MDMA-assisted therapy for PTSD: A randomized, placebo-controlled phase 3 trial

The proposed use is MDMA-assisted therapy. Take a dose, talk to a therapist. Wait a month, repeat. You seem to be imagining people popping the stuff like SSRIs.

Intuitively, this makes a lot of sense. MDMA is a fun drug because of the fact that it makes it basically impossible to feel negative emotion under its effect. PTSD is characterized by extreme negative emotion around a particular trauma, to such an extent that it becomes disruptive to living a normal life. Just talking about the traumatic inducing experience can lead to uncontrolled emotional responses, making it difficult to approach therapeutically. The MDMA acts as a shortcut around that last bit: by blocking the patient from feeling negative emotion while they talk about their trauma, they can re-evaluate it in a more removed way.

Combine that with theories about how we edit memories when we recall them, and you've got a pretty obvious method of action.

It's not intended to be a chronically taken treatment. But the results were pretty massive. That CAPS-5 score they talk about the reduction by 24 points versus therapy alone's 15 is on an 80 point scale, with the bare minimum for PTSD diagnosis at a 12, and "moderate" PTSD being in the 23-35 range.

Compared to most results coming out of the mental illness treatment field, MDMA's looking like a silver bullet.

As with all of these studies, it’s important to remember that this isn’t evidence that taking MDMA by itself is therapeutic. The therapy sessions are the primary treatment in this study and the MDMA is being explored as an adjunct to therapy.

I don’t know who needs to hear this, but: Taking MDMA you bought off the street and hoping it’s going to cure whatever ails you isn’t even remotely similar to what’s being studied here. MDMA is also well known to produce depressive rebound effects in the following days that can worsen mental health problems if the patient isn’t properly monitored and prepared. (and no, taking some supplements and 5-HTP won’t save you from all the side effects no matter what that guy on the internet claims)

Importantly, both the MDMA-assisted therapy and the regular therapy groups improved over the course of this study. It should go without saying that regular old therapy is and will continue to be the first-line treatment for PTSD. People will debate the relative safety of MDMA all day long, but no matter how you look at it, MDMA will always be more risky than therapy alone. The MDMA group had a 1-in-10 incidence of treatment related adverse events, for example.

Another important piece of context is that true placebo control is impossible in these studies. Patients and caregivers will know which patients received MDMA due to the dramatic effects of the drug. This doesn’t negate the study, but you do have to consider the fact that these patients went into this study expecting to maybe get MDMA with the expectation that MDMA would help them. They would no doubt be either excited or disappointed after realizing which group they were in. This will, unfortunately, impact the results in ways that can’t be measured.

I hope future studies will compare against an active control group. It would be much better to compare, for example, therapy with placebo, therapy with SSRI, and therapy with MDMA. It’s easy to differentiate from placebo, but it’s much harder to find new treatments that outperform existing options.

Another alternative would be to trial an active placebo group. For example, if one group received MDMA and another group received a dose of amphetamine then both groups would know they had received a psychoactive drug with euphoriant properties, but if they were truly drug naive (as asked in the intake screener) then theoretically they wouldn’t be able to tell which group they were in. This would more effectively isolate MDMA’s unique properties, if any, without breaking the blinding as much.

Alupis is simply trying to help out Science in an objective and apolitical way by pointing out that some phrases can rile people up into hooting and hollering. Phrases like “assigned female at birth” can, to use an empirical term, “whip one up into a real doozy of a tizzy” that can only be quelled by posting. Anything that might trigger Poster’s Rage is definitionally Not Science because scientific words do not make people “get all flustered”

Blinding isn’t just about the patients - It’s about the therapy providers as well. We would like to think they’d provide the same treatment regardless of what the patient received but over-eager researchers tend to get more excited about the active group and provide them more attention and enthusiasm.

Niacin isn’t a great placebo these days because it’s not the 70s any more and people going into these studies will probably Google what to expect from the drug. Also Niacin is short acting and makes people itchy and uncomfortable, so it’s not really compatible with therapy.

> Mass is usually referenced instead of Weight

You’re telling me buddy! People actually think that doctors weigh babies and write down the numbers they see on the scale when everybody really smart knows they measure infant Mass by measuring their liquid displacement and multiplying it by the density of the standardized homogenous baby slurry provided by NIST.

It’s like dang John Stewart in every delivery theater I tell you what