GDS 2020: MDMA: not just about the dose but how you divide it (or not)

Professor Adam R Winstock, Consultant Psychiatrist and CEO, GDS

Last year saw a record number of people die from MDMA in the UK, up over 50% from 63 in 2016 to 92 people in 2018. The rise is thought to reflect both more people consuming the drug and the widespread availability of high dose pills and high purity MDMA powder. While some causes of death such as liver failure and SIADH (water intoxication) are pretty random, others such as hyperthermia, (overheating), dehydration and possibly cardiovascular incidents are more predictable and potentially avoidable.

MDMA dose, polydrug use and behaviours like physical exertion and not rehydrating might all be possible points of intervention that could reduce these risks of harms associated with the use of MDMA. We also know that the risk of harm increases with frequency of use.  Although 3% of respondents to GDS2019, reported using MDMA on 50 or more occasions in the last 12 months, most people report using MDMA on 10 or less occasions per year.

Over the last 8 years GDS has tracked the usual amount of MDMA people report using over the course of a session.  Doses of over 150mg are considered high, because this the upper limit used in human studies and shown to be safe within clinical settings. Since GDS2016 the reported dose of MDMA consumed has remained pretty constant at about 0.3gm of powder or about 1-1.5 pills on a day of use. However over 15% of people reported taking 2 or more pills in session and 20% more than half a gram of MDMA powder. In the absence of any obvious change in either accompanying behaviours or polydrug use patterns, the recent spike in deaths is most likely to be attributable to more people taking MDMA and the larger doses some people (especially younger) are taking.

MDMA time to onset and redosing. The effects of MDMA when taken orally usually begin after 30–45 mins (this can show very wide variation with onset being much quicker after dissolved powder and much slower with some highly compressed pills). After a dose of 75-150mg people report peaking at 60–90 mins and start to come down after 2-3 hours. Consequently, many users take further doses if they want their evening to continue. The problem is that the way our bodies breakdown MDMA can be unpredictable and varies between people and redosing can be difficult to get right.

A bit of science….

 MDMA is broken down in your body by enzymes in your liver. These enzymes produce other substances some of which don’t do anything but some of which do a lot.  What’s a bit weird is that one of the breakdown products of MDMA actually stops one of the major enzymes involved in MDMA metabolism working. This means that your body may become less effective at breaking down MDMA after a certain dose. The consequence of this is that small increases in MDMA dose can lead to unexpectedly large increases in blood level. The higher the blood level of MDMA, the greater the increases are in things like heart rate, blood pressure and other stresses on your body

The scientific term for disproportionate increases in blood level following small increases in dose is known as non-linear kinetics. It is also important to know that you don’t make new enzymes for 10 days, which means the risks remain for over a week. It’s reassuring to know that 75% of people who use MDMA do so less than 10 days a year, on average more than 4 weeks between doses. That is very sensible. But because of differences in our genetic make-up, people breakdown MDMA differently, especially after they have taken a first dose. Second doses taken by different people can lead to very different effects; one might feel unwell, while another just gets a better buzz. In addition, the link between how much you take, and your blood level depends on the size of each dose, the time you leave between doses and whether or not you have consumed alcohol.

GDS has already identified that being drunk before you take your first dose is big risk for seeking emergency medical treatment. Don’t have alcohol on board (especially lots of alcohol) before you take your first dose of MDMA.

So dosing is complex, and the results may be unpredictable. Ending up in the emergency department is fortunately rare, suggesting most people have worked out how to use MDMA without experiencing severe harm. The risks are higher for young people and women. That approximately 1% of MDMA users reporting having sought emergency medical treatment over the last 12 months,  means that over the course of the year, thousands of people who use MDMA are exposing themselves to harm that could be reduced if they altered the way they chose to consume the drug. Based on what we learned from the Global Drug Survey Highway Code, we suspect that once we analyse the data, we’ll conclude that  safer use is  more enjoyable use.

This year we want your help to better identify dosing patterns associated with risk. We want to know how and when you decide to take a second dose or third dose how this alters your experience. This will add to the findings from previous surveys and will help us develop even more nuanced advice to people, who we know want to have fun, stay safe and keep their mates safe.

So if you have taken MDMA in the last 12 months and want to help us make drug use safer for other people, please take 20-30 minutes to take part in GDS2020: