Here's crazy case report of man who "overdosed" on placebos given to him as part of a blinded clinical trial.

https://pubmed.ncbi.nlm.nih.gov/17484949/

His blood pressure crashed (80/40 initally, 100/62 after several hours of IV fluids) and his heart rate was over 100 bpm. When he found out the pills he had taken were inert, he bounced back almost immediately.

just a panic attack

It's obviously psychosomatic (which is why I brought it up) but it's different from a garden-variety panic attack:

- Blood pressure tends to shoot up, rather than down, during a panic attack.

- Four hours would be incredibly long; they're usually more like 20 minutes

Wow, that is bizarre. At first I'd say it seems unbelievable, but then when you think of people in churches speaking in tongues, etc. -- I guess I could see it.

But if you've ever done MDMA you'd certainly know it was a placebo, so it feels like these are people who never had, but imagined what they thought it ought to be like.

I'd actually be incredibly curious to hear their description of it? Especially since everyone knows what people act like when drunk or on cocaine... but I'm not quite sure people have as definite an idea of MDMA?

The first MDMA experience is usually very surprising, yes, but not for everyone. Depending on how you usually regulate your serotonin release, getting a very similar feeling to that of a run of the mill "roll" may happen if you are just very happy or melancholic or introspective. A very deep conversation about something that you have been wanting to let go for a while or a therapy breakthrough can elicit that feeling.

I don't know about this couples therapy thing, but remember that in most of this trials researchers are dealing with somehow of an "unstable" brain chemistry. Individuals with PTSD or ASD tend to dissociate even when sober and to be very sensitive to mindset and setting and believing they took a pill that is going to make their struggles go away while talking with a therapist can be a very warm and welcoming setting.

That being said, I also would like to point out that how people act on cocaine is usually heavily misunderstood and most of the stereotype of someone under the influence of cocaine is usually how people act on cocaine+some other strong stimulant like pseudo-efedrine. Cocaine was used medically for a long while and it's effects are very well understood and not similar to the usual "that person is on coke" stereotype.

Indeed. It's something I rarely hear mentioned, but I have found valuable about recreational drugs - they teach you a lot about how your body works and what certain things feel like. A lot like tasting a spice in isolation allows you to pick it out in a complete dish.

I remember kids at school acting drunk because they thought someone gave them a drink.

I think it's like hypnosis - they say that just allows people to do what they want to do anyways. It's just permission to act differently and that be OK.

> But if you've ever done MDMA you'd certainly know it was a placebo

What's the dose used in the experiment? Similar to a recreational dose, or much smaller? If it was much smaller, i could imagine people not really being able to tell.

EDIT: The paper [1] says there are two MDMA 'sessions', about three weeks apart, and:

> Each partner was given 75 mg MDMA in the first MDMA session, and 100 mg in the second MDMA session, with an optional supplemental half-dose 1.5 hours later in both sessions (participants were informed that the supplemental half-doses could prolong the therapeutic window of MDMA effects).

I am told that a typical recreational dose of MDMA is 100 mg. More concretely, an Orange Tesla is ~250 mg, so make of that what you will.

[1] https://www.tandfonline.com/doi/full/10.1080/20008198.2020.1...

1mg per lb of body weight is about what is required to “roll” for a very infrequent user. I personally think it is a pretty ideal drug to use no more than twice per yer with a partner, and you sure as hell don’t want a therapist in the room, as it would waste the physical intimacy effects.

It depends what you're going for. Maps.org's research with MDMA-assisted psychotherapy for PTSD had incredible results. If you do it recreationally with a partner you'll become physical-intimate with, you'll be able to distract yourself away from yourself more - if doing it solo with guidance and support of someone else, you'll more be able to focus and process on thoughts/feelings/memories that come up. There's benefit and space for both.

> But if you've ever done MDMA you'd certainly know it was a placebo, so it feels like these are people who never had, but imagined what they thought it ought to be like.

There have been times when the effect of coffee or marijauna hits me after a few sips/a bite of an edible, which feels placebo-y. But then I'm aware that it seems to be too fast, even as I start to feel it so fast, so could that still be a placebo effect?

I don't know, but it confuses me.

I too have noticed this when I tried an edible. An almost imperceptible high that occurred for a few minutes just after ingestion. However this should be impossible as the time taken to metabolize THC is typically an hour or two.

My only guess is that some of the THC is absorbed orally, but in a small quantity. That might explain the high feeling. Can't say I would know what the mechanism for this is, just a guess.

There are quite a few reports of people experiencing powerful somatic effects just from the anticipation of taking a drug, without having taken any.

Experiencing an unusual taste in the mouth is common. I've heard of some people feeling a need to vacate their bowels when they are anticipating taking a drug.

So it's not at all surprising that when you actually take a drug you experience something right away, even before the drug has had time to work.

The mind is a powerful thing.

This is a completely untested hypothesis, but I wonder if these kinds of effects are somehow related to hallucinogen persisting perception disorder (HPPD). People experience some really powerful effects under the influence, and maybe the mind somehow learns to reproduce some of these effects on its own.

Its a common joke in teen tv shows, where the main character is supposed to obtain alcohol but can't so buys non alcoholic beer, but everybody thinks its the real thing and nobody notices.

Not sure how based in reality that is, but seems to imply a similar effect for other drugs might be real.

I'd bet that that was one of the controls in the study - targeting participants who had never used MDMA before. Otherwise it would affect the integrity of the placebo group.

Clearly you've never seen one of the kegger pranks where someone buys a keg of non-alcoholic beer and everyone acts drunk :P

This is certainly possible. I've relaxed and loosened up on 0% beer as though it had alcohol when I knew that's what it was too.

I strongly suggest with little evidence that if you took 10 people who had previously taken MDMA and gave them placebos at least 9 would know it if not all 10. A single digit percentage of the control who don't know they got a placebo probably renders it pretty useless.

The BBC did a doco [1] on MDMA as a symptom mitigator for parkinson's disease with a stuntman who had it bad but liked to party at music festivals and saw it completely alleivated the symptoms. They did the two trials thing with him, take a pill (once mdma, another time placebo) and try to perform specific tasks in a gym and grade how well he could do it. The cameras got him saying something like this to the boffins in white coats: "I know this is the real thing because I can do it all easily and THE MUSIC ISN'T LOUD ENOUGH!!!"

[1]https://www.bbc.co.uk/science/horizon/2000/ecstasyagony.shtm...

I drink decaf coffee sometimes and still feel the same boost as drinking caffeinated even though I know is has much less caffeine. I guess its mostly in my head. Although decaf does have some caffeine.

This is all about previous association - your body reacts to the thing because it has worked before.

The same happens when you take a paracetamol, you always feel better as soon as you've taken it, but it's because previously it did really work.

A similar thing happens with cursing - you can put up with more pain while shouting swear words than normal words, it is believed that is because you associate all those swear words with previously painful/traumatic times in your life and you're kind of drawing on those for extra strength.

The brain is strange and marvellous.

You're not wrong, but those are definitely edge cases. You couldn't give placebo MDMA to a group of 50 people without the majority of them calling your bluff.

The problem then becomes the "nocebo" effect, wherein the patients who know they haven't been dosed with a powerful psychoactive substance assume that their treatment will be ineffective, and therefore stop giving it the required effort.

With therapy, it's important that the patient be onboard with and believe in the therapy. Giving people obvious placebos is a reliable way to lower expectations and instill doubt.

Also people who didn’t receive a placebo who didn’t seem to respond at all and claimed to have received a placebo.

Interesting. Got a link to a study?

Not off hand. About a year ago I watched and listened to a huge number of talks and videos on psychedelics in general and psychedelic therapy in particular, and it was at one of those that I heard an MDMA researcher mention this.

My best guess is that it was at a video of a talk or interview given on the Aware Project[1], or on an episode of the Psychedelic Salon[2]

[1] - https://www.youtube.com/channel/UC0oErWkP157InE47YAuhzPg

[2] - https://psychedelicsalon.com/