The Science of MDMA & Its Therapeutic Applications

To date, at least to my knowledge, there don't seem to be any data in either non-human primates or in humans showing toxicity of MDMA at clinically relevant doses provided it is pure MDMA.

For moderate, meaning people who have taken ecstasy anywhere from 20 to 50 times in their lifetime, as well as heavy users of MDMA—so, these are people who have taken MDMA anywhere from 60 to 450 times in their lifetime—there was little evidence of decreased cognitive performance in standard assays for cognitive performance.

You will see protocols that people put out on the Internet such as, 'Oh, you know, after taking MDMA, you should take a bunch of 5-HTP or other precursors to serotonin or dopamine' ... There's really no evidence that any of those things can be beneficial and there is, actually, some reason to believe that it might be detrimental...

I also want to highlight the fact that, nowadays, all recreational drugs, but certainly MDMA included, are often—in fact, very often—contaminated with fentanyl ... The current estimates are as much as 60%, maybe even 80%, of drugs sold on the gray market are being repackaged or reformulated with fentanyl...

MDMA ingestion is known to dramatically increase prolactin, and people are starting to realize that it perhaps is the increase in prolactin... after ingestion of MDMA that leads to at least some components of the so-called crash ... Some people have started to explore the use of things like P5P... which is known to suppress prolactin as a way to try and buffer some of that crash.

The increases in serotonin that MDMA creates are at least three times and maybe as much as eight times greater than the amount of dopamine release that MDMA causes.

The major effect of MDMA for the treatment of PTSD is not to cure PTSD but rather to make the therapy, the talk therapy, for PTSD much more effective ... MDMA taken on its own does not cure PTSD; MDMA can augment or boost the effects of talk therapy for PTSD.

The typical dosages of MDMA used in these neuroimaging studies and in the clinical studies of PTSD... range anywhere from .75 mg per kg of body weight to 1.5 mg per kg of body weight. So, for somebody like me—I weigh 220 pounds, that's 100 [kg]—1.5 mg per kg of body weight would therefore be 150 mg in a single dose.

If you've heard that taking caffeine within the hours or same day as MDMA can increase the toxicity of MDMA, that does appear to be true based on animal studies.

The primate studies... which are the sorts of animal studies that most closely mimic what one expects to see in the human brain... There, the data start to get kind of complicated in a way that suggests the MDMA might not be as neurotoxic as is thought based on the rodent studies.

MDMA is very different than the other psychedelics. And my hunch is that, over the next few years, we will stop talking about MDMA as a psychedelic because it does not tend to produce visual hallucinations or auditory hallucinations of the sort that classic psychedelics do...

There is still the risk of neurotoxicity if people are taking high doses of MDMA or taking it very frequently or certainly if they are taking it in conjunction with other drugs or... taking MDMA in settings that can promote neurotoxicity. And the settings I'm referring to are any settings in which blood pressure or body temperature have the propensity to be greatly increased.

MDMA has a bi-directional effect on our perception of others' emotions, making people more likely to rate something as positive if it's initially positive or even a little bit positive and less likely to rate a threatening face as more threatening.

Like any drug, the toxicity of MDMA does scale with the dosage that's applied.

What's also been done is to give people 1.5 milligrams per kilogram of MDMA, and to look at the connectivity between the amygdala and the insula ... There's a weakening of connections between the amygdala and the insula and that scales very directly with the relief of symptoms from PTSD.

MDMA is currently granted breakthrough status, which means it's now something that scientists and clinicians can study if they have authorization to do that. It is, as I mentioned earlier, still a schedule 1 drug, so it's illegal to possess unless you are one of these scientists who has been granted permission to study it in the clinical setting or the laboratory setting.

MDMA, because it has this methamphetamine component, prevents the reuptake of dopamine and, in doing so, creates net increases in dopamine.

One of the key things that quality MDMA therapy consists of is not just having a very good rapport and communication with the therapist that's guiding the PTSD treatment but also rapport and a willingness to engage in conversations with oneself.

When people are on MDMA, their response to threatening faces or other threatening stimuli is reduced—and it's reduced in a very specific way, which is reductions in activity of the amygdala.

If you give somebody an SSRI prior to them taking MDMA, you actually block the pro-social and empathogen of MDMA.

It does not appear that the increases in oxytocin produced by taking MDMA are the source of the pro-social effects of MDMA.