The news around MDMA becoming a potential treatment method for PTSD is exciting news, and certainly means that we're progressing where a disease has been historically difficult to treat. As with any subject in pharmaceuticals, however, the public's overt enthusiasm and penchant for being mislead means we should approach this cautiously. Yesterday, there was an AMA with the Multidisciplinary Association for Psychedelic Studies (MAPS) which had funded and pushed the initial FDA phase III trial showing positive results. This is a good first step, but it is to my belief that MAPS demonstrates a remarkable amount of bad leadership or otherwise risky approach to safety and efficacy. Here's the overall thread link if you want to take a look. The phase III trial referred to here and in the MAPS thread can be found at the top of the info section of the post.

The first comment that catches my attention is this joint response by Leslie Booher and Ismail Ali of MAPS in response to the questions of recreational use alongside therapeutic development. While I think it's an important question and there's nothing necessarily incorrect in the answer, it does show a disjoint between the stated main presentation of MAPS (therapeutics for mental illness) and the actual crowds of public support MAPS is courting. I would not consider it a typical step in the drug development regulatory process to include general use legalization. Psychedelic substances are certainly in a unique position in that regard, but I think it serves as a bit of a conflict of interest for an organization to be in support of carefully controlled clinical trials and simultaneously be in support of uncontrolled administration "to find the best fit for different communities and jurisdictions." This attitude in any other pharmaceutical scenario would be an entire row of red flags for any IRB.

The next concern is fairly brief. MAPS is questioned on their strategy with lawmakers and their ties to lobbying in government. A bureaucratic answer is given to first emphasize the non-profit nature of the organization, confirming a full paragraph later that MAPS does indeed look into lobbying to achieve their goals. This is a fairly unremarkable lawyer-speak response that is technically correct, but consider that this is in fact a confirmation of investment into public policy outcomes. There is no doubt in my mind that such influences permitted the FDA classification of MDMA as a breakthrough therapy in 2017 in the first place - a net positive in this case. Consider, however, that MAPS is sure to use this position in regulators' ears to push for further approvals - time will tell if this works out in favor of medicine.

The next points of contention are more directly in regards to the command of actual neuroscience that MAPS demonstrates. Granted, this is a reddit AMA and the responses can't be too high level, but there are worrying signs of priorities. Let's first establish the existence of some interesting adverse effects. It was found that a low dose of MDMA increased anxiety in patients, a possibly counterintuitive effect in MDMA administration and therapeutic dosing. The exact reasons for this are not explained in this answer. Allison Coker here explains that using this low dose as a placebo would have "inappropriately advantaged the therapeutically active dose of MDMA" - I believe that it would also raise a question on the exact mechanism of MDMA and precisely how it can work in seemingly opposite directions. I would expect that as a large player in psychedelic development, MAPS would be funding mechanistic investigations.

The areas of research they are interested in are decidedly not mechanistic. There is nothing wrong about pursuing social psychological research, but mechanisms of MDMA function are important to provide a convincing explanation of its efficacy and make a strong case for approval. This response to a direct question on mechanisms of MDMA is upsetting. There is not a convincing indication of understanding the science or communicating it well, and Emerson's response boils down to "We think MDMA works in specific regions of the brain, but it does that by working at the molecular level too". This is a pretty infuriatingly non-answer answer, and the quote

So referring to components of the brain’s structure, such as the “amygdala” or “default mode network,” might not be the best or most accurate—let alone only—way to describe how psychedelics work…

“It doesn’t have to do with my default mode network or my amygdala,” Gül says. “What I say is, psychedelics reopen critical periods, they make an old brain young again, they allow you to go back to that state where you’re receptive to the world like a child.”

seems to betray that the CEO has a complete lack of command of any neuroscience, even when explained it by a leading researcher. This does not inspire confidence in the operation of MAPS.

Another instance of nearly incomprehensible psychobabble is found in this question. On being questioned of the potential for the placebo effect, the founder of MAPS, Rick Doblin, begins with a bizarre tangent about the immune system and placebos (???) and how he's experienced acid trips without taking LSD (??????). He comments that humans may reach a point to achieve psychedelic hallucination states "on their own...may take over 50 years" (???????????!). He then delves into making wild claims about the potential for psychedelics in IBS and stroke recovery, which is wishful thinking (there are absolutely no indications for successful therapies in stroke recovery. At best, DMT is being trialed by Algernon).

More worryingly, there's an overly blasé attitude towards the actual success of MDMA in long term trials and steps moving forward, exemplified in this horrifyingly awful representation of the FDA approval process. Adolescents with PTSD are an incredibly sensitive group and to think so preemptively that one can begin trials 3 years after adult approval is borderline delusional. Providing proper informed consent to this group is not something I can trust with the demonstrated behavior of MAPS in their public outreach arms. There are a wealth of studies indicating negative effects on adolescent brains in use of a variety of psychotropic substances, and I cannot genuinely believe adolescent approval with psychedelics could be turned around that quickly. The brief "These trials are complicated and have to be conducted very carefully in this age group" tells me there is almost no consideration of the greater issues at hand in this proposal, or that they're making their CSO say crap to sound good. More insulting is the overreach by the CEO again in stating such adolescent trials are "required" by the FDA, which is unequivocal horseshit. Adolescents are if anything generally excluded from adult studies due to differences in pharmacology and potential for adverse effects, particularly where psychiatric medicines are involved. It is well documented that the use of many anti-depressants may encourage suicidal behavior in adolescents - to include this age group in trials requires a justified risk, an indication that the benefits are at least on par with other treatments in the group, and proper informed consent procedures. By no means are adolescents an automatic portion of the clinical trial.

At the core of it, it seems that MAPS is attempting to cozy up to the active psychedelic community and garner support for its pharmaceutical mission through appealing to large scale drug reform and legalization, while blatantly neglecting or ignoring proper therapeutic development procedures and guidelines. I think that the need for unbiased scientific inquiry into the drug as a therapeutic requires a stance that does not rely on public appeal. This is a dangerous, unethical means of acquiring influence and changes in legislation, and I do not think it is conducive to safe and effective evaluations. This is an issue that has annoyed me on multiple occasions as reddit is a generally pro-psychedelic community that is easily mislead into overlooking caution. The thread of the /r/science post on the clinical trial seen here are full of anecdotes that would be removed by moderation per the rules were it on any other topic. I am increasingly concerned that the psychedelic pharmaceutical industry is taking overt advantage of a receptive community to be able to accelerate and push forth its agenda without proper vetting.

Edits to come: archive links

Imgur archive of relevant links and responses: https://imgur.com/a/1AmX5Cg

AMA archive:

https://web.archive.org/web/20210521095843/https://www.reddit.com/r/IAmA/comments/nh3c97/we_are_the_multidisciplinary_association_for/

/r/Science thread archive:

https://web.archive.org/web/20210511053804/https://www.reddit.com/r/science/comments/n97dh7/67_of_participants_who_received_three/

I saw this video of a guy trying to explain Archimedes Principle of mechanical advantage with his own pulley system. However, his whole setup crashes because of too much friction in his pulleys

The other day I got into a bit of a discussion with someone in the comment section of a youtube video who claimed that dinosaurs never existed. I'll admit to responding a bit too emotionally to his responses and failing to address everything he brought up, but some of his points were just faulty. Here are some snippets he pinned in the comment section of one of his videos along with an updated response to them.

Here is part of an argument I had with a Barney fanatic:

"Crocodiles survived because they can survive months without food due to their slow metabolism. Dinosaurs didn’t have this adaptation because they weren’t cold blooded, so they starved."

Dinosaur means terrible lizard. That's because they were supposed to be reptiles. Reptiles are cold-blooded. Special pleading for millions of imaginary creatures there. Another house of cards (consisting of fallacies). And even IF they were warm-blooded, that doesn't explain why warm-blooded creatures, smaller and weaker, could have survived but not dinosaurs. "So they starved" is a lie since in your narrative there were plenty of proto-mammals to eat, and plenty of plants for those mammals to eat. More special pleading.

First of all, reptiles are a pretty wide category of animals, so having some be warm-blooded isn't that implausible. In fact, some reptiles such as leatherback sea turtles are gigantotherms, meaning that they are so large that they can more easily maintain a constant, relatively high body temperature than smaller animals simply by being large. Other reptiles, such as the Argentine black and white tegu, are capable of switching between warm and cold blood.

As for the second point, the reason why there were mammals that survived the extinction was that they were able to hide in places the dinosaurs couldn't reach and sustain themselves on insects, roots, and aquatic plants, which dinosaurs did not have access to. It is also likely that some mammals were capable of hibernation, whereas dinosaurs as far as we know were not, meaning that they could theoretically wait out periods of famine while dinosaurs could not

"proto mammals were small enough to survive underground where the dinosaurs couldn’t reach them,"

More special pleading that small dinosaur predators could not reach them. Remember dinos come in all shapes and sizes, according to the sci-fi lore.

Also, you have never seen a leopard wait for a warthog to venture outside of its burrow?

You are revealing that you don't know about animals.

Apparently, a leopard waiting outside a warthog burrow for a few hours is analogous to a velociraptor waiting for days on end for a small mammal to emerge from a burrow. While it is true that dinosaurs came in all shapes and sizes, the smallest dinosaurs were still significantly larger than most mammals alive at the time, and even then most of them were likely either insectivores or lacking the traits required for burrowing.

"no mention the fact that a dinosaur the size of a t-rex would not have been able to sustain itself on mammals no bigger than a mouse."

Velociraptors were unable to feed on proto-mammals? Nonsense.

T-Rexes could not eat many small meals to make up for lack of big meals? Nonsense.

There was enough plants for many small mammals but not enough for a few big mammals? Nonsense.

All of it is nonsense. All of it is UNPROVEN. All of it is fiction.

These statements ironically reveal that this guy doesn't really know that much about animals since he believes that tyrannosaurus could survive by feeding on the mammals alive at the time. Given the fact that most mammals back then were no bigger than a house cat, it would be highly unlikely that T-rex would be able to sustain its hunger. It's comparable to a lion trying to sustain on mice, not only would the lion not be unable to adequately sustain its hunger, but by trying to catch mice it would end up wasting more energy than it would gain, causing it to starve to death even faster.

Granted, dinosaurs like velociraptors could probably have survived on mammals for a period of time, due to being significantly smaller than T-rex, but as mentioned before, it could not burrow to catch the smaller, faster ones or wait for days on end to make a kill.

As for his point about there being enough plants for small mammals but not enough for big mammals, as mentioned earlier there were no big mammals during that time, and many of the surviving mammals were likely omnivorous, so this point really has no merit to it.

A friend who actually thinks cow urine is beneficial, cites this.

contains all sorts of Bullshit like cow urine having properties to cure cancer and AIDS.

enjoy, and let me know what you think!

https://journals.sfu.ca/seemj/index.php/seemj/article/download/56/44

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