JohnBoy2000
Bluelighter
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Apparently both work to activate BDNF.
Are the two remotely comparable in terms of outcome?
Are the two remotely comparable in terms of outcome?
N&PD Moderators: Skorpio | thegreenhand
.. 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...
Very interesting! Thank you for that.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
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
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?
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...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...
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 questionsIs 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.
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.