I have heard that some people believe that each married couple should do MDMA together once each year. I've heard it is magic.

I don’t know why you brought up dissociatives. Those NMDA receptors - whilst yes, typically activated by glutamate, are located on GABAergic neurons, preventing the release of GABA in to the synapses.

Additionally the effects of psychedelics are more closely linked to changes in endocrine hormone distribution and GABA, glutamate and acetylcholine balance. The 5-HT2A, 2C and 1A receptor complexes which are thought to be the starting point for psychedelic effects all regulate the distribution of these compounds, along with dopamine and norepinephrine. Many do not seem to understand that inhibition of the NMDA receptor is a core mediator of effects from classical psychedelics. The activation of the 5-HT2A receptor directly prevents the activation of any NMDA receptors located on the same neuron.

It is also worth noting that SSRIs stimulate neuroplasticity and neurogenesis as well - through the same mechanism (inhibition of mTOR, mGlu2,3,7 and various cortisol functions and subsequent release of NGF and BDNF in to various brain regions).

MDMA does this as well, although the dose and frequency makes the poison. Same can be said, perhaps more surprisingly, about other amphetamines such as methamphetamine and mixed amphetamine salts. All these compounds are also capable of producing neurotoxicity as well, however this effect is only paradoxical with methamphetamine. The neurotoxicity of MDNA and things like Adderall appears to disconnected from the direct effects of the chemicals themselves (even in high doses, MDMA injected straight in to the brain does not cause toxicity - for example)

Also as of like, last month, “we don’t know how psychedelics induce this neuroplastic change” is an outdated statement. They trigger a highly novel mechanism through penetration of the cell membrane, rather than activating surface receptors. Similar to how dopamine receptors server different functions depending on their location on or within the cell, so too do serotonin receptors.

I have a lot more I want to say but I am high as balls right now. I will leave this by saying that it is unlikely that the NMDA receptor plays any role whatsoever on the antidepressant effects that have been discovered in ketamine and DXM. In fact, despite both being dissociatives with similar MoAs, it is likely the antidepressant effects are being cause by entirely different mechanisms from eachother (DXM with sigma-1 activation, ketamine has a strong link with its stimulation of adenosine release and AMPA receptor activation).

SSRIs also cause downregulation of certain serotonin receptors, namely 5-HT1A, which tends to be over active in people with anxiety and has even be speculated to play a role in the development of neural inflammation in chronic amphetamine, nicotine and alcohol abusers. It also regulates the distribution of glutamate and stress hormones like cortisol, vasopressin and epinephrine. But since having too much glutamate is linked to neural inflammation and excitoxicity, it is likely that this mechanism plays a strong role in their effects

But that's what I need you to understand. As much as it may sound like an excuse. Some people just don't have time. Personally, its on my list of things to do, but I care for a family and I'm working on a massive project (shameless plug at the end). I'll get to it.

For me its an ethical question and the OP's post is a convincing thought experiment. I want to get there, I see its good. Im just traveling through time

Ssri saved my life, just sayin

I want to do this therapy SO BAD!!! I can't take SSRI's/SNRI's and this is exactly the issue I deal with on the regular....Hope Medicare covers this type of therapy soon.

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I understand and felt the same at first, but now I would compare it to learning a different way to tie shoe laces or something. It is not the complex thing it is often made out to be, unless you're trying to go whole foods only or some other such additional restriction.

There are many free introductory resources and meal plans to try to make it as easy as possible.

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Woah woah woah, at what point was daily administration of MDMA a real consideration? I am genuinely curious, because I only ever heard of MDMA as a short-term tool for use in a therapeutic setting. It seems to me that people who distort the argument for daily use of MDMA are only trying to undermine its actual therapeutic usage. Maybe I am wrong, but I have personally NEVER heard of a proposition for MDMA to be used as a daily medication. I have heard of it only to be used under a therapeutic setting, only after significant trust and connection has been made with a given patient. Again, not once have I heard that MDMA should be a daily used substance. Personally, I think that might be one of the major miscommunications which undermines the legitimacy of psychedelic therapy. I don't think any logical researcher would be considering MDMA, psilocybin, or LSD to be a daily regimen. I feel like I Can't emphasize that enough.

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MDMA will always be my favorite illicit substance. Some super clean molly is just the best. Hard to find though.

*for the morons who have no idea what they are talking about, you can buy super cheap testing kits for mdma that will tell if your connection is legit or selling you garbage. Also, it’s not meth, if you are basing that on the fact the name contains the word “meth” in it then it’s probably a safe assumption that you failed chemistry and should keep your mouth shut about things you don’t understand.

Well, spent a few decades eating meat and I don't know how to meet nutritional needs without meat. I need to learn and dont have time yet

Why not at this time?

So I actually have one of these one the way (recommended to me by my doc for anxiety, though), and will try to remember to report back how it functions.

As far as I know all studies (certainly most studies) that have found antidepressants as “effective treatments” for depression are much shorter than the durations for which antidepressants are typically prescribed. Most studies last a few months at most. The evidence for long term effectiveness is lacking, however, there is certainly evidence of long term harm.

https://pubmed.ncbi.nlm.nih.gov/21459521/

Unfortunately there is insufficient data on long term outcomes because such studies would be expensive to conduct and the results of such studies would almost certainly be harmful to the extremely lucrative sales of antidepressants.

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It was not a virus, and from space not from petmafrost

NMDA antagonists are of interest, but not because of the NMDA receptor blockade. It's because of the increase in neuroplasticity they many induce, for still not well understood reasons. This is believed to be part of both ketamine and psychedelic therapy, but we really don't understand it well.

It's also worth noting that psychedelics and MDMA are also believed to work mostly through the serotonergic system, with traditional psychedelics being partial HT-2a and HT-2b agonists. MDMA is a serotonin reuptake inhibitor and releasing agent, as well as the other amphetamine effects. Serotonin is still believed to be the main cause of the empathogenic and mild hallucinogenic effects of MDMA, but it isn't an agonist or antagonist, just a re-uptake inhibitor and releasing agent. This means it floods neurons with more serotonin than usual through two separate mechanisms.

I do think we need to investigate animals as sentient more and as we do, we'll likely stop eating them. This idea, however, is extremely progressive and even I --knowing it is a good idea-- cannot say I completely agree to it at THIS time.

It seems, however, tat most of the role serotonin plays in depression has more to do with its relationship with glutamate than any specific function of serotonin itself.

That is to say that too much glutamate activity is linked to depression symptoms and certain serotonin receptors modulate glutamate levels in the brain. So by increasing serotonin activity, you can decrease glutamate activity and this helps with depression symptoms in some people.

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Eloquent words. Let's lessen the stigma towards pyschedelics. With anyone interested knowing more. Checkout the Multidisciplinary Association for Psychedelic studies. maps.org

I don't disagree with the sentiment. They are not by any metric highly successful drugs nor is the side effect profile negligible. We also can't let personal experience cloud our analysis. They are not almost worthless in data. Here's a relatively modern meta-analysis: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889788/. They are usually on the lower end of of the spectrum of the four main classifications that most anti-depressants fall into: MAOIs, tricyclics, SSRIs and SNRIs. They also are usually on the lower end of the spectrum in terms of tolerability. Tricyclics and irreversible MAOIs are generally more effective, but also more "dirty drugs" meaning a lower specificity in action. Some irreversible MAOIs are still used as drugs of last resort in treatment resistant depression, but they are fairly dangerous comparatively.