MAPS The Effects of Psilocybin & MDMA on Resting State Hippocampal Functional Connectivity

[MAPSbryce]

The Effects of Psilocybin & MDMA on Resting State Hippocampal Functional Connectivity

Video: The Effects of Psilocybin and MDMA on Resting State Hippocampal Functional Connectivity

Abstract: The effects of psilocybin and MDMA on resting state hippocampal functional connectivity were analyzed in two separate studies. In the psilocybin study, 15 healthy volunteers were scanned on two separate occasions, once while receiving intravenous (IV) saline (placebo) and once while receiving 2mg of psilocybin IV. In the MDMA study, 25 healthy volunteers were scanned on two separate occasions, once after receiving a placebo pill (vitamin C), and once after receiving 100mg of MDMA HCl per Os. Hippocampal functional connectivity analyses for the MDMA study are currently underway. In addition to helping broaden our understanding of the mechanism of psychedelic drugs, the results may help inform our understanding of the DMN and its functional relationship with the hippocampus, and to explain how MDMA differs from psilocybin in its effects on hippocampal functional connectivity.

Luke Williams has a long-standing interest in psychedelic science. He originally studied philosophy and history of science, then completing Master's degrees in history and philosophy of science from Cambridge University and philosophy from Sussex University, with a focus on enactive/phenomenological approaches to cognitive science. After a period outside academia, Luke is currently completing an MSc in cognitive neuroscience at Birkbeck, University of London, with his research project based at Imperial College's neuropsychopharmacology unit, supervised by Robin Carhart-Harris, involving the study of functional connectivity in humans under psilocybin and MDMA.

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[AlphaMethylPhenyl]

Maps, MDMA is decidedly neurotoxic. It shouldn't carry a large part in your push for the integration of hallucinogenic drugs into institutional medicine.

 

[Reverend Random]

Maps, MDMA is decidedly neurotoxic. It shouldn't carry a large part in your push for the integration of hallucinogenic drugs into institutional medicine.

Could you provide more evidence, Hoatshee? I'm very interested in the definite science. I do believe that a large review study headed by David Nutt for the British government showed MDMA to be relatively benign.

I think it's the speaker's (and David Nutt's) colleague David Erritzoe at Imperial who claimed that MDMA did cause some neurotoxicity, but I'm not sure.

Conclusions We found evidence that MDMA but not hallucinogen use is associated with changes in the cerebral presynaptic serotonergic transmitter system. Because hallucinogenic drugs primarily have serotonin2A receptor agonistic actions, we conclude that the negative association between MDMA use and cerebral SERT binding is mediated through a direct presynaptic MDMA effect rather than by the serotonin2A agonistic effects of MDMA. Our cross-sectional data suggest that subcortical, but not cortical, recovery of SERT binding might take place after several months of MDMA abstinence.

 

[AlphaMethylPhenyl]

Cognitive impairments in humans as revealed by two meta-analyses:

http://link.springer.com/article/10.1007/s11065-009-9124-z
http://onlinelibrary.wiley.com/doi/...sCustomisedMessage=&userIsAuthenticated=false

http://link.springer.com/article/10.1007/s00213-009-1688-z

Decreased oxytocin long-term, no thanks http://link.springer.com/article/10.1007/s00213-010-1986-5

Benefits, yes, but is it worth it? http://m.jop.sagepub.com/content/27/1/28.short

Want your baby to have two heads (joke, but it is teratogenic and toxic to cells)
http://www.sciencedirect.com/science/article/pii/S088723331000069X

Here's the kicker: http://m.jnnp.bmj.com/content/83/1/83.short

Are you aware of how important hippocampal growth and health is to psychophysiological well-being?

The number of studies I've found on scidirect/pubmed concerning this is astounding

 

[Reverend Random]

Cognitive impairments in humans as revealed by two meta-analyses:

http://link.springer.com/article/10.1007/s11065-009-9124-z
http://onlinelibrary.wiley.com/doi/10.1002/hup.1270/abstract?deniedAccessCustomisedMessage=&userIsAuthenticated=false
[url]http://link.springer.com/article/10.1007/s00213-009-1688-z[/URL]

'Ecstasy' does not equate MDMA! And most definitely does not equate MDMA in a controlled clinical setting. The third one is even on 'ecstasy' polydrug users! I mean, come on... too many variables to be able to say anything useful about the effects of MDMA.

Decreased oxytocin long-term, no thanks [url]http://link.springer.com/article/10.1007/s00213-010-1986-5[/URL]

Rats received daily intraperitoneal injections of GHB (500 mg/kg), methylenedioxymethamphetamine (MDMA; 5 mg/kg) or their combination (GHB/MDMA) over ten consecutive days.

5 mg/kg? That would've been an equal dose of about 400 mg. for me. And in combination with GHB? I'm scared! And mind you, this is research in rats. Rats don't equal humans.

Benefits, yes, but is it worth it? http://m.jop.sagepub.com/content/27/1/28.short

Sounds like it, doesn't it? Compared to the side effects that most accepted pharmaceuticals have, I'd take a single (or a few at most) session of MDMA any time. Seriously man, the side effects of most antidepressants, antipsychotics, mood stabilizers etc. etc. is just horrifying. Doesn't stop doctors from prescribing them.

Want your baby to have two heads (joke, but it is teratogenic and toxic to cells)
[url]http://www.sciencedirect.com/science/article/pii/S088723331000069X[/URL]

“Ecstasy” or methylenedioxymethamphetamine (MDMA) is primarily a recreational drug commonly used during the child bearing period, thus, there is a major concern regarding the embryonic and fetal toxicity of this drug. Here, we report the cardio- and neuro-toxic effects of MDMA on beating embryoid bodies (EBs) and neural cell-containing EBs derived from mouse embryonic stem cell (ESCs).

Does this strike you as sensible research? Putting MDMA in a petri dish with embryonic stem cells from mice?! I'm sorry if I'm not immediately convinced.

Here's the kicker: [url]http://m.jnnp.bmj.com/content/83/1/83.short[/URL]

So they're comparing heavy ecstasy users with a polydrug using control. How monodrug do you think the ecstasy using group is? How well do you think they care of their bodies? Did they control for lack of sleep? For going out with too little clothes on after they return from a rave? Once again, et cetera et cetera. Also ecstasy is not the same MDMA. Who knows what was in the pills these guys took? And who's telling me they didn't smoke ciggies, a spliff, drank a few drinks, did a line here and there...

Are you aware of how important hippocampal growth and health is to psychophysiological well-being?
I wasn't, but I'll take your word for it.

The number of studies I've found on scidirect/pubmed concerning this is astounding

Well, that is because most researchers are funded to do research into how bad 'ecstasy' is for ya. How many research groups do you think are paid to research the possible therapeutic effects of MDMA?

All in all, these studies really don't convince me. And that's not because I'm biased towards MDMA. I just think that if you have a good look at all the studies investigating MDMA, you can find some fault with most of them.

Last point: did you have a look at David Nutt's review of the dangers of MDMA? (Posted in the above message?)

 

[AlphaMethylPhenyl]

How many people do you think just take MDMA and no other drugs?

I don't think you addressed all aspects of the studies, just picked out some inconsistencies in a few, which I guess is ok, but the majority of them hold.

400mg isn't an unreasonable dose for the experienced user.

Oy, nutt is a good scientist but he makes many unreasonable conjectures.

Even if most of them are faulted, there are literally so many that the basic fact still holds: its neurotoxic.

I demonstrated acute negative effects from human cognitive studies and rat/mice studies, want me to cut open some user's brain then?

 

[Reverend Random]

How many people do you think just take MDMA and no other drugs?

No idea really. I just think it's pretty unlikely that heavy MDMA users don't take anything else and it's even harder to prove in a scientific fashion. Doesn't mean you shouldn't try, but you should be clear about what you're studying and that ecstasy does not equate MDMA. Can't stress that point enough.

I don't think you addressed all aspects of the studies, just picked out some inconsistencies in a few, which I guess is ok, but the majority of them hold.

Well, you're quite right I didn't address all aspects of the studies, I just took quotes from the abstracts and reacted in where I didn't find them completely convincing. I can also read the whole studies you posted, but I don't have the time and I have heard most arguments before.

400mg isn't an unreasonable dose for the experienced user.

400 mg. isn't an unreasonable dose? Well, I guess we can agree to disagree then. I don't know about you man, but where I'm from and where the ectasy tablets contain mostly MDMA, 120 mg. is considered a serious dose. Sure, some idiots take a lot more, but that's not what I'd consider reasonable dosing.

Oy, nutt is a good scientist but he makes many unreasonable conjectures.

Care to give me some examples? I'm open minded.

Even if most of them are faulted, there are literally so many that the basic fact still holds: its neurotoxic.

I'm sorry dude, but that's a logical fallacy: 'There are so many' - they must be right! My argument would be that there are so many because that's what governments who have criminalized MDMA (i.e. all of them) are giving out grants to research institutes for, to show just how bad MDMA is for you. You didn't address that argument. Do you disagree?

I demonstrated acute negative effects from human cognitive studies and rat/mice studies, want me to cut open some user's brain then?

No, you quoted a number of papers which I found fault with. I would like some more conclusive proof before I can agree that MDMA is indeed neurotoxic, and I'm just not convinced yet.

And even then, what does that really mean? When is MDMA neurotoxic in humans? In which setting, under which circumstances? I think it makes a huge difference that most studies base their results on recreational ecstasy users. MAPS (which is where this discussion started) are looking to use MDMA as a psychotherapeutic adjunct in a clinical setting, and those studies have shown no serious acute or long term side effects.

I mean, that's the point of this discussion to me. You stated that MAPS shouldn't be pushing too hard for MDMA being used in psychotherapy because of its supposed neurotoxicity. I am doubting whether that's really the case. I'd be grateful for some more input here... but at the same time, this is the same discussion I witnessed at a conference two years ago between proponents of the use of MDMA in psychotherapy and opponents who said that "ecstasy is bad". It's not a very fruitful debate.

Some food for thought here. And just to show I'm not a one sided debater, here's a review study of the alleged neurotoxicity of MDMA in which the authors also state that more research is necessary.

 

[AlphaMethylPhenyl]

I will respond to your last statement first: most scientific studies will state that more research is necessary. Its usually meaningless.

The studies I cited involving poly-drug users is more representative of those who use MDMA than not.

You don't have to read the entire studies. I didn't. No problem.

I'm surprised you haven't read Nutt, considering your position. Are you aware that he thinks horse riding is more dangerous than mdma? I rest my case.

In that case, why not say empirical evidence is a logical fallacy, because that's the implication.

I see very little/nothing about any toxicity of psilocybin, and that's a schedule on drug which probably has more potential to change society and alleviate illness than mdma. Your point is moot.

I'm really not trying to be rude about this, but how many studies involving how many PhDs from how many liberal countries do you want me to cite. Here's one, controlling for other drug usage http://bjp.rcpsych.org/content/193/4/289.short

Controlled for other drugs, decent doses, etc.

http://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.2012.03977.x/full

Are you affiliated with MAPS?

And importantly: I support only, only medical use of MDMA for PTSD when every single other option has been exhausted.

 

[Reverend Random]

I'd love if someone else chimed in, otherwise it's just a discussion between two people who disagree, while I hope to gather a somewhat more thorough understanding of the relative harmfulness of MDMA.

I have read Nutt, but I was wondering which of his statements you find "unreasonable conjectures". Do you think his provocative comparison of horse riding and taking ecstasy is meaningless? Do you disagree? I think the point he's trying to get across is you don't minimise harm to either individuals or society by prohibiting or criminalising dangerous behaviour. And statistically, people do have a much higher chance of hurting themselves seriously riding horse than taking ecstasy. They're not quite comparable, but his point is valid, imho.

Toxicity for psilocybin is indeed very low. I don't see what this has to do with the discussion. Yes, I'd be in favour of rescheduling psilocybin, as would I be in favour of rescheduling any other psychedelic, MDMA, cannabis and in all honesty, about all other illegal substances as well (but that's for a whole other discussion).

I'm not affiliated with MAPS, but I do see a therapeutic potential for the use of MDMA. It does make sense to try other approaches first, but if there's a substance that can help some people in some circumstances, why not allow that?

Btw, that last study you posted looks interesting. I knew about the NeXT study.

Anyway, I don't disagree that MDMA is potentially harmful, because so are many therapeutic substances. I just don't think that's a reason not to investigate its potential applications in therapy. That never stopped so many other pharmaceuticals from being used on a large scale. Do you really believe MDMA is going to be that harmful for the people MAPS is investigating in giving it to? Or do you think it's going to make the argument for allowing psychedelics as psilocybin harder to come across?

 

[Magickduck]

I think MDMA is definitely neurotoxic, but I believe it to be something to do with re-dosing and the effects that has on the serotonin system. I think used in a therapeutic and clinical setting at a specific dosage and not frequently that they would be fairly benign - and entirely beneficial.

 

[Pretty_Diamonds]

I'll chime in...

400mgs is considered a VERY HIGH DOSE. 100-120mg, standard. More experienced users play more in the 200mg field.

It's hard to find reports of non-poly drug users because everyone who's used ecstasy usually has done marijuana.. at least. Then, do they report the freg. of each use? Sometimes it's only, "have you used other drugs?".

Short-term and long-term studies on MDMA are VERY different. Short-term with it being introduced to a (human) patient-- is WAAY too risky (chances of addiction make it (almost) unethical). I've read various studies done in Holland with regards to administering MDMA to human patients but I can't be bothered to get them.

 

[shishigami]

http://www.sciencedirect.com/science/article/pii/S0376871604000626 Users who used 25-50 times showed no cognitive deficits, users who used more than that showed deficits compared to non-users. While I can't currently read the article as these users are "young" one can assume that the heavy users are using rather frequently which could be contributing to the cognitive effects.

http://archpsyc.jamanetwork.com/article.aspx?articleid=1151061 Users show chronically altered serotonin functioning. I've talked to this particular researcher and she told me that even though these users showed altered serotonin functioning they show no cognitive deficits.

Food for thought.

EDIT:

The studies I cited involving poly-drug users is more representative of those who use MDMA than not.

Why would studies relating to harms of MDMA use in poly-drug users be relevant to this discussion of potential MDMA use in institutionalized medicine?

I don't think anyone is suggesting that we give people with PTSD MDMA and then have them dance their asses off and stay up till 5 in the morning without having any water (or maybe drinking too much water as the case sometimes is).

 

[SONN]

MDMA certainly does put stresses on the mind as most stimulants do, that does not mean we should stop fighting for the therapeutic use of it.

I would agree that psilocybin is likely to be a better candidate for therapy considering we already have this evidence promoting our cause.

 

[AlphaMethylPhenyl]

Because if MDMA becomes more available medically it will certainly become more available to the general population. And how many people who experience it will want to do it again, especially after the serotonergic depletion makes them depressed?

Its scary how benign my friends think this stuff is.

 

[SONN]

I would agree that far too many people take MDMA far too often but most of those people are very uneducated, i.e. they hear about "mollies" on the radio and ask someone for that drug, they don't even know that they hope to be taking the drug MDMA. They don't realize the personality changes and possible neurological damage they're going to undergo from doing it too often nor do they know what too often would be. If they got it from a doctor they would have to be informed at least a little bit beforehand. I think there might be some potential for habit forming in fact I know personally a girl who claims to be addicted to "molly," or "rolling."

however, MDMA can offer some therapeutic/creative benefits, at least I think so and i'm pretty sure there's research to support such a notion.

Psychedelics definitely are a much better cause to be fighting for. I recently watched this video and my god this guy is the man. The portrayal of psychedelics in the media has almost never been that they can make you smarter, and that video shows that there is pretty solid evidence that they can. The magic part is that it's only if you care enough about getting smarter that it will work. We should be giving microdoses to all of the smartest people in the world IMHO.

 

[Sturnam]

Well, this is the crux of good neuropsychopharmacology isn’t it? Knowing the dose, knowing the compound(s). And by compounds, I mean ecstasy, molly, triple-stacked pills, ‘pure’ MD(M)A and everything else under the sun. Here is an article that I thought did a great job explaining the issues with understanding MDMA neurotoxicity in adults in laboratory conditions, and not under rave conditions.

Lost in translation: preclinical studies on 3,4-methylenedioxymethamphetamine provide information on mechanisms of action, but do not allow accurate prediction of adverse events in humans

3,4-Methylenedioxymethamphetamine (MDMA) induces both acute adverse effects and long-term neurotoxic loss of brain 5-HT neurones in laboratory animals. However, when choosing doses, most preclinical studies have paid little attention to the pharmacokinetics of the drug in humans or animals. The recreational use of MDMA and current clinical investigations of the drug for therapeutic purposes demand better translational pharmacology to allow accurate risk assessment of its ability to induce adverse events.

Recent pharmacokinetic studies on MDMA in animals and humans are reviewed and indicate that the risks following MDMA ingestion should be re-evaluated. Acute behavioural and body temperature changes result from rapid MDMA-induced monoamine release, whereas long-term neurotoxicity is primarily caused by metabolites of the drug.

Therefore acute physiological changes in humans are fairly accurately mimicked in animals by appropriate dosing, although allometric dosing calculations have little value.

Long-term changes require MDMA to be metabolized in a similar manner in experimental animals and humans. However, the rate of metabolism of MDMA and its major metabolites is slower in humans than rats or monkeys, potentially allowing endogenous neuroprotective mechanisms to function in a species specific manner.

Furthermore acute hyperthermia in humans probably limits the chance of recreational users ingesting sufficient MDMA to produce neurotoxicity, unlike in the rat. MDMA also inhibits the major enzyme responsible for its metabolism in humans thereby also assisting in preventing neurotoxicity.

These observations question whether MDMA alone produces long-term 5-HT neurotoxicity in human brain, although when taken in combination with other recreational drugs it may induce neurotoxicity.

http://www.ncbi.nlm.nih.gov/pubmed/22188379

And here are their conclusions:

Nothing that has been reviewed in this paper should be taken to suggest that MDMA is always a safe recreational drug to ingest.
What it does suggest is that most published studies on MDMA must be interpreted with caution when attempting to translate effects seen in animals to potential adverse effects in humans.

Taking into account the differences in the pharmacokinetic profile of MDMA in rats and humans, what we also propose is that the doses currently being used to investigate the possible therapeutic benefits of the drug are unlikely to produce any severe acute or importantly any long-term neurotoxic damage in the human brain, particularly if given as a single acute administration in the absence of other agents in a therapeutic milieu.

There was a rebuttal, in which they stated:

In this issue of the BJP, Green et al. suggest that animal data could not be used to predict the adverse effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans and that MDMA did not produce 5-HT neurotoxicity in the human brain. This proposal was, however, not accompanied by a review of the empirical evidence in humans. The neuroimaging data on 5-HT markers in abstinent recreational ecstasy/MDMA users are extensive and broadly consistent. Reduced levels of the 5-HT transporter (SERT) have been found by research groups worldwide using a variety of assessment measures. These SERT reductions occur across the higher brain regions and remain after controlling for potential confounds. There are also extensive empirical data for impairments in memory and higher cognition, with the neurocognitive deficits correlating with the extent of SERT loss. Hence, MDMA is clearly damaging to humans, with extensive empirical data for both structural and functional deficits.

http://www.ncbi.nlm.nih.gov/pubmed/22404300

However, the scientific smackdown came in the response to that comment by the original authors;

We had no intention of suggesting that there was no evidence for some recreational Ecstasy users presenting with evidence of 5-HT neurotoxicity, albeit it is clear from the literature that some of this evidence remains open to several interpretations. What we did claim was that pure 3,4-methylenedioxymethamphetamine (MDMA) taken alone was unlikely to cause 5-HT neurotoxicity in man. Here we must emphasize the term MDMA, as it is crucial to our discussion. Parrott, in contrast, uses the term ‘Ecstasy/MDMA’ several times when discussing neurotoxicity. This association of Ecstasy with MDMA is one of the major problems of translation that we addressed….

And this brings us to the crux of the problem and weakness of all the clinical data cited by Parrott (2012). A basic tenet of all good clinical pharmacology is accurate knowledge of the doses administered, frequency of administration and any confounding factors such as other drugs being consumed. None of these data are available with any precision in the clinical studies quoted. Of course one has some indication as to dose (although as Vogels et al., (2009) reported, the dose contained in illicitly obtained tablets is highly variable) and frequency of drug ingestion, but this information is generally obtained from the user whose recall is likely to be limited or who decides to obfuscate. Crucially, the information can never take into account the problem of drug tablet adulteration. The fact that hair or urine samples detect MDMA merely shows the user has consumed the drug, not how much or when or what other drugs were taken concurrently.

http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2012.01940.x/abstract

Ecstasy and studies relating to recreational users cannot be compared to known doses of pure compound administered in therapeutic settings. This is because that the users fundamentally do not know what they are getting in that pill. Marquis tests can be useful, but as far as I know they do not detect substances such as caffeine, which has been shown to increase the neurotoxicity of MDMA.
So far, I would say that given the large differences in metabolism and dosing between rodents and humans, or even primates and humans, that I’m not convinced that infrequent, therapeutic doses of pure MDMA in a clinical setting will create permanent neurotoxic changes.

Lastly, I know all these articles you can only get with subscriptions, but I will be happy to email anyone a PDF of the article(s) who wants it.

 

[MrSpeedyG]

I'd be more worried about the potential and permanent damage of SSRI use causes... MDMA used in a controlled dose and setting damn well has great therapuetic value.

I am honestly extremely dissapointed in how people are missing the fact that MDMA is one of if not the best tool in psycotherapy and when used properly it is of great use.

There is a big friggin difference between the use of pure pharmaceutical MDMA in a controlled dose and setting compared to using steet synthed MDMA+fuck knows whatever, plus redosing, plus dancing in a hot environment, plus poly drug use, plus abuse/using every weekend or every month. My point is, you are comparing apples with oranges and quite frankly is pissing me off becauase it is hindering the advancement of an extremely powerful and proven to work like nothing else compound that is helping people with serious, mental health issues. I'd be more worried about beign drugged up with tons of meds making my quality of life worse than therapeutic MDMA that changes my life for the better.

 

[AlphaMethylPhenyl]

^What a mess

I kinda like you, so I'll respond.

SSRIs are so safe compared to other drugs its scary.

Source that claim.

No need to bold your writing - its not making it any more persuasive, unless you're trying to scare people, which you better not be trying to do.

Yes there is a difference between those two things.

However, and I won't spell this out in detail for you because you're a smart kid, consider the availability and potential misuse of a substance which has (a looooot of) recreational potential when it becomes used medically.

If you really need me to clarify I will.

 

[any major dude]

How is it that you think putting MDMA in schedule 2 & allowing it to be used as per the protocol in the Phase II clinical trials would affect black market availability? If they were proposing just prescribing it to people & letting them take it home, i would see where you're coming from. However being that it's used under close supervision in a hospital or psychiatrists office, and in very limited quantities i think you're pretty far off base. Not to mention it's already "Avlailable in every region of the country" according to the DEA. The closest analogy i can think of in this regard would be ketamine (a schedule 2 drug used all but exclusively in a clinical setting that has considerable recreational potential), and it's rarely diverted from medical supplies & almost entirely manufactured illicitly (albeit sometimes in pharmaceutical factories on the Indian subcontinent).

Lastly, I don't think there's any evidence to suggest that clinical use of MDMA will have any effect on black market availability or misuse.

 

[MrSpeedyG]

Ho-Chi-Minh, any major dude's above reply is exactly on par with what my reply would have consisted of. It's not goign to be handed out like lollies I strongly and logically like any one else here, would asume that if MDMA is legalised for treatment of PTSD and/or other mental health issues that it is not going to be prescribed to take daily or per-as-needed basis at the discretion of the patient, but rather administered then and there by the psyciatrist and supervised by too.

Unless the psychiatrist is corrupt and they are somehow diverting the MDMA, mind you I would again logically presume there is going to be heavy controll on this, and even if they did so what it means a few doses of pharmacy grade MDMA make it to the street amongst the already stomped on MDMA/who knows these days is floating around.

My strong opposition to what your saying Ho-Chi-Minh is nothing personal, I just find you are over looking the potential for MDMA use in PTSD when I and many others believe it has proven itself as an extremely useful and successfull tool in combatting many hard to already combat mental disorders and worried about a few doses making it to the street somehow... if someone wants MDMA it is around and not hard to find and lets face the facts here, prescription medicine will always make it to the streets whether you want to believe it or not.

In terms of neurotoxicity, sure like I said comparing apples and oranges here yes MDMA does have neurotoxic potential I'm not going to be some MDMA fan boy and say what I want to believe is true, but in a controlled setting and controlled doses I don't think this is of much concern. Keep in mind, methamphetamine is well-known as one of the most neurotoxic substances that is abused yet also prescribed in therapuetic doses to change peoples lives for the better... then there is adderall/amphetamine, benzos have shown to causes irreversible brain changes, prescription opiates... All have the potential for damage. The difference between these drugs and MDMA is that MDMA won't be handed out as easy as what these drugs with abuse potential are and as I said before and logically presume MDMA if legalised would be administered then and there on the spot and not handed out - handing it out after all would be useless anyway as it needs to be taken and for the therapeutic effects of it to be used... again it has to be used in conjunction with a trained person in this.

SSRIs are so safe compared to other drugs its scary.

I may be anti-SSRI as many others here are, but what good is a bandaid solution that comes with a hefty price for most people as far as I have seen and in a lot of cases people have to go through different SSRI/variants to find one that "works" for them... It is well known, unless your living under a rock, that they have put people even worse off than without them and some have been left with permament side effects... Sexual function comes to mind and that can severly quite frankly, fuck someones future up.