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The Genetics of an Ecstasy Hangover (5/4/05)

     MDMA ('ecstasy') users have long noticed that some people are more negatively effected by frequent use than others; while some people became quite sketchy on twice-a-month usage, a few seemed able to use every weekend for years without serious negative emotional consequences. According to researchers at Cambridge, England there may be a genetic factor at work.

    The study focused on the gene that produces the Serotonin Transporter (SERT), the protein that recovers serotonin after it's released (and which MDMA interferes with in order to cause an intoxicating massive release of serotonin.)  One form of the SERT gene is more active than the other; it produces more SERT proteins.  As a result, individuals with two copies of the highly expressed 'long' gene produce about twice as much of the SERT protein as individuals with two copies of the low expression 'short' gene.

    Prior research indicated that 'short' gene (lower SERT production) individuals were at greater risk of psychological problems, such as depression. Theorizing that MDMA use (which itself has a disruptive effect on the mood-stabilizing serotonin system) might affect people with different genetic makeups differently, the researchers genetically tested and evaluated the emotional health of 66 'ecstasy' users, 30 marijuana users, and 28 healthy non-drug users.

     They found that there was some correlation between 'ecstasy' user's SERT genes and their emotional health.  Among non-drug users and marijuana-only users, levels of depression were not strongly affected by genetic makeup. Within the 'ecstasy' user group, however, people with two copies of the 'short' (low SERT production) gene had significantly higher levels of depression than the 'ecstasy' users with genes for higher SERT production.

    As this is the first piece of research to examine how genetics may affect MDMA side-effects it's premature to draw too strong a conclusion from it, but it's tantalizing none-the-less as the first evidence of a possible genetic basis for a phenomenon that users have noticed for years.

Download journal article (.pdf).

• Related reading: How MDMA works.