical arsenal for treating depression and other mental illnesses - perhaps just like cocaine and other substances that we would consider crude instruments now did in the past.

Whether or not it is psilocybin itself turns out to be demonstrably, repeatably useful, or instead some future derivative of psilocybin produced as a result of this research, is really irrelevant, the point is that these substances at this moment in time appear to have significant potential - even if all the research ultimately turns out to be a complete dead end. It would have done no-one any good to just blanket ban all research into cocaine back in Freud's day, and the barriers to psychedelic research do no-one any good now, except to delay potentially important discoveries, one way or the other - even if that discovery does turn out to be that this research was just a complete waste of time.

This is why I take such issue with casually dismissive phrases that only serve to propagate harmful stereotypes about both psychedelic drugs and psychedelic drug users - or, indeed, drugs and drug users in general. These stereotypes only serve to fuel prohibitionist propaganda and do nothing good for anyone.
 
Is there any academic data that would allude to that?

So this psychedelic hysteria is actually well founded and goes beyond some stoners trying to promote their culture?
I've been following this dude in England by the name of David Nutt, who raves about the benefits of psychedelics but - for whatever reason I never paid much attention to that specifically until recently.
Imho the hysteria surrounding psychedelics use in treating moods disorders (MDD, PTSD, Anxiety) is actually well-founded. The scientific data is pretty solid and certainly more data will confirm it in coming years. Ketamine really was the one which shook things up .. See that paper published couple of months ago from the University of California Davis and all the references cited therein (highlighted). It is free access. Anybody interested can email Pr Dave Olson, the main author of the study (his email in the print): he'll be more than happy to answer your questions

Psychedelics Promote Structural and Functional Neural Plasticity Cell Rep. 2018 Jun 12; 23(11): 3170–3182.

....Ketamine has demonstrated remarkable clinical potential as a fast-acting antidepressant (Berman et al., 2000; Ionescu et al., 2016; Zarate et al., 2012), even exhibiting efficacy in treatment-resistant populations (DiazGranados et al., 2010; Murrough et al., 2013; Zarate et al., 2006).

...Like ketamine, serotonergic psychedelics and entactogens have demonstrated rapid and long-lasting antidepressant and anxiolytic effects in the clinic after a single dose (Bouso et al., 2008; Carhart-Harris and Goodwin, 2017; Grob et al., 2011; Mithoefer et al., 2013, 2016; Nichols et al., 2017; Sanches et al., 2016; Os?rio et al., 2015), including in treatment- resistant populations (Carhart-Harris et al., 2016, 2017; Mithoefer et al., 2011; Oehen et al., 2013; Rucker et al., 2016). In fact, there have been numerous clinical trials in the past 30 years examining the therapeutic effects of these drugs (Dos Santos et al., 2016), with 3,4- methylenedioxymethamphetamine (MDMA) recently receiving the “breakthrough therapy” designation by the Food and Drug Administration for treating PTSD.

Furthermore, classical psychedelics and entactogens produce antidepressant and anxiolytic responses in rodent behavioral tests, such as the forced swim test (Cameron et al., 2018 and fear extinction learning (Cameron et al., 2018; Catlow et al., 2013; Young et al., 2015), paradigms for which ketamine has also been shown to be effective (Autry et al., 2011; Girgenti et al., 2017; Li et al., 2010). Despite the promising antidepressant, anxiolytic, and anti-addictive properties of serotonergic psychedelics, their therapeutic mechanism of action remains poorly understood, and concerns about safety have severely limited their clinical usefulness.

That paper shows convincing data yet that 5HT2aR activation is required for psychedelics induced neurogenesis/AD/anxiolytic responses. The biggest issue is that activation of 5HT2aR is also the mechanism by which psychedelics induce hallucinations. So the question become: is it possible to separate the 2 effects since both the hallucinations and the neurogenic/anti-depressant/anxiolytic effects of serotonergic psychedelics are due to activation of the serotonin 5TH2a receptor subtypes?? Believe me, you'll make a lots of money if you can come up with a non-hallucinogenic psychedelic drug (oxymoron?) which is also neurogenic!

With ketamine actually lots of research going on to separate its fast acting AD effects from its psychotomimetic effects.. google “ketamine antidepressant mechanism” if interested to learn more)

The interesting thing about that study is that the dose required to promote neurogeneis/AD/anxiolytic effects by serotonergic psychedelics maybe lower than that inducing hallucinations. LSD was actually the most robust neurogenesis inducer they found. So conceivably microdosing may be the way to go around this issue of hallucinations. Or even nanodosing (ie microdosing microdoses) because LSD is already a super-potent 2a agonist,active at microdoses...

But keep in mind in this day and age, scientific evidence-based data doesn't really sell, only all kinds of nonsensical bullshit screamed by all kinds of nonsensical professional bullshitters sell! ..this true even among so-called “scientific establishment”.. So people like Professor Nutt are not taken seriously at first until ppl realize the “bullshits” they been talking about may not be as “bullshitting as they thought before ..

Incidentally, Professor Nutt family name doesn't help sell his ideas to mass media regardless of the scientific validity of what he is saying. Can you imagine a presenter going on TV like: “.. and now I present to you Pr Nutt..whose research show that magic mushroom actually makes you smarter, less depressed, less anxious..etc etc” People might think: is this some kind of comic show? Pr Nutt? Psychedelic shrooms?.. is he wel.. nut?? With all due respects, that's just the way people react. Has nothing to do with reason!

but he's got a point: they do! Serotonergic psychedelics like LSD, DMT, Psylocybin, Noribogaine and psychedelic phenetylamines like DOI regrow/repair (literally!!) the part of human brain fucked up by depressive, anxious thoughts patterns. The Prefrontal cortex in particular which plays a key role in neuropsychiatric mood disorders like MDD, PTSD,..etc. They work as good as or even better than ketamine as fast-acting antidepressants even in TRD and bipolar depression. Certainly much better than SSRIs. And they all seem to do that by activating 5HT2aR, the same receptor that give psyhedelic hallucinogenic response once activated!

Ketamine is now getting wider acceptance by medical establishment as a fast acting AD but remember for more than 60 years, it was known more as a anaesthetic used as recreational dissociative “streets drugs” than a potential AD drug.
MDMA has been now given Breakthrough Drug Status by the US FDA for PTSD, meaning it is a major discovery in the field and studies are ongoing now. Remember Sasha Shulgin? he was once a pariah, a mad chemist the DEA was all too happy to see gone! But now the establishment is full of hysteric oohhs and ahhhhs for MDMA in PTSD, I guess Sasha is havin the last laugh from his grave.
 
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